CN113180614B - Detection method for guide-wire-free FFR, guide-wire-free IMR and guide-wire-free CFR - Google Patents

Detection method for guide-wire-free FFR, guide-wire-free IMR and guide-wire-free CFR Download PDF

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CN113180614B
CN113180614B CN202110615301.5A CN202110615301A CN113180614B CN 113180614 B CN113180614 B CN 113180614B CN 202110615301 A CN202110615301 A CN 202110615301A CN 113180614 B CN113180614 B CN 113180614B
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blood vessel
free
pressure
model
coronary
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CN113180614A (en
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赵清华
张超
毛益进
冯辉
岳会强
刘伟
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Beijing Yueying Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/02028—Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/021—Measuring pressure in heart or blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/026—Measuring blood flow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A61B8/0891—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of blood vessels
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F30/00—Computer-aided design [CAD]
    • G06F30/20—Design optimisation, verification or simulation
    • G06F30/28—Design optimisation, verification or simulation using fluid dynamics, e.g. using Navier-Stokes equations or computational fluid dynamics [CFD]
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T17/00—Three dimensional [3D] modelling, e.g. data description of 3D objects
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T7/00—Image analysis
    • G06T7/10—Segmentation; Edge detection
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06F—ELECTRIC DIGITAL DATA PROCESSING
    • G06F2119/00—Details relating to the type or aim of the analysis or the optimisation
    • G06F2119/14—Force analysis or force optimisation, e.g. static or dynamic forces
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/10—Image acquisition modality
    • G06T2207/10004—Still image; Photographic image
    • G06T2207/10012—Stereo images
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T2207/00—Indexing scheme for image analysis or image enhancement
    • G06T2207/30—Subject of image; Context of image processing
    • G06T2207/30004—Biomedical image processing
    • G06T2207/30101—Blood vessel; Artery; Vein; Vascular

Abstract

The application provides a detection method of a guide wire-free FFR, a guide wire-free IMR and a guide wire-free CFR. The method comprises the following steps: acquiring a 2D coronary image of a blood vessel to be measured; constructing a 3D blood vessel model according to the 2D coronary image; obtaining the central arterial pressure of a blood vessel to be measured by using a noninvasive measurement method; constructing a 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the middle cardiac pulse pressure; the filar-free CFR, filar-free FFR, and filar-free IMR are calculated from the 3D coronary CFD model. The noninvasive detection of CFR, FFR and IMR by adopting the DSA image auxiliary technology is realized.

Description

Detection method for guide-wire-free FFR, guide-wire-free IMR and guide-wire-free CFR
Technical Field
The present application relates to the field of coronary artery physiology, and in particular, to a detection method, apparatus, computer readable storage medium and processor for filar-free FFR, filar-free IMR and filar-free CFR.
Background
Coronary physiology plays an increasingly important clinical role in cardiology. Fractional flow reserve (Fractional Flow Reserve, FFR for short), coefficient of circulatory resistance (Index of Microcirculatory Resistance, IMR for short), and coronary flow reserve (Coronary Flow Reserve, CFR for short) are the most commonly used functional core indicators that characterize the extent of coronary lesions. Are widely used to assess the extent of functional ischemia (assessed by FFR), microvascular ischemia without significant occlusion (assessed by IMR), and coronary system ischemia (assessed by CFR) involving epicardial and microvascular vessels, respectively. Fractional Flow Reserve (FFR) the fractional flow reserve capacity of the vessel is calculated by dividing the stenosis distal coronary pressure during maximum hyperemia by the arterial pressure. FFR is considered a gold standard for assessing whether coronary stenosis causes functional ischemia; and simultaneously, the coronary downstream microcirculation system disease is also an independent cause of adverse events of coronary heart disease, and the corresponding clinical evaluation indexes comprise core indexes such as microcirculation resistance coefficient (IMR), coronary artery blood flow reserve (CFR) and the like. Symptomatic patients without significant obstructive plaque may still have significant non-obstructive coronary atherosclerosis and microvascular ischemia, resulting in an increased incidence of Major Adverse Cardiovascular Events (MACEs). The clinical significance of IMR is in assessing stable patients for chest pain and/or abnormal pressure testing to find no obstructive epicardial coronary artery disease. CFR is defined as the ratio of coronary blood flow at maximum hyperemia to baseline and represents the ability of the coronary circulation to respond to increased physiological oxygen demand and corresponding increases in blood flow. CFR includes epicardial blood vessel and microcirculation function information of the whole coronary system, FFR provides epicardial segment blood vessel information, IMR reflects coronary microcirculation function status. The three are mutually complemented to provide complete coronary circulation information. The objective detection indexes are fully used, so that a clinician can know the coronary artery functional state of a patient in detail, the blood vessels of criminals and lesions of criminals are clarified, an intervention strategy is optimized, the microcirculation functional state is evaluated, the drug treatment is guided, and more accurate prediction is provided for prognosis of a Percutaneous Coronary Intervention (PCI) patient.
The primary clinical acquisition means of FFR, IMR and CFR today is the invasive single point measurement with pressure guidewire at a designated location within the target vessel. The measurement method has various intra-operative risks and high cost, has high professional requirements for operators, is difficult to acquire the parameter values of all positions of the coronary artery, and needs to reduce the risk and cost brought by invasiveness in a technical upgrading mode. In recent years, a variety of medical imaging techniques have provided an auxiliary option for diagnosis of coronary vessels, including Digital Silhouette Angiography (DSA), positron Emission Tomography (PET) and cardiac magnetic resonance, myocardial ultrasound imaging, and computed tomography. The new medical imaging technology can more intuitively and accurately present the geometric information of the real coronary artery and blood flow, and well help clinicians to complete disease diagnosis and treatment. However, compared with the prior imaging technology which can display the blood vessel and blood flow information perfectly, the DSA image auxiliary technology cannot be adopted to realize the noninvasive detection of FFR/IMR/CFR.
Disclosure of Invention
The main objective of the present application is to provide a detection method, device, computer readable storage medium and processor for a guide-wire-free FFR, a guide-wire-free IMR and a guide-wire-free CFR, so as to solve the problem that the non-invasive detection of FFR/IMR/CFR cannot be realized by adopting an image auxiliary technology in the prior art.
To achieve the above object, according to one aspect of the present application, there is provided a detection method of a guide-wire-free FFR, a guide-wire-free IMR, and a guide-wire-free CFR, including: acquiring a 2D coronary image of a blood vessel to be measured; constructing a 3D blood vessel model according to the 2D coronary image; obtaining the central arterial pressure of the blood vessel to be measured by using a noninvasive measurement method; constructing a 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the central arterial pressure; and calculating a guide-wire-free CFR, a guide-wire-free FFR and a guide-wire-free IMR according to the 3D coronary CFD model.
Optionally, calculating a filar-free CFR, a filar-free FFR, and a filar-free IMR from the 3D coronary CFD model comprises: determining blood flow in a resting state according to the 3D blood vessel model in the resting state; obtaining blood flow in a hyperemic state; calculating the guide wire-free CFR according to the blood flow in the resting state and the blood flow in the congestion state; applying the 3D coronary CFD model, and determining the blood vessel distal pressure during maximum hyperemia and the blood vessel proximal pressure during maximum hyperemia according to the blood flow in the hyperemic state; determining the guide wire-free FFR based on the maximum hyperemic vascular distal pressure and the maximum hyperemic vascular proximal pressure; and determining the guide wire-free IMR according to the blood vessel distal pressure at the time of maximum congestion and the maximum blood flow rate of congestion, wherein the maximum blood flow rate of congestion is the maximum value of the blood flow rate in the congestion state.
Optionally, constructing a 3D coronary CFD model of the blood vessel to be measured based at least on the 3D blood vessel model and the central arterial pressure, including: determining the pressure at the inlet of the blood vessel to be measured according to the central arterial pressure; and constructing a 3D coronary CFD model of the blood vessel to be measured in the congestion state according to the 3D blood vessel model, the pressure at the inlet of the blood vessel to be measured and the blood flow in the congestion state.
