CN116744847A - Method and system for body lumen medical device positioning - Google Patents

Abstract

Systems and methods for locating a medical device in a body lumen are provided. The first flexible elongate instrument includes a plurality of imaging markers and the positional information sensor is disposed at the first flexible elongate instrument or at a second flexible elongate instrument configured to move relative to the first flexible elongate instrument. The processor is configured to: establishing a reference coordinate system based on the plurality of imaging markers visible in a medical image comprising the first flexible elongate instrument disposed in the body lumen; receiving diagnostic scan information or therapy delivery information from the first flexible elongate instrument or the second flexible elongate instrument at a plurality of locations of the body lumen; and associating the information with the imaging markers. The display is configured to display a composite image including the associated diagnostic scan information or therapy delivery information and the imaging markers.

Description

Method and system for body lumen medical device positioning

RELATED APPLICATIONS

The application claims the benefit of the following applications: U.S. provisional application No. 63/122,233, filed on 7/12/2020; U.S. provisional application No. 63/122,424 filed on 7 of 12 months 2020; U.S. provisional application No. 63/122,433, filed on 12/7/2020; U.S. provisional application No. 63/176,342, filed at 18, 4, 2021; and U.S. provisional application No. 63/176,341 filed on 18, 4, 2021. The entire teachings of the above application are incorporated herein by reference.

Background

Intracoronary imaging is commonly used to accurately measure vessel and stenosis dimensions, assess vessel integrity, characterize lesion morphology, and assist in body lumen surgery, including Percutaneous Coronary Intervention (PCI) surgery. In recent years, the frequency of complex percutaneous coronary interventions has steadily increased, as interventions offer clinical benefits that can increase the life expectancy and quality of life of patients suffering from endovascular neurosurgical, cardiovascular and peripheral arterial diseases. Various diagnostic and therapeutic medical devices (e.g., guidewires, balloons, atherectomy, lithotripsy, stents, imaging and physiological diagnostic modalities, X-ray angiography, and fluoroscopy) enable radiologists, cardiologists, and vascular specialists to visualize the patient's internal vasculature to guide therapeutic decisions and perform interventional procedures. Typically, X-ray fluoroscopy with contrast agent injection is used to guide a physician in positioning devices (e.g., stents, guidewires, and balloons) along a guidewire within the internal vasculature toward a target lesion site.

In PCI procedures, vascular access is typically obtained through arterial access points (such as the radial, brachial, or femoral arteries), or through venipuncture. Through this access point, the physician may access the vasculature of organs such as the heart, lungs, kidneys, and brain by advancing the guidewire into the patient until the distal end of the guidewire passes through, for example, the lesion to be treated. After the guidewire position is finalized and positioned such that it is visible on the angiographic image, the desired therapeutic and/or diagnostic device is mounted at the proximal end of the guidewire. The treatment and/or diagnostic device is then advanced distally of the feature of interest.

Depending on the clinical situation, pre-interventional assessment may be performed using imaging and/or physiological probes, such as intravascular ultrasound (IVUS), optical Coherence Tomography (OCT), and Fractional Flow Reserve (FFR) devices, for example, for determining lesion location, lesion size, plaque morphology, and coronary artery pressure at the region of interest. Endoluminal diagnostic modalities such as IVUS, OCT, and FFR are capable of generating more detailed vessel lumen information than that obtained from X-ray imaging alone, and are widely used for minimally invasive PCI procedures.

Endoluminal device guidance typically requires real-time display of the device's movement inside the body lumen. The methods currently available for guiding and positioning are based on real-time X-ray angiography imaging, such that both the lumen path of the blood vessel and the equipment inside the lumen are continuously visible during surgery. X-ray imaging for vascular diagnosis and device guidance emits a number of frames of X-rays per second and typically requires the injection of a contrast agent that visualizes the blood vessel to assist the clinician in locating and positioning the medical instrument. This practice results in both the patient and clinician being exposed to high radiation and the delivery of large amounts of contrast agent to the patient, which can cause damage to the kidneys.

There is a need for improved systems and methods for providing endoluminal device guidance and positioning of medical devices within a body lumen.

Disclosure of Invention

Systems and methods for locating a medical device in a body lumen are provided. Such systems and methods may advantageously provide improved accuracy over existing positioning methods and reduce radiation exposure for clinicians and patients. The following example systems and methods are generally described in the context of an example of intravascular diagnostic scanning and radiopaque imaging markers; however, these methods and systems may be applied to other endoluminal applications and may utilize imaging markers visible in modalities other than X-rays.

A system for positioning a medical device in a body lumen includes a first flexible elongate instrument including a plurality of imaging markers (e.g., radiopaque imaging markers) and a position information sensor disposed at the first flexible elongate instrument or at a second flexible elongate instrument configured to move relatively (e.g., parallel relative movement) with respect to the first flexible elongate instrument. The system further includes a processor configured to: establishing a reference coordinate system based on the plurality of imaging markers, the plurality of imaging markers being visible in a medical image comprising a first flexible elongate instrument disposed in the body lumen; receiving diagnostic scan information or therapy delivery information from the first flexible elongate instrument or the second flexible elongate instrument at a plurality of locations of the body lumen; and associating the diagnostic scan information or therapy delivery information with the imaging markers of the plurality of locations based on the reference coordinate system and the location information sensed by the location information sensor. The system further includes a display configured to display a composite image including the associated diagnostic scan information or therapy delivery information and the imaging markers.

The processor may be further configured to receive a medical image (e.g., an X-ray image, such as an X-ray angiography) including a first flexible elongate instrument disposed in a body lumen.

The positional information sensor may be disposed on the first flexible elongate instrument. For example, the positional information sensor may be a sensor, such as an optical sensor, configured to detect a coded marker of the second flexible elongate instrument. The first flexible elongate instrument may be a guidewire and the second flexible elongate instrument may be or include a diagnostic or therapeutic device. The diagnostic device may be, for example, an intravascular ultrasound (IVUS) device, or an Optical Coherence Tomography (OCT) device, fractional Flow Reserve (FFR) catheter, a photoacoustic device, an endoscopic device, an arthroscopic device, or a biopsy device. The treatment device may be, for example, an angioplasty device, an embolization device, an ablation device, a drug delivery device, an optical delivery device, an atherectomy device, or an aspiration device. The second flexible elongate instrument may include a coded marker disposed at an inner circumferential surface of a catheter or liner configured to be advanced over the first flexible elongate instrument.

The positional information sensor may be disposed on the second flexible elongate instrument. For example, the positional information sensor may be a sensor (e.g., an optical sensor) configured to detect a coded marker of the first flexible elongate instrument. The first flexible elongate instrument may be, for example, fractional Flow Reserve (FFR) wire.

The positional information sensor may be a diagnostic sensor disposed on the second flexible elongate instrument. For example, the first flexible elongate instrument may include a signal transmitter configured to transmit a signal for detection by the diagnostic sensor. The signal emitter may be an ultrasonic transducer, an optical light emitter, or a signal reflector configured to reflect signals originating from the diagnostic sensor. Associating the diagnostic scan information with the imaging markers may include establishing a co-located position based on the detected signals.

The first flexible elongate instrument may be a diagnostic device and the position information sensor may be a sensor that detects a push distance, a pull back distance, or a combination thereof of the diagnostic device. Associating the diagnostic scan information with the imaging markers may include establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the diagnostic sensor and at least one of the plurality of imaging markers.

The second flexible elongate instrument may be a diagnostic device comprising at least one imaging marker and the position information sensor may be a sensor that detects a push distance, a pull back distance, or a combination thereof of the diagnostic device. Associating the diagnostic scan information with the medical image may include establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of at least one imaging marker of the diagnostic device and at least one of a plurality of imaging markers of the first flexible elongate instrument.

The system may include the second flexible elongate instrument. The position information sensor may be disposed at a distal portion of the first flexible elongate instrument or the second flexible elongate instrument. The reference coordinate system may be one-dimensional, two-dimensional or three-dimensional. For example, for a three-dimensional reference frame, receiving the medical images may include receiving at least two medical images including a first flexible elongate instrument disposed in a body lumen. The position information sensor may be a single element sensor.

The system may further include a direction sensor configured to detect advancement and retraction of the relative motion of the first flexible elongate instrument and the second flexible elongate instrument.

The composite image may further include a representation of therapy delivered to at least one of the plurality of vascular locations. The composite image may include a simulated representation of the position of the diagnostic or therapeutic device relative to the medical image. The simulated representation may provide a dimensional representation of the diagnostic or therapeutic device relative to the lumen.

A method for positioning a medical device in a body lumen includes establishing a reference coordinate system based on a plurality of imaging markers of a first flexible instrument disposed in the body lumen, the imaging markers being visible in a medical image including the first flexible elongate instrument. The method further includes receiving diagnostic scan information or therapy delivery information at a plurality of locations of the body lumen from the first flexible elongate instrument or a second flexible elongate instrument configured to move relatively (e.g., parallel relative movement) with respect to the first flexible elongate instrument. At least one of the first flexible elongate instrument and the second flexible elongate instrument includes a position information sensor. The method further includes associating the diagnostic scan information or therapy delivery information with the imaging markers of the plurality of locations based on the reference coordinate system and the location information sensed by the location information sensor. A composite image including the associated diagnostic scan information or therapy delivery information and these imaging markers is displayed.

Optionally, the method may further comprise receiving a medical image comprising a first flexible elongate instrument disposed in the body lumen.

The position information sensor may be a sensor configured to detect a coded marker, and the method may further include detecting a coded marker of one of the first flexible elongate instrument and the second flexible elongate instrument.

The positional information sensor may be a diagnostic sensor disposed on the second flexible elongate instrument, and the method may further include detecting a signal emitted by the first flexible elongate instrument. Associating the diagnostic scan information with the imaging markers may include establishing a co-located position based on the detected signals.

The position information sensor may be a sensor that detects a push distance, a pull back distance, or a combination thereof of the diagnostic device, and one of the first flexible elongate instrument and the second flexible elongate instrument may include the diagnostic device. Associating the diagnostic scan information with the imaging markers may include establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the diagnostic sensor and at least one of the plurality of imaging markers.

The second flexible elongate instrument may be a diagnostic device comprising at least one imaging marker, and associating the diagnostic scan information with the imaging markers may comprise establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the at least one imaging marker of the diagnostic device and at least one of a plurality of imaging markers of the first flexible elongate instrument.

The method may further include receiving direction information from a direction sensor configured to detect advancement and retraction of the relative motion of the first flexible elongate instrument and the second flexible elongate instrument.

A system for measuring relative displacement of at least two flexible elongate instruments within a body lumen includes a first flexible elongate instrument including a plurality of displacement-encoding markers and a second flexible elongate instrument including an encoding sensor configured to obtain signals from the displacement-encoding markers. The encoding sensor is disposed at a distal portion of the second flexible elongate instrument and is configured to be inserted into a body lumen. The first flexible elongate instrument and the second flexible elongate instrument are configured to move relatively (e.g., move relatively parallel).

A processor operatively arranged with the encoding sensor may be configured to determine a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals. The displacement encoding marker may be disposed circumferentially at least partially around a surface of the first flexible elongate instrument and include a reflective medium. The reflective medium may be or include a metal, metal alloy, magnet, ceramic, crosslinked hydrogel, fluoropolymer, or any combination thereof. The surface may be an inner circumferential surface of a catheter or liner of the first flexible elongate instrument. Alternatively or additionally, the surface may be an outer circumferential surface of a wire of the first flexible elongate instrument.

At least one of the first flexible elongate instrument and the second flexible elongate instrument may comprise a diagnostic device. The diagnostic device may be configured to obtain body lumen information. The processor may be further configured to correlate the obtained body lumen information with the relative displacement distance. The body lumen information may include tissue density, temperature, pressure, flow rate, impedance, electrical conductivity, or any combination thereof.

At least one of the first flexible elongate instrument and the second flexible elongate instrument may include a plurality of radiopaque markers. The processor may be further configured to: receiving at least one X-ray angiographic image of the body lumen including the plurality of radiopaque markers; associating a first engagement position of the first flexible elongate instrument and the second flexible elongate instrument with at least one of a plurality of radiopaque markers of the X-ray angiography image; and associating a subsequent position of one of the first flexible elongate instrument and the second flexible elongate instrument with at least one of the plurality of radiopaque markers of the X-ray angiography image. The display may be configured to display a composite image comprising the radiopaque imaging marker and an indicator of the subsequent location or body lumen information obtained at the subsequent location.

The processor may be configured to continuously or periodically associate a subsequent position of one of the first flexible elongate instrument and the second flexible elongate instrument with at least one of the plurality of radiopaque markers of the X-ray angiographic image. The display may be configured to continuously or periodically update the composite image with indicators of the subsequent locations or body lumen information obtained at the subsequent locations.

The system may further include a drive unit operatively arranged with at least one of the first flexible elongate instrument and the second flexible elongate instrument. The drive unit may be configured to advance and/or retract the flexible instrument(s) within the body lumen. The processor may be configured to determine a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals and to generate control commands for the drive unit based on the determined relative displacement distance and the target position.

The system may include a processor configured to determine a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals. The system may further comprise a display. The display may be configured to display a composite image including a representation of the body lumen and an indicator of a position of at least one of the first flexible elongate instrument and the second flexible elongate instrument within the body lumen.

The absolute position encoder system includes: a member comprising a position encoder track comprising alternately spaced high reflectivity and low reflectivity code lines; a light source configured to illuminate the encoder track; an optical detector. The optical detector includes a single element light sensor configured to detect the encoder lines when the member is adjacent to and moved relative to the optical detector, the single element light sensor detecting light reflected from a detection region of limited width. The width of at least one code line of the position encoder track is equal to or greater than the limited width of the detection area. The width of at least one code line of the position encoder track is narrower than the limited width of the detection area. The optical detector generates an optical signal indicative of the varying intensity. The system further includes a processor configured to convert the optical signal into code characters and to measure an absolute position of the component based on the code characters.

The alternating spaced code lines may provide at least three levels of light reflection. The optical detector may be in contact with the position encoder track. The optical detector may be disposed at the first intra-luminal medical instrument and the position encoder track may be disposed at the second intra-luminal medical instrument. For example, the first intraluminal medical device may be a guidewire and the second intraluminal medical device may be a catheter.

The optical detector may be removably coupled to the intra-luminal medical instrument and/or removably coupled to a unit including the processor. The optical detector may include an optical fiber configured to transmit light from the light source to the encoder track and transmit light reflected from the encoder track to the light intensity meter. Alternatively, the alternating high and low reflectivity code lines may be configured to provide directional information. At least one of the member and the component housing the optical detector further includes an orientation sensor.

An absolute position encoder system includes a member including a position encoder track including code lines imprinted on a surface, and an optical detector including an optical fiber communicatively coupled to an Optical Coherence Tomography (OCT) instrument or an optical light reader. The tip of the optical fiber is disposed at the detection region and is configured to detect the imprint depth of each code line as the member is moved adjacent to and relative to the optical detector. The optical detector generates an optical signal indicative of the varying imprint depth. The system further includes a processor configured to convert the optical signal into code characters and to measure an absolute position of the component based on the code characters.

The position encoder track may comprise code lines of at least three different depths. The surface of the position encoder track may be cylindrical and the code lines may be imprinted circumferentially on the surface. The optical detector may be in contact with the position encoder track. For example, the optical detector may be disposed at a first intra-luminal medical instrument and the position encoder track may be disposed at a second intra-luminal medical instrument. The first intraluminal medical device may be a catheter and the second intraluminal medical device may be a guidewire.

The optical detector may be removably coupled to the intra-luminal medical instrument and/or removably coupled to a unit including the processor. Alternatively, the code lines may be configured to provide directional information. At least one of the member and the component housing the optical detector may further comprise an orientation sensor.

A method of determining an absolute position, direction of motion, or speed of motion of a medical device inserted into a subject includes: using an absolute position encoder system: an optical signal comprising at least two reflected intensities or at least two imprint depths is detected as the member translates relative to an optical detector, at least one of the optical detector and the member being disposed at the medical device. The method further includes identifying an absolute position, direction of movement, or speed of movement of the medical device based on the time and duration of the at least two reflected intensities or at least two imprint depths.

The guide wire comprises a plurality of radiopaque imaging markers and embedded optical fibers; and a single element sensor disposed at a distal portion of the guidewire and operatively coupled to the optical fiber. The single element sensor is configured to detect a positional information encoding of the flexible elongate device.

The provided devices, systems, and methods are generally described in the context of X-ray applications, where the medical image may be an X-ray image or video (e.g., an X-ray angiography, computed Tomography (CT) image), and the imaging marker may be a radiopaque imaging marker. The provided devices, systems, and methods may alternatively or additionally be used in the context of other imaging and sensing modalities. For example, the medical image may be a Magnetic Resonance (MR) image (including MR-derived angiography), and the imaging markers may be MR-visible markers. The medical image may be a Positron Emission Tomography (PET) image or other radionucleotide derived image, and the imaging marker may be a radiation emission marker. The medical image may be an ultrasound image and the imaging markers may be passive or active acoustic markers. The medical image may be obtained by an optical, thermal and/or photoacoustic modality, and the imaging markers may be detected or visible by that modality. The medical image may include a hybrid image generated from at least two imaging modalities. For example, the methods and systems may utilize or include multi-modality sensor acquisition (e.g., MR/PET), wherein the medical image is a multi-modality image and the imaging marker is a multi-modality visual marker.

Drawings

The foregoing will be apparent from the following more particular description of exemplary embodiments, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments.

FIG. 1 is a schematic diagram of an example system for locating a medical device in a body lumen.

Fig. 2A depicts a simulated image obtained by an example IVUS scan and FFR scan without utilizing a consistent positioning system.

Fig. 2B depicts a simulated image generated by an example IVUS scan and an FFR scan with an example consistent positioning system.

FIG. 3 is a flow chart depicting a standard diagnostic process and a process for consistent position measurements between multiple modalities.

FIG. 4 is a schematic diagram of an example apparatus in which a diagnostic sensor and imaging markers are disposed on the same flexible elongate instrument.

FIG. 5A is a schematic view of an example apparatus with imaging markers disposed on a guidewire for use with a separate flexible elongate instrument including a diagnostic sensor.

Fig. 5B is a simulation of an X-ray angiographic image obtained with the apparatus of fig. 5A.

Fig. 6 is a schematic diagram of an example apparatus including a position signal transmitter (e.g., an ultrasound transducer) with a flexible elongate instrument with imaging markers.

FIG. 7 is a schematic diagram of another example apparatus including a position signal emitter (e.g., an optical light emitter) with a flexible elongate instrument of imaging markers.

Fig. 8 is a simulation of an IVUS image obtained during co-location with the device of fig. 6.

Fig. 9A is a schematic view of an example flexible elongate instrument having radiopaque markers of different sizes.

Fig. 9B is a schematic view of another example flexible elongate instrument having a different size radiopaque marker.

Fig. 10 is a flow chart depicting an example coronary intervention performed using the apparatus of fig. 4.

FIG. 11 is a flow chart depicting an example coronary intervention performed using the apparatus of FIG. 5A.

Fig. 12A is a schematic view of an example apparatus including a sensor for detecting displacement-encoded markers for a flexible elongate instrument.

FIG. 12B is a schematic diagram of an example optically encoded liner for use with the apparatus of FIG. 12A.

FIG. 13A is a schematic diagram of an example system including a flexible elongate instrument with an optically encoded sensor and a liner with encoded indicia.

FIG. 13B is a graph of an example signal and output generated using the system of FIG. 13A.

FIG. 13C is a schematic diagram of another example of an optical lining encoder and associated signals generated for displacement measurement.

FIG. 14 is a schematic diagram of another example system for detecting displacement-encoded markers of a flexible elongate instrument for displacement measurement.

FIG. 15 is a schematic view of an example system for use with a flexible elongate instrument having an encoding sensor in combination with a treatment device delivering an angioplasty balloon.

FIG. 16 is a simulation of an example display including composite images generated using displacement encoding that may be used to guide catheter advancement without real-time X-ray guidance.

Fig. 17 is a flow chart depicting a standard procedure using real-time X-ray guidance and a procedure using system guidance including flexible elongate instrument(s) with coded and image markers.

Fig. 18 is a schematic diagram of an example system for use in a catheterization laboratory.

Fig. 19 is a simulation of a composite image produced by co-locating with an angiographic image using a guidewire model and a treatment/diagnostic device positioned within the lumen.

FIG. 20 is a block diagram of an example model generation process.

Fig. 21 is a diagram illustrating a 2D to 3D guidewire modeling configuration.

FIG. 22 is a block diagram of an example data processing architecture.

Fig. 23 is a flow chart of a guided surgical workflow using a co-location system.

FIG. 24 is a flow chart of a workflow for imaging and lumen location correlation.

FIG. 25 is an example display of a co-location system with location co-location between multiple modalities.

Fig. 26 is a flow chart of a workflow for treatment and lumen location association.

Fig. 27 is a flow chart of a typical percutaneous interventional workflow.

Fig. 28 is a flow chart of a percutaneous interventional workflow with an example co-location system providing guidance.

Fig. 29 is a block diagram of a co-location system and communication overview.

Fig. 30 is a schematic diagram of a prior art multi-track code for absolute position encoding and illustrating the amplitude versus time relationship of the resulting signal.

Fig. 31 is a schematic diagram of a prior art single track code with absolute position encoding using an array sensor.

FIG. 32A is a schematic diagram of an example detector including a single photosensor for detecting a single track code.

FIG. 32B is a schematic diagram of another example detector including a single photosensor for detecting a single track code.

FIG. 33 is a diagram illustrating an example of determining absolute position using a single element sensor and an example resulting signal.

Fig. 34 is an example of a signal generated by using the apparatus shown in fig. 32A or fig. 32B and the code detection shown in fig. 33. The example signal includes detection of random velocity motion and includes four directional changes.

FIG. 35A is a schematic diagram of an example code track for detection by a single photosensor.

FIG. 35B is a graph of an example signal generated from the code track of FIG. 35A.

FIG. 35C is a schematic diagram of another example code track for detection by a single photosensor.

Fig. 35D is a graph of an example signal generated from the code track of fig. 35C.

Fig. 35E is a schematic diagram of yet another example code track for detection by a single photosensor.

Fig. 35F is a graph of an example signal generated from the code track of fig. 35E.

FIG. 36 is a schematic diagram of an example system including two flexible elongate instruments (as illustrated, a guidewire and a monorail catheter) including a detector having a single photosensitive element for detecting absolute position encoding.

FIG. 37 is a schematic diagram of an example optical system for position-coded detection of an endoluminal instrument.

Fig. 38 is an example of seven-bit encoding providing absolute position detection and direction change detection.

Fig. 39 is a graph of an example signal generated from a device having the encoding shown in fig. 38.

Detailed Description

The description of the exemplary embodiments follows.

Devices, systems, and methods for locating medical devices in a body lumen are provided. Such devices, systems, and methods may advantageously provide improved accuracy over existing positioning methods and reduce radiation exposure for clinicians and patients. The example devices, systems, and methods described herein are generally described in the context of Percutaneous Coronary Intervention (PCI) surgery; however, the devices and systems provided may be applied to or used in the context of other types of endoluminal surgery (e.g., gastrointestinal surgery).

Intravascular diagnostic and therapy delivery methods are typically performed using X-ray angiography to aid in visualizing the vessel portion of interest. When performing an intravascular diagnostic scan, the sensor receives vessel specific information (e.g., vessel size, tissue morphology, pressure, density, or temperature) while moving longitudinally within the vessel, and records the vessel specific information for each examined portion.

Standard X-ray angiography projects the inspected vessel in two dimensions from outside the vessel, while intravascular diagnostic modalities inspect the vessel from within the vessel lumen, and such modalities can generate thousands of location-specific data points during diagnostic scans along the lumen/vessel segment.

A disadvantage of intravascular assessment modalities like intravascular ultrasound (IVUS), optical Coherence Tomography (OCT) and Fractional Flow Reserve (FFR) is that it is difficult to identify vessel locations on an X-ray angiography image and correlate these locations with corresponding locations in an intravascular diagnostic scan and vice versa. Furthermore, it is often difficult to locate some type of vessel observation (such as calcium deposition and the location of significant pressure changes) obtained during an intravascular diagnostic scan on an X-ray angiographic image. The clinician may attempt to use features (e.g., vessel branching or severe vessel stenosis) detectable in both the X-ray angiographic image and the intravascular longitudinal diagnostic scan to help identify the corresponding location in mind. However, there is no general feature present in all patients, which places the process under the skill and experience of the clinician.

Some X-ray device manufacturers provide continuous monitoring during angiography while recording device motion within the blood vessel during a vascular diagnostic scan. Post-processing calculations may be employed to correlate the position in the intravascular scan with the vessel position on the acquired X-ray angiographic image. However, this approach exposes the clinician and patient to high X-ray radiation levels and does not provide real-time correlation to the clinician. Furthermore, generating three-dimensional vessel models in this manner can be cumbersome, can disrupt the clinician's workflow, and is inaccurate.

Interventional procedures performed under the guidance of X-ray angiography involve similar drawbacks. Once diagnostic imaging information (e.g., cross-sectional view, longitudinal view, and physiological index) is obtained, the imaging probe is withdrawn and then a treatment device (e.g., a catheter carrying a balloon or stent) is deployed under the guidance of X-ray fluoroscopy. X-ray angiography is often required to locate the position of a guidewire within the body vasculature and the position of the therapeutic and/or diagnostic device because there is a certain amount of travel between the entry point and the target location and linear distance tracking during device insertion or pullback is often inaccurate.

There is a need for a simple method of correlating a vessel position identified from an intravascular diagnostic scan with a vessel position on an X-ray angiographic image. There is also a need for improved methods of measuring medical device displacement in a body lumen and reducing the difference between the measured displacement and the actual device displacement in the body. There is a further need for such a method that significantly reduces radiation exposure for patients and clinicians relative to existing continuous X-ray angiography.

An example system for positioning a medical device in a body lumen includes a first flexible elongate instrument 110, and optionally a second flexible elongate instrument 112 configured for parallel relative movement with respect to the first flexible elongate instrument. The first flexible elongate instrument includes a plurality of imaging markers 130a-130d, which may be, for example, radiopaque imaging markers. The positional information sensors 120, 126 may be disposed at the first flexible elongate instrument 110. For example, the position information sensor 120 may be disposed on or in an instrument distal portion of the first flexible elongate instrument, and/or the position information sensor 126 may be disposed at a proximal portion of the instrument (e.g., a push and/or pull sensor, which may optionally be a drive unit configured to advance and/or retract the instrument or a component of the drive unit) that remains located outside of the patient's body. Alternatively or additionally, the position information sensor 122 may be disposed at the second flexible elongate instrument. As illustrated, a position information sensor 122 of a second flexible elongate instrument is disposed at a distal portion of the instrument; however, it may alternatively be disposed at the proximal portion (e.g., a push and/or pull sensor similar to sensor 126). The first flexible elongate instrument 110 can be, for example, a guidewire including a diagnostic sensor (e.g., FFR guidewire), a guidewire including a therapeutic device (e.g., atherectomy guidewire). The second elongate instrument 112 may be, for example, a catheter (e.g., an IVUS or OCT catheter, a balloon delivery catheter, a catheter of a biopsy device or aspiration device, an endoscopic catheter, etc.). Examples of various arrangements of the location information sensor(s) 120, 122, 126, FFR, IVUS, and OCT diagnostic embodiments of the system 100, and therapy delivery embodiments of the system 100 are further described herein in sections 1-4.

The system further includes a processor 105 and a display 107. The processor 105 may optionally receive at least one medical image including a first flexible elongate instrument 110 disposed in a body lumen. Additionally or alternatively, the medical images may be received and displayed independently by a separate system processor. The processor is configured to establish a reference coordinate system based on the plurality of imaging markers 130a-d visible in the medical image and receive diagnostic scan information or therapy delivery information from the first flexible elongate instrument or the second flexible elongate instrument at a plurality of locations of the body lumen. The processor is further configured to associate the diagnostic scan information or the therapy delivery information with the imaging markers of the plurality of locations based on the reference coordinate system and the location information sensed by the location information sensor. The medical image may be, for example, an X-ray image, such as an X-ray angiographic image.

As used herein, the term "medical image" is intended to include any image produced by a medical imaging system for viewing internal anatomy of a patient. Medical images may be obtained by, for example, magnetic Resonance (MR) imaging, nuclear Magnetic Resonance (NMR) imaging, computed Tomography (CT), X-ray and Positron Emission Tomography (PET), and other imaging modalities. The medical image may include one or more still images. For example, the medical image may be an ultrasound video.

As used herein, the term "X-ray image" is intended to include any image produced by X-rays passing through the body, including, for example, X-ray angiographic images, X-ray fluoroscopic images, and Computed Tomography (CT) images. An "X-ray image" may include one or more still images. For example, an "X-ray image" may be an angiographic video comprising a plurality of images.

While the system 100 is generally described with respect to radiopaque markers and X-ray images, the system 100 may alternatively be used with other imaging modalities including, for example, magnetic Resonance (MR) imaging, nuclear Magnetic Resonance (NMR) imaging, and Positron Emission Tomography (PET). For such modalities, the markers 130a-d may be modality specific markers. For example, the markers 130a-d may include MR-or NMR-sensitive materials (e.g., including atoms having free nuclear spins), electromagnetic-sensitive materials, electromechanical-sensitive materials, optical-sensitive materials, and/or mechanical-sensitive materials that may be detected or distinguished in the image. In addition to X-ray images, MR, NMR or PET images, as well as other modalities, may be obtained by the processor 105 for association with diagnostic scan information or therapy delivery information.

As used herein, the term "reference frame" includes one-, two-and three-dimensional spatial reference systems in which at least one position (typically an initial position) of a first flexible elongate instrument is registered with respect to imaging markers that are visible on a medical image and subsequent positions of the first flexible elongate instrument or a second flexible elongate instrument are determined based on the imaging markers. Examples of establishing 1D, 2D, and 3D reference coordinate systems to provide position determination during an intra-luminal diagnostic scan or therapeutic intervention are further described herein in sections 1-3. For example, establishing the 1D reference coordinate system may include registering an initial position of the flexible elongate instrument in the vessel relative to the imaging markers. For further examples, establishing the 2D or 3D reference coordinate system may include generating a model of the imaging marker and optionally the vessel lumen based on a representation of the imaging marker in one or more medical images (e.g., one or more X-ray angiographic images).

As used herein, the term "diagnostic scan information or therapy delivery information" includes any information obtained during a diagnostic scan or during the delivery of a therapeutic intervention, including, for example, information related to the location of a diagnostic sensor or therapy device, the readings of the diagnostic sensor, and the images obtained by the diagnostic device.

The display 107 is configured to display a composite image including the associated diagnostic scan information or therapy delivery information and imaging markers. The composite image may be, for example, an image or graphic obtained by a diagnostic scan, such as an OCT image or FFR graphic, with a representation of the imaging marker superimposed thereon (see, for example, displays 124B, 140B of fig. 2B, display 2415 of fig. 15, fig. 16). In another example, the composite image may be an X-ray image having a representation of the location of the diagnostic or therapeutic device superimposed thereon (see, e.g., display 310 of fig. 2B, display 2450 of fig. 15, fig. 16, fig. 19). In a further example, the composite image may include an image in which information from multiple modalities or multiple device locations is indicated (see, e.g., display 20 of fig. 2B, display 2400 of fig. 15, fig. 16, fig. 19, fig. 25). The composite image may include a representation of the body lumen in which the first flexible elongate device and optionally the second flexible elongate device are disposed and an indicator of the location of the device(s) (e.g., fig. 19, 25).

