US20140313515A1 - Correlation of concurrent non-invasively acquired signals - Google Patents

Correlation of concurrent non-invasively acquired signals Download PDF

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US20140313515A1
US20140313515A1 US13/261,848 US201213261848A US2014313515A1 US 20140313515 A1 US20140313515 A1 US 20140313515A1 US 201213261848 A US201213261848 A US 201213261848A US 2014313515 A1 US2014313515 A1 US 2014313515A1
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target
light field
imaging device
radiation
interference signal
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Joshua (Josh) Noel Hogan
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Compact Imaging Inc
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Compact Imaging Inc
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00—Measuring instruments characterised by the use of optical techniques
    • G01B9/02—Interferometers
    • G01B9/0209—Low-coherence interferometers
    • G01B9/02091—Tomographic interferometers, e.g. based on optical coherence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/0016—Operational features thereof
    • A61B3/0025—Operational features thereof characterised by electronic signal processing, e.g. eye models
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/102—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for optical coherence tomography [OCT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/12—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for looking at the eye fundus, e.g. ophthalmoscopes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
    • A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
    • A61B3/14—Arrangements specially adapted for eye photography
    • 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
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/117—Identification of persons
    • A61B5/1171—Identification of persons based on the shapes or appearances of their bodies or parts thereof
    • A61B5/1172—Identification of persons based on the shapes or appearances of their bodies or parts thereof using fingerprinting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement

Definitions

  • the invention relates to non-invasive analysis in general.
  • the invention relates to optical techniques involving both infra-red and shorter wavelength (visible or ultra violet) radiation for imaging and analyzing surface and sub-surface structures; and relates to the use of Optical Coherence Tomography (OCT) for sub-surface imaging and analysis.
  • OCT Optical Coherence Tomography
  • Non-invasive analysis which for purposes of this application includes non-destructive analysis, is a valuable technique for acquiring information about systems or targets without undesirable side effects, such as damaging the system being analyzed.
  • Non-invasive analysis has a broad range of applications including, non-destructive analysis of artifacts for defects, verification of the authenticity of documents, such as, bank notes, biometric analysis and bio-medical analysis of living entities.
  • undesirable side effects of invasive analysis include the risk of infection along with pain and discomfort associated with the invasive process.
  • OCT optical coherence tomography
  • Time Domain or TD-OCT of which Multiple Reference OCT or MRO is a particular variation (described in more detail in two of the U.S. Pat. Nos. 7,526,329 and 7,751,862 incorporated herein by reference; Spectral Domain or SD-OCT; Fourier Domain or FD-OCT.
  • OCT will include any interferometric system including, but not limited to, the above-mentioned OCT variations.
  • OCT imaging or analysis consists of (a) generating probe radiation, at least a portion of which is applied to a target to generate back-scattered radiation; (b) generating reference radiation; (c) combining at least a portion of the back-scattered radiation and the reference radiation to produce at least one interference signal; (d) detecting the resulting interference signal by means of a detector; (e) extracting information from the detected interference signal; and (f) processing the extracted information to generate one or more depth scans of the target which may be further processed to determine an attribute of the target.
  • Attributes of a target that can be determined by OCT include, but are not limited, to the following: a depth scattering profile; structural aspects such as layer thicknesses; a one, two or three dimensional image of the target; concentration of an analyte such as glucose concentration.
  • Such an image of the target area can be derived, for example, from a conventional charged coupled device (CCD) detector and displayed on a conventional LCD or TFT display (liquid crystal display (LCD) or thin film technology (TFT) display).
  • CCD charged coupled device
  • LCD liquid crystal display
  • TFT thin film technology
  • Provisional application, docket number CI111101PR also incorporated herein by reference describes generating a first image of a target using a conventional camera and by synchronously illuminating the target with at least one specific wavelength while performing at least one interferometric based depth scan by means of an interferometric device (such as an OCT system) at a location within the target wherein the location of the depth scan is registered with the first image.
  • an interferometric device such as an OCT system
  • the use of a conventional camera or imaging device requires that the camera be focused correctly to obtain a clear image of the target while the OCT system has to be correctly depth aligned to obtain depth measurements of the target at the appropriate depth.