Optionally, obtaining the central arterial pressure of the blood vessel to be measured using a non-invasive measurement method, including: acquiring brachial artery pressure, radial artery pressure and carotid artery pressure by using the noninvasive measurement method; the central arterial pressure is calculated from at least one of the brachial artery pressure, the radial artery pressure, and the carotid artery pressure.
Optionally, obtaining the central arterial pressure of the blood vessel to be measured using a non-invasive measurement method, including: acquiring a parameter set of the blood vessel to be measured, wherein the parameter set comprises geometric information, arterial inlet flow, an outlet boundary model and a blood vessel elasticity model; determining a one-dimensional hydrodynamic model according to the parameter set; calculating a first pressure waveform at a measuring point according to the one-dimensional fluid mechanics model, wherein the measuring point comprises a radial artery and a brachial artery; acquiring a second pressure waveform at the measuring point by using the non-invasive measuring method, wherein the non-invasive measuring method comprises an ultrasonic method and a nuclear magnetic method; determining a target difference value, wherein the target difference value is a difference value between the first pressure waveform and the second pressure waveform; updating each parameter in the parameter set until the target difference is smaller than a preset value under the condition that the target difference is larger than or equal to the preset value; determining an optimized one-dimensional fluid mechanics model according to the updated parameter set; and determining the central cardiac pulse pressure based on the optimized one-dimensional fluid mechanics model.
Optionally, the 2D coronary image includes 2D coronary images at different angles, and constructing a 3D blood vessel model according to the 2D coronary images includes: extracting a plurality of 2D target blood vessels from the 2D coronary images under different angles; the 3D vessel model is constructed from a plurality of the 2D target vessels.
Optionally, extracting the 2D target vessel from the 2D coronary image includes: and extracting the 2D target blood vessel from the 2D coronary artery image by adopting a central line calculation algorithm and a level set image segmentation algorithm.
According to another aspect of the present application, there is provided a detection device for a leadless FFR, a leadless IMR, and a leadless CFR, comprising: the first acquisition unit is used for acquiring a 2D coronary image of a blood vessel to be measured; a first construction unit for constructing a 3D vessel model from the 2D coronary images; the second acquisition unit is used for acquiring the central arterial pressure of the blood vessel to be measured by using a noninvasive measurement method; a second construction unit, configured to construct a 3D coronary CFD model of the blood vessel to be measured according to at least the 3D blood vessel model and the central arterial pressure; a calculation unit for calculating a filar-free CFR, a filar-free FFR and a filar-free IMR from the 3D coronary CFD model.
According to still another aspect of the present application, there is provided a computer readable storage medium, where the computer readable storage medium includes a stored program, and when the program runs, controls a device in which the computer readable storage medium is located to execute any one of the detection methods of the leadless FFR, the leadless IMR, and the leadless CFR.
According to yet another aspect of the present application, a processor is provided for running a program, wherein the program when run performs any one of the detection methods of no-guidewire FFR, no-guidewire IMR, and no-guidewire CFR.
By applying the technical scheme, the method comprises the steps of obtaining a 2D coronary image of a blood vessel to be measured, constructing a 3D blood vessel model according to the 2D coronary image, obtaining the central arterial pressure of the blood vessel to be measured through a noninvasive measurement method, constructing a 3D coronary CFD model at least according to the 3D blood vessel model and the central cardiac pulse pressure, and finally calculating a guide wire-free CFR, a guide wire-free FFR and a guide wire-free IMR according to the 3D coronary CFD model. The whole scheme does not involve an invasive measurement method, and the noninvasive detection of CFR, FFR and IMR is realized by adopting an image auxiliary technology.
Drawings
The accompanying drawings, which are included to provide a further understanding of the application and are incorporated in and constitute a part of this application, illustrate embodiments of the application and together with the description serve to explain the application and do not constitute an undue limitation to the application. In the drawings:
FIG. 1 illustrates a flow chart of a method of detection of a leadless FFR, a leadless IMR, and a leadless CFR according to an embodiment of the present application;
FIG. 2 shows a schematic representation of the volume change of a 3D model of the same vessel at different times according to an embodiment of the present application;
FIG. 3 shows a schematic diagram of a 3D vessel model reconstructed from two 2D target vessels at different angles according to an embodiment of the present application;
FIG. 4 illustrates a schematic diagram of extracting a 2D target vessel from the 2D coronary DSA image according to an embodiment of the present application;
FIG. 5 shows a schematic diagram of a 55-segment human arterial network according to an embodiment of the present application;
FIG. 6 illustrates a Tube-Load model according to an embodiment of the present application;
FIG. 7 illustrates a vessel model inlet pressure versus flow graph according to an embodiment of the present application;
FIG. 8 illustrates a FFR/IMR calculation result display diagram in accordance with an embodiment of the present application;
FIG. 9 shows a schematic diagram of a detection device for a leadless FFR, a leadless IMR, and a leadless CFR, according to an embodiment of the present application;
fig. 10 shows a central arterial pressure waveform diagram according to an embodiment of the present application.
Detailed Description
It should be noted that, in the case of no conflict, the embodiments and features in the embodiments may be combined with each other. The present application will be described in detail below with reference to the accompanying drawings in conjunction with embodiments.
In order to make the present application solution better understood by those skilled in the art, the following description will be made in detail and with reference to the accompanying drawings in the embodiments of the present application, it is apparent that the described embodiments are only some embodiments of the present application, not all embodiments. All other embodiments, which can be made by one of ordinary skill in the art based on the embodiments herein without making any inventive effort, shall fall within the scope of the present application.
It should be noted that the terms "first," "second," and the like in the description and claims of the present application and the above figures are used for distinguishing between similar objects and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used may be interchanged where appropriate in order to describe the embodiments of the present application described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
It will be understood that when an element such as a layer, film, region, or substrate is referred to as being "on" another element, it can be directly on the other element or intervening elements may also be present. Furthermore, in the description and in the claims, when an element is described as being "connected" to another element, the element may be "directly connected" to the other element or "connected" to the other element through a third element.
As described in the background art, in the prior art, the DSA image auxiliary technology cannot be adopted to realize the noninvasive detection of the FFR/IMR/CFR, so as to solve the problem that the DSA image auxiliary technology cannot be adopted to realize the noninvasive detection of the FFR/IMR/CFR, the embodiments of the application provide a detection method, a device, a computer readable storage medium and a processor for the guide-wire-free FFR, the guide-wire-free IMR and the guide-wire-free CFR.
According to embodiments of the present application, a method of detection of a guidewire-free FFR, a guidewire-free IMR, and a guidewire-free CFR is provided.
Fig. 1 is a flow chart of a method of detection of a leadless FFR, a leadless IMR, and a leadless CFR according to an embodiment of the present application. As shown in fig. 1, the method comprises the steps of:
step S101, acquiring a 2D coronary image of a blood vessel to be measured;
Step S102, constructing a 3D blood vessel model according to the 2D coronary image;
step S103, obtaining the central arterial pressure of the blood vessel to be measured by using a noninvasive measurement method;
step S104, constructing a 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the central cardiac pulse pressure;
step S105, calculating a guide-wire-free CFR, a guide-wire-free FFR, and a guide-wire-free IMR according to the 3D coronary CFD model.
Specifically, the 2D coronary image may be a 2D coronary DSA image, and of course, may be another type of 2D coronary image other than the 2D coronary DSA image. The method has high efficiency, good robustness and good accuracy for calculating the functional index FFR/IMR/CFR of the blood vessel in the coronary DSA image, and can realize instant 3D blood vessel analysis.