The methods and systems described herein may advantageously significantly reduce X-ray exposure compared to typical PCI procedures. Conventional PCI methods not only rely on constant real-time or near real-time X-ray angiography and fluoroscopy feeds for device displacement measurement and position tracking, but also do not provide real-time, accurate position correlation in all device toolsets used throughout PCI surgery. Thus, conventional methods involve exposing the patient and/or clinician to high levels of radiation. Furthermore, the lack of real-time or near real-time positional correlation between angiography, diagnostic modalities, treatment devices and associated diagnostic measurements typically results in additional X-ray imaging, contrast and time, further increasing radiation exposure and affecting policy decisions and treatment outcomes throughout the PCI procedure.

Current PCI procedures rely heavily on real-time or near real-time fluoroscopy. Because the images are taken in real time throughout the procedure, a significantly greater amount of X-ray radiation is required compared to a single radiograph (e.g., an image of a fracture). There are known exposure thresholds for patient-related tissue damage, such as skin erythema (2 Gy) and permanent skin damage (5 Gy). The ocular lens is susceptible to the operator, and the risk of cataract increases when acute exposure is as low as 0.1Gy and chronic exposure is as low as 5 Gy. Random effects (including cancer) involve longer latency and also present a lifetime-responsible risk, but are difficult to quantify. Child patients and pre-existing health patients face a higher radiation safety risk in PCI surgery due to the radiation sensitivity of the tissue. Angiography uses radiopaque contrast agents to image the vasculature. In addition to X-ray exposure, patients may also suffer from side effects of radiopaque contrast agents, including pain, adverse drug interactions, and renal failure. There is also a risk of X-ray exposure and orthopedic injuries (e.g., lower back strain) for doctors and staff due to the extra weight of lead aprons and other protective equipment.

The methods and systems described herein enable reduced X-ray exposure for patients and/or operators when performing PCI procedures. Excessive X-ray exposure is harmful to the human body and can lead to complications such as cancer, hair loss, and cataracts. While conventional X-ray dose baselines vary depending on the nature of the procedure, the artifacts, the X-ray equipment, the staff dose recording accuracy, etc., on average, baseline X-ray exposure ranges from about 3 to 5Gy (gray) for procedures that take about 20 minutes to about 15Gy for PCI procedures. The methods of the present disclosure may provide PCI procedures that may achieve a significant reduction in the total X-ray dose due to reduced "on" time of the X-rays during the PCI procedure. The X-ray "on" time of the methods described herein may be reduced by up to 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% relative to conventional PCI surgery. The X-ray dose that a patient receives during the PCI methods described herein can range from less than 500mGy (reduced from about 3 to 5 Gy) for a PCI procedure lasting about 20 minutes to about 2Gy (reduced from about 15 Gy) for a complex procedure. The patient may receive an X-ray dose of less than about 500mGy, less than about 400mGy, less than about 300mGy, less than about 200mGy, or less than about 100mGy during PCI surgery.

1. Body lumen longitudinal positioning method and system

Endoluminal procedures typically require the use of X-rays, often with the aid of contrast agent injection, to allow a user (e.g., a physician) to visualize a blood vessel so that a guidewire and additional intravascular devices can be positioned and guided to the correct vessel branch. X-rays using contrast agents can also be used as a preliminary diagnostic scan for vascular/tissue conditions. Typically, additional diagnostic procedures involving other modalities (e.g., intravascular IVUS, OCT, and FFR) are performed for more critical assessment of disease conditions. In a typical operating room where catheterization is performed, the X-ray angiographic images and other additional imaging modalities are displayed on different screens or within different partitions on a large panel screen. The vessel position observed from an intravascular diagnostic modality (e.g., IVUS, FFR, or OCT) screen is not correlated with the X-ray vessel image, and vice versa.

A guidewire having a plurality of radiopaque markers with known spacing has been used to provide a length estimate of a vascular or internal body lumen feature on an X-ray image. However, such markers are not relevant to other diagnostic scan information (e.g., IVUS, OCT, and FFR).

Typically, an intravascular diagnostic system combines intravascular diagnostic information obtained from an ultrasound transducer (as in an IVUS system), from an optical transducer (as in an OCT system), or from a pressure transducer (as in an FFR system) with a displacement tracking unit (as in a motor drive unit) to generate an intravascular displacement scan image. Diagnostic sensors (e.g., ultrasound transducers, optical transducers, or pressure sensors) are placed within the blood vessel under real-time X-ray angiography guidance. During a vascular diagnostic scan, thousands of vascular diagnostic data points are generated, each vascular diagnostic data point corresponding to a measured displacement point. However, the vessel position of each displacement point is not quantified, as there is no vessel position reference frame within the body lumen to quantify the sensor position or the sensor generated data point position. Even if the sensor is detectable on X-rays and the starting point of the sensor during an intravascular scan is detected by an X-ray angiography image, the lack of a vessel length scale and the two-dimensional projection properties of the three-dimensional vessel in the X-ray angiography image makes it difficult to correlate the vessel position between the two-dimensional X-ray vessel image and the vascular diagnostic scan image (which is displayed with respect to the measured linear distance).

A flexible elongate instrument (e.g., flexible elongate instrument 110) having a plurality of radiopaque markers strategically located on and visible on an X-ray angiographic image of a blood vessel may advantageously provide fixation points along a body lumen from which a linear position reference system may be defined. The linear position reference frame may enable a positional correlation between the X-ray angiographic image, the diagnostic scan image or map, and/or the treatment delivery device. The flexible elongate instrument may remain in the same position in the body lumen such that subsequent positioning of additional flexible elongate instruments within the body may be correlated with or without the use of real-time X-ray angiography.

Fig. 2A illustrates an example display 10 of images obtained from a typical endoluminal procedure, including IVUS and FFR scans, without the use of a uniform positioning system. An X-ray angiographic image 110 including coronary vessels is shown. A contrast agent (typically an iodine solution) is injected into the vessel portion of interest so that the vessel can be displayed on an X-ray angiographic image. Without the radiopaque markers, catheter devices disposed within the blood vessel are generally not clearly detectable in the X-ray angiographic image.

The display 10 further includes a longitudinal IVUS pullback scan view 124a from which the size and morphology vessel features obtained by the ultrasound sensor are displayed with respect to pullback scan distance (as detected by a pullback sensor disposed outside the body). A cross-sectional IVUS view 130 is shown further comprising the blood vessel, which illustrates the lumen size and morphology at dashed line 135 in the field of view 122. Current IVUS and OCT systems are equipped so that the lumen cross-sectional view can be displayed at any displacement position selected by the user with respect to the longitudinal view. The IVUS sensor rotates during pullback, generating a 360 degree view of the vessel morphology along the scanned length of the vessel.

Display 10 further includes a longitudinal FFR pull-back scan view 140a of the blood vessel from which a fractional reserve ratio (e.g., the ratio of blood vessel pressure at the distal location to aortic pressure) is displayed for the length of the scan distance.

The vessel lumen information obtained from the IVUS and FRR during the displacement scan provides the clinician with more relevant diagnostic information of the vessel segment of interest than vessel lumen information obtained from the X-ray angiography alone.

The data set generated by IVUS, OCT, FFR and other intravascular scanning modalities typically registers vessel information with respect to longitudinal pullback. This type of dataset is based on linear distance and lacks three-dimensional vessel curvature information. The fact that the X-ray vessel image is a two-dimensional projection of a three-dimensional vessel makes the determination of the distance between, for example, the views 110, 124a, 130, 140a more difficult.

When only the longitudinal pull-back scan views 124a and 140a are viewed, it is difficult to correlate the position from these scan images with the vessel position on the X-ray angiographic image 110. In general, even when a scan start point is identified, it is still difficult to point to an angiographic vessel position at a defined distance from the start point due to the 2D projection effect of the X-ray angiographic image. The IVUS vessel scan position marked by dashed line 135, for example, does not include any clear reference that may be used to correlate the position with the angiographic vessel position in view 110.

Similarly, the FFR pullback scan position indicated by dashed line 145, where a change in FFR ratio is observed, is also difficult to correlate with the position shown on the X-ray angiographic vessel image 110.

Fig. 2B illustrates an example display 20 of images obtained from an endoluminal procedure, including IVUS and FFR scans, utilizing a uniform positioning system. A flexible elongate instrument, such as flexible elongate instrument 110 (fig. 1), is positioned within the blood vessel and a visualized X-ray angiographic image 310 is obtained that includes a radiopaque marker 330 of the instrument. The location of the vessel-related marker (as detected by the X-ray angiography image) is projected onto the longitudinal IVUS pullback scan view 124b as the marker 310 and onto the longitudinal FFR pullback scan view 140b as the marker 220.

The IVUS angiography location indicated by dashed line 135 may now be associated with the X-ray angiography vessel location indicated by dashed line 335. It can be easily inferred that the IVUS vessel cross-sectional view 130 is located at the position of the dashed line 335 in the X-ray angiography view.

Similarly, the FFR pullback scan position indicated by dashed line 145 may be readily associated with the position indicated by dashed line 245 on X-ray angiographic vessel image 310.

FIG. 3 is a flow chart depicting a method that includes a standard diagnostic process 210 and a process for making consistent position measurements 200 among multiple modalities to obtain association information as illustrated in FIG. 2B. During a vascular diagnostic scan, vascular information 230 from the diagnostic sensor and sensor displacement information 240 are combined to generate a dataset 250 comprising vascular information and sensor displacement. The dataset (e.g., views 124a, 130, 140a of fig. 2A) is then displayed 290. In the displayed image, vascular diagnostic information is displayed displaced relative to the sensor. The vessel diagnostic information at any sensor displacement point is uncorrelated with any vessel position seen on the X-ray angiographic image of the vessel.

Using the additional functionality depicted in method 220, an accurate correlation of sensor displacement points with vessel locations on an X-ray vessel image may be provided. To provide accurate positional correlation with the X-ray angiographic image, the image may include a vessel length scale and a vessel position correlation point, both of which may be provided by a radiopaque marker of a flexible elongate instrument, such as instrument 110 (fig. 1). In particular, 260X-ray angiographic images are obtained using a flexible elongate instrument located in a suitable position in a vessel of interest. A plurality of markers of the instrument (which are detectable within the blood vessel) provide a blood vessel length scale and visual reference point(s) for blood vessel position correlation. Markers (as visualized on an X-ray angiography image) are particularly useful as vessel position references, because the X-ray angiography image is a 2D projection of a vessel segment in 3D space and the linear length scale in the diagnostic image is not directly convertible to a position seen on the 2D projection. The plurality of markers may also provide quantification of the location of the diagnostic sensor.

Once the positions of the diagnostic sensor relative to the plurality of markers are quantified 270, the positions of the plurality of markers in the scan displacement zone may be measured 280 and projected onto the composite image 295 for display (e.g., views 124B, 140B in fig. 2B).

The method 220 provided does not specify an order between the items 240, 260, and 270. Depending on the equipment and instrumentation used in a particular application, there are many methods for quantifying sensor positions with reference to multiple imaging markers. Typically, when quantifying the sensor position with reference to at least one of the plurality of markers, the sensor position in the scan length may be measured for each other position. The following are examples of various methods of quantifying sensor position according to the placement of the flexible elongate instrument(s).

Fig. 4 depicts an example flexible elongate instrument 440 that includes both a diagnostic sensor 420 and a radiopaque marker 430. The device 440 may be, for example, an FFR wire. When obtaining an X-ray angiographic image, the position of the diagnostic sensor 420 relative to the marker 430, as detected by the X-ray angiographic image, is known and thus may be initially quantified. For devices such as FFR wire 440, the position information sensor may be a sensor that detects the pull-back distance of the wire (e.g., sensor 126 of fig. 1).

Clinicians typically perform FFR pullback scans to better assess pressure changes in portions of a blood vessel that may have been relieved or may include more than one lesion. The pullback scan may be performed by a motor unit positioned outside the body that records the pullback distance (e.g., pullback sensor 126 of fig. 1) and/or the push distance. Pressure sensor 420 is disposed in or on the FFR lead, proximate flexible distal end 410 of the lead. As illustrated, the radiopaque markers 430 are located at a known distance proximal to the pressure sensor.

The X-ray angiographic image of the vessel and marker can be obtained at any point along the pullback scan, provided that the scan pullback distance from which the X-ray angiographic image was obtained is also recorded. Because the distance of the radiopaque marker to the sensor is already known and remains fixed, the position of the sensor relative to the marker when the X-ray angiographic image is obtained is also known, and the marker position can be calculated relative to the scan length and projected onto the FFR diagnostic scan display.

In an example workflow using device 440, an X-ray angiographic image may be obtained prior to the start of an FFR diagnostic scan, and the known FFR sensor position relative to the marker may coincide with the scan start point or zero displacement point. The position of the marker relative to the scan length can be measured and displayed. In order to allow all markers on the instrument to be visualized on the pullback scan display and to provide the widest range of position references, the position at which the X-ray angiographic image is obtained may be essentially the position at which the physical position of the sensor is furthest (typically at the beginning of the diagnostic scan).

Fig. 5A and 5B depict an example system in which a flexible elongate instrument 540 includes a radiopaque marker 550 and is used with a second flexible elongate instrument 510 having a diagnostic sensor 520. As shown in this example, the first flexible elongate instrument 540 is a guidewire. The length of each marker and the spacing between markers 550 is known (e.g., 10 mm). The second flexible elongate instrument 510 is a diagnostic device (e.g., FFR wire) having a diagnostic sensor 520.

Unlike the example shown in fig. 4, the position of diagnostic sensor 520 relative to the plurality of markers 550 cannot be measured based on the design of the instrument. In the vicinity of the diagnostic sensor 520, several radiopaque markers 530 are attached to the shaft in the vicinity of the sensor (e.g., the sensor is set 1mm from the distal-most marker). In this example, diagnostic sensor 520 is not detectable by X-rays, which is the case for most types of diagnostic sensors. The markers 530 are spaced relative to each other and relative to the sensor such that the distance of each marker to the sensor can be easily measured (e.g., marker length and spacing of 1 mm).

The guidewire-based markers 550 are configured to be easily distinguishable from the diagnostic instrument-based markers 530. An X-ray angiographic image 560 of a blood vessel is shown in fig. 5B, wherein both a guidewire-based marker and a diagnostic instrument-based marker are detectable. The position of the diagnostic sensor in this example relative to the guidewire marker can be measured (e.g., just over 8mm away from the distal-most marker on the guidewire using the hypothetical parameters provided in this example).

In this example, the markers for vascular reference are attached to a guidewire that need not be moved during diagnostic intravascular scanning. Although real-time or near real-time X-ray angiography images may be obtained during a diagnostic scan, vessel position correlation may alternatively be performed with recorded X-ray angiography images.

Guidewire-based markers may also be useful when inserting an interventional device or vascular treatment device after an initial diagnostic procedure. Since the markers remain in the vessel during the diagnostic procedure and the interventional procedure, the markers may provide improved correlation with the diagnostic data during the interventional procedure and may optionally also be used for guiding the interventional device to a desired vessel position under real-time X-ray guidance or guidance with pre-acquired X-rays.

Using the example device of fig. 5A, the position information sensor may be a sensor (e.g., sensor 126 of fig. 1) that detects a pull-back distance of the diagnostic device 510. As described above, the correlation of diagnostic scan information with the X-ray angiographic image may establish a starting position of the diagnostic sensor 520 based on the relative positions of the imaging markers according to the diagnostic device 530 and the radiopaque imaging markers 550 of the guide wire.

Fig. 6 depicts an example system in which a flexible elongate instrument 620 or 640 includes a position information sensor 610 or 660 disposed at a distal portion of the device. In the example to be described, the plurality of markers 630 and the diagnostic sensor 660 are located on different flexible elongate instruments, and the position of the diagnostic sensor relative to the markers (as detected by the X-ray angiography image) is unknown.

In this example, the first flexible elongate instrument is a guidewire 620 having a plurality of markers 630 and including a signal transmitter or transducer 610 having a modality that is detectable by a diagnostic sensor 660 located at the second flexible elongate instrument 640. As illustrated in this example, the second elongate instrument is a diagnostic catheter 640. The diagnostic catheter may be, for example, an IVUS catheter, an OCT catheter or an FFR catheter. The signal transmitter 610 may provide co-location information in conjunction with the diagnostic device 640.

For IVUS catheters, the guidewire signal transducer 610 may be an ultrasound transducer or a signal reflector. For OCT catheters, the guidewire signal transducer 610 may be a fiber-based transmitter/receiver.

As illustrated in fig. 6, the signal transducer 610 is disposed on the guidewire such that it coincides with the intermediate radiopaque marker 630 a. However, the transducer 610 may be located anywhere along the distal portion of the guidewire 620.

The radiopaque markers 630 may each have a known length. For example, if each marker length and the gap between two markers is 10mm, then in this figure showing 5 markers, the total indicated distance that can be observed from the X-ray angiographic image and accurately measured is 90mm.

The diagnostic catheter 640 may be, for example, a rotating IVUS catheter or OCT catheter that has been inserted over a guidewire and allowed to move along the guidewire when advanced or retracted within a vessel. The over-the-wire sliding track portion 650 of the catheter (commonly referred to as the catheter guidewire lumen) is located at the distal end of the diagnostic catheter 640. The guidewire lumen allows the catheter to be loaded onto the guidewire and follow the guidewire when inserted into a blood vessel. As illustrated, diagnostic sensor 660 is mounted at the distal end of a rotating core 670 of the diagnostic device. During a diagnostic scan, when the diagnostic device is pulled back by the motor drive unit (which also measures the displacement of the device), the rotating core 670 rotates, thereby generating a 360 degree diagnostic view of the blood vessel along the length of the pull back.

For IVUS, the diagnostic sensor 660 may be an ultrasonic transducer (e.g., operating in the 5-60MHz range). For OCT, diagnostic sensor 660 may be an optical sensor, such as a small optical mirror that reflects a light beam at 90 degrees to the fiber so that the light is projected perpendicular to the catheter.

During diagnostic pullback scanning, the rotating core 670 and transducer 660 are moved in close proximity, thereby generating a cross-sectional image of the blood vessel at each rotation, which is registered with the pullback distance.

As the diagnostic sensor 660 passes the guidewire signal transducer 610, the signal emitted from the guidewire transducer may be detected by the diagnostic sensor and vice versa (see fig. 8), and the pullback distance of the detected signal may be recorded. Because the position of the guidewire transducer 610 relative to the plurality of markers is known, the position of the diagnostic sensor 660 relative to the plurality of markers can be quantified when the diagnostic sensor 660 detects the signal emitted by the transducer 610. The determination of when the guidewire transducer and diagnostic sensor are adjacent to each other may be based on signal timing and/or signal strength measurements. Once the diagnostic scan displacement points of the diagnostic sensor 660 adjacent the guidewire transducer 610 are calculated, the position of the plurality of radiopaque markers 630 relative to the diagnostic sensor can be established and projected onto the vascular diagnostic scan image.

The intensity of the wire transducer emission may be adjusted, for example, to be sufficiently weak so that only the nearest few frames register the signal, thereby providing improved position accuracy. However, this approach may increase in difficulty in detecting these several frames after the pull-back scan is completed. Alternatively, the transducer emissions may be adjusted to be stronger so that signals may be more easily detected across a greater number of frames. However, this approach may result in reduced location registration accuracy. To aid in visualization, or to distinguish the guide wire transducer emissions from the actual reflected signals of the tissue anatomy, a defined signal pattern may be emitted.

The guidewire based transducer may be configured to act only as a receiver and use the timing of the transmissions and receptions for accurate location registration, with the guidewire based transducer and diagnostic sensor connected to the same system. This may advantageously avoid generating image artifacts in the images obtained by the diagnostic sensor. The signal with the smallest time difference may provide detection of the position of closest approach of the guidewire transducer and diagnostic sensor.

As illustrated in fig. 6, diagnostic sensor 660 may act as a location information sensor. Associating the diagnostic scan information with the X-ray angiographic image may include establishing a co-located position based on the signal transmitter 610 transmitting a signal that may be detected by the diagnostic sensor 660. The signal emitter may be, for example, an ultrasonic transducer, an optical light emitter, or a characteristic signal reflector that may reflect the signal emitted by the sensor 660 for detection by the sensor 660.

Fig. 7 depicts additional examples of flexible elongate instruments that each include a signal transmitter or receiver configured to transmit signals for detection by or from a diagnostic sensor.

The flexible elongate instrument 701a is a guidewire (radiopaque marker not shown in fig. 7) that includes an ultrasound transducer 710 disposed near the distal end 705 of the guidewire and is configured for use with an IVUS imaging catheter. The flexible elongate instrument 701b is a guidewire that includes an optical light emitter/receiver 720 disposed near the distal end 705 of the guidewire and is configured for use with an OCT image catheter.

Ultrasonic transducers are typically made primarily of piezoelectric materials that can naturally act as both a signal transmitter and a signal receiver. IVUS catheters include transducers that operate at different frequencies depending on the intended location and vessel size used in the body (e.g., tubular vessel, peripheral vessel, intracardiac application, etc.). For example, an IVUS catheter may include a transducer that operates in the range of about 9MHz for a large body lumen to about 60MHz for a small body lumen. Different diameter guidewires may also be used to access different sized vessels/lumens. Transducers with different center frequencies may be used to suit different imaging catheter frequencies and guidewire diameters. For example, a 50MHz ultrasound transducer made of PZT material may have a thickness of approximately 30-50 microns. Such transducers may be provided on or in a guidewire, for example, having a diameter of about 300-400 microns, without affecting the strength and physical properties of the guidewire.

The ultrasonic transducer so configured may transmit/receive signals 360 degrees perpendicular to the length of the guidewire and may be designed such that the signals propagate in a narrow plane.

The optical light emitter/receiver 720 may include a small conical mirror 730 for reflecting light emitted from an optical fiber 735 disposed within the guidewire and may receive and direct light into the optical fiber. The optical signal generation and reception may be performed at the proximal end of the optical fiber, such as in a hub including a light source and a sensor (see, e.g., hub 240 of fig. 13A, fig. 18, and fig. 37). In the example illustrated in fig. 7, a conical mirror 730 is mounted at the distal end of the optical fiber and can provide 360 degrees of light emission perpendicular to the length of the guidewire.

The location registration with the diagnostic device may be performed in either a transmit mode or a receive mode or a combination thereof using transducers (ultrasonic transducers or optical transducers, either of which may act as transmitters and receivers) mounted on or in the guidewire. When operating in the transmit mode, the signal transmitted by the guidewire transducer may be detected by a sensor of the diagnostic scanning catheter for location registration. When operating in a receive mode, the guidewire transducer may capture a signal (e.g., an acoustic signal or an optical signal) emitted from the scanning catheter. The signals emitted by the guidewire transducer can be timed to provide accurate location registration and reduce interference with diagnostic signals.

Fig. 8 illustrates a simulation of the wire transducer transmit signal on an axial cross-sectional view of an intravascular ultrasound image of a blood vessel generated during a diagnostic pull-back scan.

The IVUS imaging transducer may operate at a high pulse rate, typically 5000Hz or higher. Hundreds of pulses may be transmitted within a single revolution of the imaging transducer. At each rotation, the signals received from each pulse are then synthesized by a processor to generate a single cross-sectional view of the vessel. As shown, the dark central hole 810 indicates the position of the catheter. White portion 820 indicates vascular tissue with more acoustic reflection and dark portion 830 indicates the lumen of a blood vessel with blood or fluid and with less acoustic reflection. The boundary between these two regions indicates the inner surface of the vessel wall. Other features of normal blood vessels (e.g., endothelium, intima, and external mold) or disease features (e.g., calcium deposition, fibrotic lesions, and fatty lesions) can also be detected and measured by trained doctors.

The pulsed signal 840 emitted from the guidewire transducer at a high rate may be visible within the frame, as detected when the imaging transducer passes over (or is co-located with) the guidewire transducer. The sound waves travel in water and soft tissue at about 1,500,000 mm/s. The guidewire transducer may be pulsed, for example, at 1,500,000hz, and the pulse signal may be detected on the IVUS image every 1mm deep from the center of the image. Intravascular cross-sectional images with a 10mm depth setting may show, for example, 9-10 bright concentrically curved white line segments that can be easily distinguished from normal fluid and tissue reflection. The transmitter pulse rate of the guidewire transducer may be adapted to more or less densely gather signals for ease of identification. The intensity of the guidewire emissions may also be adapted to appear to be detectable but not significantly interfere with the reflected tissue signals from the IVUS sensor. Catheter displacement in which these frames are observed may be recorded as a displacement position of the IVUS transducer in the vicinity of the signal transducer positioned on the guidewire.

Fig. 9A and 9B illustrate two examples of radiopaque markers of a flexible elongate instrument. At least one marker of the plurality of markers may be independently distinguished to provide an improved vascular position reference between the X-ray angiographic display and the diagnostic pullback scan display. As illustrated in fig. 9A, the flexible elongate instrument 910 (e.g., a guidewire) includes five markers, wherein the second and fourth markers 930 have a different visual appearance than the first, third, and fifth markers 940. The unique markers may facilitate visual correlation between the diagnostic image and the X-ray angiographic image without counting the markers. As illustrated in fig. 9B, the flexible elongate instrument 920 includes three shorter markers 935 that can be used to provide a finer zoom to the user and a more accurate reference at the middle position of the lead. Having at least one uniquely identifiable imaging marker may be particularly useful for measuring a series of imaging markers when not all of the plurality of imaging markers of the flexible elongate instrument are within the field of view of the X-ray image.

FIG. 10 is a flow chart of an example coronary intervention procedure involving an FFR lead with multiple markers as shown in FIG. 4. FFR diagnostic procedures begin with insertion of FFR wire into the coronary vessel of interest (1010), typically after normalization of the pressure output with arterial pressure at the distal end of the guide catheter. The locations of a plurality of markers disposed on an FFR lead in a blood vessel are detected within an X-ray angiography image or video (1020). With respect to imaging the marker to register the position of the pressure sensor (1030), this may be performed automatically by the processor when an angiographic image or short video of the marker within the vessel is detected. FFR pullback scanning begins and FFR readings are recorded a sensor pullback distance (1040). Once the pullback scan is completed, a pullback display may be generated with the locations of the plurality of markers projected on the display (1050). For example, a composite image may be generated and displayed as shown in view 140B of FIG. 2B. The clinician may use displayed markers located in the X-ray angiographic image or video and intravascular scan display to correlate the vessel characteristics using two imaging modalities (1060). The procedure shown in fig. 10 can also be used for IVUS and OCT scans, where a marker is placed on the IVUS or OCT catheter or guidewire.

Fig. 11 is a flow chart of an example coronary intervention procedure involving a guidewire with multiple markers and signal emitters as shown in fig. 6 and an IVUS catheter. The IVUS diagnostic procedure begins with inserting a guidewire into a vessel of interest, and then inserting an IVUS catheter across the guidewire into the vessel location (1110). The locations of a plurality of markers disposed on a guidewire in a blood vessel are detected within an X-ray angiographic image or video (1120). The guidewire transducer may be set to either a transmit mode or a receive mode depending on whether the guidewire is functionally connected to the IVUS system (1130) and an IVUS intravascular image scan is performed (1140). The position of the IVUS sensor is registered (1150) when the IVUS sensor is co-located with the guidewire transducer.

If the guidewire is not connected to the IVUS system, the firing mode of the guidewire transducer may be used. The pulses emitted by the guidewire transducer may be received by the IVUS sensor and displayed on the IVUS image, as shown in fig. 8. Based on the IVUS image, the user can manually measure the IVUS sensor position closest to the guidewire transducer and input that position into the system. Alternatively, detecting guidewire transducer pulses between IVUS images may be automated and performed by a processor.

If the guidewire is signally connected to the IVUS system, the receiving mode of the guidewire transducer may be used. The pulses emitted by the IVUS sensor may be received by the guidewire transducer, whereby the pull-back position of the IVUS sensor closest to the guidewire transducer may be measured and automatically registered by the IVUS system. In this example, either or both of signal strength or signal timing may be used to calculate the position of the IVUS sensor closest to the guidewire transducer.

Once the position of the IVUS sensor through the guidewire transducer is measured, the marker position relative to the IVUS transducer can be determined because the marker position relative to the guidewire transducer is known and can be projected onto the IVUS pullback scan display (1160). For example, a composite image may be generated and displayed as shown in view 124B of FIG. 2B. The clinician may use the displayed markers located in the X-ray angiographic image or video and IVUS pullback scan display to correlate the vascular features using both imaging modalities (1170).

For the projected positions of the imaging markers on the vascular diagnostic scan display, to represent the same vascular position as captured on the X-ray angiographic image, the position of the starting point of the diagnostic scan (i.e., when the diagnostic sensor is at the displacement point zero), referred to as the "zero position", may be quantified with reference to a plurality of markers captured on the X-ray angiographic image. For example, the first body lumen location may be quantified such that the distance of each body lumen point at which diagnostic data is collected may be determined relative to the first body lumen location. This relationship can be expressed as follows: DR = FR + DF, where DR is the distance from the diagnostic sensor location to the reference point, FR is the distance from the first body lumen location to the reference point, and DF is the distance from the diagnostic sensor location to the first body lumen location.

DF can be expressed as follows: df=of+ad, where OF is the distance from the sensor start point (origin) to the first body lumen location and AD is the absolute displacement OF the diagnostic sensor from zero at its origin.

Combining these two equations can yield the following result: dr=fr+of+ad. Quantification of the zero position may be performed before, during or after the diagnostic scan. For example, the neutral position may be determined from the detected co-location of the flexible elongate instrument (e.g., as described with respect to the apparatus of fig. 6-8, for example). During a vascular scan, the displacement of the diagnostic sensor on the diagnostic instrument may be actuated and tracked by a motor drive unit disposed outside the patient's body. Alternatively or additionally, sensor motion may be tracked by the X-ray device by continuously monitoring the position in the blood vessel. Alternatively or additionally, sensor motion may be tracked by a code disposed on the flexible elongate instrument, as further described herein in section 3 and section 4.

During the pullback intravascular scan, the pullback distance (i.e., the position of the transducer during the scan) may be continuously recorded. Such a displacement detection mechanism may be used when the diagnostic sensor and the plurality of imaging markers are disposed on the same flexible elongate endoluminal device. The position of the imaging marker relative to the sensor is generally known prior to obtaining an X-ray angiographic image of the vessel and the imaging marker. This may be accomplished by the design of a flexible elongate endoluminal device. An example of such an embodiment is an FFR lead that includes a plurality of radiopaque imaging markers located on a distal portion of the lead near a pressure sensor. Thus, the relative positions of the plurality of imaging markers and the pressure sensor are known when obtaining an X-ray angiographic image of the vessel and the markers. Markers may be projected on the longitudinal vessel scan such that the relative positions of these markers to the point where the X-ray angiographic image was taken are the same as the physical imaging marker positions relative to the sensor on the flexible elongate endoluminal device. When so displayed, the projected imaging marker position on the vessel scan represents the marker position relative to the vessel detected by the X-ray angiography image. One disadvantage of using pullback distance calculation as a displacement detection mechanism is that the vascular features from the diagnostic scan may not typically be correlated with the real-time X-ray angiographic image, as the flexible elongate instrument comprising the diagnostic instrument and the imaging markers has moved from the point where the X-ray angiographic image was obtained. In addition, after the intravascular scan is completed, diagnostic scanning instruments are typically removed from the patient and other treatment devices (e.g., angioplasty balloons and stents) are inserted to treat the vessel segment(s) identified from the intravascular scan. It may be beneficial for the imaging markers to remain at the vascular site to assist the clinician in guiding the treatment device to the vascular site of interest with or without real-time X-ray angiography. Thus, it may be beneficial to locate the imaging markers on an elongate instrument (e.g., a guidewire) that may be held in place in the blood vessel throughout PCT procedure.