  • the problem of acquiring a well focused image while also correctly depth aligning the OCT system is further complicated in the particular application requiring a image of the retina of an eye while also acquiring biometry or depth images of the retina by means of an OCT system.
  • the axial length of an eye can vary significantly from eye to eye.
  • a variation in axial length affects both focusing and depth alignment of the OCT system.
  • a fundus camera is currently used in conjunction with an OCT system to make retinal measurements at known locations.
  • the focusing requirements of a fundus camera require either a complex alignment system or a trained operator.
  • Digital Light Field Photography is well known. Recent developments in computer science and fabrication techniques of detector and micro-lens arrays make Digital Light Field Photography technical feasible for consumer devices. A good treatment of Digital Light Field Photography may be found in the dissertation of Ren Ng, entitled “Digital Light Field Photography”, copyright 2006 submitted to Stanford University in partial fulfillment of the requirements for the degree of doctor of philosophy.
  • Digital Light Field Photography does not require a skilled operator for focusing. Moreover Digital Light Field Photography provides information regarding the distances between images that can be used to facilitate alignment.
  • integrating a plenoptic camera (i.e. field of light imaging device) with an OCT system is full of difficulties, not the least of which is ensuring the OCT system is correctly depth aligned with the region of interest in the target.
  • the invention is a method, apparatus and system for non-invasive analysis.
  • the invention includes an optical source and an optical processing system that provides probe and reference radiation. It also includes a means that applies the probe beam to the target to be analyzed, re-combines a portion of the scattered probe and the reference beams interferometrically, to generate one or more concurrent interferometric signals that are detected and processed.
  • the location within the target to which an interference signal relate is aligned and registered with respect to the target by means of a field of light imaging device (i.e. a plenoptic camera also commonly referred to as a light field camera or a light field imaging device).
  • a field of light imaging device i.e. a plenoptic camera also commonly referred to as a light field camera or a light field imaging device.
  • An embodiment of determining an attribute of a target comprises the steps of generating probe radiation; applying at least a portion of the probe radiation to the target to generate back-scattered radiation; generating reference radiation; combining the back-scattered radiation and the reference radiation to produce at least one interference signal; detecting the interference signal by means of a detector; extracting concurrent information from the detected interference signal; acquiring a light field based image of the target using a light field imaging device; registering the concurrent information extracted from the detected interference signal with the light field based image; and outputting data.
  • a preferred embodiment for a system comprises a system for determining an attribute of a target, said system comprising: an optical system for generating probe radiation and reference radiation, and configured to apply at least a portion of the probe radiation to the target to generate back-scattered radiation and configured to combine the back-scattered radiation with the reference radiation to produce an interference signal; a detector that detects the interference signal from which interference signal concurrent information is extracted, and where the concurrent information is used by a processing and control module to register the optical image (derived from one or more OCT scans) with a light field image of the target; a light field imaging device coupled to the optical system, and positioned to acquire a light field image of the target; a light field optical source illuminating the scene of the target; an illumination module functionally coupled to the light field imaging device and the light field optical source, so as to control illumination of the target scene; a mirror coupled to the optical system and the light field imaging device, where the mirror is transmissive at wavelengths of the optical system probe radiation and reflective at wavelengths illumina
  • the inventive system and method are suitable for determining attributes of targets, such as, for example, measurement of layer thickness of tissue, or the concentration of glucose within human tissue.
  • targets such as, for example, measurement of layer thickness of tissue, or the concentration of glucose within human tissue.
  • the invention is not limited to in vivo analysis.
  • FIG. 1 is an illustration depicting ophthalmic application, of the overall analysis system according to the invention.
  • FIG. 2 is an illustration of the steps of the inventive method in an ophthalmic application, using the overall analysis system represented in FIG. 1 .
  • FIG. 3 is an illustrative flowchart of a variation of the method represented in FIG. 2 .
  • FIG. 4 is an illustrative flowchart of an alternate embodiment of the inventive method, using registration marks and where the output is in the form of data.
  • FIG. 5 is an illustrative flowchart of an alternate embodiment of the inventive method of FIG. 4 , where the output in in the form of an image.