Alternatively, the central arterial pressure of the blood vessel to be measured may be obtained by means of non-invasive measurement such as ultrasonic detection, nuclear magnetic detection, and a blood pressure measuring instrument capable of recording waveforms.
Specifically, the calculation results of the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR are displayed in real time, so that visualization is realized. The invention has good processing capacity, efficiency and precision for single or multiple coronary vessel trees. The overall treatment time for multiple vessels was less than 1 minute.
In the above scheme, the 2D coronary image of the blood vessel to be measured is obtained, then a 3D blood vessel model is constructed according to the 2D coronary image, the central arterial pressure of the blood vessel to be measured is obtained through a noninvasive measurement method, a 3D coronary CFD model is constructed at least according to the 3D blood vessel model and the central cardiac pulse pressure, and finally the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR are calculated according to the 3D coronary CFD model. The whole scheme does not involve an invasive measurement method, and the noninvasive detection of CFR, FFR and IMR is realized by adopting an image auxiliary technology.
It should be noted that the steps illustrated in the flowcharts of the figures may be performed in a computer system such as a set of computer executable instructions, and that although a logical order is illustrated in the flowcharts, in some cases the steps illustrated or described may be performed in an order other than that illustrated herein.
In one embodiment of the present application, calculating a filar-free CFR, a filar-free FFR, and a filar-free IMR from the 3D coronary CFD model described above includes: determining blood flow in a resting state according to the 3D blood vessel model in the resting state; obtaining blood flow in a hyperemic state; calculating the guide wire-free CFR based on the blood flow in the resting state and the blood flow in the congestion state; applying the 3D coronary CFD model, and determining the blood vessel distal pressure during maximum hyperemia and the blood vessel proximal pressure during maximum hyperemia according to the blood flow in the hyperemic state; determining said guidewire-free FFR based on said maximum hyperemic vascular distal pressure and said maximum hyperemic vascular proximal pressure; and determining the guide wire-free IMR according to the blood vessel distal pressure at the time of maximum congestion and the maximum blood flow rate of congestion, wherein the maximum blood flow rate of congestion is the maximum value of the blood flow rate in the congestion state.
In practical application, a 2D coronary DSA image of a blood vessel to be measured in a resting state is easy to obtain, but the 2D coronary DSA image of the blood vessel to be measured in a hyperemic state cannot be obtained, so that a 3D blood vessel model of the blood vessel to be measured in the hyperemic state cannot be obtained, and further, the blood flow in the hyperemic state cannot be obtained according to the 3D blood vessel model in the hyperemic state, which affects the measurement of the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR. According to the embodiment, the blood flow in the hyperemia state can be determined according to the blood flow in the resting state without acquiring a 2D coronary DSA image in the hyperemia state, so that the measurement of the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR is realized.
Optionally, the blood flow in the hyperemic state is obtained by at least the following ways:
first kind: determining blood flow in a hyperemic state according to the blood flow in the resting state, and constructing a theoretical model;
determining the blood flow in the hyperemic state based on the theoretical model, the theoretical model being expressed as:
q_hyper=a×q_rest+b, where q_hyper represents the blood flow in the hyperemic state and q_rest represents the blood flow in the resting state, where a and B are parameters related to the performance of the object to be detected. In practical application, a 2D coronary DSA image of a blood vessel to be measured in a resting state is easy to obtain, but the 2D coronary DSA image of the blood vessel to be measured in a hyperemic state cannot be obtained, so that a 3D blood vessel model of the blood vessel to be measured in the hyperemic state cannot be obtained, and further, the blood flow in the hyperemic state cannot be obtained according to the 3D blood vessel model in the hyperemic state, which affects the measurement of the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR. The blood flow in the hyperemic state can be determined based on the blood flow in the resting state, thereby achieving the measurement of the filar-free CFR, the filar-free FFR and the filar-free IMR.
Second, a flow sensor may be directly used to measure blood flow in a hyperemic state.
Thirdly, determining the blood flow in the hyperemic state by adopting an empirical formula, wherein the empirical formula comprises parameters such as the heart rate, the diastolic pressure, the total myocardial mass of the object to be detected, a 3D blood vessel model of the blood vessel to be measured and the like.
Of course, the way of obtaining the blood flow in the hyperemic state is not limited to the above, and a person skilled in the art may select an appropriate way to obtain the blood flow in the hyperemic state according to the actual situation.
In one embodiment of the present application, constructing the 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the central cardiac pulse pressure includes: determining the pressure at the inlet of the blood vessel to be measured according to the central arterial pressure; and constructing a 3D coronary CFD model under the congestion state of the blood vessel to be measured according to the 3D blood vessel model, the pressure at the inlet of the blood vessel to be measured and the blood flow under the congestion state. The 3D blood vessel model is obtained according to a 2D coronary image obtained in a resting state, the pressure at the inlet of the blood vessel to be measured is detected in a hyperemic state, and the 3D coronary CFD model in the hyperemic state is constructed. And obtaining the guide wire-free FFR and the guide wire-free IMR of the blood vessel according to the 3D coronary CFD model under the hyperemia state. Determining a blood vessel distal pressure at maximum hyperemia and a blood vessel proximal pressure at maximum hyperemia by using a 3D coronary CFD model in a hyperemic state, and determining the guide wire-free FFR according to the blood vessel distal pressure at maximum hyperemia and the blood vessel proximal pressure at maximum hyperemia; determining said filamentless IMR based on said maximum hyperemic vascular distal pressure and maximum hyperemic blood flow.
In one embodiment of the present application, the obtaining the central arterial pressure of the blood vessel to be measured by using a non-invasive measurement method includes: acquiring brachial artery pressure, radial artery pressure and carotid artery pressure by using the noninvasive measurement method; the central cardiac pulse pressure is calculated from at least one of the brachial artery pressure, the radial artery pressure, and the carotid artery pressure. Specifically, a non-invasive measurement manner may be adopted to obtain a brachial artery pressure waveform, a radial artery pressure waveform and a carotid artery pressure waveform, and then the above-mentioned central artery pressure is calculated according to at least one of the brachial artery pressure waveform, the radial artery pressure waveform and the carotid artery pressure waveform, so as to obtain an accurate central artery pressure.
In one embodiment of the present application, the obtaining the central arterial pressure of the blood vessel to be measured by using a non-invasive measurement method includes: acquiring a parameter set of the blood vessel to be measured, wherein the parameter set comprises geometric information, arterial inlet flow, an outlet boundary model and a blood vessel elasticity model; determining a one-dimensional fluid mechanics model according to the parameter set; calculating a first pressure waveform at a measuring point according to the one-dimensional fluid mechanics model, wherein the measuring point comprises a radial artery and a brachial artery; acquiring a second pressure waveform at the measuring point by using the non-invasive measuring method, wherein the non-invasive measuring method comprises an ultrasonic method and a nuclear magnetic method; determining a target difference value, wherein the target difference value is a difference value between the first pressure waveform and the second pressure waveform; updating each parameter in the parameter set until the target difference is smaller than the preset value when the target difference is larger than or equal to the preset value; determining an optimized one-dimensional fluid mechanics model according to the updated parameter set; and determining the pressure of the central cardiac pulse based on the optimized one-dimensional fluid mechanics model. In this embodiment, the first pressure waveform and the second pressure waveform are both pressure waveforms in a time domain, that is, the first pressure waveform and the second pressure waveform contain time sequence information, compared with the scheme that the radial artery pressure or the brachial artery pressure in the prior art is only one pressure value, compared with the scheme that the average arterial pressure is obtained by adopting a common empirical formula in the prior art (accuracy is irrelevant to time sequence), the scheme of the application is more accurate because of the time sequence waveforms; further ensuring the accuracy of the functional index of the blood vessel to be measured. In addition, by continuously adjusting each parameter in the parameter set until the target difference value is smaller than the preset value, the one-dimensional hydrodynamic model at the moment is determined to be closer to the real vascular hydrodynamic model under the condition that the target difference value is smaller, so that the central arterial pressure is determined more accurately based on the optimized one-dimensional hydrodynamic model.