Diagnostic instruments such as IVUS and OCT catheters can be moved along a guidewire that has been positioned inside a blood vessel. The guide wire need not be moved as other catheters are moved along the guide wire. After the diagnostic procedure, the guidewire may be left in place inside the vessel for use with other catheter devices. Markers disposed on the guidewire may assist a clinician in guiding other devices to vascular features observed from intravascular scans as they are inserted and advanced along the guidewire. This is particularly useful because the markers can help guide the other device not only to the vascular location on the real-time X-ray, but also to the location shown on the longitudinal vessel scan image by correlating the location of the other device from, for example, the real-time X-ray back to the intravascular scan image. In the case where the position of the guidewire in the vessel has moved, the guidewire can be easily repositioned back to the original X-ray captured image location simply by using anatomical vessel markers (e.g., branches).

When the position of the imaging marker relative to the diagnostic sensor is unknown, but can be measured from the obtained X-ray angiographic image, a displacement calculation mechanism involving the initial measurement can be used. An example of this type of embodiment is an IVUS catheter that is positioned in a blood vessel along a guidewire that includes a plurality of imaging markers attached to a distal portion thereof. The radiopaque imaging markers may be attached near or at the IVUS transducer such that when an X-ray angiographic image is obtained, the IVUS radiopaque imaging markers may also be detected on the X-ray angiographic image. Because the distance between each of the plurality of imaging markers and each imaging marker size of the guidewire is known, the relative positions of the IVUS transducer recorded by the X-ray angiography image and the plurality of imaging markers on the guidewire can be measured automatically using an imaging processing algorithm or manually by a trained operator.

When the position of the imaging marker relative to the diagnostic sensor is unknown, but can be measured during an intravascular pullback scan, a displacement calculation mechanism involving at least one co-location determination can be used. Diagnostic instruments such as IVUS and OCT include ultrasonic sensors and optical sensors, respectively, for vascular diagnosis. Ultrasonic transducers made of piezoelectric material can be used as both signal transmitters and receivers. Optical sensors using fiber optic cables may also be configured to function as both transmitters and receivers. For the purposes of this description, both the IVUS sensor and the OCT sensor are referred to as diagnostic sensors. The signal transducer may be adapted to be mounted on the guidewire at a location near or within a guidewire segment comprising a plurality of imaging markers. With this adaptation, the position of the signal transducer mounted on the guide wire is known and fixed relative to the marker. Signals from the guide wire mounted transducer and diagnostic sensor may be registered when the sensors are aligned adjacent to each other at a location in the blood vessel. Signals from a transducer mounted on the guidewire may be received by the diagnostic sensor and may also be displayed on the vascular pullback scan. The position of the received signal on the pullback scan can be determined as the position at which the transducer mounted on the guidewire and the diagnostic sensor are aligned. The imaging processor may even more readily measure the alignment position if the guidewire based signal transducer is connected to the diagnostic instrument system. Both signal pattern and signal timing can be used to measure alignment position. When the guidewire transducer is aligned with the diagnostic sensor, the position of the guidewire marker relative to the diagnostic sensor can be measured. Because the diagnostic sensor scan distance is tracked, the position of the plurality of markers relative to the sensor at the time of taking the X-ray angiographic image can be calculated from the travel distance of the diagnostic sensor.

2. Coding method and system

The body lumen diagnostic modality typically requires that the diagnostic device scan through the length of the body lumen, generating body lumen information at closely spaced displacement points. In most currently available systems, the displacement of the diagnostic device is actuated by a motor drive unit placed outside the patient, and tracking of the displacement is also performed outside the body lumen. There may be a large difference between the measured displacement of the diagnostic device estimated by the motor drive unit and the actual sensor displacement inside the body lumen. The differences may be due to diameter differences between the moving medical instrument and the guide catheter and the effects of intrinsic vascular elasticity. Accurate length measurements of vascular features may be required to properly select the size of the treatment device (e.g., angioplasty balloon, cutting balloon, and stent). While constant X-ray angiography may be used to track the movement of the diagnostic sensor displacement, this approach exposes the patient and/or operator to high levels of X-ray radiation.

Once an intravascular diagnostic procedure is performed that provides more detailed information about the vessel lumen than information from X-ray angiography, treatment decisions are typically made based on the intravascular diagnostic information. The treatment decision may be based on the exact location of the lesion within the vessel. Typically, the subsequent treatment procedure is guided solely by X-ray imaging. Even if it benefits from a vascular location correlation between an X-ray image and an intra-luminal diagnostic image, it may be desirable to visualize the location of a treatment device moving inside the vascular lumen directly in real time or nearly in real time on a previously generated intra-luminal diagnostic image to help locate the diagnostic and/or treatment device at a vascular location of interest that has been identified on the diagnostic image. In some cases, the clinician may use features visible on both the X-ray and the endoluminal diagnostic scans (such as vessel branches or severe stenoses) to help identify the corresponding locations in an attempt to improve the measurement accuracy of the treatment device and/or diagnostic device directed during PCI.

When performing an endoluminal diagnostic scan, the diagnostic sensor receives vessel specific information (e.g., vessel size, tissue morphology, pressure, temperature, etc.) while moving longitudinally within the vessel segment, and the acquired vessel information data and sensor displacement are recorded and correlated.

The resulting dataset includes pairs of displacement point data and vessel information collected at each displacement point (e.g., as shown in fig. 2A). The data sets are output to the processor and may be displayed on the screen in digital and/or representative graphical form.

Standard X-ray angiography imaging presents a 2-D projection of a blood vessel from outside the vessel, while an intravascular assessment modality assesses the vessel from within the vessel lumen, and can generate vessel lumen information at thousands of displacement points during a diagnostic scan.

In order to provide a more accurate positional correlation between an X-ray angiography and a diagnostic and/or therapeutic device location, systems and methods are described that provide more accurate device tracking within a vessel.

For example, a positional information sensor (e.g., sensors 120, 122) may be disposed on one of the two flexible elongate instruments and configured to detect a coded marker disposed on the other of the two flexible elongate instruments. Coded markers may be provided at and detected at a distal portion of the flexible elongate instrument to provide accuracy of the intravascular location of interest. One of the two flexible elongate instruments may further comprise an imaging marker to provide correlation with the X-ray image.

As illustrated in fig. 12A, the first flexible elongate instrument 2110 can be a guidewire (guidewire imaging markers are not shown in fig. 12 for clarity), with an optically encoded sensor 2120 mounted to the distal portion of the flexible elongate instrument. The guidewire is used in conjunction with a second flexible elongate instrument 2130, as illustrated in fig. 12B, which is a phased array IVUS catheter that can generate body lumen morphology information when inserted into a body lumen. However, any catheter may be configured for use with such a guidewire such that the displacement of the catheter relative to the guidewire may be measured and output to a processor/computer. The displacement information may be correlated with diagnostic body lumen information obtained at each diagnostic point. The phased array IVUS catheter 2130 includes a phased array acoustic transducer 2140 attached near its distal end. The catheter includes a portion with one or more displacement encoding markers and a portion without displacement encoding markers, which may optionally be configured in a periodic order. The monorail portion 2135 of the IVUS catheter includes a liner 2150 marked with an optical linear coding. The liner 2150 may be disposed within a monorail portion of the IVUS catheter such that the sensor 2120 detects the optical code as the catheter passes over the guidewire 2110.

As further illustrated in fig. 12A, the displacement signal may be transmitted through an optical fiber 2160. The guidewire 2110 can include, for example, a 45 degree polished fiber optic terminal 2170 with a reflective coating configured to divert light from the fiber optic toward the aperture 2172 and reflect light from the coded marker back toward the aperture 2172 down the fiber optic toward the light meter. The encoder sensor 2120 detects the encoded signal from the monorail lining inner diameter surface and sends the signal to a signal processor to convert it into displacement information. In a simplified example embodiment, the optical encoder sensor may detect changes in reflected light intensity due to encoded markers of different reflectivity at specific intervals when there is relative motion between the guidewire and catheter. A processor (e.g., processor 105, alternatively referred to as a computing unit) may be configured to count changes in signal strength, from which displacement between the IVUS catheter and the guidewire may be determined.

Alternatively, each displacement-encoded marker 2152a-c may include a different color (e.g., red, green, and blue (RGB)) or different gray scale intensity, with white light illumination from the optical transducer 2120 and RGB-sensitive or gray scale-sensitive detector (e.g., sensor 2260, fig. 13). This embodiment has the advantage of providing different reflected signal time patterns, so that automatic direction detection can be achieved.

Catheter 2130 may be displaced at a constant velocity whereby the distance/time between each coded marker and/or the reflectivity of the selected coded marker may be used for displacement detection of the marker. In such embodiments, the displacement from the starting position may be marked in conjunction with a code, thereby eliminating the need to count a specific number of coded markers to measure the displacement distance between the sensor and the flexible elongate instrument comprising the displacement coded markers.

In the above examples, the coded sensor is disposed on or in the guidewire (as a first flexible elongate instrument) and the coded marker is disposed on or in the catheter guidewire lumen lining within the catheter (as a second flexible elongate instrument). However, the positioning of the coded sensor and the coded marker may vary. For example, because the motion between the two flexible elongate instruments is relative, an equivalent measurement may be obtained if the guidewire is configured to provide a linear encoding and the catheter is configured to include an optical sensor that may be used to detect the encoded signal.

Fig. 13A-13C illustrate another example system 2200 that includes fiber-based linear encoding and encoding detectors. The light beam may be input via an optional detachable connection 2210 at its proximal end 2212 into an optical fiber 2270 built into or on a flexible elongate instrument 2200, such as a guidewire or any catheter-based device. The light beam may originate from a light source 2220 arranged outside the body. The system components that may remain external to the body are indicated at 2225, which may advantageously provide a flexible elongate instrument to maintain a minimal profile of insertion. Light from light source 2200 may be transmitted into optical splitter 2240 via optical fiber 2230, to detachable connection 2210, and into instrument 2200. Light may be projected from the optical fiber 2270 at the optical coded sensor aperture 2290, and light reflected from the coded marker 2250 of the catheter or catheter liner 2252 may be returned into the optical fiber 2270, transmitted back through the optical splitter 2240, the optical fiber 2280, and to the light intensity meter 2260. The intensity changes due to the relative motion between the optical reader 2290 and the coded marker 2250 may be tracked by a signal processor (e.g., processor 105) as illustrated in graph 2205 of fig. 13B and converted to a relative displacement between the guidewire and catheter device as illustrated in graph 2215 of fig. 13B. Alternatively, the transducer may comprise a light source. The light source may be, for example, a laser or a light emitting diode. Alternatively, the light source may alternatively be positioned within the guidewire. Depending on the encoding, the light source may be a monochromatic light source with a preferred wavelength, or a multi-wavelength light source. Longer wavelengths in the infrared range may be less susceptible to potential contamination (e.g., of blood or other bodily fluids).

Reflected light from the coded mark 2250 may be transmitted back through the optical fiber 2270 and split by the splitter 2240. At least a portion of the reflected light is delivered to light meter 2260 through optical fiber 2280.

An optical fiber (Polymicro technologies, phoenix, arizona) is available with a 50 micron core having an overall diameter of 65 microns that is small enough to be positioned inside a guidewire or catheter device. The optical fibers disposed in or on the flexible elongate instrument may range in diameter from about 20 microns to about 1000 microns.

The emitted light may be continuous or pulsed rapidly so as not to cause confusion during rapid movements. The code on the instrument 2252 may include two reflective regions, as illustrated by the code marker 2250 in fig. 13A. For example, in some regions, the two reflective regions may be black/white, red/blue, green/red, black/gray, or blue/green. While fig. 13A shows a guidewire 2200 with an integrated optical fiber and a catheter portion with coded markers, the displacement coded markers may alternatively be configured to be located on the outer diameter of the guidewire and the coded sensors may be located on the inner diameter of the catheter guidewire lumen, or vice versa. In the event that one flexible elongate instrument fails to provide a fibre channel, the variety of available changes in the relative positions of the coded markers and sensors provides flexibility.

The measured reflected intensity signal over time from the reflection encoded markers may be binary, as shown in the example plot 2205 of fig. 13B. The processor may count peaks and valleys (e.g., positive or negative second derivatives, respectively) to measure the distance traveled by the optical reader along the encoded surface. The displacement over time may be calculated and/or displayed as shown in the example graph 2215 of fig. 13B.

As illustrated in fig. 13A, the coded markers occur at a uniform density along the length of the instrument 2252. However, the coding may comprise a plurality of regions, wherein each region has a different density of coded markers, for example at the distal or proximal region. Alternatively or additionally, the encoding may comprise different densities of markers for providing the direction indication.

A three-reflection code is shown on instrument 2225 in fig. 13C. As illustrated, markers 2226, 2227, and 2228 have different gray densities. The time-varying reflected light intensity signal from a three-reflection encoding in one direction is shown in example graph 2235. If the instrument is traveling in the opposite direction, the shape of graph 2235 is reversed. The three reflective coding may advantageously provide directional information of the relative movement between the guidewire and the catheter. Thus, the user does not need to manually input the travel direction at the beginning of the displacement process.

The coded indicia may be positioned on an outer diameter surface or an inner diameter surface of the flexible elongate instrument. Alternatively, the displacement coded marker on the outer diameter surface may comprise a first pigment of a selected reflection, while the coded marker on the inner diameter surface may comprise a second pigment of a different selected reflection. Different reflective pigments may result in different reflectance profiles.

The displacement encoded markers may comprise laser inscription such that micro-grooves of different depths are provided on the encoded surface. For example, deeper grooves may result in reduced reflected intensity compared to shallower grooves.

One option for creating coded markers is to use a laser to remove the dark oxide layer on the already anodized metal surface. Another option for creating coded markers is to paint the coded surface with rings of different pigments (e.g., red, green, and blue). The displacement encoded markers and encoded sensors may be based on optical, capacitive, inductive, resistive, electromagnetic, piezoelectric, or magnetic properties.

Typically, blood contaminates the coded surface or optical reader little because the gap between the outer diameter of the guidewire and the inner diameter of the catheter guidewire lumen is small (typically less than 50 microns).

Fig. 14 depicts another example system 2300 that includes fiber-based linear encoding and encoding detectors. As illustrated, the first flexible elongate instrument 2310 is an FFR lead having a blood pressure sensor 2320 at a distal portion of the device and having a portion marked with optical coding 2340. Radiopaque markers may also be included on instrument 2310 (not shown in fig. 14 for clarity). The second flexible elongate instrument 2350 includes a coded reading catheter 2306 having an optical coded sensor 2308 mounted at an inner surface of its guidewire lumen 2307 and facing the guidewire when the guidewire is inserted.

The readout catheter 2306 may be comprised of a short and low profile wire upper portion 2312 for minimizing blood flow disruption and a long axis portion 2370 containing an optical fiber 2380 connected to a subsystem 2390 including an optical transmitter and optical intensity meter 2392 and a signal processor 2394. The system 2300 may further include a display 2396 configured to display the FFR ratio versus displacement distance, as shown in graph 2305.

FFR lead 2310 may be first inserted into a coronary vessel and advanced to a location of interest. The read microcatheter 2306 can then be inserted over and follow the FFR wire until the coded sensor 2308 reaches a region including the coded marker 2340 near the location of interest on the FFR wire. The microcatheter may remain stationary relative to the vessel. During FFR diagnostic vessel scanning, the FFR wire is pulled back in the coronary vessel while blood pressure readings are obtained, and the encoding sensor provides an encoding signal to a signal processor that converts the encoding signal into a distance displacement. For example, the reading catheter may remain fixed at a coronary vessel location proximal to the coronary ostia, which may provide minimal disturbance to coronary blood flow.

In conventional approaches, FFR pullback distance is measured by a motor drive unit external to the body, or tracked by X-ray angiography to continuously monitor the motion of the FFR wire. The placement of the motor drive unit outside the body may result in large measurement differences due to the size differences between FFR wire and catheter and/or relaxation of wire motion caused by multiple tortuous bends, and due to the long path of the device before reaching the coronary vessel. Tracking FFR lead motion using continuous X-ray angiography can result in a significant X-ray radiation dose to the clinician and/or patient. In general, FFR procedures require that the pullback speed not be too fast, as an average heartbeat pressure is required to accurately determine the FFR value. For example, to obtain an accurate FFR value with a pullback distance resolution of less than 1mm, if the heart rate of the patient is 60 times/sec, the wire pullback speed is limited to about 1mm/sec. At a speed of 1mm/sec, a pull-back distance of 90mm takes 90 seconds to complete, which corresponds to a continuous X-ray exposure of 90 seconds.

The systems and methods described herein may enable a clinician to obtain accurate FFR pressure measurements at precise locations with high pullback distance resolution without fear of excessive X-ray radiation exposure. The described method can also push the FFR wire back again to re-evaluate the readings at any vessel point of interest while maintaining accurate pullback distance measurements. For example, FFR lead may be pushed (rather than pulled) and displacement measured using coded markers may provide accurate positional information.

Fig. 15 illustrates an example system 2400 that provides for location determination of a treatment device. As illustrated, the first flexible elongate instrument 2430 is a guidewire with a plurality of radiopaque imaging markers 2460 located at a location of interest in a vessel lumen 2420. The second flexible elongate instrument 2410 is a catheter with the angioplasty balloon 2400 mounted thereon.

The length of each radiopaque imaging marker 2460 and the distance between each imaging marker is known. When depicting an angiography X-ray image 2450 capturing a plurality of vascular lumens of the radiopaque markers 2460, the position of the angioplasty balloon 2400 can be measured relative to the vascular markers 2440. Angiographic image 2450 need not be a real-time image and the X-ray imager need not be turned on and emit X-rays to determine the position of balloon 2400 relative to image 2450. Angiographic image 2450 may be obtained by inserting guidewire 2430 into vessel 2420 such that a plurality of imaging markers 2460 and vessel 2420 may be identified in the image. Alternatively, multiple X-ray angiographic body lumen images may be obtained from different angles, with the guidewire held at the same body lumen location, which may advantageously provide 3D modeling of blood vessels and intravascular devices, as described further below.

The angioplasty balloon catheter 2410 includes an optical code 2470 located a selected distance near the balloon. The encoding sensor 2480 is attached to or included in a guidewire that is a selected distance from the plurality of imaging markers 2460. Thus, when the encoder sensor 2480 is first engaged with the encoder 2470 on an angioplasty catheter, the relative position between the angioplasty balloon on the catheter and the plurality of markers on the guidewire can be known. As shown, this position is referred to as a first engaged position. A dashed line 2490 appearing in x-ray image 2450 depicts the position of the distal end of the balloon when the balloon catheter is in an engaged position with the guidewire. Once an angiographic image of the blood vessel is obtained and the locations of the plurality of imaging markers along the blood vessel are identified in the image, the position of the angioplasty balloon in the blood vessel at the first junction location may be measured. Assuming that the encoder sensor remains within the encoded region of the angioplasty balloon catheter, the vascular position of the angioplasty balloon may thereafter be measured continuously. The position of the angioplasty balloon in the vessel can be displayed in real-time in a linear fashion (e.g., as shown in display 2415), with the simulated depiction of vessel marker 2440 presented as marker 2425 and the simulated depiction of balloon 2400 presented as balloon 2435. The representation of balloon 2400 may be scaled in size relative to the vessel lumen to represent a true indication of its overall location.

If the coded sensor 2480 moves out of range of the code 2470, the balloon position can be reacquired when the coded sensor is reengaged with the coded region. When the encoding sensor is within the length of the encoding region, the balloon may stay within the length of the plurality of radiopaque imaging markers to maximize the range of assistance that the plurality of imaging markers may provide as a vascular location association.

When tracking and displaying the angioplasty balloon position in real-time or near real-time relative to the positions of multiple imaging markers, the imaging markers may be used to correlate balloon positions in the vessel images in angiography for navigation thereof, rather than using real-time X-ray imaging to reduce radiation exposure.

Fig. 16 illustrates an example display 2500 that provides real-time guidance of an angioplasty balloon as the inside of a blood vessel is moved to an identified vascular stenosis location 2530 using the system of fig. 15. The real-time position of the balloon represented by the simulated balloon 2540 is displayed in a diagnostic IVUS scan image 2520 previously obtained using an IVUS catheter and guidewire arrangement.

In the example shown in fig. 16, the first flexible elongate instrument is an IVUS catheter that includes one or more displacement encoding markers located at a selected distance from the ultrasound transducer (e.g., as shown in fig. 12B). The second flexible elongate instrument is a guidewire comprising a plurality of radiopaque imaging markers detectable by X-ray angiography and a coded sensor located at a selected distance from the plurality of markers (e.g., as shown in fig. 12A). Imaging marker locations 2550 detected in an X-ray angiographic image of a blood vessel 2510 with an inserted guidewire may also be projected in the IVUS scan image 2520 and displayed as analog markers 2570.

In this example, the IVUS diagnostic procedure can provide an identification of the vascular stenosis location 2530, based on which a treatment decision to place the angioplasty balloon can be made. Following the IVUS procedure, the IVUS catheter may be removed, while a guidewire with a plurality of radiopaque imaging markers remains in place in the blood vessel. The angioplasty balloon can then be inserted and advanced into the vessel via the same guidewire. Once the angioplasty balloon catheter is advanced to the first engagement position, the position of the balloon can be measured and a simulated representation of the balloon 2540 can be projected in real time onto the IVUS scan image previously obtained on the displacement axis. The length of the simulated balloon 2540 may be based on the length of the actual balloon used.

As the balloon advances distally within the vessel, the real-time display may show that the simulated balloon is moving from right to left in the IVUS scan image toward the stenosis 2530. In the diagnostic IVUS scan image shown here, the distal end of the balloon is near a second marker, which is correlated to a location 2560 in the angiographic vessel image. The display may further include an indication within or projected onto angiographic vessel image 2510 or balloon position 2560.

Alternatively, when multiple angiographic images are obtained from different perspectives, the multiple angiographic images may be displayed along with the diagnostic IVUS scan image to provide vessel positions from different perspectives.

Advanced rendering of the vessel lumen may be generated based on the vessel lumen diagnostic scan image and/or the X-ray angiographic image, including, for example, a 3D display and/or a lumen view display. The location of the imaging markers and the location of the diagnostic device may be projected on such a display.

Fig. 17 is a flowchart depicting a method 2610 that includes a standard therapy delivery procedure involving real-time X-ray guided device navigation and a method 2615 of delivering therapy using marker guided device navigation using, for example, the system shown in fig. 11-16. In standard therapy delivery workflows for uncomplicated IVUS and/or OCT guided PCI surgery, X-ray imaging is used as the primary means of intravascular guidance. Conversely, after performing the initial angiographic angiography 2625 and guidewire insertion 2635, the workflow using the devices described herein may be performed without X-ray imaging. The gray shaded boxes in fig. 18 represent steps involving X-ray angiographic guidance and contrast agent injection. As can be seen in the figure, of the five steps involved in the current standard workflow 2610 (i.e., steps 2620, 2630, 2640, 2660, and 2680) involving X-ray and contrast agent injection, the three steps may be replaced by the endoluminal device-based guidance methods described herein (i.e., steps 2640, 2660, and 2680), thereby reducing the number of procedural steps involved in X-ray exposure from five to two.

Currently, in standard PCI workflow, angiographic examination of blood vessels is performed to identify coronary branches requiring intervention (2620), followed by insertion of a guidewire into the identified coronary branches (2630). Both procedure steps (2620, 2630) are performed under angiographic X-ray imaging and guidance. Once the guidewire is in place, a diagnostic device (e.g., an IVUS, OCT, and/or FFR device) is inserted to perform a more detailed examination of the blood vessel. Insertion and placement (2640) of the diagnostic device is performed using real-time X-ray guidance. Once the diagnostic device is positioned at the desired vascular location, a vascular lumen diagnostic scan (2650) may be performed and the vascular location for treatment may be measured. The diagnostic device is then removed from the vessel so that a therapeutic device can be inserted over the guidewire.

Insertion and placement (2660) of the treatment device is guided by real-time X-ray angiography to the identified vascular location. In case the vessel position identified from the diagnostic scan image cannot be correlated with the angiographic X-ray vessel image, the target vessel position in the X-ray image is estimated. The accuracy of placement of the treatment device to the selected location is highly dependent on the experience and training of the clinician. Once the treatment device is at the target site, standard treatment procedures such as balloon inflation, stent expansion, etc., may be performed without X-ray angiography (2670). After the treatment is performed, the diagnostic device may optionally be reinserted to verify the effectiveness of the treatment (2680).

In contrast, in a guidewire-based position measurement method, after angiographic angiography (2625) and guidewire insertion (2635), treatment device guidance may be performed with X-rays turned off. As illustrated in fig. 17, insertion of an intravascular diagnostic device (2645), vascular assessment (2655), insertion of a therapeutic device (2665), treatment (2675), and optionally reinsertion of the diagnostic device to verify the effectiveness of the treatment (2685) may be performed without X-rays. Furthermore, the treated vessel position may be projected onto a vessel diagnostic scan image from which the target site is identified, thereby providing an estimate of the position in the angiographic X-ray image, such that the treatment device is placed more accurately in the vessel. Still further, the guidewire-based position measurement methods of the present disclosure can guide the diagnostic device back to the treated target vascular site without the use of an X-ray instrument to verify the treatment. Optionally, short-lived X-ray angiography may be used to verify the accuracy of the treatment device location. However, the X-ray emission time may be very short and verification may be performed without additional contrast agent injection, as the imaging markers are detectable in the X-ray image.

3. Multi-modality imaging co-location system and method

In order to optimize clinical decisions and results of endovascular interventions in an effective, efficient, safe and cost-sensitive manner, co-localization-based accurate, real-time position detection may be performed between multiple diagnostic treatment devices and systems in complex percutaneous interventional procedures. Methods, systems, and workflows for such a bootstrap are described herein.

Intravascular interventional procedures are provided that yield better clinical decisions, results, and safety for the operator and/or patient. A flexible elongate instrument equipped with position sensing may provide real-time position co-location of the guidewire and diagnostic or therapeutic device. The methods described herein enable an operator (e.g., a technician or physician) to obtain real-time or near real-time image customization and flexibility during each procedure step while minimizing radiation exposure.

The methods and systems provided are described below by way of example involving an endoluminal device, a flexible elongate instrument having a plurality of imaging markers of known spacing and size as a device position reference(s), and the same or different flexible elongate instruments having displacement sensing capabilities. Examples are described in the context of an interventional cardiology catheterization laboratory. Data acquisition and processing, position detection, communication, and real-time co-localization between multiple modality displays are described by way of example via X-ray angiographic images, diagnostic intravascular images (e.g., IVUS and OCT), physiological probes (e.g., FFR and iFR), and therapeutic devices (e.g., balloon catheters and stents that may be mounted on a guidewire (e.g., guidewire 110, 2110, 2210, 2310)).

Co-location information regarding the position of a second flexible elongate instrument (e.g., a treatment and/or diagnostic device) relative to a first flexible elongate instrument (e.g., a guidewire) may be obtained by a method comprising using a treatment and/or diagnostic device comprising a transducer (e.g., an ultrasound or light emitter and detector) and a flexible elongate instrument comprising a plurality of radiopaque markers and a transducer or sensor: (a) first inserting a first flexible elongate instrument into a body lumen, (b) inserting a treatment and/or diagnostic device or a catheter comprising a treatment and/or diagnostic device into the body lumen using the flexible elongate instrument as a guidewire, (c) the transducer of the treatment and/or diagnostic device passing through the plurality of radiopaque markers in a push mode or a pull mode, (d) the transducer of the treatment and/or diagnostic device emitting a signal (e.g., ultrasound or light), (e) the transducer or sensor of the first flexible elongate instrument detecting a signal emitted from the transducer of the treatment and/or diagnostic device, (f) the transducer or sensor of the first flexible elongate instrument emitting a signal to a computing unit comprising information about the time, intensity and/or pattern of the detected signal, and (g) the computing unit comparing the signal emitted from the transducer with expected signal information of a preselected location of the treatment and/or diagnostic device relative to at least one radiopaque marker on the first flexible elongate instrument. Optionally, the method further comprises: (h) The computing unit receives information from a secondary imaging method of the body lumen (which may or may not include X-ray imaging), (i) the computing unit superimposes the intended relative position of the treatment and/or diagnostic device and/or the flexible elongate instrument with the body lumen, (j) the computing unit sends a signal to a display to display the superimposed intended relative position of the treatment and/or diagnostic device and/or the flexible elongate instrument within the body lumen. Obtaining co-location information regarding the position of the treatment and/or diagnostic device relative to the first flexible elongate instrument may be repeated at selected intervals (e.g., per unit of displacement during pullback or pushing).

Referring now to fig. 18, an example system for performing the provided methods in the form of a reference integrated system 3105 and associated apparatus for use in a catheterization laboratory is illustrated. The reference integrated system 3105 may include subsystems for any of the following: (1) Receiving real-time or near real-time angiographic information with a flexible elongate instrument disposed within a patient's body and processing the angiographic information to create a 2D and/or 3D model of a plurality of radiopaque markers on the flexible elongate instrument for superimposition on corresponding lumen images; (2) Receiving real-time or near real-time position and/or displacement information of the therapeutic/diagnostic device from a device position acquisition system (e.g., a system including sensors and marker markers disposed on the first flexible elongate instrument and/or the second flexible elongate instrument, such as system 100), integrating the position/displacement information with the 2D and/or 3D models of the plurality of radiopaque markers, generating a real-time or near real-time device position map and overlaying the 2D and/or 3D models, generating a position-related display via real-time or near real-time data integration between the 2D/3D models of the radiopaque markers and any of the following: corresponding lumen image(s), simulation device graphic(s), diagnostic and treatment system data, and angiography data; (3) Providing data storage for X-ray imaging, device location acquisition system data, modeling data, and location-associated display data; and (4) providing bi-directional data communication with a body imaging system (e.g., an X-ray angiography system), a therapeutic and/or diagnostic system, sensors, a data storage device, a display, an operator/physician interface, and a local and/or external computer network system.

As illustrated in fig. 18, a patient 3101 is located on an angiography table 3102. The angiography table 3102 is arranged to provide sufficient space for positioning a set-up X-ray system 3103 (e.g. comprising an angiography/fluoroscopy device) at a surgical position relative to the patient 3101 on the table 3102. The X-ray imaging data may be acquired by the X-ray system 3103 in the presence of contrast agent flow in the patient's blood vessel under different projections to assess the lesions of interest. The guidewire 3104 is inserted into a lumen (e.g., a blood vessel, such as a coronary artery) of the patient 3101. During guidewire insertion, the X-ray system 3103 acquires real-time or near real-time fluoroscopic images of the guidewire in the absence of contrast agent flow at the target vessel(s). The final position of the guidewire 3104 corresponding to the lesion 3210 of interest (fig. 19) is measured. When the guidewire is inside a vessel, one or more angiographic and/or fluoroscopic images may be acquired from one or more angiographic projections with and/or without a flow of contrast agent. The angiographic/fluoroscopic images are archived in an angiographic data store 3108 which is connected via interface 3111 to a local data store 3106 inside the catheterization laboratory, optimally in various user-selected formats, such as local binary and DICOM formats. The therapeutic and/or diagnostic system in this example includes: a guidewire 3104, which may be equipped with a linear code reader at its distal end to measure device displacement (e.g., sensors 120, 2120, 2290); an electronic device, referred to as a hub 3109, attached to the proximal end of the guidewire and converting the device displacement signal into an electrical signal; and an interface 3110 to a reference integration system 3105. Treatment and/or diagnostic device positioning data acquired by the guidewire 3104 is streamed from the hub 3109 to the reference integrated system 3105 via the interface 3110.