  • FIG. 6 is an illustrative flowchart of an alternate embodiment of the inventive method of FIG. 4 , where the target is skin tissue and the analyte is glucose.
  • FIG. 7 depicts a system according to the invention, in an application where the target is tissue.
  • the invention taught herein is an imaging or analysis system suitable for non-invasive sub-surface imaging or measurement with robust alignment.
  • the preferred embodiment is illustrated in and described with respect to FIG. 1 of Sheet 1 .
  • An interferometric system such as an OCT system 101 generates probe and reference radiation and applies at least a portion of the probe radiation to the target 103 , which in a preferred embodiment is an eye.
  • At least some of the probe radiation is scattered within the target (typically at refractive discontinuities, such as occur at layer boundaries). A portion of the scattered probe radiation is scattered back in the direction of the OCT system 101 to form back-scattered radiation.
  • the OCT system 101 also generates reference radiation that it combines with the reference radiation to produce one or more interference signal which is detected by a detector. Suitable detectors include, a photo-diode, a multi-segment diode, or a photo-diode array including but not limited to a CCD (Charged Coupled Device).
  • CCD Charged Coupled Device
  • interference signal includes: a substantially single frequency interference signal; a composite interference signal with more than one frequency present; raw or processed versions of interference signals, such as their envelopes, etc.
  • the detected interference signal is processed to extract information related to the attribute of the target.
  • an attribute of interest is the thickness of the retinal nerve fiber layer (BNFL) as the thickness of this layer can provide valuable information regarding the onset of glaucoma.
  • the distance between the inner limiting membrane (INL) and the retinal pigment epithelium (RPE) is valuable as the thickness of this layer can provide valuable information regarding the onset or progression of age related macular degeneration.
  • the layer boundary positions In order to accurately measure attributes (such as those mentioned above) of the target, the layer boundary positions must be measured simultaneously or at high speed with respect to motion of the target to minimize motion artifacts.
  • the information extracted from interference signals that are acquired either at high speed or simultaneously is referred to herein as concurrent information.
  • concurrently includes simultaneously or at a high speed with respect to motion artifacts.
  • concurrent signals includes simultaneous signals and also signals occurring at a high speed with respect to motion artifacts, thereby making such signals substantially insensitive to motion artifacts.
  • location of the site at which the attribute of the target is being measured refers to the point on a surface of the target that is capable of being imaged by non-interferometric means and through which the probe beam passes.
  • location of the site at which the attribute of the target is being measured would be the point at which the probe radiation enters the front surface of the retina.
  • the location of a measurement site can be determined by using a conventional camera or imaging device in conjunction with the interferometric or OCT measuring system and where the probe radiation of the OCT system has a known (or determined) alignment relationship with the imaging device.
  • the image generated by a non-interferometric imaging device is herein referred to as a spatial image.
  • the location of the interferometric measurement can then be determined from the registration marks in the spatial image, as described in U.S. Pat. No. 7,248,907 (incorporated herein by reference).
  • the location of measurement sites may be identified by using characteristics of the target.
  • Such characteristics include, but are not limited to: blood vessels; finger prints; freckles; or edges of tissue blemishes; artificial marks such as tattoos; and in the specific case of the retina of an eye being a target, a fovea pit; an optic nerve; defects in an eye (layer separation, fovea deformations, etc.). For purposes of this application these characteristics are referred to as registration marks.
  • the spatial image is a light field based image (alternately referred to as a field of light based image) that is acquired by a light field imaging device (alternately referred to as a field of light imaging device).
  • a light field imaging device also referred to as a plenoptic camera, is a camera that uses a micro lens array to capture 4D light field information about a scene.
  • a light field based image that is acquired by a light field based imaging device is referred to as a target scene.
  • a light field imaging device or plenoptic camera captures the entire light field, which consists of substantially all of the light traveling in every direction in every point in space from the target.
  • a light field imaging device does not require focusing.
  • the data acquired by the field of light imaging device can be processed to produce well-focused spatial images of multiple aspects of the target scene.