In a specific embodiment of the present application, obtaining geometric information of a blood vessel to be measured includes: establishing a 55-segment human body artery network structure (the 55-segment human body artery network structure is shown in figure 5), and determining initial network structure parameters according to the 55-segment human body artery network structure, wherein the initial network structure parameters comprise geometric information such as the length, the radius and the like of a blood vessel. The 55 segments of human artery geometry information are shown in table 1.
TABLE 1 human arterial geometry information at 55 segment
Numbering device Artery name Length (cm) Proximal radius (cm) Radius of distal end (cm)
1 Ascending aorta 4 1.525 1.42
2 Aortic arch 3 1.42 1.342
3 Brachiocephalic 4 0.95 0.7
4,15 R+L Subclavian 4 0.425 0.407
5,11 R+L Com.carotid 17 0.525 0.4
6,16 R+L Vertebral 14 0.2 0.2
7,17 R+L Brachial 40 0.407 0.25
8,19 R+L Radial 22 0.175 0.175
9,18 R+L Ulnar 22 0.175 0.175
10 Aortic arch 4 1.342 1.246
12 Thoracic aorta 6 1.246 1.124
13 Thoracic aorta 11 1.124 0.924
14 Intercostals 7 0.63 0.5
20 Celiac axis 2 0.35 0.3
21 Hepatic 2 0.3 0.25
22 Hepatic 7 0.275 0.25
23 Gastric 6 0.175 0.15
24 Splenic 6 0.2 0.2
25 Abdominal aorta 5 0.924 0.838
26 Superior mesenteric 5 0.4 0.35
27 Abdominal aorta 2 0.838 0.814
28,30 R+L Renal 3 0.275 0.275
29 Abdominal aorta 2 0.814 0.792
31 Abdominal aorta 13 0.792 0.627
32 Inferior mesenteric 4 0.2 0.175
33 Abdominal aorta 8 0.627 0.55
34,47 R+L External iliac 6 0.4 0.37
35,48 R+L Femoral 15 0.37 0.314
36,49 R+L Internal iliac 5 0.2 0.2
37,50 R+L Deep femoral 11 0.2 0.2
38,51 R+L Femoral 44 0.314 0.2
39,40,52,53 R+L Ext.+Int.carotid 16 0.275 0.2
41,54 R+L Post.tibial 32 0.125 0.125
42,55 R+L Ant.tibial 32 0.125 0.125
43,46 R+L Interosseous 7 0.1 0.1
44,45 R+L Ulnar 17 0.2 0.2
In a specific embodiment of the present application, obtaining arterial inlet flow of a blood vessel to be measured includes: and determining the flow-time relation in a complete heartbeat period at the inlet of the arterial tree, and determining the arterial inlet flow of the blood vessel to be measured according to the flow-time relation. The flow-time relationship can be determined through the fitting relationship of a large amount of data, namely, a plurality of flows at the inlet of the arterial tree are acquired, and the flows are fitted on a time domain to obtain the flow-time relationship in a complete heartbeat period; the flow-time relationship in a complete heartbeat cycle can also be obtained by means of non-invasive measurement such as ultrasonic detection or nuclear magnetic detection.
In a specific embodiment of the present application, obtaining an exit boundary model of a blood vessel to be measured includes: and estimating the parameters such as impedance, capacitance and the like of each truncated blood vessel at the outlet of the arterial tree based on the circuit model, and determining an outlet boundary model of the blood vessel to be measured according to the parameters such as impedance, capacitance and the like.
In a specific embodiment of the present application, obtaining a vascular elasticity model of a blood vessel to be measured includes: constructing a one-dimensional hemodynamic control equation based on a three-dimensional incompressible flow wiener-stokes (NS) equation:
wherein A is the cross-sectional area of the blood vessel, q is the blood flow, v is the kinematic viscosity, delta is the thickness of the boundary layer, r 0 For the radius of the vessel when it is undeformed, the pressure p is determined by the state equation based on the elastic modelCalculation, p 0 ,A 0 The pressure and the cross-sectional area of the undeformed blood vessel respectively, E represents the Young's modulus of the blood vessel wall, h represents the thickness of the blood vessel wall, wherein the cross-sectional area of the blood vessel is determined according to the radius of the blood vessel, and the flow-time in a complete heartbeat period at the inlet of the arterial tree is determinedThe relationship determines blood flow.
Specifically, in the calculation of the functional index, the intravascular arterial pressure is an indispensable parameter, and the arterial pressure-related parameter is derived from the cardiac functional index. Conventionally, the Mean Arterial Pressure (MAP) is obtained by an empirical formula in statistical sense, and parameters such as FFR are estimated according to the Mean Arterial Pressure (MAP), for example, the empirical formula is:
Wherein HR, SBP, DBP respectively represent heart rate, systolic blood pressure and diastolic blood pressure of the patient. The empirical formula does not fully reflect patient-specific physiological parameters. And the one-dimensional computational fluid dynamics method corrects parameters related to a patient in the one-dimensional computational fluid dynamics model based on the upper limb artery of the noninvasive measurement by establishing an arterial tree of the human body. These patient-specific parameters are adjusted in a reciprocating manner to obtain an optimal model for the current patient. Therefore, the central cardiac pulse pressure is calculated from the model, and the pressure related parameters can be calculated more accurately. On the other hand, this method can obtain the complete central artery pressure waveform in one heartbeat period, as shown in fig. 10, and not only the high-low pressure and the average pressure. This is very advantageous for CFD simulation of transients, which can provide complete pressure boundary conditions within one cycle.
In an alternative embodiment of the present application, the one-dimensional hemodynamic control equation may also be expressed as follows:
where α is the Coriolis coefficient, μ is the dynamic viscosity, γ v Is a parameter defining the radial distribution of velocity. When α=1，
The equation can also be written in the form of a, u:
Where u is the axial velocity.
The state equation based on the elastic model can also be written as:
where v is poisson's ratio.
The state equation is also based on the form of a viscoelastic model:
wherein gamma is s Is the viscoelastic coefficient.
Of course, there are other forms of one-dimensional hemodynamic control equations and state equations, not limited to those listed herein.
In an embodiment of the present application, the 2D coronary image includes 2D coronary images at different angles, and the constructing a 3D blood vessel model according to the 2D coronary images includes: extracting a plurality of 2D target blood vessels from the 2D coronary images under different angles; the 3D vessel model is constructed from a plurality of the 2D target vessels. In particular, the number of 2D target vessels may be varied, including a single vessel, multiple vessels, and the entire coronary system.
In an embodiment of the present application, extracting a 2D target blood vessel from the 2D coronary image includes: and extracting the 2D target blood vessel from the 2D coronary artery image by adopting a central line calculation algorithm and a level set image segmentation algorithm.
In one specific embodiment of the present application, the specific way to calculate a guide-wire-free CFR is: constructing a 3D blood vessel model in a resting state according to DSA images in resting states at different angles; acquiring a set of coronary vessel 3D models in a resting state which are continuous in time; calculating the blood flow in a resting state by calculating the volume change rate of the 3D blood vessel model at two continuous moments (for DSA images obtained by continuous shooting, the blood flow in the time period is obtained by dividing the change amount of the blood vessel volume (congestion amount) between two adjacent frames by the time interval between two frames); and determining the blood flow in the hyperemic state. The guidewire free CFR is the ratio of the blood flow in the most congested state to the blood flow in the resting state. As shown in fig. 2, fig. 2A, 2B, and 2C are 3D models of a blood vessel obtained at different times, the volume change amount of the model in the figures is calculated, and the blood flow amount of the blood vessel at the time is obtained by dividing the time between two figures, fig. 2A1 and 2A2 are 2D contours corresponding to fig. 2A, fig. 2B1 and 2B2 are 2D contours corresponding to fig. 2B, and fig. 2C1 and 2C2 are 2D contours corresponding to fig. 2C.