The displacement of the therapeutic and/or diagnostic device inside the lumen may be measured via a linear code reader of the guidewire. Alternatively or additionally, the displacement of the treatment and/or diagnostic device inside the lumen may be measured via the diagnostic and/or treatment system (e.g., by pulling back the sensor 126). The displacement data is part of the diagnostic and/or therapeutic system data 3130, which is connected to the reference integrated system 3105 via the interface 3125. Alternatively or additionally, the displacement of the therapeutic and/or diagnostic device inside the lumen may be measured via the X-ray system 3103. Such displacement data is connected via an interface 3115 to a reference integration system 3105 from an angiographic data storage 3108. The reference integrated system 3105 is connected to angiography data storage 3108, data storage 3106, diagnostic and/or therapy system data 3130 and IT infrastructure 3140 via interfaces 3115, 3120, 3125 and 3145, respectively. The display 3107 may be connected to the reference integrated system 3105 and the X-ray system 3103 via interfaces 3150 and 3151, respectively, for data output visualization and providing an operator/physician interface.

Based on at least one angiographic image at least one projection angle of the guidewire, a guidewire-based modeling may be performed, as further described with respect to fig. 20.

Communication and storage

After the guidewire is deployed at the desired location inside the body lumen, the reference integration system 3105 may receive one or more angiographic/fluoroscopic images (e.g., received via interface 3115 by DICOM-RTV (real-time DICOM)) from angiographic data store 3108 via electronic or wireless communication, and store these images (3330).

Pretreatment of

Preprocessing (3320) of the angiographic/fluoroscopic image(s) may be performed to remove noise from the image while preserving edges. In this step, the input image may be filtered, for example, with a 2D kernel or with an anisotropic filter. The preprocessed output image(s) are then fed to a segmentation stage (3325).

Detection of a region of interest (ROI)

Features of interest (e.g., radiopaque markers, vessel lumen boundaries) may be separated from the rest of the image, and a connection region (3335) representing these features may be formed. Filters (which may include, for example, top hat structures, canny filters, gabor filters, phase consistency based filters) may be used in this step to enhance and detect edges, and then region detection algorithms may be used to separate the region of interest from the background.

Contour detection

For example, an active serpentine algorithm may be used to detect the profile of the guidewire (3340A).

Automatic thresholding

An automatic thresholding (3340B) may be performed to classify the image components into one of three categories: radiopaque markers, lumen boundaries, and background. For example, the threshold may be calculated using a 2D multi-level Otsu method.

Classification

The image from the region of interest (3335) and the automatic thresholding (3340B) step may be combined for classification (3350). Classification may separate objects of interest (e.g., markers, lumen boundaries) from the background. A region algorithm may be used to link classified pixels belonging to the object of interest into a connected region. Constraints (e.g., known size and/or spacing of radiopaque markers) may be applied to increase the degree of linking.

Regional structure

Morphological operations (3360) such as erosion and dilation may be performed to form a region representing the boundaries of the guidewire and lumen. The background may be removed.

Centerline detection and modeling

Each segment of the centerline and/or marker of the vessel lumen may be detected (3370). For example, a black plug matrix (Hessian matrix) algorithm may be used to detect line segments. From the output of the marker decisions (3361), a centerline model may be established via parametric modeling of the marker(s) (3380) or via spline modeling of the lumen wall (3370A). Spline fitting (3370A) may be used to approximate two boundary lines of the vessel lumen, followed by calculation of the vessel lumen width (diameter) at a pre-measured location along the vessel (3370B). The width value may be stored. When multiple views are available, the width of each view may be calculated and stored. Parametric modeling (3380) may include using a Hough transform (Hough transform) to determine parametric equations for the centerline of each marker segment. As a result, the calculated shape and size may be utilized to build (3385) a 2D model(s) of the radiopaque marker and/or the vessel lumen. Modeling (3382) may provide a 2D model, a 3D model, or both. Optionally, when images from two or more known projections are available (3381), the above procedure (3320-3380) may be applied to each image to generate a 2D model of the marker segment and/or lumen, which may then be processed (3390) to construct a 3D model (3395). The process of reconstructing a 3D model from a 2D image (3390) may be performed as described further herein, such as by Direct Linear Transformation (DLT).

As shown in fig. 21, point P may be projected to 2 image planes U at points P1 and P2 _L V _L And U _R V _R Is a kind of medium. Can find the projection lineIs the position of P.

Direct Linear Transformation (DLT) may be used to solve the above problems. The projected coordinates can be written by the following equation:

symbol L ₁ To L ₁₁ Is the DLT parameter. Because (u, v) is known, once the parameter (L ₁ ，L ₁₁ ) The object coordinates (x, y, z) can be calculated. In linear math, at least 6 points are required to solve (L ₁ ，L ₁₁ ). In one representative embodiment, assuming N points are acquired, the matrix equation for L can be combined using the following formula:

equation (3) is expressed as:

F _(2N,11) L _(11,1) ＝g _(2N,1) (4)

a similar matrix equation can be written for the R (right) projection (P2).

Equation (4) can be solved by pseudo-inverse (or SVD decomposition) to obtain a solution for L (left) (and similar R), for example:

L＝ (F ^T F) ^-1 F ^T g (5)

with the solution of L and R, the coordinates of points in object space can be calculated by:

the left matrix in equation (6) is not square and can be decomposed or pseudo-inverted to solve for (x, y, z) in the object coordinate space.

At least 2 points may be selected from each segment (e.g., one radiopaque marker as a segment). The points from each segment may then be linked to form a segment model of the segment, and a polynomial fit may be used to estimate the separation between any two markers.

Alternatively, the machine learning model may be trained and extrapolated for segmentation. Machine learning models may replace steps 3320 through 3360. For example, a machine learning algorithm U-net may be used, which is an effective medical image segmentation model.

When using the 3D modeling method described herein, image blur caused by measurement errors of the P position can be reduced. Position U _L 、V _L 、U _R And V _R Respectively include error degree sigma U in position measurement _L 、σV _L 、σU _R And sigma V _R . By comparing the errors measured for each of the positions at different angles, standard error measurement reduction methods known in the art can be applied to these positions to reduce the degree of error in measuring P, thereby producing a clearer image.

To model the body lumen, a fringe model (2D) may be generated using the width. The widths corresponding to the same locations may be measured (or interpolated) and then used to generate a tubular model (3D) of the blood vessel.

Guidewire markers may optionally be labeled for ML (machine learning) training. ML training on guidewire markers may include a process of processing the guidewire markers by an algorithm that adjusts the relative position of the guidewire based on the displacement data. The labeled guidewire markers may be used to construct a model of a guidewire in a patient. The ML model may be used to generate a guidewire model.

As the device travels parallel to the guidewire, its position on the guidewire can be tracked and presented to the user in real time. If a diagnostic device is used, its modality data (which may include, for example, images or waveforms) may be co-registered according to the location of the treatment and/or diagnostic device, and multimodal data from the same location may be presented. Fig. 22 illustrates a method 3500 for data processing and location association.

Device motion (3580) and tracking (3510)

As the therapeutic and/or diagnostic device is advanced parallel to the guidewire (3580), a signal modulated by the linear displacement encoded markers (e.g., markers 2250, 2340, 2470) may be generated by a sensor (e.g., sensors 2290, 2308, 2480), and the signal transmitted (3540). The signal may be sampled and modulated (3550), then the conditioned and digitized signal may be decoded (3560), and then may be shifted (3570) relative to the encoding computing device. The device displacement calculation may be based on a linear encoded signal and the device position calculation may be based on a known relationship of linear distance (or size) between the displacement encoded marker and any radiopaque marker. The calculation may be further based on the 1-D linear coordinates and the time stamp of the distance (time of receipt of its corresponding modulated signal) of the therapeutic and/or diagnostic device on the guidewire. The calculations may be performed before the data is sent to the reference integrated system 3105 (fig. 18). The reference integration system 3105 may use the 1-D linear coordinates of the guidewire and the 2D/3D model to calculate 2D/3D coordinates of the treatment and/or diagnostic device. Note that the linear encoding system and method disclosed above is one example of how displacement and position may be determined. Device location information received from any source (e.g., pullback sensor, encoder sensor, etc.) may be used as long as the location can reference a radiopaque marker on the guidewire and can be received by the reference integration system 3105 to be tracked on the 2D/3D model of the guidewire.

Position correlation (3520)

One or more images (or physiological signals, or therapeutic device signals) may be acquired from other systems, as shown in fig. 18 with respect to diagnostic and/or therapeutic system data 3130. The image (or physiological signal, or therapeutic device signal) may be time stamped and associated with the position data acquired at the most recent time instance. Optionally, system delays may be considered to improve accuracy. The diagnostic/therapeutic data may further be correlated with corresponding locations on the radiopaque marker 2D/3D model.

Presentation (3530)

As illustrated in fig. 22, one or more simulated device images may be overlaid onto the guidewire model in real-time for display (3530) (e.g., as illustrated in the example displays of fig. 2B, 14, 15, 16). The operator may choose to view real-time or near real-time diagnostic information at any location on the guidewire marker model. Alternatively, the operator may manipulate the viewing parameters (e.g., zoom in, zoom out, rotate) in real time or near real time. FIG. 22 depicts an overall data processing method for converting one or more simulated device images onto a guidewire marker model.

Device position tracking in the form of a visual real-time or near real-time illustration with distance measurement may be integrated with angiographic vasculature imaging as illustrated in the example synthetic angiographic image shown in fig. 19. When a device (e.g., a stent on a deflated delivery balloon) is advanced parallel to the guidewire 3220 with the marker 3230, the distance of travel data may be transmitted from the guidewire 3220 to the reference integration system 3105. As described above, once the trip data is received, the distance measurement results may be calculated and displayed in real time. The graphical representation 3240 of the treatment and/or diagnostic device (or a graphical representation of its location) may be superimposed simultaneously onto the composite angiographic image 3250 according to the real-time location of the treatment and/or diagnostic device. The distance may be displayed (e.g., on the display 107, 3107) along with other calculated data. The therapy and/or diagnostic device graphic 3240 superimposed on the angiographic image with precise positional co-localization can be used as a visual representation and navigation during inactive fluoroscopy. The reference integrated system 3105 may continuously or periodically update the treatment and/or diagnostic device graphical location and associated measurements throughout the procedure.

Using complex Percutaneous Cardiology Intervention (PCI) imaging as an example, a workflow of a bootstrap 3600 is shown in fig. 23, including an associated plurality of diagnostic and/or therapeutic device location co-locations and displays. X-ray in vitro imaging is commonly used for cardiac interventional workflow in catheterization laboratory environments. An example of an X-ray interventional image guidance system is Innova ^TM IGS (GE Healthcare). Following standard PCI workflow, after identifying a region of interest within a vessel via standard X-ray imaging assessment procedures using a conventional X-ray interventional image guidance system, a guidewire with a plurality of radiopaque markers (and optionally, a distal embedded encoding sensor) may be advanced and positioned over the region of interest under real-time X-ray imaging (3610). Fluoroscopic imaging may be activated at a desired imaging orientation (projection) as the contrast agent moves through the vasculature being examined. The guidewire can be delineated along with a plurality of radiopacity linesMarkers and boundaries of luminal tissue with similar radiodensities. Fluoroscopic images, which contain a lumen and a guidewire with multiple radiopaque markers at the area of the vasculature to be treated, may be captured and recorded with one or more different projection angles. The imaging information obtained in step 3610 may be transferred to a reference integration system 3105 for processing and guidewire modeling (3620). In particular, 2D and/or 3D guidewire modeling via multiple radiopaque markers may be performed by the process steps shown in fig. 20 and 21. Corresponding 2D and/or 3D vessel segment models may also be established. The guidewire modeling data may be superimposed with the corresponding X-ray image to form a selected composite image (e.g., as shown in fig. 19) (3630). With the known size and spacing of the plurality of markers, a linear distance scale along the vessel relative to a reference point at the user's choice may be established on the composite image and may be displayed, for example, on a boom display (e.g., display 3107).

For example, for the treatment device delivery phase of procedure 3600, a balloon dilation catheter may be delivered. An example of a balloon dilation catheter is Coyote ^TM Balloon dilation catheter (boston science (Boston Scientific)). In the case where the composite image remains displayed, the X-ray system may be switched to inactive. The balloon catheter is advanced from the proximal end of the guidewire to the distal end of the guidewire, and position sensing of the balloon catheter may be activated when, for example, an optical sensor on the guidewire detects an optical marker inside the balloon catheter shaft (3640). As the balloon travels along the guidewire, its optical markers pass through an optical sensor on the guidewire, and the position of the balloon relative to the catheter can be detected via optical signal transmission and reception by the guidewire sensor. The received signals may be transmitted to a signal processing component (e.g., hub 3109) at the proximal end of the guidewire via an optical fiber passing through the interior of the guidewire. The optical signals may be converted to electrical signals at hub 3109. The data may then be transmitted from hub 3109 to reference integrated system 3105 (e.g., via bluetooth or a wired connection).

Based on the known dimensions of the balloon and the known embedded optical marker sequences of the balloon catheter, the balloon travel distance can be decoded from the electrical signal to obtain a linear displacement value. Because of the guidewire radiopaque marker coordinate system pre-established on the composite image and the balloon displacement measurements with known start and end points, the position of the balloon catheter may be calculated and identified on the composite image in real-time and/or near real-time (3650). A representation or illustration of the balloon catheter (e.g., illustration 3240) may also be generated with scaled real dimensions on a 2D/3D guidewire model and corresponds to the balloon catheter position. Balloon catheter illustration 3240 may be superimposed and displayed on the composite image to represent real-time or near real-time balloon position when X-rays are inactive. While the X-rays remain inactive, balloon displacement readings, distance from the balloon to the target vessel location, as selected by the user, and a graphical representation of device movement may be updated. When the balloon reaches the target location (3660), the reference integration system 3105 may optionally signal the operator/physician. After reaching the target treatment site, position verification may optionally be performed using real-time X-ray image capture prior to balloon deployment (3670). The real-time X-ray image data may be received by the reference integration system 3105. Balloon real-time location information may be integrated with pre-established 2D and/or 3D models of the guidewire and lumen. Balloon map locations and associated positioning information may be adjusted in real time or near real time, if desired. The updated balloon map and other updated position information may be superimposed on the X-ray image and displayed as selected by the user. Alternatively, the position verification (3670) may be performed more than once, or at any time, during advancement of the balloon over the guidewire, as per the user's preference. After the balloon reaches the target treatment site, and optionally after position verification, balloon deployment is performed (3680). The reference integration system 3105 may process and update, record and store the synthetic imaging data including balloon position and illustrations in real-time or near real-time throughout the workflow 3600.

In the case where the X-ray system image is at a different projection than the initial angle at which the position verification (3670) was performed. The reference integration system 3105 may follow the same procedure described above to update the 2D guidewire model based on the new X-ray image and projection. If the previous model is 3D, the model may generate and display a 2D model in the desired projection. The associated device location and distance information under the new projection may also be updated and displayed accordingly. The illustration of the endoluminal device (e.g., balloon catheter, diagnostic device) can be adjusted accordingly as the device is moved to the desired position while maintaining X-ray inactivity.

Intravascular imaging and/or physiological assessment is typically performed as part of a diagnostic procedure for further lumen assessment and treatment strategy determination. Fig. 24 shows the workflow of the boot diagnostic routine 3700. The bootstrap 3700 can be performed prior to therapy delivery (e.g., prior to balloon delivery, prior to step 3640) and/or after therapy delivery (e.g., after balloon delivery, after step 3680). Workflow 3700 of fig. 24 is described with respect to an example embodiment in which an endoluminal diagnostic IVUS imaging probe is delivered to verify treatment. An example of an IVUS catheter used in such procedures is an eagle eye platinum catheter equipped with a nuclear mobility independent system (philips healthcare company (Philips Healthcare)).

For example, after completing the balloon dilation and retrieval procedure, as described with respect to workflow 3600, the operator/physician may select a desired lumen location for the IVUS imaging sensor from the established composite angiographic image as a target (3710). In this example, the balloon dilation location in the previous workflow is the IVUS imaging target. The displacement of the catheter relative to the guidewire sensor can be detected using embedded optical markers included in the IVUS catheter shaft. Under the same distance sensing, position tracking, destination arrival and position verification procedures described in fig. 23 at 3640, 3650, 3660 and 3670, the IVUS imaging sensor is placed at the desired lumen location (3720) and a starting point is established for catheter pullback. In case of X-ray inactivity, the IVUS imaging sensor (3730) is pulled back according to standard IVUS imaging procedures. For example, the pullback may be performed manually by an operator/physician, or automatically by an automatic pullback device. An optical sensor of the guidewire generated in response to the IVUS optical marker may detect pullback movement of the IVUS catheter inside the lumen. The light may be converted to an electrical signal and transmitted to the reference integrated system 3105 via the hub 3109. IVUS imaging sensor position tracking may be calculated (3740) via displacement data integrated with a pre-established 2D/3D model of the guidewire. When the X-rays are inactive, the imaging sensor locations and associated positioning information may be superimposed and displayed on the composite angiographic image in real-time or near real-time (3750).

Fig. 25 illustrates an example of co-location and display 3800 (illustrating the output of steps 3740, 3750) between different systems and/or devices simultaneously and when X-rays are inactive. With the known size and spacing of the plurality of markers on the guidewire, a linear distance scale along the vessel relative to a reference point at the option of the user can be established on the 3D guidewire and lumen model 3820 showing the plurality of radiopaque markers 3830 on the synthetic X-ray angiographic image 3810 and on the 3D model. Continuing with the example embodiment relating to an IVUS catheter, prior to pullback, an initial position 3801 of the IVUS imaging sensor may be obtained from an imaging sensor position verification step. Based on the displacement and associated endpoints 3805, imaging sensor position tracking may be established. As the imaging sensor generates the IVUS cross-sectional view 3840 and the longitudinal view 3850 during pullback, the guidewire marker trajectory along with the imaging sensor map overlaps with the IVUS longitudinal view based on the established coordinate system. When X-rays are inactive, the imaging sensor position and associated linear distance information may be displayed on the IVUS longitudinal view 3850. In addition, the balloon dilation position segments 3860 from the previous step may be precisely co-located and overlapping on the IVUS longitudinal view. The X-ray composite image, guidewire model, and IVUS longitudinal view may be displayed at the user's option from any X-ray projection angle and/or IVUS longitudinal view angle. The corresponding device location, lumen location information, and/or positioning information obtained from the previously described example workflow may be precisely co-located and displayed in real-time or near real-time or while the imaging sensor is being pulled back. Unlike current pullback distances measured from the proximal end of the imaging catheter or via real-time X-rays, imaging sensor motion detected by the catheter optical sensor at the distal end of the device inside the lumen represents accurate device position and displacement, which can eliminate measurement inaccuracies caused by current pullback methods. Furthermore, the accurate displacement measurement provided by the guidewire is independent of real-time X-rays and provides the operator/physician with a flexible and customizable IVUS imaging workflow that is not achievable with current procedures. In the event that the X-rays are continuously inactive, the user may utilize the recorded imaging and co-location information to complete the IVUS imaging procedure. The user can apply the same workflow on the other intra-luminal diagnostic devices (e.g., OCT and/or FFR/iFR) they choose.

In a further example, a stent implantation procedure and associated post IVUS imaging evaluation may be performed, as described by example of workflow 3900 depicted in fig. 26. An example of a stent for such surgery is Synergy ^TM Stents (Boston science Co.). As shown in fig. 25, the operator/physician can identify the target vessel location on the composite X-ray image 3810 and/or IVUS longitudinal view 3850. In the event that the X-ray system is inactive, the operator/physician may deliver the stent balloon catheter to the desired lumen location (3910) following a similar workflow as described with respect to fig. 23. When the stent balloon catheter position is detected by a position sensor on the guidewire with the X-ray system inactive, its position and associated linear displacement measurements may be co-located and displayed (3920) in real time or near real time, optionally along with a stent position map, on the composite X-ray image and composite IVUS longitudinal view, as previously obtained (fig. 24 and 25). The reference integration system 3105 may update the stent's position via the 2D/3D guidewire model during ta stent position verification (3930). Corresponding data processing may be performed, including data reception, model calculation, co-location integration, and display (3940). During and/or after stent deployment (3950), X-ray images may be taken to assess stent deployment, followed by stent apposition and vessel assessment by IVUS imaging (3960). Since the vessel locations indicated within the X-ray image(s), IVUS image(s) and device location(s) can be precisely co-located via the 2D/3D guidewire model, cross-assessment between several modalities can be performed before, during and/or after any diagnostic and/or therapeutic procedure.

As an example, the stent segment 3870 may be deployed and the position 3875 may be co-located with the lumen position of the IVUS image and the balloon-expanding segment 3860, as shown in fig. 25. Such an integrated format may provide ease of use and introduce novel clinical insight that has not been previously available. Furthermore, such complex percutaneous interventions described may provide increased flexibility and customizable workflow while minimizing radiation exposure to the user, patient, and operating environment.

Fig. 27 and 28 depict a comparative overview of the workflow of a standard PCI procedure 31000 (fig. 27) and a PCI procedure 31100 that benefits from a consistent positioning system, as described above (fig. 28).

Fig. 27 shows a current method 31000 of complex percutaneous interventional cardiology surgery as a representative standard. After the region of interest is finalized, the guidewire is advanced and positioned at the region of interest by standard angiographic assessment (31010). Intracoronary diagnosis, such as IVUS imaging, OCT and/or FFR (31020), is performed using real-time X-ray imaging visualization. By reviewing the X-ray images and the diagnostic data independently displayed on each modality system, the operator/physician thinks about integrating the data to determine the treatment strategy. Based on the treatment decision, which is highly dependent on the operator, the treatment device (e.g., balloon or stent) is delivered near the target location under the guidance of real-time X-rays (31030). Post-treatment assessment (31040) is performed to assess clinical effects and potential risks. In particular, the imaging and/or physiological device is delivered again to the treatment site under the guidance of real-time X-rays. The operator/physician conceptually integrates the treatment data with the post-stent-implantation evaluation data for each estimated lumen location of interest.

Fig. 28 illustrates a workflow of one representative method 31100 of using the provided apparatus and system, wherein advantages over the method depicted in fig. 27 are also described. The provided real-time or near real-time device co-location sensing systems and methods enable each step of a complex percutaneous interventional procedure to be highly integrated and have minimal reliance on X-ray angiography and fluoroscopy, thereby reducing X-ray exposure to the operator/physician and/or patient. After an initial assessment under X-ray angiography (31110), real-time X-ray navigation becomes optional, and diagnostic procedures (31120), treatment device delivery and deployment (31130), and post-treatment assessment (31140) can be performed without real-time X-rays. Thus, radiation exposure may be greatly reduced. Furthermore, accurate real-time sensor locations (and associated measurement results/imaging of a given location) may be determined and provided to a user. Still further, accurate co-location between multiple systems (e.g., X-ray images, diagnostic imaging, physiological assessment, and treatment device deployment) may be provided. Thus, a complete set of accurate and relevant comprehensive clinical information can be provided to the physician in real time throughout the PCI procedure to optimize treatment strategies, treatment deployments, and clinical assessments. Some of the advantages of the provided method over the current standard PCI method depicted in fig. 27 are real-time or near real-time co-location for decision making, delivery and deployment on the target, and minimal X-ray radiation exposure. Real-time or near real-time co-localization also provides a solution to the previously unmet operator/physician need for endoluminal interventions.

The systems described herein may provide data acquisition, modeling, surgical guidance, precise lumen location correlation, and display of positional information with minimal radiation. The reference integrated system 3105 may include several subsystems, as illustrated in fig. 29: (1) a communications and storage subsystem (31230); (2) a data processing and location association subsystem (31240); and (3) a user interface and display (31250).

The communication and storage subsystem (31230) may interface with external data streams 3110, 3145, 3115, 3125, store raw data on the system memory bank, and provide internal data stream 31235, allowing the data processing and location association subsystem (31240) to access different data streams, store processed data in the system memory bank, and interface with external storage devices as needed.

The device location data interface (3110) may interface with the guidewire, therapeutic device, and/or diagnostic device to obtain positioning information input (31220) and store corresponding data in a system memory bank for processing by the data processing and location association subsystem (31240).

The computer network system interface (3145) may transmit and/or receive data from local and/or external network storage systems containing information for signal processing in the subsystems 31240 and 31250. The data may be real-time or near real-time and may be acquired from different procedures and/or steps, such as, but not limited to, ECG (electrocardiogram), doppler, FFR (fractional flow reserve), FFR-CT (fractional flow reserve-computed tomography), IVUS (intravascular ultrasound), and OCT (optical coherence tomography). The computer network system interface (3145) may save the raw data and final processed data from the memory bank to a local and/or external storage system for further data processing by other therapeutic and/or diagnostic systems.

An angiographic data storage interface (3115) may interface with the angiographic data storage device (3108) to obtain real-time and/or near real-time angiographic data and store the data in a system memory set for processing by the data processing and location association subsystem (31240).

The diagnostic and/or therapeutic system data interface (3125) may access diagnostic and therapeutic information such as, but not limited to, ECG (electrocardiogram), doppler, FFR (fractional flow reserve), FFR-CT (fractional flow reserve-computed tomography), IVUS (intravascular ultrasound), and OCT (optical coherence tomography) from the diagnostic and/or therapeutic system (3130) before, during, and after surgery. The diagnostic and/or treatment system data interface (3125) may also access treatment and/or diagnostic device location data or a portion thereof specific to the configuration of the diagnostic treatment system and device, such as, but not limited to, catheter pullback distance (i.e., obtained at the proximal end of the catheter via a device that is part of the diagnostic/treatment system).

The data processing/location association subsystem (31240) may provide a variety of functions. From the angiographic information (3115) including the image of the radiopaque marker, the subsystem may utilize the dimensional information and the position relative to the lumen to build a 2D and/or 3D model of the flexible elongate instrument inside the lumen. The subsystem (31240) may receive position and/or displacement information about the therapeutic and/or diagnostic device from any of the following in real time or near real time: device location data (31220), diagnostic and/or therapeutic system data (3130), and communication and storage (31230) via an interface (31235). A subsystem (31240) may integrate the position data with a 2D and/or 3D model of the flexible elongate instrument and generate a real-time or near real-time device position representation, including overlaying the representation with the 2D and/or 3D model. The subsystem (31240) may also generate location-related display data via real-time or near real-time data integration between 2D/3D model, analog device illustration(s), diagnostic and therapy system data, and angiographic data. The subsystem (31240) may also provide for input and processing of operator/physician selected viewing options, such as 2D/3D, projection of interest, viewing angle with device signals at any location, and/or other execution requests, via a user interface and display subsystem (31250).

An internal data interface (31235) may be used as an interface between the communication and storage subsystem (31230) and the data processing/location association subsystem (31240). Raw data, which may include data from the device location data interface (3110), the computer network system interface (3145), the angiographic data storage interface (3115), and the diagnostic and/or therapeutic system data interface (3125), may reside in a local memory bank within the subsystem (31230).

The data processing/location association subsystem (31240) may access the raw data through an interface (31235). Processed data from subsystem (31240) may be stored in memory banks of subsystem (31230) through interface 31235.

The user interface and display subsystem (31250) may place the processed data (31245) from the data processing/location association subsystem (31240) in an appropriate format (3150) for display by the display system (3107), such as in a format based on a graphical representation of the user interface data input (31211) from the user interface device (31210). The operator/physician interface inputs may be embedded in the display data (3150) of the display system (3107) or may be embedded in the operator/physician interface data (31211) of the user interface (31210) as a separate display and control.

The systems and methods provided may be applied to any interventional procedure in a body lumen. Optionally, a GUI may be presented on the reference integrated system 3105 with components or controls to allow an operator to interact with the reference integrated system 3105 via command controls for execution, including providing an interface for lumen location-associated display with third party diagnostic and therapeutic systems. The form of the visual display system (e.g., display 3107) may vary, and may be or include, for example, monitors, mobile devices, wearable devices, and AR/VR headsets. The input by the operator/physician at the operator/physician interface 31210 may be performed via electronic devices such as a computer, a server with a monitor, a host workstation, a controller with a monitor, and a third party system operator/physician interface. The I/O may include a keyboard, joystick, mouse, touch display, projection device, microphone, any consumer and/or wearable electronic device (e.g., mobile phone, AR headset), pointing device, and audio feedback for communicating with the reference integrated system 3105 for programming, data presentation and visual display, data storage, and basic data processing functions. Such a connection mechanism may provide the user with an easy workflow throughout the bootstrap program with sufficient customization flexibility for real-time or near real-time lumen location association and associated data processing steps. The interface connections 3110, 3145, 3125, 31211, 3150 and 3115 with the reference integrated system 3105 as shown in fig. 29 may be established via various connection mechanisms, such as cables, cellular networks (4 g,5 g), local and/or wide area networks (LAN and WAN), bluetooth networks or wireless networks.

The ML method may further include curve fitting techniques to develop a model of the catheter within the body lumen. The curve fitting may be done manually or may be fully or semi-automatic. For example, on one X-ray image, 3-16 boundary points along the guidewire may be selected as guidewire markers. After placement of the boundary points, a cubic spline interpolation technique may be used to fit the curve between each boundary point. The curve may satisfy the following equation:

S _n (x) ＝ a _n x ³ + b _n x ² + c _n x + d _n (7)

by solving a system of n equations (where n is the number of boundary points selected (manually or automatically)), a cubic spline of the catheter length (i.e., the distance from the proximal end to the distal end of the therapeutic and/or diagnostic device) can be obtained.

The "boundary points" may be selected from edges of the image feature or a centerline of the image feature. The edges of the image may be determined by methods known in the art, including methods that detect sharp changes in the brightness of the image or have discrete locations.

Optionally, the diagnostic and/or therapeutic device may further include pre-measured modeling data, which may be transmitted to the computing unit (e.g., with reference to the integrated system 3105). Although a typical diagnostic device for PCI surgery is described in the above examples, the diagnostic device may be another modality, such as 3D MRI or CT. The pre-measured modeling data may include distance signal information that is desired for a body lumen of a patient previously imaged using 3D MRI (magnetic resonance imaging) and/or CT (computed tomography) based on MRI, CT or X-ray angiography data of the patient.

Alternatively, the relative position of the first flexible elongate instrument and the second flexible elongate instrument may be measured from a plurality of sensors, with the first sensor on one of the flexible elongate instruments (e.g., sensor 120) and the second sensor external to the patient's body (e.g., sensor 126) and connected to the other flexible elongate instrument. The sensor external to the patient's body may be, for example, part of a robotic arm, or a motor-driven position unit. The two sensors may be used in a hypertortuous body lumen, such as in the brain, where displacement measurements taken at the distal and proximal ends may be quite different. The relative co-location identification within the body lumen provides accurate displacement relative to the plurality of imaging markers, and such data may be communicated to help guide the robotic arm to advance one of the two flexible elongate instruments.

4. Position coding and single element detector

The flexible elongate instrument may include a single element sensor for detecting codes on other flexible elongate instruments to provide positioning information during endoluminal procedures. The code may be a single code track configured to provide absolute position detection. Such a configuration may advantageously provide for position detection of an instrument, for example for use in percutaneous interventional procedures, by providing a compact form suitable for use on or with an endoluminal instrument.

Absolute position encoding typically uses a sequence of code lines of different widths that are unique to different positions. For example, for a common binary location code, a code sequence representing a location requires four code characters: a number separator character, a "0" character, a "1" character, and a position segment separator character. For constant speed motion, duration may be used instead of a digital separator. For pseudo-random sequence binary position codes, a position segment separator character may not be required, as the sequence change from each additional digit may represent a new position. In short, at least three code characters are required for absolute position encoding performed with existing methods.

Current techniques for single code track, absolute position, binary encoding typically use an array sensor to detect a range of code mark widths. The array sensor includes a number of photosensitive elements or pixels that can capture an image of the code lines in at least one direction and thereby determine the width of each code line.

In some cases, when the relative speed of motion between the code track and the detector is constant, a single sensing element detector may be used, as the code line width may be calculated based on the duration of a given signal level. If the movement between the code track and the code detector is random, the duration cannot be used to determine the code line width.