  • the data acquired by the light field imaging device is processed to generate a well focused spatial image of the retina while also the same data may be processed to generate one or more well focused spatial images of the anterior chamber region of the eye.
  • some of the meta data developed in generating the well-focused spatial images of the retina and of the anterior chamber region of the eye provides information regarding the distance between these images.
  • images and meta data generated or developed in processing the data acquired by the field of light imaging device can be used to: (a) align the combined light field imaging device and the OCT with the eye such that the OCT system will measure at the desired location or set of locations; (b) depth align of the OCT system with the region of interest within the retina; and (c) measure separation distances.
  • the light field imaging device 105 collects light from the target scene, in this case the eye 103 , that is reflected to the light field imaging device 105 by a mirror 107 that is coated to be reflective at wavelengths illuminating the target scene 103 by means of optical sources, such as LEDs, two of which are 109 and 111 and controlled by an illumination module 113 .
  • optical sources such as LEDs, two of which are 109 and 111 and controlled by an illumination module 113 .
  • the light field imaging device 105 can thereby acquire the data to generate spatial images of front regions of the eye, such as the cornea 117 and also the front of the retina in the region indicated by the double arrow 119 .
  • the mirror 107 is also transmissive at the wavelength of the OCT probe radiation 115 thereby enabling the OCT system 101 to generate interference signals related to the retina at the location 121 .
  • a processing and control module 123 controls the illumination module 113 , the light field imaging device 105 and the OCT system 101 .
  • the processing and control module 123 also acquires data from the light field imaging device 105 and the OCT system 101 .
  • the processing and control module 123 processes the acquired data to generate information to align the overall imaging and analysis system and to align the OCT system with respect to the retinal region of the eye.
  • the processing and control module processes data from the field of light imaging device to perform a measurement of an attribute of interest (such as a separation distance).
  • the processing and control module 123 also provides data to one or more display modules 125 .
  • the display modules 125 may include local or remote displays or a combination of local and remote displays.
  • One or more local displays can be used by the subject of the ophthalmic analysis or by a caregiver.
  • Data may also be transmitted for display or archival storage and display at a later time.
  • Displayed information can include, but is not limited to: an image of at least a portion of the fundus of the eye (i.e. the interior surface of the eye, opposite the lens optic disc, macula and fovea, and posterior pole); a one, two or three dimensional image of a region of the retinal area; an image of the fundus image of the eye with a clear indication of the location of one or more measurements of an attribute of the eye; a numerical or graphical representation of one or more measurements of an attribute of the eye; one or more images of the anterior chamber of the eye.
  • an image of at least a portion of the fundus of the eye i.e. the interior surface of the eye, opposite the lens optic disc, macula and fovea, and posterior pole
  • a one, two or three dimensional image of a region of the retinal area an image of the fundus image of the eye with a clear indication of the location of one or more measurements of an attribute of the eye
  • Relevant attributes of the eye include, but are not limited to: the thickness of one or more layers of the retina; the axial length of the eye; the thickness of one or more regions of the cornea; corneal angles; corneal curvature; the thickness of one or more regions of the crystalline lens.
  • displayed information can also include a fixation image (which may be a point image) which may be used to induce the eye of the subject to be appropriately aligned with respect to the OCT system, so that a desired location can be analyzed by the OCT system.
  • a fixation image which may be a point image
  • a display visible to the fellow eye of the subject of ophthalmic analysis can display information that can include a fixation image.
  • FIG. 7 depicts the inventive system as in FIG. 1 , wherein a tissue contains the target scene: a tissue depth 708 extending from the surface 717 of the target to a second surface 721 deeper within the tissue.
  • FIG. 7 also depicts the surface tissue layer thickness 719 , typically the epidermis.
  • 723 represents structures located between the surface 717 and the deeper surface 721 . In an embodiment where 717 is epidermis, structures 723 is commonly a blood vessel or a membrane.
  • System components 101 through 123 are as set forth in the discussion of FIG. 1 . It can be appreciated that the method as set forth in FIG. 6 can be understood in terms of glucose as such an analyte of interest, where glucose concentration is determined from scattering profiles due to scattering by structures within the target, such as 723 , FIG. 7 . Attention is hereby called to the numbering in the figures, wherein elements and steps typically retain an assigned number when repeated in subsequent figures.
