WO2015089308A1 - Apparatus and method for high-speed full field optical coherence microscopy - Google Patents

Apparatus and method for high-speed full field optical coherence microscopy Download PDF

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Publication number
WO2015089308A1
WO2015089308A1 PCT/US2014/069800 US2014069800W WO2015089308A1 WO 2015089308 A1 WO2015089308 A1 WO 2015089308A1 US 2014069800 W US2014069800 W US 2014069800W WO 2015089308 A1 WO2015089308 A1 WO 2015089308A1
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Prior art keywords
radiation
arrangement
radiations
anatomical structure
photodetector
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PCT/US2014/069800
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French (fr)
Inventor
Guillermo J. Tearney
Ali Motafakker-Fard
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The General Hospital Corporation
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Publication of WO2015089308A1 publication Critical patent/WO2015089308A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/02034Interferometers characterised by particularly shaped beams or wavefronts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/05Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances characterised by the image sensor, e.g. camera, being in the distal end portion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/06Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
    • A61B1/0661Endoscope light sources
    • A61B1/0676Endoscope light sources at distal tip of an endoscope
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062Arrangements for scanning
    • A61B5/0066Optical coherence imaging
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01BMEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
    • G01B9/00Measuring instruments characterised by the use of optical techniques
    • G01B9/02Interferometers
    • G01B9/0209Low-coherence interferometers
    • G01B9/02091Tomographic interferometers, e.g. based on optical coherence
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4795Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B23/00Telescopes, e.g. binoculars; Periscopes; Instruments for viewing the inside of hollow bodies; Viewfinders; Optical aiming or sighting devices
    • G02B23/24Instruments or systems for viewing the inside of hollow bodies, e.g. fibrescopes
    • G02B23/2407Optical details
    • G02B23/2461Illumination
    • G02B23/2469Illumination using optical fibres
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B23/00Telescopes, e.g. binoculars; Periscopes; Instruments for viewing the inside of hollow bodies; Viewfinders; Optical aiming or sighting devices
    • G02B23/24Instruments or systems for viewing the inside of hollow bodies, e.g. fibrescopes
    • G02B23/26Instruments or systems for viewing the inside of hollow bodies, e.g. fibrescopes using light guides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233Special features of optical sensors or probes classified in A61B5/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6848Needles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/6852Catheters
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4788Diffraction
    • G01N2021/479Speckle
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/06Illumination; Optics
    • G01N2201/067Electro-optic, magneto-optic, acousto-optic elements