Most endovascular medical devices have a low profile so that the device can be positioned and moved within the vessel. Array sensors and their associated wiring are not adapted in or on these devices. In addition, when using these devices, their speed of movement in the body lumen is generally not constant and unpredictable. In interventional medical procedures, it may be important to accurately determine the position of an intra-cavity diagnostic or therapeutic device inside a body cavity. There is a need for an absolute position encoding system that can meet the need for low profile and provide accurate encoded information under random motion. The position encoders incorporated into these devices can be very small and can accommodate limited wiring access space.

Fig. 30 illustrates a conventional multi-channel absolute position encoding system 4100. The 4-track, 4-channel encoded strip 4110 provides a 4-bit binary signal having 16 positions. The detector 4120 includes four sensing elements 4125, each of which generates a signal output from its respective code rail, as shown by output 4130. In this example, the white mark represents code character 0, while the black mark represents code character 1. The 4-code characters in the 4-bit binary sequence are generated simultaneously.

Fig. 31 shows a conventional array sensor 4200 for absolute position encoding. The light source 4210 illuminates the code rail 4220. Light from the light source 4210 is reflected by the code track, passes through the optical lens 4230, and is focused on the array sensor 4240. The array sensor 4240 includes several sensing elements or pixels. For example, a general array sensor may be constituted by a CCD sensor or a CMOS sensor. The array may also be a linear array oriented along the direction of motion or a two-dimensional array that may include thousands of pixels. The spacing information of the code lines is captured by the array sensor and transmitted to the computer processor.

Examples of detectors with single element sensors and encoding methods that can provide absolute position determination are provided. The detector may also allow random speed movement. With a single sensing element sensor, the detector can be made small enough to be configured as an intracavity device. The determination of the code line width based not on time information but on the intensity of reflected light may be employed. Thus, the code line width can be determined without being affected by the change in the movement speed.

As used herein, the term "single element sensor" or "single sensing element sensor" refers to a non-array sensor. The "single element sensor" may be a single pixel sensor or a multi-pixel sensor that provides a single output signal.

Fig. 32A-32B illustrate two examples of systems 4300a, 4300B having single sensing element sensors. As illustrated in fig. 32A, the code track 4310 is illuminated by a light source 4320. Any type of light source may be used for illumination. Light is projected onto the code track 4310, illuminating a limited illumination area 4352 having a limited width 4350 in the direction of movement between the code track 4310 and the detector 4360. Reflected light from code track 4310 is captured by sensor 4370, which is a single sensing element sensor, also referred to as a single pixel sensor. Alternatively, multiple sensing elements or pixels may be used, but each sensing element or pixel does not provide a separate output; instead, sensing is incorporated into a single output or single channel, such that the positional information for each individual pixel is not captured.

As illustrated in fig. 32A-32B, the detector 4362 includes an optical fiber 4315 that transmits light from the light source 4316. The reflective surface 4325 is shown as a 45 degree polished end face of the optical fiber 4315 with a reflective coating. The coating may be made of a variety of materials (e.g., aluminum, silver, chromium, gold, platinum, etc.) that may be applied to the surface via, for example, vacuum deposition. The light is reflected by the reflective surface 4325, exits the window 4365, and illuminates a limited illumination area 4335 on the code track 4310. The limited area 4335 has a limited width 4355 in the direction of movement. A portion of the reflected light from the code track 4310 re-enters the window 4365 and reaches the light sensor along the optical fiber (see, e.g., fig. 36). The optical fiber may transmit light from the light source to illuminate the code track and transmit reflected light from the code track to the light sensor.

Fig. 33 is a schematic diagram 40 showing the principle of operation of recognizing different code characters based on the width of a code line using a single sensing element sensor. The code rail 4400 is shown by example photosensitive areas 4410, 4420, 4430, 4440 provided by detectors passing through code lines. The single sensing element may be sensitive to a limited area on the code track adjacent to the sensor element. Such limited areas are referred to herein as photosensitive areas. The code marks outside the photosensitive area are not detected by the sensing element. The photosensitive area may be created by illuminating a limited area on the code track or by a size of the sensor element or a size limited area of a mask or window placed between the sensor element and the code track, the mask or window defining an area on the code track where light can reach the sensor element.

When the mark width of the high-reflectivity surface or the low-reflectivity surface is equal to or wider than the light-sensitive area (4430, 4440), an all-high signal and an all-low signal are generated, respectively. Code lines that are wider than code lines that produce an all high or all low signal do not change the output signal level of the sensor.

When the mark width does not completely cover the photosensitive area (4410, 4420), a partial signal is generated. When different mark widths are calibrated to produce different signal levels, the signal levels may be used to determine the mark width of the produced signal, and the different mark widths may be used to represent different code characters. The examples of photosensitive areas shown by 4410, 4420, 4430 and 4440 are generally circular, but it should be understood that the shape of the photosensitive areas may be modified depending on the light/sensor design and use.

Graph 4450 shows theoretical calculations of light intensity profile changes when full width, 1/2 full width, 1/4 full width, and 1/8 full width high reflectivity code lines pass through a circular photosensitive area and when full width low reflectivity code lines are on both sides of the code line.

The portion 4460 of the 4-bit code track includes, for example, three position segments 4470, and 4490. In section 4460, the widest high reflectivity code line (e.g., code line 4462) represents a position segment separator code character. The low reflectivity code lines (e.g., code line 4464) represent numeric separator code characters. The narrowest and middle high reflectivity code lines represent binary code characters "0" and "1", respectively. As the detector passes through the code track, a reflected light intensity signal 4495 is generated. The 4-bit position codes 0110, 0111, and 1000 represent three unique adjacent positions on the code track.

The example portion 4460 provides a binary position code comprising 4 signal levels for position encoding. For some coding algorithms, such as pseudo-random sequence codes, 3 signal levels may be sufficient.

Fig. 34 shows the result of decoding position and time of random motion between a 4-bit code track and an encoded detector with a single element sensor. Reflected light intensity signals 4510 from the code tracks are shown adjacent to the location of the motion and time plot 4520. As this example illustrates, the random motion includes four direction changes, which may be determined based on a comparison with a previous adjacent code sequence.

Fig. 35A-35F illustrate further examples of systems having single sensing element sensors that can generate signals that provide absolute positioning information, including position, direction of motion, and speed of motion. The systems 5300a, 5300b, 5300c illustrate three different embodiments of code track construction that can provide absolute position binary encoding for 4-bit sequences. These systems may utilize what is referred to herein as "OCT-based position encoding" in which the code line imprint depth is detectable by an optical detector. The sensor may comprise a portion of a single optical fiber through which light is transmitted from the light source to the code rail and through which reflected light is transmitted from the code rail to the photodetector. While the described examples provide encoding with a 4-bit sequence, other types of binary encoding (such as pseudo-random sequences) may alternatively be provided by OCT-based position encoding and any number of bits of the sequence length, which may be determined by the number of positions to be encoded.

Fig. 35B illustrates an example reflected signal detected by the system 5300a shown in fig. 35A. The reflected signal is detected in a single pulse light emission from the sensor 5312 to a code track 5310 in which the imprinted code line is wider than the beam width from the fiber. Light is transmitted by the optical fiber 5360 and reflected through the optical window 5350 toward the code rail 5310 (e.g., as illustrated, reflected at 90 degrees by the 45 degree polished end face 5370). The code track has an outer surface 5320, a shallow depth imprint code line 5330, a medium depth imprint code line 5340, and a deep imprint code line 5342. When the sensor 5312 remains a constant distance from the code rail 5310 during relative motion, reflected light signals from lines 5320, 5330, 5340 and 5342 are shown by signals 5315, 5325, 5335 and 5345 in fig. 35B, respectively.

As an example, the encoding algorithm may be assigned such that signal 5315 represents a bit separator code character, 5325 represents a "0" code character, 5335 represents a "1" code character, and 5345 represents a position segment separator. When so allocated, in the illustrated example, the code lines imprinted in 5310 represent binary sequences 0, 1.

Fig. 35C-35D illustrate another example embodiment. The code rail 5313 in fig. 35C differs from the code rail 5310 in fig. 35A in that a translucent coating 5380 is applied. The translucent layer may also reflect light from the sensor, thereby creating a signal peak. Thus, when light is reflected from the surface 5313, shallow code line 5323, intermediate depth code line 5343, and deep code line 5346, not only do each line produce its own peak (as shown by signals 5318, 5327, 5337, 5347 in fig. 35D), but also an additional peak 5317 from the translucent coating 5380. An advantage of this embodiment is that the sensor 5312 does not need to be kept at a constant distance from the code rail 5313. The distance between the two signal peaks is not affected by the distance between the sensor 5312 and the code rail 5313 and may be uniquely different for each code line. Thus, the distance may also be used to represent different code characters.

Fig. 35E to 35F illustrate another example embodiment. The code track 5390 differs from the code track 5310 shown in fig. 35A in that the imprinted code line is narrower than the beam width. When the light beam 5395 is reflected by the code track surface 5328, a single peak is generated in the reflected signal 5319. However, when light is reflected by the code line, a portion of the light beam is reflected by the adjacent surface 5328 and a portion of the light beam is reflected by the code line, thereby producing two peaks. The distance between the two peaks may be proportional to the depth of the imprinted code line. The signals 5329, 5339, and 5349 are reflected signals from the code lines 5338, 5348, and 5349, respectively. In this example, four different reflected signals may be used to represent four different code characters.

Fig. 36 illustrates an optical fiber-based detector 4600 configured into an interventional medical device system including a monorail catheter having a guidewire lumen 4620 and a medical guidewire 4630. Only the distal portion 4650 of the monorail catheter is shown here. The window 4640 at the inner surface of the guidewire lumen may allow light from the reflective end face 4660 of the optical fiber 4670 to be reflected out and onto the encoded surface 4680 of the guidewire 4630. When the monorail catheter is moved relative to the guidewire 4630, or vice versa, light carried by the optical fiber 4670 may be projected out of the window 4660 and reflected back through the window 4660 to the optical fiber 4670 to be carried back to the photometer. The light intensity modulation and time from the encoded guidewire surface 4680 can be recorded and analyzed by a processor, which can then be used to calculate the position of the distal portion 4650 of the monorail catheter relative to the guidewire 4630.

Optionally, the detector 4600 may include additional sensors 4645 configured to provide directional information of the guidewire 4630 (or other type of flexible elongate instrument). For example, the direction sensor 4645 may be a load cell configured to provide an additive signal indicative of guidewire advancement and/or a subtractive signal indicative of guidewire retraction. The inclusion of a directional sensor in the system may provide directional information using codes that do not provide directional information, or may be used in conjunction with directional codes. The direction sensor may be included in a system that provides position coding in addition to absolute position coding. As illustrated, the direction sensor 4645 is shown disposed at a distal portion of the flexible elongate instrument; however, the direction sensor may alternatively be disposed at a proximal portion of the flexible elongate instrument (e.g., at or near a pullback or push sensor, such as at or near sensor 126 of fig. 1).

FIG. 37 illustrates an example fiber-based system and illustrates an optical pathway through the system. The optical system box 4700 includes a light source 4730 that provides a light beam for introduction into the optical fiber 4740. It should be understood that the light source may be an LED light source or a laser light source, or any other type of light source with sufficient illumination power. In case OCT based position coding is used, the light source may be an OCT light source. Time domain OCT light sources typically provide monochromatic light. Frequency domain OCT light sources typically provide polychromatic light.

The optical fiber 4740 may be connected to a fiber coupler 4760 that provides coupling with the light return optical fiber 4750. The fiber coupler 4760 may be, for example, a 2 x 2 fiber coupler. The light return fiber 750 may transmit the reflected light to a detector 4775 (e.g., a light intensity meter or an optical detector, such as an OCT detector). Light emitted by the light source 4730 may pass through the coupler 4760 and be transmitted into the fiber optic connector 4780 (e.g., a connector mounted on a surface of the optical system box 4700).

The flexible elongate instrument 4790 (e.g., monorail catheter, guidewire) may include a fiber optic connector 4785 at its proximal end that may be detachably connected to the optical connector 4780. The flexible elongate instrument 4790 includes an optical fiber (e.g., optical fiber 4670 in fig. 36, optical fiber 2270 in fig. 13A) built-in or attached that delivers light from the connector 4785 to the distal portion 4765 of the instrument that includes an optical window (e.g., window 4640) that can be used as an encoder detector sensor. The reflected light is collected by the optical window 640 and transmitted back through the optical fiber 4790 to the connector 4780 and the optical fiber coupler 4760. At least a portion of the reflected light may be split and allowed to enter the detector 4775 through the light return fiber 4750 by the coupler 4760. The light collected at detector 4775 may provide a measured intensity signal and/or depth profile signal, which may then be provided to a data acquisition processor and converted into code characters.

32-35 are illustrated as providing a four-bit position code; however, the code track and encoding algorithm may provide and utilize any number of bits for a given location code. Examples of six or seven bit position encodings that may also provide direction determination are shown in fig. 38 and 39. A six bit code may define up to 64 unique locations; and a seven bit code may define up to 128 unique locations.

As illustrated in fig. 38, the example code portion 4800 includes several of each of the following: black (or low reflectivity) separator bar 4802; white (or high reflectivity) spacer bars 4804; black (or low reflectivity) character bar 4806; and white (or high reflectivity) character gaps 4818, 4810. As shown, character gap 48108 defines a "0" character, while character gap 4810 defines a "1" character. As shown, seven bits are provided, encoded as "010001". For six-bit encoding, one less character may be provided.

The width of each of the strips 4802, 4804, 4806, 4808, 4810 can vary depending on the size of the instrument on which the code is applied (e.g., by reflective coating, depth of imprint, etc.) and the size of the optical fiber/window used for detection. For example, the width of each

The width of the code bars 4802, 4804, 4806, 4808, 4810 can be about 20 μm to about 1000 μm. For example, for small fiber applications, the width may be about 30 μm to about 200 μm, while for large fiber applications, the width may be about 50 μm to about 500 μm. In large fiber applications, for example, the width of the black spacer bar 4802 may be about 500 μm, the width of the white spacer bar 4804 may be about 250 μm, the width of the black character bar 4806 may be about 100 μm, the width of the character gap 4818 may be about 56 μm, and the width of the character gap 4810 may be about 160 μm. For small fiber applications, for example, the width of the black spacer bar 4802 may be about 170 μm, the width of the white spacer bar 4804 may be about 105 μm, the width of the black character bar 4806 may be about 42 μm, the width of the character gap 4808 may be about 32 μm, and the width of the character gap 4810 may be about 68 μm.

An example signal generated using the encoding defined by the example configuration shown in fig. 38 is shown in fig. 39. As can be seen in the figure, the forward "0" and the forward "1" are distinguishable from the backward "1" and the backward "0", and the change in the direction of movement is clearly detectable.

5. Definition and examples

As used herein, the term "patient" or "patient in need thereof" refers to humans as well as non-human animals, such as domesticated mammals, including, but not limited to, pigs, cats, dogs, and horses. The systems and methods provided are not limited to imaging of humans, and are also applicable to veterinary imaging.

As used herein, the term "body lumen" refers to the interior space of a tubular or hollow structure within a patient. For example, the body lumen may be an artery, vein, or capillary (also referred to as a "blood vessel") in which blood flows. The body lumen may be the colon, cranial vasculature, uterus, lung, air duct, ear canal, bladder, urethra or uterine canal.

As used herein, the term "distal end" of a component or device is understood to mean the end furthest from the user's hand (e.g., the physician implementing the PCI), while "proximal end" is understood to mean the end closest to the user's hand. Also, in the present application, "distal direction" is understood to mean the insertion direction, while "proximal direction" is understood to mean the direction opposite to the insertion direction.

As used herein, the term "flexible elongate instrument" refers to a medical instrument adapted for use inside a body lumen via a small hole through the skin and tissue or via an orifice. The medical device is generally elongated to impart flexibility and may optionally be smooth to enable access deep within the body lumen. More than one flexible elongate instrument may be used to perform an endoluminal procedure, in which case the plurality of flexible elongate instruments are referred to herein as a first flexible elongate instrument and a second flexible elongate instrument.

As used herein, terms such as "first" and "second" and other numerical terms do not imply a sequence or order unless clearly indicated by the context. For example, "first flexible elongate instrument" and "second flexible elongate instrument" are not intended to refer to one flexible elongate instrument being inserted into a body lumen before another flexible elongate instrument or prior to another flexible elongate instrument.

The flexible elongate instrument (alternatively referred to herein as a "flexible elongate endoluminal instrument") may be adapted to navigate within a body lumen to access a target location. The flexible elongate instrument may be a guidewire and/or may include portions that perform therapeutic and/or diagnostic functions within the body lumen. For example, at least two flexible elongate instruments may be used in an endoluminal procedure, wherein a first flexible elongate instrument is a guidewire or catheter and a second flexible elongate instrument is a diagnostic and/or therapeutic device or a catheter of a diagnostic/therapeutic device. In further examples, when two or more flexible elongate instruments are used in an endoluminal procedure, a first flexible elongate instrument may include an aperture through which a second flexible elongate instrument may pass. For example, when a portion or all of the first flexible elongate instrument is positioned within the body lumen, the first flexible elongate instrument may include a central axis and the central axis of the second flexible elongate instrument may run parallel or nearly parallel to the central axis of the first elongate instrument. Where the flexible elongate instrument is a catheter, it may further comprise at least one lumen to run over and parallel to another flexible elongate instrument (e.g. a guidewire).

The flexible elongate instrument may be a guidewire including a sensor and a plurality of radiopaque markers. The sensor may be a location information sensor, such as a sensor that detects one or more displacement-encoded markers on another device and/or a sensor that detects signals from a diagnostic device for co-location position determination. The functional mode of the sensor may be optical, magnetic or capacitive in nature.

In an example configuration, a first flexible elongate instrument (e.g., a guidewire) includes a sensor that acts as a marker code reader, and a second flexible elongate instrument (e.g., a catheter) includes a displacement coded marker (e.g., an imprinted marker disposed on the second flexible elongate instrument engaged with the sensor as the second flexible elongate instrument passes along the guidewire or heat shrink tubing, the second flexible elongate instrument being inserted through the heat shrink tubing, followed by application of heat sufficient to shrink the tubing). When the second flexible elongate instrument is moved parallel to the first flexible elongate instrument, the relative displacement of the first flexible elongate instrument and the second flexible elongate instrument can be measured by a sensor that reads the displacement-encoded markers. When a plurality of radiopaque markers are disposed on a first flexible elongate instrument (e.g., a guidewire), the radiopaque markers may be used as a reference coordinate system, as detected by an X-ray angiography image, such that the position of a second flexible elongate instrument relative to the coordinate system may be measured in real-time or near real-time. The second flexible elongate instrument may be a therapeutic and/or diagnostic device.

The flexible elongate instrument may include, at least in part, one or more rigid portions or components. For example, the flexible elongate instrument may include or provide for the advancement of a biopsy device or aspiration device, which may include a rigid needle or other rigid structure(s) to enable the acquisition of a diagnostic sample or to provide for the delivery of therapy.

As used herein, the term "therapeutic and/or diagnostic device" refers to an area of a flexible elongate endoluminal device adapted to perform a function within a body lumen. Examples of therapeutic and/or diagnostic devices on flexible elongate endoluminal devices include stents, balloons, ablation tips, electrodes, ultrasound imaging transducers, pressure sensors, and optical coherence tomography luminescence tips.

As used herein, the term "diagnostic device" or "diagnostic system" refers to an active or passive medical device, medical system, instrument, or component, apparatus, or substance thereof used in medical procedures (including interventional procedures inside and/or outside the body) for detecting, analyzing, and/or measuring a disease or medical condition of a patient. The diagnostic device may, for example, measure temperature, pressure, electrical conductivity, density, blood flow velocity, oxygen level, or tissue morphology of the lumen. Examples of diagnostic devices that may be used with the provided methods and systems include intravascular ultrasound (IVUS) devices, optical Coherence Tomography (OCT) devices, photoacoustic sensing devices, fractional Flow Reserve (FFR) devices, endoscopic devices, arthroscopic devices, biopsy devices, and other devices that include sensors configured to measure tissue constituents, physical properties, physiological properties, and/or molecular properties of an anatomical structure.

As used herein, the term "therapeutic device" of a "therapeutic system" refers to an active or passive medical device, medical system, instrument, or component, apparatus, or substance thereof used in medical procedures (including interventional procedures) for treating a disease or medical condition of a patient, and for preventing a disease or condition, alleviating a disease or condition, or maintaining or restoring health. Examples of treatment devices that may be used with the provided methods and systems include angioplasty devices, stents, embolic devices, atherectomy devices, ablation devices, drug delivery devices, optical delivery devices, aspiration devices, and other devices capable of delivering mechanical or physical interventions, chemical interventions, or energy delivery interventions.

The therapeutic and/or diagnostic device may include one or more sensors. The sensors may be ultrasound transducers (for IVUS), optical light emitters/receivers (for OCT), pressure sensors (for FFR). The sensor may be configured as part of (e.g., by being mounted or secured to) a flexible elongate instrument (e.g., a catheter or guidewire). The therapeutic and/or diagnostic device may or may not include: IVUS, OCT, FFR or iFR.

Examples of IVUS imaging instruments suitable for use in the systems and methods described herein include: polar, philips (volcanic) (Phillips (Volcano)) S5, philips S5i, philips core movement (Phillips CORE Mobile), philips SyncVision, philips IntraSight, and ACIST HDi. Examples of OCT imaging instruments for use with the systems and methods described herein include: yapei (san utada) (Abbott (st. Jude)) OPTIS, taylor (Terumo) Lunawave, and taylor mausfastview. The cardiology imaging instrument that may be used to perform the methods described herein may or may not include any of the foregoing OCT or IVUS imaging instruments: the Boston science company Avvigo, atlanta Radianalyzer Xpress, atlanta QUANTIEN, atlanta pressure line receiver, ACIST RXI, opsens Optowire, and Conavi Novasight hybrid systems.

The diagnostic and/or therapeutic device may be a guidewire, microcatheter, thrombectomy catheter, steerable catheter, balloon catheter, device delivery catheter, cardiac catheter, renal catheter, urinary catheter, tumor catheter, robotic catheter/guidewire, biopsy device, atherectomy device (which may or may not include a peripheral arterial disease catheter), lithotripsy device, or neuromodulation device. The cardiac catheter may or may not include a radiofrequency ablation catheter, a mapping catheter, a Percutaneous Transluminal Angioplasty (PTA) catheter, an embolic protection device, a chronic total occlusion device, an infusion catheter, a snare, a support catheter, a thermal dilution catheter, and a valvulotome. The diagnostic and/or therapeutic device may be configured for use in a body lumen with or without blood flow.

As used herein, the term "diagnostic scan" or "body lumen information scan" or "vascular displacement scan" refers to imaging or assessing a portion or all of a body lumen using a diagnostic device. The diagnostic scan may measure any of pressure, temperature, density, electrical conductivity, inductance, tissue morphology, etc. at selected locations along the body lumen.

As used herein, the term "radio-opaque" refers to opacity from radio waves of the electromagnetic spectrum to the X-ray portion. The radiopaque composition served as a control when viewed with X-rays. From month 10 of 2020, the radiopaque material may be made of, for example, titanium, platinum, gold, palladium, tungsten, barium, zirconia, or any material determined by ASTM F640 standard test methods for measuring medical radiopacity.

As used herein, the term "IVUS" refers to a method of imaging tissue using intravascular ultrasound. The IVUS method may include the use of a device that includes an ultrasound probe attached to the distal end of the treatment and/or diagnostic device. The proximal end of the therapeutic and/or diagnostic device may be connected (wired or wireless) to a computer. X-ray angiography is used to visualize the body lumen from outside the body and guide the physician in maneuvering the IVUS catheter along the guidewire and imaging from inside the body lumen. IVUS data analysis methods are described, for example, in the following documents: U.S. patent nos. 4,794,931, 5,000,185 and 5,313,949; U.S. patent nos. 5,243,988 and 5,353,798; U.S. patent No. 4,951,677; U.S. patent No. 5,095,911, U.S. patent No. 4,841,977, U.S. patent No. 5,373,849, U.S. patent No. 5,176,141, U.S. patent No. 5,240,003, U.S. patent No. 5,375,602, U.S. patent No. 5,373,845, U.S. patent No. 5,453,575, and U.S. patent No. 5,135,486, the teachings of which are incorporated herein by reference.

The IVUS catheter may be moved along a flexible elongate instrument comprising a transducer, and the flexible elongate instrument may send distance signal information to a computing unit to generate displacement information. When the IVUS system includes or is coupled to the computing unit, the flexible elongate instrument may send distance signal information to the IVUS system to generate displacement information. In the IVUS method, the second flexible elongate instrument may be a catheter including a plurality of radiopaque markers and sensors. The catheter may be an IVUS catheter that is movable inside a body lumen. The IVUS catheter may further comprise a motor drive connected to the proximal end of the catheter outside the patient's body. Before performing IVUS catheter pullback, the operator/physician may take X-ray images capturing the body lumen and the radiopaque markers inside the body lumen, thereby establishing a relationship between the plurality of radiopaque marker markers with reference to the body lumen image captured by the X-rays. During pullback, the distance traveled by the IVUS transducer may be measured by a motor driven pullback device on the proximal end of the catheter, external to the body. The motor drive position may determine the position of the IVUS transducer and may establish the relationship of the IVUS transducer position to the imaging marker based on the transducer and the imaging marker being disposed on the same catheter at a known distance. The travel displacement from the motor drive unit may be input to the calculation unit to locate the position of the IVUS transducer during the pullback scan using the captured X-ray images containing the plurality of imaging markers as a reference. Alternatively, X-ray imaging may be applied at the beginning of the procedure and then turned off after one X-ray image is acquired that includes the contours of the plurality of radiopaque markers. The second flexible elongate instrument may be an IVUS catheter attached to a robotic arm. The second flexible elongate instrument may be selected from: IVUS, OCT, treatment catheters (which may or may not include sinus resections or intuitive surgical arms or lung probes or the corndus vascular robotic platform of siemens). The displacement may be measured by a motor drive on a robotic system coupled to the second flexible elongate instrument.

As used herein, the term "OCT" (optical coherence tomography) refers to a medical imaging method using a luminescent probe configured to acquire a three-dimensional image (e.g., of micron resolution) from within an optical scattering medium (e.g., biological tissue). In general, OCT methods involve a light source that delivers a light beam to an imaging device to image target tissue. The OCT light source may be selected from a broad spectrum of wavelengths, or provide a limited spectrum of wavelengths (e.g., near infrared light). The OCT light source may be applied in the form of a pulse duration or a continuous wave. Examples of suitable OCT light sources include diodes, diode arrays, semiconductor lasers, ultra-short pulse lasers, and supercontinuum light sources. The OCT light source may be filtered and the OCT system may optionally allow the operator to select the wavelength of light to be amplified. Wavelengths typically used in medical applications include near infrared light (e.g., between about 800nm and about 1700 nm) for tissue penetration. OCT systems and methods include those described in the following documents: U.S. patent No. 8,108,030, U.S. patent No. 8,989,849, U.S. patent No. 8,531,676, U.S. patent No. 10,219,780, U.S. patent No. 8,125,648, U.S. patent No. 7,929,148, U.S. patent No. 7,474,407, U.S. patent No. 5,321,501, and U.S. patent No. 9,046,339, the teachings of which are incorporated herein by reference.

As used herein, the term "angiography" refers to a medical imaging method that involves a combination of X-ray angiography imaging (typically fluoroscopy) and injection of radiopaque contrast media into a patient to identify the structure of the patient's vasculature. During PCI surgery, real-time vasculature images may be displayed on a monitor so that an operator/physician may view the operation of the guidewire or inserted device in real-time or with minimal delay. The displayed image (i.e., angiography) may be processed in software and displayed on a computer, or the image may be a closed-loop image of a flickering surface combined with a visible fluorescent material.

As used herein, the term "FFR" or "fractional flow reserve" refers to its meaning in the art and includes methods for measuring blood pressure differences over a body lumen, wherein the body lumen is a coronary artery. The blood pressure difference may be caused by stenosis. FFR methods generally involve measuring pressure, temperature, and/or blood flow using a flexible elongate instrument that includes a pressure transducer. FFR is typically performed when the patient develops maximum blood flow (hyperemia). Maximum blood flow may be obtained by administering a vasodilator to a patient. The flexible elongate instrument is pulled back (e.g., in a "pull back" scan) and the pressure on the body lumen is recorded. FFR can be measured as the ratio of maximum distal blood flow (p_d) of a stenotic lesion to normal maximum blood flow (p_a) in a blood vessel, as provided by: ffr= { p_ { d }/{ p_ { a }.

As used herein, the term "iFR" or "instantaneous wave-free ratio" refers to its meaning in the art and includes methods for measuring blood pressure differences over a body lumen. The body lumen may be a coronary artery and the method does not require administration of a vasodilator to the patient. In iFR, a flexible elongate instrument comprising a pressure transducer is positioned to a point distal to the stenotic lesion. During diastole, called the "wave free phase", the iFR then calculates the ratio of the distal coronary pressure (Pd) to the pressure in the aortic outflow tract (Pa). During this period, the blood flow is negligible, which completes the measurements complicating them.

As used herein, the term "stent" refers to a tube that is placed in a body lumen to keep a passageway open. Stents may be placed, for example, in a coronary lumen to treat coronary artery disease, in a cerebrovascular lumen to treat cerebrovascular disease, in a peripheral lumen to treat peripheral disease, in a ureteral lumen to treat ureteral disease, and in a gastrointestinal lumen to treat gastrointestinal disease.

As used herein, the term "real-time or near real-time" means that an event occurs at a current time or is delayed by a certain amount of time due to circuitry delays of system components. An almost real-time event refers to an event that would be real-time if there were no delay in data transmission (electronically or wirelessly). The delay of the data transmission may range, for example, from 1 nanosecond to 1 second, including any time period therebetween.

The position of the sensor relative to the plurality of displacement-encoded markers may be measured as a function of time and speed of movement of the sensor relative to the plurality of encoded markers.

As used herein, the term "linear position" refers to the distance between two objects or two identified regions in a body lumen measured along the path of the body lumen. Thus, the shape of the wire may be straight or curved. The curved line may comprise a plurality of curves. The term "linear position" is used to distinguish from the term "linear distance" which refers to the distance between two selected objects or two identified areas.

As used herein, the term "body lumen reference point" refers to a body lumen location that coincides with a location on the flexible elongate instrument that has a plurality of imaging markers and is located inside the body lumen when an external body or angiographic image of the body lumen and the flexible elongate instrument is obtained. The location on the flexible elongate instrument has a known distance to the plurality of imaging markers. This position may coincide with the imaging marker itself (e.g. when the diagnostic sensor is on the same flexible elongate instrument as the plurality of imaging markers, so the diagnostic sensor position is known relative to the imaging marker, as in the example shown in fig. 4; or when the diagnostic sensor and the plurality of imaging markers are on different flexible elongate instruments, but the position of the diagnostic sensor relative to the imaging marker is determined from angiographic images, as in the examples shown in fig. 5A-5B). Alternatively, the location may be a location of a signal transducer used to determine when another transducer (e.g., a diagnostic sensor) is adjacent or coincident therewith, as in the example shown in FIG. 6.

As used herein, the term "body lumen diagnostic scan" refers to a scan performed by a body lumen diagnostic sensor that obtains body lumen information when displaced inside a body lumen. The obtained body lumen information may be related to the measured displacement.