Specifically, the same steady state solver is adopted for solving FFR and IMR, and the boundary conditions of the coronary vessel are inlet pressure given, outlet flow given and no-slip wall surface for the vessel wall. The inlet pressure boundary and outlet flow boundary of the CFD model are shown in fig. 7. The FFR and IMR calculations are based on CFD solutions under hyperemic conditions to obtain pressure values Pd for points within the vessel. Fig. 8 is a 3D model CFD result containing one bifurcation point and two sub-vessels. FFR/IMR display: the calculated FFR/IMR is shown on the 3D model of fig. 8. As shown, FFR and IMR values corresponding to points within the target vessel are shown in fig. 8, respectively. The results of the present invention can show the parameter values at all locations within the vessel, with respect to the limitation of the number of measurement points at the time of invasive measurement.
In an embodiment of the present application, the 2D coronary DSA image includes DSA images at different angles, and reconstructing the 3D blood vessel model according to the 2D target blood vessel includes: reconstructing the 3D vessel model from a plurality of the 2D target vessels at different angles. The method of reconstructing a 3D vessel from 2D vessels at different angles comprises: 1) Correcting the position of the 2D blood vessel segmentation result under different angles relative to the position of the light source to obtain a projection image corrected by the light source; 2) Constructing a space curved surface area according to the number of the light sources; 3) Intersecting a plurality of curved surface areas in a 3D space to obtain a space convex hull, namely an initial three-dimensional blood vessel model; 4) Acquiring an initial three-dimensional blood vessel central line, and calculating the radius of all points on the central line; 5) Performing central line expansion by using a given radius of each point on the central line to obtain an intermediate state blood vessel model; 6) And smoothing the vessel profile by using a smoothing algorithm to obtain a reconstructed final 3D vessel model. A method of three-dimensional reconstruction of a 2D target vessel at two different angles is shown in fig. 3. And (3) carrying out position correction on the 2D blood vessel segmentation result C2' under different angles relative to the light source position, and obtaining a projection image C2 after light source correction. A space curved surface region (hatched portion in fig. 3) is constructed according to the number of light sources. And intersecting the curved surface areas in a 3D space to obtain a space convex hull (vessel in the figure). A three-dimensional vessel centerline is acquired and the radius size at all points on the centerline is calculated. The initial vessel model is obtained by centerline expansion at a given radius for each point on the centerline. And smoothing the vessel profile by using a smoothing algorithm to obtain a reconstructed 3D vessel model. The 2D vessel contours at different angles are shown in fig. 3B1 and 3B2, and the final reconstruction result is shown in fig. 3B3.
In a specific embodiment of the present application, extracting a 2D target blood vessel from the 2D coronary DSA image includes: and extracting the 2D target blood vessel from the 2D coronary DSA image by adopting a central line calculation algorithm and a level set image segmentation algorithm. Fig. 4 shows a process of DSA image 2D vessel extraction. The image segmentation of fig. 4A using the level set algorithm results in a full-image segmentation result as shown in fig. 4B. The centerline of the target vessel is obtained by using a fast-marching algorithm on the basis of the original image of fig. 4A as shown in fig. 4C. And combining the full-graph segmentation result with the center line of the target blood vessel, and expanding the center line to obtain the final target blood vessel as shown in fig. 4D. Combining the blood vessel central line calculation and the level set image segmentation algorithm, the main steps for obtaining the segmentation result of the target 2D coronary artery target blood vessel comprise: 1) Preprocessing an original image to generate a binarized image; 2) Automatically (e.g., location selection) or interactively selecting at least two endpoints on the binarized image, including a first endpoint and a second endpoint, for each vessel in the target vessel/vessel tree; 3) Extracting a target vessel center line from the first endpoint to the second endpoint in the binarized image by using a fast marching algorithm; 4) Dividing the binarized image by using a level set dividing algorithm; 5) Carrying out standardization processing on the segmented image, and solving a corresponding distance image of the obtained image; 6) Calculating the shortest distance from the point on the central line to the blood vessel outline through the distance image; 7) Performing expansion operation on the central line of the blood vessel by using the shortest distance corresponding to each point to obtain a target blood vessel shape model; 8) And summing the segmentation result and the blood vessel shape model with specific weights to obtain the final target blood vessel.
In an alternative embodiment of the present application, calculating the central cardiac pulse pressure from at least one of the brachial artery pressure, the radial artery pressure, and the carotid artery pressure includes: the central cardiac pulse pressure is calculated from at least one of the brachial artery pressure, the radial artery pressure, and the carotid artery pressure by using a transfer function method, a one-dimensional hemodynamic method, or a Tube-Load method.
Specifically, the specific steps of the transfer function method include: 1) Collecting carotid artery pressure waveforms and brachial (radial) artery pressure waveform sets; 2) Construction of personal transfer function y (t) +a from radial artery to carotid artery based on autoregressive exogenous model 1 y(t-1)+…+a na y(t-na)＝b 1 u(t-nk)+…+b nb u (t-nb-nk+1) +e (t), where na, nb is the order of the model, nk is the time delay of the model, e (t) is white noise disturbance, u (t) is the input radial pressure, y (t) is the output carotid pressure; 3) And (3) averaging the personal transfer functions in all measured data sets to finally obtain a general transfer function (generalized transfer function), and applying the general transfer function to the clinically measured brachial artery blood pressure waveform to obtain the central cardiac pulse pressure waveform.
Specifically, the Tube-Load method comprises the following specific steps: 1) Establishing a Tube-Load model as shown in FIG. 6, wherein p c (T) is the pressure of the central artery pressure over time, T d Is the propagation time of the pulse wave from the central artery inlet to the measuring point (radial artery), Z c Is the characteristic impedance of the artery, R is the peripheral resistance; 2) According to the formulaCalculating the pulse wave reflection coefficient; 3) According to T d Physiological range of Γ, i.e. T d ∈[0,0.15](units: seconds), Γ ε [0,1 ]]At an interval of delta T d ＝5×10 -3 ,ΔΓ＝5×10 -2 Generation (T) d Γ) pairs; 4) Measuring a time-varying pressure waveform p at the brachial or radial artery r (t); 5) By the formula T-0.4 (1-e -2T ) Calculating a diastole interval corresponding to the central arterial pressure waveform, wherein T=60/HR, and HR is the number of beats per minute; 6) Each (T) d Γ) pairs according to the formula
Calculating a corresponding central artery pressure waveform, and smoothing the central artery pressure waveform through a low-pass filter; 7) For each pair (T) d The smoothed central cardiac pulse pressure waveform calculated by gamma) is subjected to logarithmic transformation, the pressure corresponding to the diastole interval is subjected to linear regression fit straight line, and all (T) are recorded d Gamma) fitting error for the pair; 8) The central artery pressure waveform with the minimum fitting error is the final required waveform.
The embodiment of the application also provides a detection device for the guide-wire-free FFR, the guide-wire-free IMR and the guide-wire-free CFR, and it is noted that the detection device for the guide-wire-free FFR, the guide-wire-free IMR and the guide-wire-free CFR can be used for executing the detection method for the guide-wire-free FFR, the guide-wire-free IMR and the guide-wire-free CFR provided by the embodiment of the application. The detection devices provided by the embodiments of the present application, namely, the filar-free FFR, the filar-free IMR, and the filar-free CFR, are described below.
Fig. 9 is a schematic diagram of a detection device for a no-guidewire FFR, no-guidewire IMR, and no-guidewire CFR according to an embodiment of the application. As shown in fig. 9, the apparatus includes:
a first acquiring unit 10 for acquiring a 2D coronary image of a blood vessel to be measured;
a first construction unit 20 for constructing a 3D vessel model from the 2D coronary images;
a second acquisition unit 30 for acquiring the central arterial pressure of the blood vessel to be measured by using a non-invasive measurement method;
a second constructing unit 40 for constructing a 3D coronary CFD model of the blood vessel to be measured based on at least the 3D blood vessel model and the central cardiac pulse pressure;
a calculation unit 50 for calculating a filar-free CFR, a filar-free FFR and a filar-free IMR from the above-described 3D coronary CFD model.