  • FIG. 2 of Sheet 2 An example of the steps by which the overall system would be used to perform an ophthalmic analysis of a subject is described in FIG. 2 of Sheet 2 , and alternate embodiments in FIGS. 3 through 6 , and consists of the following steps:
  • Step 1 acquiring and processing light field data related to the target scene (step 201 , FIG. 2 ); in the alternate embodiment of FIG. 6 , the target scene is skin tissue (step 601 ).
  • Step 2. aligning the overall analysis system with respect to the target scene (where the “overall analysis system includes the light field imaging system and the OCT system) (step 202 , FIG. 2 ); in an alternate embodiment as depicted in FIG. 3 , step 302 , meta data generated by the light field data is used to align the overall analysis system with respect to the target scene; in the alternate embodiment of FIG. 6 , step 602 , this step is performed with respect to skin tissue.
  • Step 3. using meta data generated by processing the light field data to depth align the OCT system (step 203 , FIG.
  • Step 4 guiding the subject's eye to align probe one or more locations using an illuminated fixation point (where such guidance is implemented by displaying a fixation image such that it is visible to the eye being analyzed or its fellow eye and where such guidance locates the region of interest, referred to as a target site, of the target in the path of the OCT probe radiation) (step 204 , FIG. 2 ); in alternate embodiments, depicted in FIGS.
  • the probe is aligned with one or more locations in the target scene using identified registration marks—see steps 404 and 604 .
  • Step 5. acquiring one or more data sets from one or more selected target sites using the OCT system (step 205 , FIG. 2 ); in FIG. 6 , this step is numbered 605 .
  • Step 6. processing one or more data sets acquired by the OCT system to determine an attribute of the target (and where the data related to the attribute of the target may be correlated with previously acquired data, for the purpose of averaging in the case of recent previously acquired data, or for the purpose of monitoring for change in the case of archived previously acquired data) (step 206 , FIG. 2 ); in FIG.
  • Step 6 this step appears as step 606 , the data sets acquired by the OCT system are processed to determine glucose concentration;
  • Step 7. displaying an image of the target scene in conjunction with a value and location of the target attribute (where such displaying may be local so as to be visible to the subject or a caregiver, or remote so as to be visible to a physician or other interested party) (step 207 , FIG. 2 ).
  • output is either a value of the attribute of the target ( FIG. 4 , step 407 ), an image of the attribute of the target ( FIG. 5 , step 507 ), or a glucose concentration value ( FIG. 6 , step 607 ).
  • the above description is intended to be illustrative and not restrictive.
  • the invention can be used in many different applications including, but not limited to: bio-metric imaging or analysis of skin tissue; defect analysis of artifacts; authentication of documents, such as bank notes; monitoring glucose levels non-invasively.
  • identification of individuals may be made more accurate by combining a three dimensional map of skin and sub-surface tissue with conventional fingerprint analysis techniques.
  • fingerprint includes a conventional fingerprint and the three dimensional map of skin, sub-surface tissue and any substance in proximity to the surface of the skin.
  • artifacts such as, plastic or ceramic parts, biological enzymes, or semiconductor components can be analyzed to ensure they are defect free.
  • an advantage of this approach is that internal sub-surface or embedded characteristics can be analyzed and used to authenticate the note.
  • the source of optical probe and reference radiation can be an SLD; a wavelength tunable laser; a mode-locked laser; a VCSEL (Vertical Cavity Surface Emitting Laser), an LED; or arrays of such devices.
  • the selection of the source is related to the type of OCT system being used.
  • LEDs as the illuminating light
  • structured illumination could be used to extract more detailed information from target surfaces.
  • the practitioner of average skill can appreciate that although the preferred embodiment discussed herein is an in vivo application of the method and system, the invention is applicable to target analysis where the target is tissue other than the eye, and analysis is other than in vivo analysis.
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US8888284B2 (en) 2014-11-18
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US20140002794A1 (en) 2014-01-02
WO2013067468A1 (fr) 2013-05-10

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