As used herein, the term "imaging marker" refers to a segment of limited length located on a flexible elongate instrument that is visually distinguishable from a "no-marker" portion when viewed through an external body imager. An example of an imaging marker on a catheter or guidewire for an X-ray imager is a radiopaque marker made of heavy elements that block more X-rays than natural catheter or guidewire materials. The X-ray angiography and diagnostic sensors may be simultaneous or at different timesImaging markers are detected. Imaging markers may be MR and/or NMR sensitive (e.g., including atoms with free nuclear spins), electromagnetically sensitive, electromechanically sensitive, optically sensitive, and/or mechanically sensitive. The imaging markers may be ultrasound sensitive (e.g., include a band filled with a medicament having an acoustic impedance that is different from the acoustic impedance of human blood). The imaging markers may be detected in one or more imaging modalities. For example, the imaging markers can include nanoparticles (e.g., emeryGlide ^TM Lead (bernoun interventional systems limited (b.braun Interventional Systems inc.)).

The plurality of imaging markers (e.g., radiopaque markers) on the first flexible elongate instrument may be used as a basis for quantifying the position of an object (e.g., a sensor disposed on the second flexible elongate instrument) in a coordinate system. Once the displacement calculation mechanism detects the displacement or movement (Δx) of the target relative to the plurality of imaging markers, the position of the target may be established in the coordinate system. The displacement calculation mechanism may be based on pull-back time, reading of the encoded markers, or a combination thereof.

As used herein, the term "displacement" refers to an absolute value from zero, using a reference position as zero. The reference position may be used as a basis for determining a subsequent position of the one or more flexible elongate instruments in a 2D or 3D reference coordinate system. For example, the displacement may be calculated from the displacement-encoding markers using the following formula: position = displacement + offset. The offset is the distance from the starting point of the device to the selected displacement encoded marker or point between encoded markers. Alternatively or additionally, the displacement relative to the reference position may be measured by calculating the pull-back speed(s) based on the pull-back timestamp. In the IVUS method, typical pull-back rates may vary between 0.5mm and 1mm per second. In OCT methods, a typical pullback speed is 20mm per second, with a pullback length of about 50mm. As a non-limiting example, when the pullback speed is 1mm per second and pullback is performed for 50 seconds, the displacement distance may be calculated to be about 50mm.

The diagnostic device (e.g., a flexible elongate instrument having a diagnostic device) may include a displacement sensor, a displacement encoded marker, or both. Separately, the guidewire may include a displacement encoding marker, a displacement sensor, or both. The displacement sensor may detect relative movement of one or more coded markers relative to the sensor or the distance traveled by the sensor along the flexible elongate instrument relative to a reference position such that the displacement may be measured. The sensor may be an optical sensor, an electrical sensor, an electromagnetic sensor, a mechanical sensor, a pressure sensor, a chemo-selective sensor, and/or an ultrasonic sensor. The displacement sensor may optionally detect the relative position of the encoded markers. The sensor may be, for example, a transducer selected to transmit and/or receive electromagnetic (e.g., inductive, resistive, voltage), optical, ultrasonic, or pressure signals.

In systems and methods for measuring displacement using coded markers, the coded markers may be configured to be located on a cannula separate from the flexible elongate instrument. The cannula may be positioned parallel to or share the axis of the flexible elongate instrument and may be configured to travel along the length of the flexible elongate instrument. For example, the sleeve may include a heat shrink tube such that the sleeve will shrink around the flexible elongate instrument when heated. The shape of the displacement encoding elements around the sleeve may be a "zig-zag" pattern such that when the heat shrink tube is heated, the "zig-zag" periodically decreases, but the encoding elements have a greater density per unit area around the flexible elongate instrument. Alternatively, the coded marker may be configured to be located on the flexible elongate instrument and surrounded by the cannula.

The flexible elongate instrument may generally include a proximal end, a distal end, and at least one of a sensor and a plurality of elements positioned circumferentially or partially circumferentially around the flexible elongate instrument. The sensor disposed on or in the flexible elongate instrument may be shaped and adapted for insertion into a body lumen. These elements may be imaging markers, displacement encoding markers, or both. The plurality of elements may be independent of a selected distance, a selected dimension (e.g., width), and/or a selected shape from each other. The width of the element may range from 0.01mm to 3cm. The number of elements may range from 2 to 500. The number of elements may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 80, 82, 98, 82, 95, 82, 93, 82, 93, or 93. Alternatively, the elements may provide a checksum, e.g. the width of three consecutive elements may be equal to the width of the fourth consecutive element.

As used herein, the term "displacement encoding" refers to an area on a flexible elongate instrument that includes a plurality of encoding elements (also referred to as "encoding markers") that are spaced apart on the flexible elongate instrument at selected distances. The encoding element may be detected by an encoding sensor.

As used herein, the term "encoder sensor" refers to a device that can detect or measure displacement encoding. The displacement code may be positioned to be located on a first flexible elongate instrument and the code sensor may be positioned to be located on a second flexible elongate instrument. The encoder sensor may detect one or more encoder elements as the encoder sensor approaches the displacement encoder. The encoder sensor may, for example, comprise a transducer capable of transmitting and/or receiving a physical signal. The physical signal may be an optical, electrical, magnetic, inductive or capacitive signal. The change in the signal generated by the encoder sensor on the second flexible elongate instrument may be used to measure the relative displacement of the encoder sensor on the second flexible elongate instrument with respect to the encoded portion on the first flexible elongate instrument as the encoder sensor approaches and moves in a direction parallel to the first flexible elongate instrument.

6. Computer-implemented system

The systems and methods provided herein are generally useful for predicting the location of diagnostic and/or therapeutic devices within a body lumen. The methods may be implemented on a computer server accessible over one or more computer networks. In some embodiments, one or more computer networks may interface with a computer server. A computer server implementing these methods may in principle be any computing system or architecture capable of performing the calculations and storing the necessary data. The exact specifications of such systems may vary with the development and pace of technology, and thus the example computer systems and components described herein should not be considered limiting. The system will typically include storage space, memory, one or more processors, and one or more input/output devices. It should be appreciated that the term "processor" as used herein is intended to include any processing device, for example, one that includes a CPU (Central processing Unit). The term "memory" as used herein is intended to include memory associated with a processor or CPU, such as RAM, ROM, and the like. In addition, the term "input/output device" or "I/O device" as used herein is intended to include, for example, one or more input devices (e.g., a keyboard) for conducting queries and/or inputting data to the processing unit and/or one or more output devices (e.g., a display and/or a printer) for presenting query results and/or other results associated with the processing unit. The I/O device may also be a connection to a network from which queries are received and the results are directed to one or more client computers. It should also be understood that the term "processor" may refer to more than one processing device. Other processing devices on a computer cluster or in a multiprocessor computer server can share elements associated with the processing device. Thus, as described herein, software components including instructions or code for performing the methodologies of the invention, may be stored in one or more of the associated memory or storage devices (e.g., ROM, fixed or removable memory) and, when ready to be utilized, loaded in part or in whole into memory (e.g., RAM) and executed by a CPU. The storage means may further be used for storing program code, genome sequence databases, etc. The storage device may be any suitable form of computer storage including a conventional hard disk drive, solid state drive, or ultrafast disk array. In some embodiments, the storage device comprises a network attached storage device that is operatively connectable to a plurality of similar computer servers comprising a computing cluster.

The data may be real-time or near real-time and/or the data may be acquired from different procedures and/or steps such as, but not limited to, ECG (electrocardiogram), doppler, FFR (fractional flow reserve), FFR-CT (fractional flow reserve-computed tomography), IVUS (intravascular ultrasound) and OCT (optical coherence tomography). The computer system may also save the raw data and the final processed data from the memory bank to a local and/or external storage system for further data processing by other therapeutic and/or diagnostic instruments.

The system and method of the present invention may be applied to any interventional procedure in a body lumen. The body lumen may or may not include: vascular, lymphatic and nervous system vasculature, various structures of the gastrointestinal tract (including lumens of the small intestine, large intestine, stomach, esophagus, colon), pancreatic ducts, bile ducts, hepatic ducts, lumens of the reproductive tract (including vas deferens, uterus and fallopian tubes), structures of the urinary tract (including urinary tracts, tubular ducts, ureters and bladder), structures of the head and neck and structures of the pulmonary system (including sinuses, parotid glands, trachea, bronchi and lungs).

The methods described herein may be performed on a computer that may or may not include a non-transitory memory containing a set of instructions for performing the methods. The systems described herein may include a computer and at least one non-transitory machine readable medium storing instructions that, when executed by a programmable processor, cause the programmable processor to perform operations comprising the selected methods described herein.

The computer system of the present disclosure may include a visual display. The form of the visual display system may vary, such as, but not limited to, monitors, mobile devices, wearable devices, and AR/VR headsets. Input from the operator/physician is performed via electronic devices such as a computer, a server with a monitor, a main workstation, a controller with a monitor, and a third party system operator/physician interface. In some embodiments, the display may include a 2D depiction of a body lumen including a flexible elongate instrument using voxels.

The equations and methods described herein may be executed on a computer processor. A processor suitable for executing a computer program comprising the equations and methods described herein may or may not comprise a general purpose computer microprocessor, a special purpose microprocessor, and combinations thereof. A processor will receive instructions and data from a read-only memory or a random access memory or both. A computer includes a processor for executing instructions and one or more memory devices for storing instructions and data. In some embodiments, a computer will also include or be operatively coupled to receive data from or transfer data to one or more mass storage devices for storing data, e.g., magnetic, magneto-optical disks, or optical disks. Information carriers suitable for embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices (e.g., EPROM, EEPROM, NAND-based flash memory, solid State Drives (SSDs), and other flash memory devices); magnetic disks (e.g., internal hard disks or removable disks); magneto-optical disk; and optical discs (e.g., CD and DVD discs). In some embodiments, the processor and the memory may be supplemented by, or incorporated in, special purpose logic circuitry.

The computer may further comprise I/O (input-output) devices for enabling interaction with an operator/doctor. In some embodiments, the I/O device may or may not include CRT, LCD, LED or projection devices for displaying information to the operator/physician, as well as input or output devices through which the operator/physician may provide input to a computer, such as a keyboard and pointing device (e.g., a mouse or trackball, virtual reality goggles, wearable touch pad, and finger-mounted pointing device). In some embodiments, the I/O device may transmit information from the operator/physician to the computer via sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback), and may receive input from the operator/physician in any form, including acoustic, speech, or tactile input. In some embodiments, the computing unit may be connected to the display, the input-output device, or both, by a method selected from an electronic connection or a wireless connection. The wireless connection may be bluetooth (a wireless technology standard for exchanging data between a fixed device and a mobile device over short distances using UHF radio waves in the industrial, scientific and medical radio frequency band of 2.402GHz to 2.480 GHz), wiFi (IEEE 802.11 standard), or a cellular network such as 3G, 4G, 5G, or a combination thereof.

The computers described herein may further include a computing system that further includes a back-end component (e.g., a data server), a middleware component (e.g., an application server), a front-end component (e.g., a client computer having an operator/physician graphical interface, or a web browser through which a physician/operator can interact with an implementation of the patient subject matter described herein), or any combination thereof. In some embodiments, components of a computer system may be interconnected by any form or medium of digital data communication (e.g., a communication network) through a network. In some embodiments, the communication network may or may not include: cellular networks (3G, 4G, 5G), personal area networks (wireless personal area networks such as infrared, zigBee, bluetooth, and ultra wideband or UWB, and wired connections such as USB or FireWire), local area networks (LANs such as ethernet (IEEE 802.3) and Wi-Fi/WLAN (IEEE 802.11)), and Wide Area Networks (WANs), e.g., the internet.

The equations and methods described herein may be performed on a computer system that further includes one or more computer programs tangibly embodied in an information carrier (e.g., in a non-transitory computer readable medium) for execution by, or to control the operation of, data processing apparatus (e.g., a programmable processor, a computer, or multiple computers). In some embodiments, a computer program (also referred to as a program, software application, macro, or code) may be written in any form of programming language, including compiled or interpreted languages (e.g., C, C ++, perl, machine language, assembly language, c#, python, matLab), and it may be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. In some embodiments, the computer system may include programming languages known in the art including, but not limited to C, C ++, C#, perl, java, activeX, HTML, visual Basic, machine language, assembly language, python, matLab, or JavaScript. In some embodiments, when using the c++ programming language, the computer program may or may not include the following tools: a powerful visualization tool package (VTK) library (https:// www.vtk.org /), an image segmentation and registration tool package (ITK) for implementing different medical volume segmentation algorithms (https:// ITK. Org /), a Qt library for GUIs (https:// www.qt.io /), a generic tool package (CTK) for operator/doctor interaction elements used with VTKs and CTKs (http:// www.commontk.org/index. Php/main_page), a base-level DICOM (GDCM) library for acting with DICOM files (https:// sourceforges/subjects/GDCM /), a Boost for type-safety dimension analysis using information about measurement units. All of the above websites were cut off to 11/1/2020 (as can be confirmed by the Wayback machine).

One or more aspects or features of the subject matter described herein may be implemented in digital electronic circuitry, integrated circuitry, specially designed Application Specific Integrated Circuits (ASICs), field Programmable Gate Arrays (FPGAs) computer hardware, firmware, software, and/or combinations thereof. These various aspects or features may include being implemented in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which may be coupled for special or general purpose, to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device.

These computer programs (which may also be referred to as programs, software applications, components, or code) include machine instructions for a programmable processor, and may be implemented in a high-level procedural, object-oriented, functional, logical, and/or assembly/machine language. As used herein, the term "machine-readable medium" refers to any computer program product, apparatus and/or device, such as magnetic disks, optical disks, memory, and Programmable Logic Devices (PLDs), used to provide machine instructions and/or data to a programmable processor, including a machine-readable medium that receives machine instructions as a machine-readable signal. The term "machine-readable signal" refers to any signal used to provide machine instructions and/or data to a programmable processor. The machine-readable medium may store such machine instructions non-transitory, for example, as non-transitory solid state memory or a magnetic hard drive or any equivalent storage medium. The machine-readable medium may alternatively or additionally store such machine instructions in a transitory form, e.g., as if a processor cache or other random access memory associated with one or more physical processor cores were storing such machine instructions.

In some embodiments, a computer program may be deployed to be executed on one computer or on multiple computers or processing units that are distributed across multiple sites and interconnected by a communication network.

In some embodiments, the computer program for performing the equations and methods described herein may further comprise writing a file. In some embodiments, the file may be a digital file (e.g., stored on a hard drive, SSD, CD, or other tangible, non-transitory medium). Files may be sent from one device to another device over a communication network as data packets sent from a server to a client.

Writing a file may include transforming a tangible, non-transitory computer-readable medium, for example, by adding, removing, or rearranging particles (e.g., particles having a net charge or dipole moment) into magnetization patterns by a read/write head, which then represent a new collocation of information that is desired by and useful to the user. In some embodiments, the writing involves physical transformation of materials in a tangible, non-transitory computer readable medium having certain properties so that the magnetic read/write device can then read new and useful information collocations. In some embodiments, writing the file includes using flash memory, such as NAND flash memory, and storing the information in a memory cell array including floating gate transistors. Methods of writing files are well known in the art and may be invoked automatically, for example, by a program from software or programming language.

Any of the above-described electronic devices and/or components and associated interfaces in the system may be controlled and/or coordinated by operating system software, such as Windows OS (e.g., windows XP, windows 8, windows 10, windows Server, etc.), windows CE, mac OS, iOS, android, chrome OS, unix, linux, vxWorks, or other suitable operating systems. In other embodiments, the electronic device may be controlled by a proprietary operating system. Conventional operating systems control and schedule system processes for execution, perform memory management, provide file systems, networking, I/O services, and provide user interface functions such as Graphical User Interfaces (GUIs), among other systems and/or devices.

7. Exemplary embodiments of the invention

A1. A system for measuring body lumen locations and displaying information obtained from a diagnostic device at each body lumen location, the system comprising: a computer processor configured to obtain body lumen location information and generate display information, and a display, wherein the computer processor is further configured to obtain at least one X-ray angiographic image of a body lumen comprising a flexible elongate intracavity instrument inserted therein and a plurality of imaging markers configured to be positioned on the instrument such that both the body lumen and the one or more imaging markers are detectable, optionally wherein the computer processor is further configured to obtain body lumen diagnostic scan data comprising body lumen diagnostic information from a diagnostic device at least one location defined by a selected distance from a starting point, optionally, wherein the computer processor is further configured to obtain a position of at least one body lumen reference point defined by a plurality of imaging markers identified from an X-ray angiographic image of the body lumen such that a linear distance between the reference point and two or more of the plurality of imaging markers is known, optionally wherein the computer processor is further configured to obtain a position of the starting point, the position being a distance between the starting point and the body lumen reference point, optionally wherein the computer processor calculates the position of the at least one diagnostic point, identifies a relative position of the at least one diagnostic point and the plurality of imaging markers, and displays diagnostic position and associated diagnostic information referencing the plurality of imaging markers.

A2. The system of A1, wherein the computer processor is further configured to interface with a display.

A3. The system of A1, wherein the computer processor is further configured to display a plurality of imaging markers on the IVUS pullback distance scale.

A4. A system for measuring a body lumen location and displaying the location and information obtained from a diagnostic device, the system comprising: a first flexible elongate endoluminal device configured to be positioned within a body lumen, wherein the flexible elongate endoluminal device comprises a plurality of imaging markers; a second flexible elongate endoluminal device comprising a diagnostic and/or therapeutic device configured to be positioned as a first flexible elongate endoluminal device within the body lumen and configured to travel parallel to the first flexible elongate endoluminal device, wherein a relative displacement between the first flexible elongate device and the second flexible elongate device is measured; a position computer processor configured to obtain body lumen position information and generate a display of diagnostic information from a diagnostic device engaged with the display, wherein the position computer processor obtains a position of at least one reference point located on the first flexible elongate endoluminal instrument such that a distance between the reference point and one or more imaging markers is known; optionally, a display, one or more X-ray angiographic images of the body lumen, wherein the body lumen and the plurality of imaging markers are detectable within the X-ray angiographic images, thereby defining at least one body lumen reference point, the at least one body lumen reference point being a body lumen point of the at least one reference point when the X-ray angiographic images were generated.

A5. The system of A4, wherein the plurality of imaging markers are positioned at a distal portion of the first flexible elongate endoluminal device and each imaging marker comprises a selected size, a distance between each marker is a selected distance, and at least one imaging marker is uniquely identifiable.

A6. The system of A4, wherein the second flexible endoluminal elongate instrument is an IVUS.

A7. The system of A4, wherein the position computer processor is further configured to interface with a displacement measurement unit.

A8. The system of A4, wherein the position computer processor is further configured to obtain at least one displacement of the diagnostic and/or therapeutic device measured from the starting point.

A9. The system of A8, wherein the position computer processor is further configured to obtain a position of the starting point, the position being a distance between the diagnostic sensor and the body lumen reference point at the beginning of a diagnostic scan.

A10. The system of A4, wherein the position computer processor is further configured to calculate a position of the diagnostic and/or therapeutic device from the received one or more imaging markers and transmit to a display the position and diagnostic information obtained from the diagnostic device regarding the plurality of imaging markers.

A11. A system for measuring body lumen locations and displaying those locations and diagnostic information obtained from a diagnostic device, the system comprising: a first flexible elongate endoluminal device configured to be positioned within a body lumen comprising a plurality of imaging markers, an image generated by an X-ray angiography device comprising at least one of the imaging markers of the flexible elongate endoluminal device inserted into the body lumen, wherein the body lumen and the plurality of imaging markers are both detectable and the detectable imaging markers provide a fixation point for a linear position reference system of the body lumen on the generated X-ray angiography image; and a position computer processor configured to receive body lumen position information and transmit the body lumen information, the linear position reference, and the X-ray angiography image to a display, wherein the position computer processor obtains at least one body lumen position with respect to the plurality of imaging markers shown on the X-ray angiography image.

A12. The system of a11, wherein the plurality of imaging markers are configured to be positioned at a distal portion of the flexible elongate instrument.

A13. The system of a11, wherein each of the plurality of imaging markers comprises a selected dimension and has a selected distance separating each of the imaging markers.

A14. The system of a11, wherein at least one of the plurality of imaging markers is uniquely identifiable.

A15. The system of a14, wherein at least one of the plurality of imaging markers comprises a selected indicium.

A16. The system of a11, further comprising: a second flexible elongate instrument comprising a plurality of displacement encoding markers, wherein the second flexible elongate instrument is inserted into the body lumen, wherein the second flexible elongate instrument is configured to travel parallel to a central axis of the first flexible elongate instrument; and an interface to a displacement measurement component comprising an encoded sensor configured to detect a displacement encoded marker of the second flexible elongate instrument when moved within the body lumen, wherein the first flexible elongate instrument comprises a diagnostic and/or therapeutic device that is a selected distance from the selected imaging marker, the distance between the two defining a first quantified body lumen position, wherein the displacement measurement component comprising the encoded sensor detects at least one of the plurality of displacement encoded markers from a starting position, wherein the distance between the starting position and the first quantified body lumen position is zero, and the position computer processor is configured to calculate the position of the at least one of the plurality of displacement encoded markers within the body lumen and display the calculated position.

A17. The system of a11, further comprising: a second flexible elongate instrument comprising a diagnostic and/or therapeutic device and a plurality of displacement-encoding markers, wherein the second flexible elongate instrument is located within the body lumen and the diagnostic and/or therapeutic device is configured to travel within the body lumen; an interface to a displacement measurement component comprising an encoded sensor configured to measure a displacement encoded marker of the diagnostic and/or therapeutic device when moved inside the body lumen, wherein the second flexible elongate intracavity instrument further comprises at least one of a plurality of imaging markers having a selected length and a selected distance therebetween, wherein the at least one imaging marker is a selected distance from the diagnostic and/or therapeutic device, wherein the distance between the diagnostic and/or therapeutic device and the plurality of imaging markers on the first flexible elongate intracavity instrument defines a first quantized body lumen position from an X-ray angiographic image, wherein the displacement measurement component comprising the encoded sensor detects at least one of the plurality of displacement encoded markers from a starting position, wherein the distance between the starting position and the first quantized body lumen position is zero, and the position computer processor calculates the body lumen position of the at least one of the plurality of displacement encoded markers and transmits the calculated position to a display.

A18. The system of a17, wherein the calculated position is transmitted to and depicted on the display.

A19. The system of any one of a16 or a17, wherein the diagnostic and/or therapeutic device comprises a diagnostic sensor configured to obtain body lumen information related to at least one of a plurality of displacement encoded markers, and the system further comprises an interface to receive the generated body lumen information, and wherein the body lumen information is related to the calculated body lumen position, and the body lumen information related to the calculated body lumen position is transmitted to a display and optionally further displayed.

A20. The system of a11, further comprising: a body lumen diagnostic sensor positioned on a flexible elongate instrument inserted into the body lumen, wherein the diagnostic body lumen diagnostic sensor is configured to travel within the body lumen; a position computer processor in combination with a displacement measurement component comprising an encoding sensor configured to measure displacement encoded markers of the diagnostic sensor when moved inside the body lumen, wherein the position computer processor is further configured to detect a displacement measurement from a starting position, wherein the diagnostic sensor detects body lumen information related to at least one of the plurality of displacement encoded markers, and the position computer processor further comprises an interface to receive the generated body lumen information.

A21. The system of a20, wherein the diagnostic sensor is on a second flexible elongate endoluminal device.

A22. The system of a21, wherein the first flexible elongate endoluminal device further comprises a signal transducer operating in a detectable modality and range of the diagnostic sensor, the signal transducer positioned at a selected distance from one of the plurality of imaging markers, wherein the distance defines a first quantified body lumen position.

A23. The system of a22, wherein the signal transducer is engaged with a signal unit capable of generating and optionally receiving a signal.

A24. The system of a23, wherein the sensor measures a displacement position of the diagnostic sensor in cooperative alignment with the signal transducer based on diagnostic sensor information generated when measuring a displacement encoded marker from a starting position, wherein a distance between the starting position and the first quantified body lumen position is a displacement of the diagnostic sensor at a cooperative alignment point.

A25. The system of a24, wherein the position computer processor is configured to calculate a body lumen position of at least one of the plurality of displacement-encoded markers, and the body lumen information is related to the calculated body lumen position and optionally displayed.

A26. The system of a11, wherein the position computer processor further comprises an interface to the signal unit, wherein a co-alignment position between the diagnostic sensor and the signal transducer is measured based on a signal received by the signal transducer.

A27. The system of a11, wherein the position computer processor further comprises an interface to the signal unit, wherein a co-alignment position between the diagnostic sensor and the signal transducer is measured based on timing between the transmitted signal and the received signal.

A28. The system of any one of a11 to a27, wherein the body lumen location and/or body lumen information in combination with the generation and display of the body lumen location is real-time or near real-time when the body lumen distance from the first body lumen point is received.

A29. The system of any one of a 11-a 28, wherein the diagnostic and/or therapeutic device comprises a defined size positioned in the body lumen, and the position computer processor further receives the defined size of the diagnostic and/or therapeutic device, generates a graphical representation of the diagnostic and/or therapeutic device, and displays with respect to the graphical representation of the plurality of imaging markers.

A30. A method for measuring and displaying body lumen locations and diagnostic information associated with the locations, the method comprising: inserting a flexible elongate endoluminal device comprising a distal end and a proximal end into a body lumen, wherein the flexible elongate endoluminal device further comprises a plurality of imaging markers at a distal portion of the device and each marker comprises a selected dimension and a selected distance between each imaging marker, wherein the flexible elongate endoluminal device further comprises a displacement measurement member positioned at a selected distance from the plurality of imaging markers, the displacement measurement member being capable of generating body lumen information and adapted to displace within the body lumen, and the selected distance between the diagnostic displacement measurement member and the plurality of imaging markers is received by a position computer processor, wherein the displacement measurement member is configured to measure displacement-encoded markers; obtaining at least one X-ray angiographic image of the body lumen with the inserted flexible elongate intraluminal device such that both the body lumen and the plurality of imaging markers are detectable and at least one imaging marker is uniquely identifiable; performing a body lumen diagnostic scan starting from a starting position (e.g., a position in an obtained X-ray angiography image) where the diagnostic sensor is located at a relative position of the plurality of imaging markers, transmitting the body lumen information and displacement measurements to a diagnostic processor; correlating the body lumen information with the measured displacement encoding markers; transmitting the associated displacement-encoded markers and body lumen information to a position computer processor, wherein the position computer processor is configured to measure the position of each received displacement point by calculating the distance of each received displacement point to the plurality of imaging markers and correlate the body lumen information with the positions, and then output body lumen information associated with the positions to a display; and optionally displaying the information.

A31. A method for measuring and displaying body lumen locations and diagnostic information associated with the locations, the method comprising: inserting a first flexible elongate endoluminal device comprising a distal end and a proximal end into the body lumen, wherein the first flexible elongate endoluminal device comprises a plurality of imaging markers at a distal portion of the device, each marker size is a selected length and a distance between each of the imaging markers is a selected distance; inserting a second flexible elongate endoluminal device comprising at least one body lumen diagnostic sensor capable of obtaining body lumen information and a plurality of imaging markers located at a selected distance from the at least one body lumen diagnostic sensor, wherein displacement of the encoded markers relative to the diagnostic sensor is measured by a displacement measurement member; obtaining at least one X-ray angiography of the body lumen with the inserted flexible elongate intraluminal device such that the body lumen and the plurality of imaging markers in the first and second flexible elongate intraluminal devices are both detectable and at least one imaging marker on the first flexible elongate intraluminal device is uniquely identifiable; measuring distances between the diagnostic sensor and the plurality of imaging markers on the first flexible elongate endoluminal device from the plurality of imaging marker positions on the two flexible elongate endoluminal devices detected by the X-ray angiographic images and outputting the measured distances to a position computer processor; performing a body lumen diagnostic scan starting from a starting position (e.g., a position in an acquired X-ray angiographic image) of the relative positions of the plurality of imaging markers on the first instrument by the diagnostic sensor, outputting the body lumen information and displacement measurements to a diagnostic processor, wherein the body lumen information is associated with the measured displacement encoded markers; and transmitting the associated displacement-encoded markers and body lumen information from the diagnostic processor to the position computer processor, wherein the position computer processor is configured to measure the position of each received displacement point by calculating the distance of each received displacement point to the plurality of imaging markers and correlate the body lumen information with the positions and then output body lumen information associated with the positions to a display.

A32. A method for measuring and displaying a body lumen location and diagnostic information associated with the location, the method comprising: inserting a first flexible elongate endoluminal device comprising a distal end and a proximal end into the body lumen, wherein the first flexible elongate endoluminal device comprises a plurality of imaging markers at a distal portion of the device, each marker dimension is a selected width and a distance between each of the imaging markers is a selected distance, wherein the first flexible elongate endoluminal device comprises a signal transducer at a selected distance from the plurality of imaging markers and the selected distance is received by the position computer processor and the signal transducer is engaged with the signal unit; inserting a second flexible elongate endoluminal device comprising at least one body lumen diagnostic sensor capable of generating body lumen information and adapted to be displaced inside the body lumen, wherein the displacement between the body lumen diagnostic sensor and the imaging markers is known or measured by a displacement measuring means, wherein a signal transducer on the first flexible elongate endoluminal device operates in a detectable mode and range of a diagnostic sensor on the second flexible elongate endoluminal device; obtaining at least one X-ray angiography of the body lumen with the inserted flexible elongate intraluminal device such that at least one of the plurality of imaging markers in the body lumen and the first flexible elongate intraluminal device is detectable and at least one imaging marker is uniquely identifiable; performing a body lumen diagnostic scan from a starting location, outputting body lumen information and displacement measurements to a diagnostic processor, wherein the body lumen information is related to the measured displacement encoded markers; measuring a co-alignment distance defined by a displacement of the diagnostic sensor from the starting position to a position when co-aligned with the signal transducer; transmitting the co-alignment distance to the position computer processor and transmitting related displacement and body lumen information from the diagnostic processor to the position computer processor, wherein the position computer processor is configured to measure the position of each received displacement point by calculating the distance of each received displacement point to the plurality of imaging markers and correlate the body lumen information with the positions and then output body lumen information related to the positions to a display; and optionally displaying the information.

A33. The method of a32, wherein the position computer processor further comprises an interface to the signal unit, wherein a co-alignment position between the diagnostic sensor and the signal transducer is measured based on a signal received by the signal transducer.

A34. The method of a32, wherein the position computer processor further comprises an interface to the signal unit, wherein a co-alignment position between the diagnostic sensor and the signal transducer is measured based on timing between the transmitted signal and the received signal.

A35. The method of a32, wherein the flexible elongate endoluminal device comprising the plurality of imaging markers is a medical guidewire.

A36. The method of any one of a32 to a35, wherein the generation and display of body lumen locations and/or body lumen locations and body lumen information is performed in real time or near real time when the body lumen diagnostic scan is performed.

A37. A system for identifying imaging marker locations on a diagnostic imaging display and an X-ray angiography display, the system comprising: one or more flexible elongate endoluminal devices configured for insertion into a body lumen comprising a plurality of imaging markers at a distal end of the device, each imaging marker being a selected width and a distance between each of the plurality of markers being a selected distance, an X-ray angiography comprising an image of the body lumen and the one or more imaging markers, wherein at least one flexible elongate endoluminal device in the body lumen comprises at least one diagnostic sensor (diagnostic device) that receives diagnostic information of the body lumen and is adapted to travel longitudinally inside the body lumen, a sensor displacement measurement unit comprising a displacement sensor that measures sensor displacement inside the body lumen; a body lumen information processor configured to obtain sensor displacement information from the sensor displacement measurement unit and body lumen information from the sensor, sensor position information relative to the plurality of imaging markers, and correlate the information and optionally transmit the information to a display, wherein the diagnostic sensor is configured to perform a body lumen diagnostic scan from inside the body lumen by passing longitudinally through the body lumen interior, wherein a position of the body lumen scan references the plurality of imaging markers detected by X-ray angiography.