Specifically, the 2D coronary image may be a 2D coronary DSA image, and of course, may be another type of 2D coronary image other than the 2D coronary DSA image. The method has high efficiency, good robustness and good accuracy for calculating the functional index FFR/IMR/CFR of the blood vessel in the coronary DSA image, and can realize instant 3D blood vessel analysis.
Alternatively, the central arterial pressure of the blood vessel to be measured may be obtained by means of non-invasive measurement such as ultrasonic detection, nuclear magnetic detection, and a blood pressure measuring instrument capable of recording waveforms.
Specifically, the calculation results of the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR are displayed in real time, so that visualization is realized. The invention has good processing capacity, efficiency and precision for single or multiple coronary vessel trees. The overall treatment time for multiple vessels was less than 1 minute.
In the above scheme, the first acquisition unit acquires a 2D coronary image of a blood vessel to be measured, the first construction unit constructs a 3D blood vessel model according to the 2D coronary image, the second acquisition unit acquires a central arterial pressure of the blood vessel to be measured through a noninvasive measurement method, the second construction unit constructs a 3D coronary CFD model at least according to the 3D blood vessel model and the central arterial pressure, and the calculation unit calculates a guide wire-free CFR, a guide wire-free FFR and a guide wire-free IMR according to the 3D coronary CFD model. The whole scheme does not involve an invasive measurement method, and the noninvasive detection of CFR, FFR and IMR is realized by adopting an image auxiliary technology.
In one embodiment of the present application, the computing unit includes a first determining module, a first obtaining module, a first computing module, a second determining module, a third determining module, and a fourth determining module, where the first determining module is configured to determine a blood flow in a resting state according to a 3D blood vessel model in the resting state; the first acquisition module is used for acquiring blood flow in a hyperemic state; the first calculating module is used for calculating the guide wire-free CFR according to the blood flow in the resting state and the blood flow in the congestion state; the second determining module is used for determining the blood vessel distal pressure during maximum hyperemia and the blood vessel proximal pressure during maximum hyperemia according to the blood flow in the hyperemic state by applying the 3D coronary CFD model; the third determining module is used for determining the guide wire-free FFR according to the blood vessel distal end pressure during the maximum congestion and the blood vessel proximal end pressure during the maximum congestion; and the fourth determining module is used for determining the guide wire-free IMR according to the blood vessel distal pressure and the maximum blood flow rate in the maximum blood filling, wherein the maximum blood flow rate is the maximum value of the blood flow rate in the blood filling state.
In one embodiment of the present application, the second construction unit includes a fifth determining module and a first construction module, where the fifth determining module is configured to determine the pressure at the inlet of the blood vessel to be measured according to the central arterial pressure; the first construction module is used for constructing a 3D coronary CFD model under the blood vessel hyperemia state according to the 3D blood vessel model, the pressure at the inlet of the blood vessel to be measured and the blood flow under the hyperemia state. The 3D blood vessel model is obtained according to a 2D coronary image obtained in a resting state, the pressure at the inlet of the blood vessel to be measured is detected in a hyperemic state, and the 3D coronary CFD model in the hyperemic state is constructed. And obtaining the guide wire-free FFR and the guide wire-free IMR of the blood vessel according to the 3D coronary CFD model under the hyperemia state. Determining a blood vessel distal pressure at maximum hyperemia and a blood vessel proximal pressure at maximum hyperemia by using a 3D coronary CFD model in a hyperemic state, and determining the guide wire-free FFR according to the blood vessel distal pressure at maximum hyperemia and the blood vessel proximal pressure at maximum hyperemia; determining said filamentless IMR based on said maximum hyperemic vascular distal pressure and maximum hyperemic blood flow.
In one embodiment of the present application, the second obtaining unit includes a second obtaining module and a second calculating module, where the second obtaining module is configured to obtain the brachial artery pressure, the radial artery pressure and the carotid artery pressure by using the non-invasive measurement method; the second calculation module is used for calculating the central cardiac pulse pressure according to at least one of the brachial artery pressure, the radial artery pressure and the carotid artery pressure. Specifically, a non-invasive measurement manner may be adopted to obtain a brachial artery pressure waveform, a radial artery pressure waveform and a carotid artery pressure waveform, and then the above-mentioned central artery pressure is calculated according to at least one of the brachial artery pressure waveform, the radial artery pressure waveform and the carotid artery pressure waveform, so as to obtain an accurate central artery pressure.
In one embodiment of the present application, the second obtaining unit includes a third obtaining module, a fifth determining module, a third calculating module, a fourth obtaining module, a sixth determining module, an updating module, a seventh determining module, and an eighth determining module, where the third obtaining module is configured to obtain a parameter set of the blood vessel to be measured, where the parameter set includes geometric information, arterial inlet flow, an outlet boundary model, and a blood vessel elasticity model; the fifth determining module is used for determining a one-dimensional fluid mechanics model according to the parameter set; the third calculation module is used for calculating a first pressure waveform at a measuring point according to the one-dimensional fluid mechanics model, wherein the measuring point comprises a radial artery and a brachial artery; the fourth acquisition module is used for acquiring the second pressure waveform at the measuring point by using the non-invasive measurement method, wherein the non-invasive measurement method comprises an ultrasonic method and a nuclear magnetic method; the sixth determining module is configured to determine a target difference, where the target difference is a difference between the first pressure waveform and the second pressure waveform; the updating module is used for updating each parameter in the parameter set until the target difference value is smaller than the preset value under the condition that the target difference value is larger than or equal to the preset value; the seventh determining module is used for determining an optimized one-dimensional fluid mechanics model according to the updated parameter set; the eighth determining module is used for determining the central cardiac pulse pressure based on the optimized one-dimensional fluid mechanics model. In this embodiment, the first pressure waveform and the second pressure waveform are both pressure waveforms in a time domain, that is, the first pressure waveform and the second pressure waveform contain time sequence information, compared with the scheme that the radial artery pressure or the brachial artery pressure in the prior art is only one pressure value, compared with the scheme that the average arterial pressure is obtained by adopting a common empirical formula in the prior art (accuracy is irrelevant to time sequence), the scheme of the application is more accurate because of the time sequence waveforms; further ensuring the accuracy of the functional index of the blood vessel to be measured. In addition, by continuously adjusting each parameter in the parameter set until the target difference value is smaller than the preset value, the one-dimensional hydrodynamic model at the moment is determined to be closer to the real vascular hydrodynamic model under the condition that the target difference value is smaller, so that the central arterial pressure is determined more accurately based on the optimized one-dimensional hydrodynamic model.
In an embodiment of the present application, the 2D coronary image includes 2D coronary images under different angles, and the first construction unit includes an extraction module and a second construction module, where the extraction module is configured to extract a plurality of 2D target blood vessels from the 2D coronary images under different angles; the second construction module is used for constructing the 3D blood vessel model according to a plurality of the 2D target blood vessels. In particular, the number of 2D target vessels may be varied, including a single vessel, multiple vessels, and the entire coronary system. Reconstructing a 3D vessel model from a 2D target vessel at different angles comprises: 1) Correcting the position of the 2D target blood vessel segmentation result under different angles relative to the position of the light source to obtain a projection image corrected by the light source; 2) Constructing a space curved surface area according to the number of the light sources; 3) Intersecting a plurality of curved surface areas in a 3D space to obtain a space convex hull, namely an initial three-dimensional blood vessel model; 4) Acquiring an initial three-dimensional blood vessel central line, and calculating the radius of all points on the central line; 5) Performing central line expansion by using a given radius of each point on the central line to obtain an intermediate state blood vessel model; 6) And smoothing the vessel profile by using a smoothing algorithm to obtain a reconstructed final 3D vessel model.