A38. The system of a37, wherein the diagnostic information of the body lumen is selected from pressure, temperature, size, oxygen level, density, or tissue morphology.

A39. The system of a37, wherein when the body lumen diagnostic sensor and the plurality of imaging markers are not on the same flexible elongate endoluminal device, the system further comprises: a signal transducer operating in a detectable mode and range of a body lumen diagnostic sensor attached to the flexible elongate endoluminal device, the flexible elongate endoluminal device comprising a plurality of imaging markers and the position of the markers relative to the signal transducer at a selected distance; wherein the signal transducer comprises an interface to a signal unit capable of generating and optionally receiving a signal.

A40. The system of a39, wherein the position of the body lumen diagnostic sensor relative to the plurality of imaging markers is measured based on signal interactions between the signal transducer and the body lumen diagnostic sensor.

A41. The system of a39, further comprising an interface between the signal unit and a body lumen information processor, wherein the position is measured when the signal transducer and body lumen diagnostic sensor are within a selected distance from each other.

A42. The system of a41, wherein the position is measured based on timing information and optionally signal strength information.

A43. The system of a39, wherein the interface between the signal unit and the body lumen detector processor is wireless.

A44. The system of a37, wherein the plurality of imaging markers and the body lumen diagnostic sensor are mounted on the flexible elongate endoluminal device and are disposed a selected distance from each other when the X-ray angiography detects an inserted flexible elongate device comprising a plurality of imaging markers.

A45. The system of a37, wherein the flexible elongate endoluminal device comprising a body lumen diagnostic sensor further comprises at least one imaging marker located at a selected distance from the body lumen diagnostic sensor.

A46. The system of a44, wherein the position of the body lumen diagnostic sensor relative to the plurality of imaging markers is measured based on the X-ray angiography.

A47. The system of claim, wherein at least one of the plurality of imaging markers is displayed in real-time or near real-time with the body lumen information as a function of distance displacement during the body lumen information scan.

A48. A method for displaying the location of an imaging marker on a diagnostic imaging display and an X-ray angiography, the imaging marker configured to be positioned on an elongate medical instrument, the method comprising: inserting at least one flexible elongate instrument into the body lumen, the at least one flexible elongate instrument comprising a distal end, a proximal end, and a plurality of imaging markers at a distal portion of the instrument, wherein each marker dimension is a selected width and a distance between each of the plurality of imaging markers is a selected distance; obtaining at least one X-ray angiography of a body lumen with an inserted flexible elongate instrument such that the body lumen and at least one of the plurality of imaging markers are both detectable and a sequence of the markers are identifiable, wherein the flexible elongate instrument further comprises at least one body lumen diagnostic sensor capable of receiving information (pressure, temperature, size, density, oxygen level, tissue morphology) of the body lumen and configured to travel longitudinally within the body lumen; performing a body lumen displacement scan to obtain body lumen diagnostic information; obtaining displacement information using a displacement measurement unit comprising a displacement encoding sensor; combining the displacement information with body lumen diagnostic information obtained by the body lumen diagnostic sensor to generate position-dependent body lumen diagnostic information; measuring the position of a sensor from the scan of the body lumen relative to a plurality of imaging markers detected by the X-ray angiography; measuring the position of the body lumen diagnostic sensor relative to a plurality of imaging markers from a selected location; measuring the position of the body lumen scan relative to the plurality of imaging markers; the position-related body lumen diagnostic information and the linear positions of the plurality of imaging markers detected by the X-ray angiography are displayed.

A49. The method of a48, wherein the plurality of imaging markers and the body lumen diagnostic sensor are positioned on the flexible elongate instrument and their relative positions are determinable from an X-ray angiography that includes the body lumen and the imaging markers.

A50. The method of a48, wherein the plurality of imaging markers are positioned on a first flexible elongate instrument and the at least one body lumen diagnostic sensor is positioned on a second flexible elongate instrument, and the second flexible elongate instrument further comprises at least one imaging marker located at a defined distance from the body lumen diagnostic sensor such that when both flexible elongate instruments are inside the body lumen, the position of the body lumen diagnostic sensor relative to the plurality of imaging markers on the first flexible elongate instrument is measured from the obtained body lumen images using the X-ray angiography.

A51. The method of a50, wherein the second flexible elongate instrument comprises a second plurality of imaging markers at a selected distance from the body lumen detector, and the first plurality of imaging markers is distinguishable from the second plurality of imaging markers on the first flexible elongate instrument.

A52. The method of a50, wherein the plurality of imaging markers are positioned on a first flexible elongate instrument and the at least one body lumen diagnostic sensor is positioned on a second flexible elongate instrument, and the first flexible elongate instrument further comprises a signal transducer (optionally, a signal transmitter, a signal receiver, or both) positioned at a defined distance from the plurality of imaging markers and operating within a detectable modality and range of the body lumen diagnostic sensor, and the position of the body lumen diagnostic sensor is measured from signal transmissions between the signal transducer and the body lumen diagnostic sensor.

A53. The method of a52, wherein the signal transducer is engaged with the body lumen diagnostic sensor to measure the distance of the body lumen diagnostic sensor relative to the signal transducer by a signal timing and/or signal strength device, and optionally wherein the signal transducer may be in a transmit or receive mode.

A54. The method of a53, wherein a second flexible elongate instrument comprising the body lumen detector is signally coupled to the signal transducer on the first flexible elongate instrument by using a separate transducer also mounted on the second flexible elongate instrument.

A55. The method of a48, wherein the flexible elongate instrument comprising the plurality of imaging markers is a medical guidewire.

A56. The method of a48, wherein at least one of the plurality of imaging markers is uniquely identifiable.

B1. A system for measuring relative displacement of at least two flexible elongate instruments within a body lumen, the system comprising: a first flexible elongate instrument comprising a proximal end, a distal end, a central axis, and one or more displacement encoding markers configured to be positioned between the proximal end and the distal end; and a second flexible elongate instrument comprising a proximal end, a distal end, a central axis, and a coded sensor configured to obtain a signal from a displacement coded marker of the first flexible elongate instrument, wherein the second flexible elongate instrument is configured to travel parallel to the central axis of the first flexible elongate instrument.

B2. The system of B1, wherein the encoder sensor comprises an interface to a signal processor that converts the obtained encoded signal into a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument in real time or near real time.

B3. The system of B1, wherein the displacement-encoded markers comprise a plurality of displacement-encoded markers configured to circumferentially or partially circumferentially surround the first flexible elongate instrument and comprise a medium that reflects a signal.

B4. The system of B1, wherein the first flexible elongate instrument is configured to be positioned entirely or partially inside the body lumen when in use.

B5. The system of B1, wherein the medium that reflects the signal is selected from the group consisting of a metal or metal alloy, a magnet, a ceramic, a crosslinked hydrogel, or a fluoropolymer.

B6. The system of B1, wherein the first flexible elongate instrument, the second flexible elongate instrument, or both the first flexible elongate instrument and the second flexible elongate instrument further comprise a treatment and/or diagnostic device (which may or may not comprise a diagnostic or therapeutic device) configured to be positioned at a distal portion of the elongate instrument.

B7. The system of B6, wherein the displacement encoding markers and/or the position of the encoding sensor are known when at least one flexible elongate instrument comprises a therapeutic and/or diagnostic device.

B8. The system of B1, wherein the therapeutic and/or diagnostic device is a diagnostic device that obtains body lumen information.

B9. The system of B8, wherein the diagnostic device is in electronic or optical communication with the signal processor.

B10. The system of B9, wherein the signal processor calculates body lumen information per displacement distance from the obtained displacement information.

B11. The system of B10, wherein the body lumen information per displacement distance is electronically transmitted to a display.

B12. The system of B11, wherein the display is a component of a diagnostic system.

B13. The system of B12, wherein the diagnostic system is an IVUS.

B14. The system of B10, wherein the body lumen information is selected from tissue density, temperature, pressure, flow rate, impedance, or electrical conductivity.

B15. A system for measuring the position of a therapeutic and/or diagnostic device within a body lumen relative to a selected location of the body lumen, the system comprising: a first flexible elongate instrument comprising one or more displacement encoding markers positioned on the first flexible elongate instrument and one or more radiopaque imaging markers positioned on the first flexible elongate instrument; and a second flexible elongate instrument comprising a proximal end, a distal end, and a coded sensor, wherein the coded sensor and the displacement coded markers on the first flexible elongate instrument form a first engaged position when the coded sensor begins to detect the displacement coded markers, at least one X-ray angiographic image of a body lumen into which the flexible elongate instrument is fully or partially inserted, wherein the image comprises one or more radiopaque imaging markers on the flexible elongate instrument such that both the body lumen and the plurality of radiopaque imaging markers are identifiable and at least one of the radiopaque imaging markers is individually identifiable, wherein the obtained X-ray angiographic image identifies the position of the plurality of radiopaque imaging markers in the body lumen, and wherein the second flexible elongate instrument is configured to travel parallel to the longitudinal axis of the first flexible elongate instrument.

B16. The system of B15, wherein the position of the functional device relative to the position of the plurality of radiopaque imaging markers obtained by X-ray angiography images is measured (optionally, continuously).

B17. The system of B15, further comprising a plurality of radiopaque imaging markers configured to be positioned on the first flexible elongate instrument or the second flexible elongate instrument such that a position of the plurality of radiopaque imaging markers relative to the encoded region or the encoded sensor on the selected flexible elongate instrument is known.

B18. The system of B16, wherein the first flexible elongate instrument or the second flexible elongate instrument is a treatment and/or diagnostic device and the treatment and/or diagnostic device is at a selected distance relative to a location of an encoded region or an encoded sensor on the flexible elongate instrument and optionally further defines a starting location that is a location of the treatment and/or diagnostic device relative to the plurality of radiopaque imaging markers at the first engagement location.

B19. The system of B18, further comprising a signal processor configured to obtain a signal from the encoder sensor, convert the encoded signal to a displacement information location, and calculate the location.

B20. The system of B19, wherein the signal processor displays the positions relative to the positions of the plurality of radiopaque imaging markers obtained from the X-ray angiography image and diagnostic information obtained from the treatment and/or diagnostic device.

B21. The system of B18, wherein the starting position is obtained by the signal processor when the encoder sensor first begins to detect the displacement encoded markers.

B22. The system of B21, wherein the signal processor continuously or intermittently obtains data from the encoding sensor and correlates the position of the therapeutic and/or diagnostic device with the plurality of radiopaque imaging markers.

B23. The system of B15, further comprising a display.

B24. The system of B15, wherein the therapy and/or diagnostic device provides diagnostic information at each test location, the diagnostic sensor further comprises an interface to a signal processor, and the signal processor displays diagnostic body lumen information related to the location of the plurality of radiopaque imaging markers presented in the X-ray angiography image.

B25. The system of B15, wherein the position of the treatment and/or diagnostic device is presented to the display in a manner that depicts the position of the treatment and/or diagnostic device relative to the position of the plurality of radiopaque imaging markers obtained in the X-ray angiography images on the simulation line.

B26. The system of any of B15-B25, wherein presentation of the position of the therapeutic and/or diagnostic device within the body lumen is presented to the display in real-time or near real-time.

B27. The system of B15, wherein when displacement measurements are performed at different times (and optionally using different therapy and/or diagnostic devices), the location of the therapy and/or diagnostic device and associated diagnostic information provided by the diagnostic device are provided to the display when the location of the measurement results of the times are measured relative to the locations of the plurality of radiopaque imaging markers obtained from the X-ray angiography image.

B28. The system of B15, wherein the signals emitted and/or obtained by the displacement-encoding markers and the encoding sensors are selected from optical signals, electromagnetic signals, capacitive signals, or acoustic signals.

B29. A computer-implemented method for measuring relative displacement of a first flexible elongate instrument and a second flexible elongate instrument relative to the first flexible elongate instrument while the first flexible elongate instrument and the second flexible elongate instrument are positioned wholly or partially within a body lumen, the method comprising: receiving a plurality of coded signals from a coded sensor that is part of a second flexible elongate instrument that includes a proximal end, a distal end, and a coded sensor that is inserted into a body lumen, wherein the coded signals reflect one or more coded markers that are part of a first flexible elongate instrument that is inserted into the body lumen; transmitting the plurality of encoded signals from the encoding sensor to a signal processor that converts the obtained encoded signals into one or more displacement values of a relative displacement difference between the first flexible elongate instrument and the second flexible elongate instrument to calculate a relative displacement; and transmitting the calculated relative displacement to a display through an interface, wherein the first flexible elongate instrument or the second flexible elongate instrument or both further comprise at least one therapeutic and/or diagnostic device.

B30. The method of B29, wherein the at least one therapeutic and/or diagnostic device is selected from a body lumen diagnostic sensor capable of obtaining diagnostic information about the body lumen, and is further coupled with the signal processor and generates body lumen information at each relative displacement.

B31. A system comprising at least one non-transitory machine readable medium storing instructions that, when executed by a programmable processor, cause the programmable processor to perform operations comprising the method of any of B29 to B30.

B32. A computer-implemented method for measuring a position of a first flexible elongate instrument within a body lumen, the method comprising: obtaining encoded information obtained by performing the steps of: (i) inserting a first flexible elongate instrument into the body lumen, the first flexible elongate instrument comprising a plurality of displacement encoded markers or comprising an encoded sensor, (ii) inserting a second flexible elongate instrument into the body lumen, the second flexible elongate instrument being configured for use in conjunction with the first flexible elongate instrument, and wherein when the first flexible elongate instrument comprises a plurality of displacement encoded markers, the second flexible elongate instrument comprises an encoded sensor, or when the first flexible elongate instrument comprises an encoded sensor, the second flexible elongate instrument comprises a plurality of displacement encoded markers, (iii) obtaining encoded signals from the displacement encoded markers detected by the encoded sensor to generate encoded information, obtaining at least one X-ray angiographic image of the body lumen with the flexible elongate instrument, the flexible elongate instrument comprising a plurality of radio-opaque imaging markers partially or fully disposed within the body lumen, such that both the body lumen and the plurality of radio-opaque imaging markers are identifiable, and at least one of the plurality of radio-opaque imaging markers is identifiable, or when the first flexible elongate instrument comprises an encoded sensor, wherein the plurality of displacement encoded markers is converted into the radio-opaque imaging markers by the flexible instrument to obtain the encoded information by a plurality of displacement encoded markers, the position of the flexible elongate instrument is processed in contrast imaging device, the position of the radio-opaque imaging markers is processed by the second flexible instrument to obtain the radio-imaging signals, thereby identifying the location of the first flexible elongate instrument, wherein the first flexible elongate instrument or the second flexible elongate instrument further comprises a plurality of radiopaque imaging markers, and the radiopaque imaging markers are located a selected distance from a displacement sensor or plurality of displacement encoded markers on the respective flexible elongate instrument.

B33. The method of B31, wherein the location of the function device is continuously measurable.

B34. The method of B31, wherein the step of obtaining at least one X-ray angiographic image of the body lumen with the flexible elongate instrument is performed prior to the coded sensor and the coded first engagement, the flexible elongate instrument comprising a plurality of radiopaque imaging markers partially or fully disposed inside the body lumen such that both the body lumen and the plurality of radiopaque imaging markers are identifiable, but the flexible elongate instrument with the plurality of radiopaque imaging markers is not moved from its imaging position when the first engagement occurs.

B35. The method of B31, wherein the starting position is obtained by the signal processor.

B36. The method of B31, wherein the position of the flexible elongate instrument comprising the plurality of displacement-encoding markers relative to the plurality of radiopaque imaging markers is continuously or intermittently measurable.

B37. The method of B35, wherein the period of intermittent measurement is once every 0.1 seconds, once every 1 second, once every 10 seconds, once every minute, once every 5 minutes, once every 10 minutes, once every 20 minutes, once every 30 minutes, once every 40 minutes, once every 50 minutes, or once every hour.

B38. The method of B31, wherein the first flexible elongate instrument or the second flexible elongate instrument further comprises a therapeutic and/or diagnostic device.

B39. The method of B37, further comprising displaying the positions relative to positions of radiopaque imaging markers obtained in the X-ray angiography image and diagnostic information obtained from treatment and/or diagnostic device positions.

B40. The method of B37, wherein a treatment and/or diagnostic device is located on the first flexible elongate instrument or the second flexible elongate instrument such that a position of the treatment and/or diagnostic device relative to the encoded region or the encoded sensor is known on the flexible elongate instrument, and further defining a starting position that is a position of the treatment and/or diagnostic device relative to the plurality of radiopaque imaging markers when the encoded sensor begins to obtain signals from the displacement encoded markers.

B41. The method of B37, wherein an alert is issued to the clinician when the first engagement occurs.

B42. The method of B41, wherein the alert is selected from the group consisting of: an audio alert (which may include sound) or a visual alert (which may include light or a message transmitted to a display) or a physical alert (which may or may not include a tactile feedback signal).

B43. A system comprising at least one non-transitory machine readable medium storing instructions that, when executed by a programmable processor, cause the programmable processor to perform operations comprising the method of any one of B32 to B42.

B44. A computer-implemented method for measuring a position of a therapeutic and/or diagnostic device within a body lumen, the method comprising: obtaining information from an inserted first flexible elongate instrument comprising a displacement coded marker, or comprising a coded sensor, typically positioned at a location inside the body lumen during use; obtaining information from an inserted second flexible elongate instrument configured for use in combination with the first flexible elongate instrument, wherein the first flexible elongate instrument or the second flexible elongate instrument comprises a coded sensor that obtains coded signals or one or more displacement coded markers that provide coded information to the coded sensor (depending on the design of the first flexible elongate instrument), wherein in combination with the first flexible elongate instrument comprises a first engagement position such that the coded sensor is engaged with a coded region for the first time in normal clinical use, wherein a plurality of radio-opaque imaging markers are located on the first flexible elongate instrument or the second flexible elongate instrument such that the position of the plurality of radio-opaque imaging markers relative to the coded region or the coded sensor is known on the flexible elongate instrument, wherein a treatment and/or diagnostic device is located on the first flexible elongate instrument or the second flexible elongate instrument such that the position of the treatment and/or diagnostic device relative to the coded region or the coded sensor is at the flexible elongate instrument and further defines a position of the onset position relative to the first position of the radio-opaque imaging device; engaging the encoding sensor with a signal processor capable of converting an encoding signal into a displacement between the first flexible elongate instrument and the second flexible elongate instrument, and the signal processor having an interface for receiving other inputs and being engaged with a display, wherein the starting position is obtained by the signal processor, wherein after a first engagement of the two flexible elongate instruments, the position of the therapeutic and/or diagnostic device relative to the plurality of radiopaque imaging markers is continuously measurable; obtaining at least one X-ray angiographic image of a body lumen with the flexible elongate instrument, the flexible elongate instrument having a plurality of radiopaque imaging markers disposed inside the body lumen such that both the body lumen and the plurality of radiopaque imaging markers are identifiable and at least one of the plurality of radiopaque imaging markers is individually identifiable, wherein the obtained angiographic image defines a location of the plurality of radiopaque imaging markers in the body lumen; measuring a first position of the therapeutic and/or diagnostic device relative to a position of a plurality of radiopaque imaging markers obtained by the X-ray angiographic image, or (i) obtaining angiographic images after the coded sensor and the coded first engagement, so that the position of the functional device is already continuously measurable, or (ii) obtaining the angiographic images before the coded sensor and the coded first engagement, but when a first engagement occurs, the flexible elongate instrument with the plurality of radiopaque imaging markers is not moved from its imaging position; optionally, continuously measuring the position of the functional device relative to the positions of a plurality of radiopaque imaging markers obtained from the X-ray angiographic image; optionally, the position of the therapeutic and/or diagnostic device and associated information is displayed relative to the position of a plurality of radiopaque imaging markers obtained from the X-ray angiographic image.

B45. The method of B40, wherein the functional device is selected from a body lumen diagnostic sensor that generates diagnostic body lumen information at each measurement location, and the diagnostic sensor further comprises an interface to the signal processor, and the signal processor displays diagnostic body lumen information relative to the locations of a plurality of radiopaque imaging markers obtained in the X-ray angiography image.

B46. The method of B41, displaying the position of the therapeutic and/or diagnostic device on a simulated line relative to the linear position of a plurality of radiopaque imaging markers obtained in the X-ray angiographic image.

B47. The method of B40, wherein the information is displayed in real time or near real time as it is received and calculated.

B48. The method of B40, when displacement measurements are performed from different points in time, and optionally using different treatment and/or diagnostic devices, the positions of the treatment and/or diagnostic devices and the associated information are displayed superimposed (on a single image) when the positions of the different measurement results are measured with respect to the positions of a plurality of radiopaque imaging markers obtained by the same X-ray angiography image.

B49. A system comprising at least one non-transitory machine readable medium storing instructions that, when executed by a programmable processor, cause the programmable processor to perform operations comprising the method of any one of B42 to B46.

B50. A system for identifying in real time or near real time the position of a therapeutic and/or diagnostic device while within a body lumen, the system comprising: a first flexible elongate instrument comprising a proximal end, a distal end, a central axis, and one or more displacement encoding markers; a second flexible elongate instrument comprising a proximal end, a distal end, and a coded sensor, wherein the second flexible elongate instrument is configured to travel along the first flexible elongate instrument substantially parallel to a central axis of the first flexible elongate instrument, wherein when a displacement coded marker on the first flexible elongate instrument is first detected by the coded sensor, a first engaged position is defined, a plurality of radiopaque imaging markers being located on either the first flexible elongate instrument or the second flexible elongate instrument such that a linear position of the plurality of radiopaque imaging markers relative to the coded region or the coded sensor is known on a selected flexible elongate instrument; a treatment and/or diagnostic device located on the flexible elongate instrument that does not include the plurality of radiopaque imaging markers such that a position of the treatment and/or diagnostic device relative to the encoded region or the encoding sensor is known on the flexible elongate instrument, wherein a position of the treatment and/or diagnostic device relative to the plurality of radiopaque imaging markers is known when the first flexible elongate instrument and the second flexible elongate instrument are in a first engaged position; a signal processor configured to obtain signals from the encoding sensor and optionally from the therapeutic and/or diagnostic device, convert encoded signals to relative displacement distances, optionally perform position calculations, and optionally further comprise an interface to a display, wherein the relative distances between the therapeutic and/or diagnostic device and the plurality of radiopaque imaging markers at the first engagement location are obtained by the signal processor; an X-ray imaging system configured to obtain and display one or more images of a plurality of radiopaque imaging markers in the body lumen; a display, wherein the signal processor transmits to the display in real time or near real time an analog representation of the position of the therapeutic and/or diagnostic device relative to the plurality of radiopaque imaging markers.

B51. The system of B50, wherein the position of the therapeutic and/or diagnostic device on one flexible elongate instrument relative to the plurality of radiopaque imaging markers on another flexible elongate instrument is continuously measurable after the encoding sensor is first engaged with the encoded region.

B52. The system of B50, wherein the update rate of the X-ray imaging is lower than the update rate of the analog representation of the position of the functional device relative to the display of the plurality of radiopaque imaging markers.

B53. The system of B50, wherein the X-ray imaging system is further configured to repeatedly update one or more images in real-time or near real-time as the first flexible elongate instrument moves relative to the second flexible elongate instrument.

B54. The system of B53, wherein the repetition rate is selected from once every 0.1 seconds, once every 1 second, once every 2 seconds, once every 3 seconds, once every 4 seconds, once every 5 seconds, once every 6 seconds, once every 7 seconds, once every 8 seconds, once every 9 seconds, once every 10 seconds, once every 20 seconds, once every 30 seconds, once every 40 seconds, once every 50 seconds, once every 60 seconds, once every 2 minutes, once every 3 minutes, once every 4 minutes, once every 5 minutes, once every 6 minutes, once every 7 minutes, once every 8 minutes, once every 9 minutes, once every 10 minutes, or any rate in between the above.

B55. The system of B50, wherein after the first engagement, a signal selected from an audio signal, a visual signal, or a physical signal is sent to the clinician.

B56. A computer-implemented method for measuring a position of a therapeutic and/or diagnostic device within a body lumen, the method comprising: a. obtaining displacement encoded information from the first flexible elongate instrument and the second flexible elongate instrument, the displacement encoded information obtained from a process comprising: (i) inserting a first flexible elongate instrument into the body lumen, the first flexible elongate instrument comprising a proximal end, a distal end, a central axis, and one or more displacement coded markers, (ii) inserting a second flexible elongate instrument into the body lumen, the second flexible elongate instrument comprising a proximal end, a distal end, and a coded sensor, wherein the second flexible elongate instrument is configured to travel along the first flexible elongate instrument substantially parallel to the central axis of the first flexible elongate instrument into said body lumen, (iii) forming a first engaged position when a displacement coded marker on the first flexible elongate instrument is first detected by the coded sensor, (iv) detecting the displacement coded markers with the coded sensor to generate displacement coded information, wherein a plurality of radiopaque imaging markers are located on the first flexible elongate instrument or the second flexible elongate instrument such that a linear position of the plurality of radiopaque imaging markers relative to a coded region or the coded sensor is known on a selected flexible elongate instrument, wherein a therapy and/or diagnostic device comprises a plurality of radiopaque imaging markers are located on the flexible elongate instrument and the first flexible elongate instrument and the radiopaque imaging device is the first flexible elongate instrument and the radiopaque imaging marker is located on the first flexible elongate instrument and the first flexible elongate instrument; b. obtaining one or more X-ray images of a plurality of radiopaque imaging markers in the body lumen; c. converting the displacement encoded information to known positions of the radiopaque imaging markers to measure the position of a flexible elongate instrument comprising the treatment and/or diagnostic device relative to the radiopaque imaging markers to generate measured positions of the treatment and/or diagnostic device in the body lumen relative to the radiopaque imaging markers, wherein a plurality of radiopaque imaging markers are located on the first flexible elongate instrument or the second flexible elongate instrument such that the positions of the plurality of radiopaque imaging markers relative to the encoded region or the encoded sensor are known on the flexible elongate instrument, wherein the treatment and/or diagnostic device is located on an elongate instrument without the plurality of radiopaque imaging markers such that the position of the treatment and/or diagnostic device relative to the encoded region or the encoded sensor is known on the flexible elongate instrument.

B57. The method of B56, further comprising displaying in real-time or near real-time a simulated representation of the position of the therapeutic and/or diagnostic device relative to the plurality of radiopaque imaging markers.

B58. The method of B56, wherein after the coded sensor is first engaged with the coded region, the position of the therapeutic and/or diagnostic device on one flexible elongate instrument relative to the plurality of radiopaque imaging markers on the other flexible elongate instrument is continuously measured.

B59. The computer-implemented method of B58, wherein the update rate of the X-ray image is lower than the update rate of the analog representation of the position of the functional device relative to the display of the plurality of radiopaque imaging markers.

B60. A system comprising at least one non-transitory machine readable medium storing instructions that, when executed by a programmable processor, cause the programmable processor to perform operations comprising the method of any one of B50 to B59.

C1. A co-location system, comprising: at least one first flexible elongate instrument comprising a proximal end, a distal end, a device position acquisition unit, the at least one first flexible elongate instrument being shaped and adapted for insertion into a body lumen and further comprising a plurality of imaging markers positioned circumferentially and/or partially circumferentially around each of the at least one flexible elongate instrument; at least one second flexible elongate instrument, wherein the second flexible elongate instrument is a therapeutic and/or diagnostic device; a sensor that detects relative movement of the flexible elongate instrument; a display and/or an interface to a display optionally comprising an interface to an input/output device, an interface to an external body imaging device obtaining one or more body images and providing said body images to a computing unit, an interface to a computer network, and a computing unit configured to generate one or more 2D and/or 3D models of at least one flexible elongate instrument position within a body lumen, calculate co-location information of the second flexible elongate instrument with said model, and be connected to the interface of the display and optionally to the input/output device, wherein at least a first flexible elongate instrument and/or the second flexible elongate instrument comprises a plurality of displacement coded markers, wherein the co-location information comprises position information of the treatment and/or diagnostic device within the body lumen, wherein the computing unit optionally transmits electronic data to the interface to the display, the electronic data displaying to the display information obtained from at least one treatment and/or diagnostic device at one or more positions along the first flexible elongate instrument, and wherein the at least one of the position information and the computing unit provides the position information to the at least one of the treatment and/or diagnostic device.

C2. The co-location system of C1, wherein the first flexible elongate instrument is electronically or wirelessly connected to the computing unit.

C3. The co-location system of C2, wherein the therapeutic and/or diagnostic device is electronically or wirelessly connected to the computing unit.

C4. The co-location system of C1, wherein the sensor is positioned outside the body of the patient.

C5. The co-location system of C3, wherein the sensor is configured to be located within a robotic arm.

C6. The co-localization system of C3, wherein the computing unit constructs a 2D and/or 3D model of the position of the first flexible elongate instrument within the body lumen at a different time than the acquisition of the body image.

C7. The co-location system of C1, wherein the first flexible elongate instrument is configured to further comprise the sensor.

C8. The co-localization system of C1, wherein the therapeutic and/or diagnostic device is further configured to include a displacement encoding marker.

C9. The co-location system of C1, wherein the first flexible elongate instrument is selected from a guidewire or a catheter.

C10. The co-localization system of C1, wherein the plurality of imaging markers are each independent of a selected distance from each other.

C11. The co-localization system of C1, wherein the plurality of imaging markers are each independent of the selected size.

C12. The co-location system of C1, wherein the therapeutic and/or diagnostic device comprises a central axis that is positioned parallel to or shares the same shaft center as the first flexible elongate instrument and is configured to travel parallel to the axis of the first flexible elongate instrument.

C13. The co-localization system of C12, wherein the computing unit detects a movement or distance traveled by the treatment and/or diagnostic device along the first flexible elongate instrument relative to a fixed position of the first flexible elongate instrument by comparing a first signal transmitted from the sensor and/or a signal from the treatment and/or diagnostic device when the plurality of displacement-encoded markers are detected with a second signal transmitted from the sensor and/or treatment and/or diagnostic device.

C14. The co-location system of C1, wherein the sensor is selected from an optical sensor, an electronic sensor, or an ultrasonic sensor.

C15. The co-localization system of C1, wherein the therapeutic and/or diagnostic device is an IVUS.

C16. The co-location system of C1, wherein the interface to the display, X-ray angiographic imaging device and computer network is bi-directional.

C17. The co-location system of C16, wherein the interfaces are selected from wired (via solid line communication electronic connections) or wireless (via communication electronic connections made by wavelength transmitters and receivers).

C18. The co-location system of C1, wherein the system is configured as a stand-alone instrument.

C19. The co-location system of C1, wherein the system is configured as a component of a body imaging system, or a component of a therapeutic and/or diagnostic system.

C20. The co-location system of C1, wherein the connection to the interface of the display is selected from an electronic connection or a wireless connection.

C21. The co-location system of C1, wherein the connection to the input/output device is selected from an electronic connection or a wireless connection.

C22. The co-location system of C1, wherein the computing unit is configured to:

receiving at least one external body image of the lumen and/or body lumen position information when the first flexible elongate instrument is inserted into the body lumen; generating one or more 2D and/or 3D models of the selected portion of the first flexible elongate instrument from the external body image of the first flexible elongate instrument and a plurality of imaging markers located on the 2D/3D model of the instrument portion; calculating a co-location of the body lumen location using the external body lumen image and/or data, and/or corresponding diagnostic and/or therapeutic device data, and/or data from an input/output device having the one or more 2D and/or 3D models; generating as 2D and/or 3D representations of the size and position of the therapeutic and/or diagnostic device located within the body lumen to form simulated device images; generating one or more images that overlay the one or more 2D and/or 3D models and simulated device images with one or more body images, and/or corresponding diagnostic and/or therapeutic device data, and/or input/output devices; displaying a 2D and/or 3D illustration of a therapeutic and/or diagnostic device having the one or more 2D and/or 3D models; optionally displaying 2D and/or 3D pictorial representations of the treatment and/or diagnostic device and positioning information on the external body image and/or on corresponding diagnostic and/or treatment device data and/or on an input/output device; optionally, obtaining diagnostic and/or therapeutic information from the therapeutic and/or diagnostic device; optionally, displaying diagnostic and/or therapeutic information obtained from the therapeutic and/or diagnostic device and/or body lumen location at one or more selected locations on the first flexible elongate instrument; optionally, enabling at least one interactive display among a diagnostic and/or therapeutic device/system, a control device/system and a display; optionally, the positioning information, co-location images and data are stored locally, optionally transmitted to a separate local system and/or local computer network and/or external computer network.