In an embodiment of the present application, the extracting module is further configured to extract the 2D target vessel from the 2D coronary image by using a centerline acquisition algorithm and a level set image segmentation algorithm. Combining the blood vessel central line calculation and the level set image segmentation algorithm, the main steps for obtaining the segmentation result of the target 2D coronary artery target blood vessel comprise: 1) Preprocessing an original image to generate a binarized image; 2) Automatically (e.g., location selection) or interactively selecting at least two endpoints on the binarized image, including a first endpoint and a second endpoint, for each vessel in the target vessel/vessel tree; 3) Extracting a target vessel center line from the first endpoint to the second endpoint in the binarized image by using a fast marching algorithm; 4) Dividing the binarized image by using a level set dividing algorithm; 5) Carrying out standardization processing on the segmented image, and solving a corresponding distance image of the obtained image; 6) Calculating the shortest distance from the point on the central line to the blood vessel outline through the distance image; 7) Performing expansion operation on the central line of the blood vessel by using the shortest distance corresponding to each point to obtain a target blood vessel shape model; 8) And summing the segmentation result and the blood vessel shape model with specific weights to obtain the final target blood vessel.
The detection device for the guide wire-free FFR, the guide wire-free IMR and the guide wire-free CFR comprises a processor and a memory, wherein the first acquisition unit, the extraction unit, the reconstruction unit, the calculation unit, the second acquisition unit, the determination unit, the construction unit, the second calculation unit and the like are all stored in the memory as program units, and the processor executes the program units stored in the memory to realize corresponding functions.
The processor includes a kernel, and the kernel fetches the corresponding program unit from the memory. The kernel can be provided with one or more than one kernel, and the noninvasive detection of CFR, FFR and IMR by adopting the DSA image auxiliary technology is realized by adjusting kernel parameters.
The memory may include volatile memory, random Access Memory (RAM), and/or nonvolatile memory, such as Read Only Memory (ROM) or flash memory (flash RAM), among other forms in computer readable media, the memory including at least one memory chip.
The embodiment of the invention provides a computer readable storage medium, which comprises a stored program, wherein when the program runs, equipment where the computer readable storage medium is located is controlled to execute the detection methods of the guide wire-free FFR, the guide wire-free IMR and the guide wire-free CFR.
The embodiment of the invention provides a processor, which is used for running a program, wherein the detection methods of the guide wire-free FFR, the guide wire-free IMR and the guide wire-free CFR are executed when the program runs.
The embodiment of the invention provides equipment, which comprises a processor, a memory and a program stored in the memory and capable of running on the processor, wherein the processor realizes at least the following steps when executing the program:
step S101, acquiring a 2D coronary image of a blood vessel to be measured;
step S102, constructing a 3D blood vessel model according to the 2D coronary image;
step S103, obtaining the central arterial pressure of the blood vessel to be measured by using a noninvasive measurement method;
step S104, constructing a 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the central cardiac pulse pressure;
step S105, calculating a guide-wire-free CFR, a guide-wire-free FFR, and a guide-wire-free IMR according to the 3D coronary CFD model.
The device herein may be a server, PC, PAD, cell phone, etc.
The present application also provides a computer program product adapted to perform a program initialized with at least the following method steps when executed on a data processing device:
step S101, acquiring a 2D coronary image of a blood vessel to be measured;
Step S102, constructing a 3D blood vessel model according to the 2D coronary image;
step S103, obtaining the central arterial pressure of the blood vessel to be measured by using a noninvasive measurement method;
step S104, constructing a 3D coronary CFD model of the blood vessel to be measured at least according to the 3D blood vessel model and the central cardiac pulse pressure;
step S105, calculating a guide-wire-free CFR, a guide-wire-free FFR, and a guide-wire-free IMR according to the 3D coronary CFD model.
It will be appreciated by those skilled in the art that embodiments of the present application may be provided as a method, system, or computer program product. Accordingly, the present application may take the form of an entirely hardware embodiment, an entirely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, the present application may take the form of a computer program product embodied on one or more computer-usable storage media (including, but not limited to, disk storage, CD-ROM, optical storage, and the like) having computer-usable program code embodied therein.
The present application is described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the application. It will be understood that each flow and/or block of the flowchart illustrations and/or block diagrams, and combinations of flows and/or blocks in the flowchart illustrations and/or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions specified in the flowchart flow or flows and/or block diagram block or blocks.
These computer program instructions may also be stored in a computer-readable memory that can direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture including instruction means which implement the function specified in the flowchart flow or flows and/or block diagram block or blocks.
These computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide steps for implementing the functions specified in the flowchart flow or flows and/or block diagram block or blocks.
In one typical configuration, a computing device includes one or more processors (CPUs), input/output interfaces, network interfaces, and memory.
The memory may include volatile memory in a computer-readable medium, random Access Memory (RAM) and/or nonvolatile memory, etc., such as Read Only Memory (ROM) or flash RAM. Memory is an example of a computer-readable medium.
Computer readable media, including both non-transitory and non-transitory, removable and non-removable media, may implement information storage by any method or technology. The information may be computer readable instructions, data structures, modules of a program, or other data. Examples of storage media for a computer include, but are not limited to, phase change memory (PRAM), static Random Access Memory (SRAM), dynamic Random Access Memory (DRAM), other types of Random Access Memory (RAM), read Only Memory (ROM), electrically Erasable Programmable Read Only Memory (EEPROM), flash memory or other memory technology, compact disc read only memory (CD-ROM), digital Versatile Discs (DVD) or other optical storage, magnetic cassettes, magnetic tape magnetic disk storage or other magnetic storage devices, or any other non-transmission medium, which can be used to store information that can be accessed by a computing device. Computer-readable media, as defined herein, does not include transitory computer-readable media (transmission media), such as modulated data signals and carrier waves.
It should also be noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article or apparatus that comprises an element.
From the above description, it can be seen that the above embodiments of the present application achieve the following technical effects:
1) According to the detection method of the guide wire-free FFR, the guide wire-free IMR and the guide wire-free CFR, a 2D coronary image of a blood vessel to be measured is obtained, a 3D blood vessel model is built according to the 2D coronary image, the central arterial pressure of the blood vessel to be measured is obtained through a noninvasive measurement method, a 3D coronary CFD model is built at least according to the 3D blood vessel model and the middle cardiac pulse pressure, and finally the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR are calculated according to the 3D coronary CFD model. The whole scheme does not involve an invasive measurement method, and the noninvasive detection of CFR, FFR and IMR is realized by adopting an image auxiliary technology.
2) According to the detection device for the guide wire-free FFR, the guide wire-free IMR and the guide wire-free CFR, the first acquisition unit acquires a 2D coronary image of a blood vessel to be measured, the first construction unit constructs a 3D blood vessel model according to the 2D coronary image, the second acquisition unit acquires the central artery pressure of the blood vessel to be measured through a noninvasive measurement method, the second construction unit constructs a 3D coronary CFD model at least according to the 3D blood vessel model and the central artery pressure, and the calculation unit calculates the guide wire-free CFR, the guide wire-free FFR and the guide wire-free IMR according to the 3D coronary CFD model. The whole scheme does not involve an invasive measurement method, and the noninvasive detection of CFR, FFR and IMR is realized by adopting an image auxiliary technology.
The foregoing description is only of the preferred embodiments of the present application and is not intended to limit the same, but rather, various modifications and variations may be made by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims (9)

1. A method of detecting a filar-free FFR, a filar-free IMR, and a filar-free CFR, comprising:
acquiring a 2D coronary image of a blood vessel to be measured in a resting state;
constructing a 3D blood vessel model according to the 2D coronary image;
obtaining the central arterial pressure of the blood vessel to be measured, wherein the central arterial pressure of the blood vessel to be measured is obtained by using a noninvasive measurement method;
constructing a 3D coronary CFD model under the blood vessel hyperemia state to be measured at least according to the 3D blood vessel model and the central arterial pressure;
calculating a guide-wire-free CFR, a guide-wire-free FFR and a guide-wire-free IMR according to the 3D coronary CFD model;
obtaining the central arterial pressure of the blood vessel to be measured, comprising:
acquiring a parameter set of the blood vessel to be measured, wherein the parameter set comprises geometric information, arterial inlet flow, an outlet boundary model and a blood vessel elasticity model;
Determining a one-dimensional hydrodynamic model according to the parameter set;
calculating a first pressure waveform at a measuring point according to the one-dimensional fluid mechanics model, wherein the measuring point comprises a radial artery and a brachial artery;
acquiring a second pressure waveform at the measuring point, wherein the second pressure waveform is acquired by adopting the noninvasive measuring method, and the noninvasive measuring method comprises an ultrasonic method and a nuclear magnetic method;
determining a target difference value, wherein the target difference value is a difference value between the first pressure waveform and the second pressure waveform;
updating each parameter in the parameter set until the target difference is smaller than a preset value under the condition that the target difference is larger than or equal to the preset value;
determining an optimized one-dimensional fluid mechanics model according to the updated parameter set;
and determining the central cardiac pulse pressure based on the optimized one-dimensional fluid mechanics model.
2. The method of detection of claim 1, wherein calculating a filar-free CFR, a filar-free FFR, and a filar-free IMR from the 3D coronary CFD model comprises:
determining blood flow in a resting state according to the 3D blood vessel model in the resting state;
obtaining blood flow in a hyperemic state;
Calculating the guide wire-free CFR according to the blood flow in the resting state and the blood flow in the congestion state;
applying the 3D coronary CFD model, and determining the blood vessel distal pressure during maximum hyperemia and the blood vessel proximal pressure during maximum hyperemia according to the blood flow in the hyperemic state;
determining the guide wire-free FFR based on the maximum hyperemic vascular distal pressure and the maximum hyperemic vascular proximal pressure;
and determining the guide wire-free IMR according to the blood vessel distal pressure at the time of maximum congestion and the maximum blood flow rate of congestion, wherein the maximum blood flow rate of congestion is the maximum value of the blood flow rate in the congestion state.
3. The method according to claim 2, wherein constructing the 3D coronary CFD model of the vessel to be measured based at least on the 3D vessel model and the central arterial pressure comprises:
determining the pressure at the inlet of the blood vessel to be measured according to the central arterial pressure;
and constructing a 3D coronary CFD model of the blood vessel to be measured in the congestion state according to the 3D blood vessel model, the pressure at the inlet of the blood vessel to be measured and the blood flow in the congestion state.
4. The method according to claim 1, wherein obtaining the central arterial pressure of the blood vessel to be measured comprises:
Acquiring brachial artery pressure, radial artery pressure and carotid artery pressure, wherein the brachial artery pressure, radial artery pressure and carotid artery pressure are acquired by adopting the noninvasive measurement method;
the central arterial pressure is calculated from at least one of the brachial artery pressure, the radial artery pressure, and the carotid artery pressure.
5. The method of claim 1, wherein the 2D coronary images comprise 2D coronary images at different angles, and constructing a 3D vessel model from the 2D coronary images comprises:
extracting a plurality of 2D target blood vessels from the 2D coronary images under different angles;
the 3D vessel model is constructed from a plurality of the 2D target vessels.
6. The method of claim 5, wherein extracting the 2D target vessel from the 2D coronary image comprises:
and extracting the 2D target blood vessel from the 2D coronary artery image by adopting a central line calculation algorithm and a level set image segmentation algorithm.
7. A guidewire-free FFR, guidewire-free IMR, and guidewire-free CFR detection device, comprising:
the first acquisition unit is used for acquiring a 2D coronary image under the state of resting a blood vessel to be measured;
A first construction unit for constructing a 3D vessel model from the 2D coronary images;
a second acquisition unit configured to acquire a central arterial pressure of the blood vessel to be measured, where the central arterial pressure of the blood vessel to be measured is acquired by using a non-invasive measurement method;
a second construction unit, configured to construct a 3D coronary CFD model under the blood vessel hyperemia state to be measured according to at least the 3D blood vessel model and the central arterial pressure;
a computing unit for computing a guide-wire-free CFR, a guide-wire-free FFR and a guide-wire-free IMR according to the 3D coronary CFD model;
the second acquisition unit comprises a third acquisition module, a fifth determination module, a third calculation module, a fourth acquisition module, a sixth determination module, an updating module, a seventh determination module and an eighth determination module,
the third acquisition module is used for acquiring a parameter set of the blood vessel to be measured, wherein the parameter set comprises geometric information, arterial inlet flow, an outlet boundary model and a blood vessel elasticity model;
the fifth determining module determines a one-dimensional fluid mechanics model according to the parameter set;
the third calculation module is used for calculating a first pressure waveform at a measuring point according to the one-dimensional fluid mechanics model, and the measuring point comprises a radial artery and a brachial artery;
The fourth acquisition module is used for acquiring a second pressure waveform at the measuring point, wherein the second pressure waveform is acquired by adopting the noninvasive measurement method, and the noninvasive measurement method comprises an ultrasonic method and a nuclear magnetic method;
the sixth determining module is configured to determine a target difference, where the target difference is a difference between the first pressure waveform and the second pressure waveform;
the updating module is used for updating each parameter in the parameter set until the target difference value is smaller than the preset value under the condition that the target difference value is larger than or equal to the preset value;
the seventh determining module is used for determining an optimized one-dimensional fluid mechanics model according to the updated parameter set;
the eighth determination module is configured to determine the central cardiac pulse pressure based on the optimized one-dimensional hydrodynamic model.
8. A computer readable storage medium, characterized in that the computer readable storage medium comprises a stored program, wherein the program when run controls a device in which the computer readable storage medium is located to perform the detection method of any one of claims 1 to 6 without a guide wire FFR, without a guide wire IMR and without a guide wire CFR.
9. A processor, characterized in that the processor is adapted to run a program, wherein the program when run performs the detection method of the filar-free FFR, the filar-free IMR and the filar-free CFR of any of claims 1 to 6.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103300820A (en) * 2012-03-13 2013-09-18 西门子公司 Method and system for non-invasive functional assessment of coronary artery stenosis
CN107928655A (en) * 2017-12-14 2018-04-20 江苏理工学院 A kind of central aortic blood pressure measuring method based on human body artery 3D blood vessel network models
CN110367965A (en) * 2018-09-19 2019-10-25 苏州润迈德医疗科技有限公司 The method, apparatus and system of convenient measurement coronary artery assessment parameters
CN111067494A (en) * 2019-12-27 2020-04-28 西北工业大学 Microcirculation resistance rapid calculation method based on blood flow reserve fraction and blood flow resistance model

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107730540B (en) * 2017-10-09 2020-11-17 全景恒升（北京）科学技术有限公司 Coronary parameter calculation method based on high-precision matching model

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103300820A (en) * 2012-03-13 2013-09-18 西门子公司 Method and system for non-invasive functional assessment of coronary artery stenosis
CN107928655A (en) * 2017-12-14 2018-04-20 江苏理工学院 A kind of central aortic blood pressure measuring method based on human body artery 3D blood vessel network models
CN110367965A (en) * 2018-09-19 2019-10-25 苏州润迈德医疗科技有限公司 The method, apparatus and system of convenient measurement coronary artery assessment parameters
CN111067494A (en) * 2019-12-27 2020-04-28 西北工业大学 Microcirculation resistance rapid calculation method based on blood flow reserve fraction and blood flow resistance model

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