C23. The co-localization system of C22, wherein the calculating (C) of the co-localization configuration element is performed in real-time or near real-time as the position of the treatment and/or diagnostic device relative to the first flexible elongate instrument is obtained from the sensor.

C24. The co-localization system of C22, wherein the calculating (C) of the co-localization configuration element is performed separately from obtaining the position of the treatment and/or diagnostic device on the flexible elongate instrument relative to the first flexible elongate instrument from the sensor.

C25. The co-location system of C22, wherein step (i) displays diagnostic and/or therapeutic information obtained from the therapeutic and/or diagnostic device at one or more selected locations on the first elongate instrument simultaneously or nearly simultaneously with step (a) obtaining the location of the device on the flexible elongate instrument from the sensor.

C26. The co-location system of \c22, wherein step (i) displays the diagnostic and/or therapeutic information obtained from the therapeutic and/or diagnostic device at one or more selected locations on the first elongate instrument at a different time than step (a) is performed from the location of the sensor obtaining device on the flexible elongate instrument.

C27. The co-location system of C22, wherein step (j) enabling at least one interactive display among a diagnostic and/or therapeutic device/system, a control device/system, and a display comprises obtaining position sensing data from an input/output device.

C28. The co-localization system of any one of C1 to C27, wherein the external body imaging system is an X-ray angiography system and the external body image is an X-ray angiography.

C29. A flexible elongate instrument comprising a proximal end, a distal end, and a sensor, the flexible elongate instrument being shaped and adapted for insertion into a body lumen and further comprising a plurality of imaging markers positioned circumferentially around the flexible elongate instrument.

C30. The flexible elongate instrument of C29, wherein the plurality of imaging markers are each independent of a selected distance from each other.

C31. The flexible elongate instrument of C29, wherein the plurality of imaging markers are independent of the selected size, wherein the size of the imaging markers is the selected width.

C32. The flexible elongate instrument of C29 wherein the number of imaging markers ranges from 2 to 500.

C33. The flexible elongate instrument of any of C29-C32 wherein the imaging markers are radiopaque.

C34. A method for measuring the position of a portion or all of a flexible elongate instrument within a body lumen, the method comprising: obtaining an image of a first image of a portion or all of a body lumen of a patient, wherein the body lumen comprises an inserted flexible elongate instrument comprising a plurality of imaging markers; delineating a portion or all of the body lumen; correlating the position of the flexible elongate instrument within the body lumen; developing a 2-D and/or 3-D model of a portion or all of the body lumen; and generating a geometry of a flexible elongate instrument inserted in the body lumen, thereby measuring a position of a portion or all of the flexible elongate instrument within the body lumen.

C35. The method of C34, wherein the position of the flexible elongate instrument within the body lumen is correlated by receiving electronic information from the flexible elongate instrument regarding its relative position within the body lumen.

C36. The method of C34, wherein developing the 2-D and/or 3-D model of the body lumen comprises identifying boundary points on the body lumen and fitting the 2-D and/or 3-D model of the body lumen to the boundary points.

C37. A method for constructing one or more 2-dimensional models of a flexible elongate instrument that has been inserted into a body lumen of a patient, the method comprising:

obtaining positional data electronic information from a flexible elongate instrument inserted into a body lumen of a patient, wherein the flexible elongate instrument includes a proximal end, a distal end, and a plurality of imaging markers positioned circumferentially around the flexible elongate instrument; obtaining one or more images of a plurality of imaging markers within the body lumen; a 2-dimensional model depicting dimensional information of the flexible elongate instrument as it is inside the body lumen is generated from at least one image and positional data electronic information obtained from the flexible elongate instrument, wherein the dimensional information is calculated from known spacing and dimensions of the plurality of imaging markers.

C38. A method for constructing a 3-dimensional model of a flexible elongate instrument that has been inserted into a body lumen, the method comprising: obtaining positional data electronic information from a flexible elongate instrument inserted into a body lumen of a patient, wherein the flexible elongate instrument includes a proximal end, a distal end, and a plurality of imaging markers positioned circumferentially around the flexible elongate instrument; obtaining at least two independent images from at least two orientations of a plurality of radiopaque markers within the body lumen; a 3-dimensional model of the flexible elongate instrument in the body lumen is generated from the acquired images and positional data electronic information obtained from the flexible elongate instrument, wherein the dimensional information is calculated from the known spacing and dimensions of the plurality of imaging markers.

C39. The method of any one of a37 or a38, wherein the one or more images are X-ray images, preferably X-ray angiography.

C40. The method of C39, further comprising: recording at least one body lumen image with a first flexible elongate instrument positioned within the body lumen, wherein a plurality of imaging markers are positioned partially or fully inside the body lumen in the same orientation as the model; aligning the markers from the 2-dimensional model with the imaged markers as relevant units on the at least one recorded image; the body lumen image is superimposed on the display with a model of the first flexible elongate instrument from the radiopaque marker aligned on the display.

C41. The method of C39, further comprising: storing the at least one body lumen image from the selected orientation in a physical medium with a first flexible elongate instrument having a plurality of imaging markers inside the body lumen; aligning the imaged markers from the 3-dimensional model with the markers on the recorded image having the orientation as relevant units; a model of the first flexible elongate instrument from the newly oriented body lumen image and the imaging marker from the alignment is superimposed on the display.

C42. The method of any one of C40 or C41, further comprising: storing a second body lumen image obtained from a plurality of imaging markers within the body lumen to a physical medium; aligning the intra-lumen locations of the two stored body lumen images; identifying a difference in one or more selected imaging marker locations between the two stored body lumen images; measuring differences in one or more selected imaging marker positions between the two stored body lumen images to obtain a self-correction coefficient; and optionally applying the self-correction coefficient to subsequent body lumen images obtained from a plurality of imaging markers within the body lumen.

C43. The method of C39, further comprising: generating a 2-dimensional model of the body lumen with a first flexible elongate instrument having dimensions inside the body lumen by a method comprising: obtaining at least one image of a body lumen comprising a flexible elongate instrument partially or fully inside the body lumen, the flexible elongate instrument comprising a plurality of imaging markers, each imaging marker independently having a selected distance and a selected width; and generating a 2-dimensional model of the body lumen with a first flexible elongate instrument positioned inside the body lumen, wherein the positions of the plurality of imaging markers relative to the body lumen model are measured.

C44. The method of C39, further comprising: generating a 3-dimensional (3-D) model of a body lumen with a first flexible elongate instrument having dimensions inside the body lumen by a method comprising: obtaining at least two images of a body lumen comprising a flexible elongate instrument partially or fully inside the body lumen, the flexible elongate instrument comprising a plurality of imaging markers, each imaging marker independently having a selected distance and a selected width from at least two orientations; and generating a 3-dimensional model of the body lumen with a first flexible elongate instrument positioned inside the body lumen, wherein the positions of the plurality of imaging markers relative to the body lumen model are measured.

C45. The method of any one of C43 or C44, wherein the calculation of the size information is calculated from a known interval and the sizes of the plurality of imaging markers are generated from a distance code built into at least one flexible elongate instrument.

C46. The method of any one of C43 or C44, wherein the other device is superimposed with the 2D and/or 3D model of the first flexible elongate instrument along with the display position and associated dimensional information of the first flexible elongate instrument.

C47. The method of any one of C34 to C46, wherein the imaging markers are radiopaque and the body imaging system is an X-ray angiography system.

C48. A body lumen signal correlation processing system, comprising: one or more flexible elongate instruments, wherein each flexible elongate instrument comprises a plurality of imaging markers, wherein the imaging markers are visible through the external body imager and the imaging markers comprise a length and a distance between each marker having a selected size, and at least one imaging marker is uniquely identifiable; an external body imager configured to obtain one or more body lumen images from one or more orientations, wherein the flexible elongate instrument is inserted into the body lumen, wherein the body lumen images comprise an image of the body lumen and one or more imaging markers; an interface to a computing unit, the interface configured to transmit body lumen location information relative to the plurality of imaging markers; a processor capable of receiving imaging information from the external body imager and body lumen location information about the plurality of imaging markers; and a display or interface to a display, and optionally an interface to an input/output device.

C49. The body lumen signal correlation processing system of C48, wherein the processor is configured to receive at least one external body image of a body lumen, wherein the flexible elongate instrument is inserted into the body lumen and both the body lumen contour and the plurality of imaging markers are detected and at least one individually identifiable marker is in the image area.

C50. The body lumen signal correlation processing system of C48, wherein the processor is configured to generate a 2D/3D model of the selected portion of the flexible elongate instrument using a plurality of imaging markers located on the 2D/3D model of the flexible elongate instrument, wherein the model is generated by a relationship between the received at least one image and a linear distance scale along the flexible elongate instrument (measured based on a known marker length and a known gap between each imaging marker size).

C51. The body lumen signal correlation processing system of C48, wherein the processor is configured to generate a 2D/3D model of the body lumen segment using a plurality of imaging markers located in the 2D/3D model of the body lumen segment and measure a linear distance scale along a central axis of the body lumen.

C52. The body lumen signal correlation processing system of C51, wherein the processor is configured to measure the position of one or more body lumens on the 2D/3D model based on a selected relationship between the body lumen position information about the plurality of imaging markers.

C53. The body lumen signal correlation processing system of C48, wherein the display is configured to display the body lumen location using the constructed model.

C54. The body lumen signal correlation processing system of C48, wherein the processor is configured to overlap the body lumen location with the external body image of the body lumen by aligning a plurality of imaging markers between the constructed model and the external body image.

C55. The body lumen signal correlation processing system of C48, wherein the processor is configured to display the body lumen location in real time and near real time.

C56. The body lumen signal correlation processing system of C48, wherein when the body lumen position information received by the processor is a position of a body lumen diagnostic sensor, and the processor is further configured to receive information from the diagnostic sensor and correlate the diagnostic sensor information with the sensor position information, and the diagnostic sensor information may optionally be selectively displayed at a selected position.

C57. The body lumen signal correlation processing system of C48, wherein the model of the flexible elongate instrument is generated using the recaptured external body image and the position of the device on the flexible elongate instrument model is also generated using the recaptured external body image and overlaid on the display.

C58. The body lumen signal correlation processing system of C57, wherein the external body image is an X-ray angiography and the model of the flexible elongate instrument is generated when the X-ray instrument is not emitting X-rays.

C59. The body lumen signal correlation processing system of C49, wherein the body lumen position information received by the processor is a position of a device having a defined geometry and the processor generates a simulated representation of the therapeutic and/or diagnostic device and displays the representation on the elongate instrument and/or the body lumen model or optionally overlays and displays the representation and positioning information or optionally corresponding diagnostic and/or therapeutic device data on the external body image.

C60. The body lumen signal associated processing system of C48, wherein the processor is configured to selectively engage at least one component within said system in a bi-directional manner.

C61. The body lumen signal associated processing system of C48, wherein the processor comprises a computing component, a storage component, and an input/output interface.

C62. The body lumen signal correlation processing system of C48 wherein the interfaces and connections to the system are selected from wired (via solid line communication electronic connections) or wireless (via wavelength transmitter and receiver communication electronic connections) optionally in a bi-directional manner.

C63. The body lumen signal associated processing system of C62, wherein the interfaces are selected from optionally bi-directional wired (via solid line communication electronic connection) or wireless (via wavelength transmitter and receiver communication electronic connection).

C64. The body lumen signal correlation processing system of C48, wherein the one or more body lumen position information is displayed on the at least one model and/or the external body image, or optionally on the diagnostic and/or therapeutic system data, or optionally on at least one display, at substantially the same time.

C65. The body lumen signal associated processing system of C48, wherein the processor is configured to store the processed information locally and optionally via an interface in an external computer network.

C66. The body lumen signal associated processing system of C48, wherein the processor is configured to be positioned in a separate housing from other components of the system.

C67. The body lumen signal correlation processing system of C48, wherein the processor is configured as part of an external body imaging system, and/or as part of a diagnostic and/or therapeutic device and/or system.

C68. A method of displaying a body lumen location on a body lumen image, the method comprising: obtaining at least one body image of a body lumen comprising a flexible elongate instrument inserted into the lumen, the flexible elongate instrument comprising a plurality of imaging markers entering the body lumen, wherein the markers are visible through an external body imager and the size of each imaging marker and the spacing between each imaging marker are known and at least one imaging marker is individually identifiable from at least one orientation, wherein the body lumen contour and the plurality of imaging markers are both detectable and the at least one individually identifiable imaging marker is in an image area; constructing a flexible elongate instrument and optionally a 2D or 3D model of the lumen within the body lumen using the positions of the imaging markers and displaying a linear distance scale within the body lumen along a central axis of the flexible elongate instrument, receiving body lumen positions of one or more inserted diagnostic and/or therapeutic devices inserted into the body lumen and having a central axis passing through the central axis of the flexible elongate instrument body lumen position, wherein the positions are calculated relative to the positions of the plurality of imaging markers and calculating the body lumen position received on the model; and displaying the body lumen location of the inserted diagnostic and/or therapeutic device on the external body image by overlapping the model with the external body image by alignment using the plurality of imaging markers.

C69. The method of C68, wherein the display of the location is real-time or near real-time.

C70. The method of C68, wherein the location is from a diagnostic sensor and the diagnostic sensor information is correlated to body lumen location information and the diagnostic sensor information is selectively displayed at a selected location on the body lumen image.

C71. The method of C68, wherein the flexible elongate instrument comprises a defined geometry and the processor generates a simulated representation of the therapeutic and/or diagnostic device and displays the representation and positioning information on the model or, alternatively, overlays the representation and positioning information on the body image of the body lumen.

C72. The method of C68, wherein the body lumen location is selected by interacting with a display of an external body lumen image, or optionally with a diagnostic and/or therapeutic system, or optionally with at least one device via an interface.

C73. The method of C68, wherein 2D/3D model size information is calculated from the known spacing and size of the plurality of imaging markers.

C4. The method of C69, wherein the model of the flexible elongate instrument is generated using a recaptured body image and the position of the diagnostic and/or therapeutic device relative to the position of the flexible elongate instrument model is also generated using the recaptured external body image and displayed overlapping the recaptured external body image.

C75. The method of C74, wherein the recaptured body image is an X-ray angiography obtained when the X-ray instrument is not emitting X-rays.

C76. The method of C68, further comprising: recording at least one body lumen image of the flexible elongate instrument, the flexible elongate instrument comprising a plurality of imaging markers inside the body lumen in the same orientation as the model; aligning the markers on the 2-dimensional model with corresponding markers on the at least one recorded image as relevant units; and superimposing the body lumen image and the marker aligned on the model on a display.

C77. The method of C68, further comprising: storing at least one body lumen image of the flexible elongate instrument, the flexible elongate instrument comprising a plurality of imaging markers from any orientation inside the body lumen to generate a recorded oriented body lumen image; aligning markers from the 3-dimensional model with markers on the recorded image of the directional body lumen; and superimposing the oriented body lumen image with a model of the flexible elongate instrument comprising the plurality of imaging markers on the display.

C78. The method of any one of C76 or C77, further comprising: storing a second body lumen image obtained from a plurality of imaging markers within the body lumen; aligning the lumen positions of the two stored body lumen images; identifying a difference in one or more selected imaging marker locations between the two stored body lumen images; measuring differences in one or more selected imaging marker positions between the two stored body lumen images to obtain a self-correction coefficient; and optionally applying the self-correction coefficient to subsequent body lumen images obtained from a plurality of imaging markers within the body lumen.

C79. A computer configured to perform any of the methods of C34 to C47 or C68 to C78.

While exemplary embodiments have been particularly shown and described, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the embodiments encompassed by the appended claims.

Claims (77)

1. A system for locating a medical device in a body lumen, the system comprising:

a first flexible elongate instrument comprising a plurality of imaging markers;

a position information sensor disposed at the first flexible elongate instrument or at a second flexible elongate instrument configured to move relatively with respect to the first flexible elongate instrument;

a processor configured to:

establishing a reference coordinate system based on the plurality of imaging markers, the plurality of imaging markers being visible in a medical image comprising the first flexible elongate instrument disposed in the body lumen,

receiving diagnostic scan information or therapy delivery information from the first flexible elongate instrument or the second flexible elongate instrument at a plurality of locations of the body lumen, and

Associating the diagnostic scan information or therapy delivery information with imaging markers of the plurality of locations based on the reference coordinate system and the location information sensed by the location information sensor; and

a display configured to display a composite image including the associated diagnostic scan information or therapy delivery information and the imaging markers.

2. The system of claim 1, wherein the position information sensor is disposed on the first flexible elongate instrument.

3. The system of claim 2, wherein the positional information sensor is a sensor configured to detect a coded marker of the second flexible elongate instrument.

4. The system of claim 2 or claim 3, wherein the first flexible elongate instrument is a guidewire and the second flexible elongate instrument comprises a diagnostic or therapeutic device.

5. The system of claim 4, wherein the second flexible elongate instrument comprises the diagnostic device, and the diagnostic device is an intravascular ultrasound (IVUS) device, an Optical Coherence Tomography (OCT) device, a Fractional Flow Reserve (FFR) catheter, a photoacoustic device, an endoscopic device, an arthroscopic device, or a biopsy device.

6. The system of claim 4, wherein the second flexible elongate instrument comprises the treatment device and the treatment device is an angioplasty device, an embolization device, a stent, an ablation device, a drug delivery device, an optical delivery device, an atherectomy device, or a suction device.

7. The system of any one of claims 3-6, wherein the second flexible elongate instrument comprises a coded marker disposed at an inner circumferential surface of a catheter or liner configured to be advanced over the first flexible elongate instrument.

8. The system of claim 1, wherein the position information sensor is disposed on the second flexible elongate instrument.

9. The system of claim 8, wherein the positional information sensor is a sensor configured to detect a coded marker of the first flexible elongate instrument.

10. The system of claim 9, wherein the first flexible elongate instrument is a Fractional Flow Reserve (FFR) lead.

11. The system of claim 1, wherein the positional information sensor is a diagnostic sensor disposed on the second flexible elongate instrument.

12. The system of claim 11, wherein the first flexible elongate instrument comprises a signal transmitter configured to transmit a signal for detection by the diagnostic sensor.

13. The system of claim 12, wherein the signal emitter is an ultrasonic transducer, an optical light emitter, or a signal reflector configured to reflect signals originating from the diagnostic sensor.

14. The system of any one of claims 12 to 13, wherein associating the diagnostic scan information with the imaging markers comprises establishing a co-located position based on the detected signals.

15. The system of claim 1, wherein the first flexible elongate instrument is a diagnostic device and the position information sensor is a sensor that detects a push distance, a pull back distance, or a combination thereof of the diagnostic device.

16. The system of claim 15, wherein associating the diagnostic scan information with the imaging markers comprises establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the diagnostic sensor and at least one of the plurality of imaging markers.

17. The system of claim 1, wherein the second flexible elongate instrument is a diagnostic device comprising at least one imaging marker and the position information sensor is a sensor that detects a push distance, a pull back distance, or a combination thereof of the diagnostic device.

18. The system of claim 17, wherein associating the diagnostic scan information with the imaging markers comprises establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of at least one imaging marker of the diagnostic device and at least one of a plurality of imaging markers of the first flexible elongate instrument.

19. The system of any one of claims 1-18, wherein the system further comprises the second flexible elongate instrument.

20. The system of any one of claims 1-19, wherein the sensor is disposed at a distal portion of the first flexible elongate instrument or the second flexible elongate instrument.

21. The system of any one of claims 1-20, wherein the processor is further configured to receive the medical image and the reference coordinate system is two-dimensional.

22. The system of any one of claims 1-20, wherein the processor is further configured to receive the medical image comprising at least two medical images including the first flexible elongate instrument disposed in the body lumen, and wherein the reference coordinate system is three-dimensional.

23. The system of any one of claims 1 to 10, wherein the positional information sensor is a single element sensor.

24. A method for locating a medical device in a body lumen, the method comprising:

establishing a reference coordinate system based on a plurality of imaging markers of a first flexible elongate instrument disposed in a body lumen, the imaging markers being visible in a medical image comprising the first flexible elongate instrument;

receiving diagnostic scan information or therapy delivery information at a plurality of locations of the body lumen from the first flexible elongate instrument or a second flexible elongate instrument configured to move relatively with respect to the first flexible elongate instrument, at least one of the first flexible elongate instrument and the second flexible elongate instrument including a position information sensor;

associating the diagnostic scan information or therapy delivery information with imaging markers of the plurality of locations based on the reference coordinate system and the location information sensed by the location information sensor; and

a composite image including the associated diagnostic scan information or therapy delivery information and the imaging markers is displayed.

25. The method of claim 24, wherein the positional information sensor is a sensor configured to detect a coded marker, and wherein the method further comprises detecting a coded marker of one of the first flexible elongate instrument and the second flexible elongate instrument.

26. The method of claim 24, wherein the positional information sensor is a diagnostic sensor disposed on the second flexible elongate instrument, and wherein the method further comprises detecting a signal emitted by the first flexible elongate instrument.

27. The method of claim 26, wherein associating the diagnostic scan information with the imaging markers comprises establishing a co-located position based on the detected signals.

28. The method of claim 24, wherein the position information sensor is a sensor that detects a push distance, a pull distance, or a combination thereof of the diagnostic device, one of the first flexible elongate instrument and the second flexible elongate instrument comprising the diagnostic device.

29. The method of claim 28, wherein associating the diagnostic scan information with the imaging markers comprises establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the diagnostic sensor and at least one of the plurality of imaging markers.

30. The method of claim 28, wherein the second flexible elongate instrument is a diagnostic device comprising at least one imaging marker, and wherein associating the diagnostic scan information with the medical image comprises establishing a starting position of a diagnostic sensor of the diagnostic device based on a relative position of the at least one imaging marker of the diagnostic device and at least one of a plurality of imaging markers of the first flexible elongate instrument.

31. A system for measuring relative displacement of at least two flexible elongate instruments within a body lumen, the system comprising:

a first flexible elongate instrument comprising a plurality of displacement encoding markers; and

a second flexible elongate instrument comprising a coded sensor configured to obtain signals from the displacement coded markers, the coded sensor disposed at a distal portion of the second flexible elongate instrument and configured to be inserted into the body lumen, the first flexible elongate instrument and the second flexible elongate instrument configured to move relatively.

32. The system of claim 31, further comprising a processor operatively disposed with the encoding sensor and configured to determine a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals.

33. The system of claim 31 or claim 32, wherein the displacement-encoding markers are disposed at least partially circumferentially around a surface of the first flexible elongate instrument and comprise a reflective medium.

34. The system of claim 33, wherein the reflective medium comprises a metal, a metal alloy, a magnet, a ceramic, a crosslinked hydrogel, a fluoropolymer, or any combination thereof.

35. The system of claim 33, wherein the surface is an inner circumferential surface of a catheter or liner of the first flexible elongate instrument.

36. The system of claim 33, wherein the surface is an outer circumferential surface of a lead of the first flexible elongate instrument.

37. The system of any one of claims 32-36, wherein at least one of the first flexible elongate instrument and the second flexible elongate instrument comprises a diagnostic device.

38. The system of claim 37, wherein the diagnostic device is configured to obtain body lumen information.

39. The system of claim 38, wherein the processor is further configured to correlate the obtained body lumen information with a relative displacement distance.

40. The system of claim 38 or claim 39, wherein the body lumen information comprises tissue density, temperature, pressure, flow rate, impedance, electrical conductivity, or any combination thereof.

41. A system for locating a therapeutic or diagnostic device in a body lumen, the system comprising:

The system of any one of claims 31-40, wherein at least one of the first flexible elongate instrument and the second flexible elongate instrument comprises a plurality of radiopaque markers; and

a processor configured to:

at least one X-ray angiographic image of the body lumen including the plurality of radiopaque markers is received,

associating a first engagement position of the first flexible elongate instrument and the second flexible elongate instrument with at least one of a plurality of radiopaque markers of the X-ray angiography image, and

associating a subsequent position of one of the first flexible elongate instrument and the second flexible elongate instrument with at least one of a plurality of radiopaque markers of the X-ray angiography image; and

a display configured to display a composite image including the radiopaque imaging markers and an indicator of the subsequent location or body lumen information obtained at the subsequent location.

42. The system of claim 41, wherein the processor is configured to continuously or periodically associate a subsequent position of one of the first flexible elongate instrument and the second flexible elongate instrument with at least one of a plurality of radiopaque markers of the X-ray angiography image.

43. The system of claim 42, wherein the display is configured to continuously or periodically update the composite image with indicators of the subsequent locations or body lumen information obtained at the subsequent locations.

44. An absolute position encoder system, comprising:

a member comprising a position encoder track comprising alternately spaced high reflectivity and low reflectivity code lines;

a light source configured to illuminate the encoder track;

an optical detector comprising a single element light sensor configured to detect the code lines when the member is adjacent to and moved relative to the optical detector, the single element light sensor detecting light reflected from a detection region of limited width, the width of at least one code line of the position encoder track being equal to or greater than the limited width of the detection region, the width of at least one code line of the position encoder track being narrower than the limited width of the detection region, the optical detector generating an optical signal indicative of varying intensity; and

a processor configured to:

Converting the optical signal into code characters, and

the absolute position of the component is measured based on the code characters.

45. The absolute position encoder system of claim 44, wherein the alternating spaced code lines provide at least three light reflection levels.

46. The absolute position encoder system of claim 44 or claim 45, wherein the optical detector is in contact with the position encoder track.

47. The absolute position encoder system of any one of claims 44 to 46, wherein the optical detector is disposed at a first intra-luminal medical instrument and the position encoder track is disposed at a second intra-luminal medical instrument.

48. The absolute position encoder system of claim 47, wherein the first intraluminal medical device is a guidewire and the second intraluminal medical device is a catheter.

49. The absolute position encoder system of any one of claims 44 to 46, wherein the optical detector is detachably coupled to an intra-luminal medical instrument.

50. The absolute position encoder system of any of claims 44-49, wherein the optical detector is detachably coupled to a unit comprising the processor.

51. The absolute position encoder system of any one of claims 44 to 50, wherein the optical detector comprises an optical fiber configured to transmit light from the light source to an encoder track and configured to transmit light reflected from the encoder track to a light intensity meter.

52. The absolute position encoder system of any of claims 44-51, wherein the alternating high and low reflectivity code lines are configured to provide directional information.

53. The absolute position encoder system of any of claims 44-52, wherein at least one of the member and a component housing the optical detector further comprises an orientation sensor.

54. An absolute position encoder system, comprising:

a member comprising a position encoder track comprising code lines imprinted on a surface;

an optical detector including an optical fiber communicatively coupled to an Optical Coherence Tomography (OCT) instrument, a tip of the optical fiber disposed at a detection region and configured to detect an imprint depth of each code line when the member is adjacent to and moved relative to the optical detector, the optical detector generating an optical signal indicative of the varied imprint depth; and

A processor configured to:

converting the optical signal into code characters, and

the absolute position of the component is measured based on the code characters.

55. An absolute position encoder system as claimed in claim 54, wherein the position encoder track comprises code lines of at least three different depths.

56. The absolute position encoder system of claim 54 or claim 55, wherein the surface of the position encoder track is cylindrical and the code lines are imprinted circumferentially on the surface.

57. The absolute position encoder system of any of claims 54 to 56, wherein the optical detector is in contact with the position encoder track.

58. The absolute position encoder system of any one of claims 54 to 57, wherein the optical detector is disposed at a first intra-luminal medical instrument and the position encoder track is disposed at a second intra-luminal medical instrument.

59. The absolute position encoder system of claim 56, wherein the first intraluminal medical device is a catheter and the second intraluminal medical device is a guidewire.

60. The absolute position encoder system of any one of claims 54-59, wherein the optical detector is detachably coupled to an intra-luminal medical instrument.

61. The absolute position encoder system of any of claims 54-60, wherein the optical detector is detachably coupled to a unit comprising the processor.

62. An absolute position encoder system as claimed in any one of claims 54-61, wherein the code lines are configured to provide directional information.

63. The absolute position encoder system of any one of claims 54 to 62, wherein at least one of the member and a component housing the optical detector further comprises an orientation sensor.

64. A method of determining at least one of an absolute position, a direction of movement, and a speed of movement of a medical device inserted into a subject, the method comprising:

use of a system according to any one of claims 44 to 59:

detecting an optical signal comprising at least two reflected intensities or at least two imprint depths while the member translates relative to the optical detector, at least one of the optical detector and the member being disposed at the medical device; and

the absolute position, direction of movement, or speed of movement of the medical device is identified based on the time and duration of the at least two reflection intensities or at least two imprint depths.

65. The system of any one of claims 1 to 23, wherein the medical image is an X-ray angiography and the imaging markers are radiopaque imaging markers.

66. The method of any one of claims 24 to 30, wherein the medical image is an X-ray angiography and the imaging markers are radiopaque imaging markers.

67. The system of any one of claims 1-23 and 65, further comprising a direction sensor configured to detect advancement and retraction of the relative motion of the first flexible elongate instrument and the second flexible elongate instrument.

68. The method of any one of claims 24-30 and 66, further comprising receiving direction information from a direction sensor configured to detect advancement and retraction of relative motion of the first flexible elongate instrument and the second flexible elongate instrument.

69. The system of any one of claims 1 to 23, 65, and 67, wherein the composite image further comprises a simulated representation of therapy delivered at least one of the plurality of locations.

70. The system of any one of claims 1 to 23, 65, 67, and 69, wherein the composite image further comprises a simulated representation of a position of the diagnostic or therapeutic device relative to the medical image.

71. The system of claim 70, wherein the simulated representation provides a dimensional representation of the diagnostic or therapeutic device relative to the lumen.

72. The method of any of claims 24-30, 66, and 68, wherein displaying the composite image further comprises displaying a simulated representation of therapy delivered at least one of the plurality of locations.

73. The method of any one of claims 24 to 30, 66, 68 and 72, wherein displaying the composite image further comprises displaying a simulated representation of a position of the diagnostic or therapeutic device relative to the medical image.

74. The method of claim 73, wherein the simulated representation provides a dimensional representation of the diagnostic or therapeutic device relative to the lumen.

75. A guidewire, comprising:

a plurality of radiopaque imaging markers;

an embedded optical fiber; and

a single element sensor disposed at a distal portion of the guidewire and operatively coupled to the optical fiber, the single element sensor configured to detect positional information encoding of the flexible elongate device.

76. A system for locating a therapeutic or diagnostic device in a body lumen, the system comprising:

The system of any one of claims 31-40, further comprising a drive unit operatively disposed with at least one of the first flexible elongate instrument and the second flexible elongate instrument, the drive unit configured to advance, retract, or advance and retract at least one flexible elongate instrument in the body lumen; and

a processor configured to:

determining a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals, and

a control command is generated for the drive unit based on the determined relative displacement distance and the target position.

77. A system for locating a therapeutic or diagnostic device in a body lumen, the system comprising:

the system of any one of claims 31 to 40;

a processor configured to determine a relative displacement distance between the first flexible elongate instrument and the second flexible elongate instrument based on the obtained signals; and

a display configured to display a composite image including a representation of the body lumen and an indicator of a position of at least one of the first flexible elongate instrument and the second flexible elongate instrument within the body lumen.