Definitions

  • the present disclosure relates generally to exemplary methods and apparatus for providing optical coherence microscopy, and more particularly, to exemplary embodiments of methods and apparatus for providing and/or utilizing compressive sensing, single-pixel detectors, and optical image amplification for high-speed full-field optical coherence microscopy.
  • Optical microscopy is an important technique/modality for probing living specimens with a subcellular resolution.
  • imaging modality can facilitate a visualization of vital behavior and morphological details of cells in culture or in tissue.
  • progress in understanding of their physics has been hindered by an apparent inability to observe the cellular structure and dynamics with fine three-dimensional spatial and/or temporal resolution.
  • a microscopy paradigm capable of providing fine three-dimensional spatial and temporal resolution in a highly scattering tissue can be of a high demand in medicine and biology.
  • Full-field optical coherence microscopy (FFOCM) modality is a wide-field high-resolution form of optical coherence tomography that can be useful for analyzing a microstructural morphology of biological specimen with a sub-cellular resolution deep within the tissue.
  • FFOCM systems use a spatially incoherent source and an array detector, such as, e.g., a charge-coupled device (CCD) and complementary metal-oxide- semiconductor (CMOS) imaging sensors to generate en face image of sample under test.
  • CCD charge-coupled device
  • CMOS complementary metal-oxide- semiconductor
  • an exemplary image acquisition speed of the FFOCM systems can be limited by that of the imaging sensor. This possible limitation can be a result of the fundamental trade- off between detection sensitivity and frame rate. For example, at high frame rates, fewer photons are collected, thus likely leading to a lower sensitivity.
  • exemplary methods and apparatus can be provided, which can facilitate an implementation of the highspeed FFOCM using compressive sensing.
  • Another one of the objects of the present disclosure is to provide an endoscope-based approach to perform optical coherence microscopy.
  • exemplary methods and apparatus can be provided, which enable the implementation of full-field optical coherence microscopy of anatomical structures in an endoscope or a needle.
  • the illumination light or other electro- magentic radiation can be spatially and/or temporally modulated.
  • the modulated light or other electro-magnetic radiation can enter the interferometer in which it is illuminated onto the tissue.
  • Back-scattered light and/or the other electro-magnetic radiation can be collected using a single-pixel detector. For example, multiple acquisitions can be performed to reconstruct images.
  • the interfered signal from the output of the interferometer can be collected by a single-pixel photodetector.
  • An exemplary signal processing procedure can be performed digitally to reconstruct an image.
  • Use of the exemplary single-pixel detector can facilitate an optical amplification to be performed before the photodetection. Accordingly, such exemplary procedure(s) and/or configuration(s) can improve the sensitivity and frame rate, while maintaining a beneficial and/or improved isotropic high spatial resolution, and thus can address and/or overcome the fundamental trade-off discussed above, achieving high frame rates.
  • Another exemplary objects of the present disclosure is to provide exemplary method and apparatus to perform an optical signal amplification for a significant sensitivity enhancement in compressive FFOCM.
  • an optical amplifier (which can be modified according to an exemplary embodiment of the present disclosure) can be used to amplify the optical signal which contains the image, prior to the photodetection.
  • apparatus and process for facilitating a full-field microscopic imaging of at least one anatomical structure can be provided.
  • an interferometric arrangement it is possible to (i) receive a first radiation from a reference arm and a second radiation from the anatomical structure(s), and (ii) generate a third radiation.
  • the first radiation and/or the second radiation can be modulated using at least one of a rotating diffuser, a spatial light modulator or a speckle -pattern modulator.
  • the third radiation can be a combination of the first and second radiations.
  • a single -pixel photodetector arrangement can be used to receive and detect the third radiation for facilitating the full-field microscopic imaging of the anatomical structure(s).
  • the apparatus can include a number of photodetectors that is less than a number of pixels of the at least one image of the at least one anatomical structure.
  • a computer arrangement can be provided that can be configured to digitally construct at least one image of at least one portion of the anatomical structure(s) using data generated by the photodetectors arrangement.
  • a modulation arrangement can be provided which can include at least one of a rotating diffuser, a spatial light modulator or a speckle-pattern modulator.
  • the apparatus can include a signal amplification arrangement that can be configured to receive and amplify the third radiation.
  • the signal amplification arrangement can be provided in a communication path between the interferometric arrangement and the photodetector arrangement, and can detect the amplified third radiation.
  • a computer arrangement can be provided that can be configured to digitally construct at least one image of at least one portion of the anatomical structure(s) using data generated by the photodetector arrangement based on the amplified third radiation.
  • apparatus and process can be provided for imaging of at least one anatomical structure.
  • an interferometric arrangement it is possible to receive a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generate a third radiation at a first time and a fourth radiation at a second time.
  • the first and/or second radiations can be spatially modulated, and each of the third and fourth radiations canbe a respective combination of the first and second radiations at the first and second times, respectively.
  • a photodetector arrangement it is possible to receive and detect:
  • a computer arrangement including data acquisition and compressive sensing procedure via, for example, pseudo-inverse, lo optimization, /; optimization, or greedy pursuit algorithms and/or procedures can be utilized to facilitate and reconstruct at least one portion of one image of at least one anatomical structure.
  • FIG. 1 is a diagram of a compressive FFOCM system according to an exemplary embodiment of the present disclosure
  • FIG. 2 is a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure which utilizes an optical amplification enabling high detection sensitivity;
  • FIG. 3 is a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure in which a number of photodetectors that is less than a number of pixels is utilized;
  • FIG. 4 is a diagram of the compressive FFOCM system in an endoscope according to yet another exemplary embodiment of the present disclosure
  • FIG. 5 is a schematic diagram of the compressive FFOCM system in a needle according to an exemplary embodiment of the present disclosure.
  • FIG. 6 shows a block diagram of a processing arrangement for facilitating a compressive FFOCM procedure according to an exemplary embodiment of the present disclosure.
  • FIGS. 1-6 apparatus and methods according to the exemplary embodiments of the present disclosure are generally illustrated in FIGS. 1-6. It will be appreciated that there may be other exemplary configurations of the apparatus and parts thereof, and that the exemplary methods (including the steps and sequences thereof) according to the exemplary embodiments of the present disclosure may vary, without departing from the exemplary concepts as described herein.
  • the exemplary embodiments of the present disclosure relate to devices, systems, apparatus and methods for the high-speed high-resolution imaging in one, two, three, etc. dimensions that can facilitate the image acquisition of, e.g., a deep turbid tissue.
  • the exemplary embodiments of the apparatus shown in FIGS. 1-6 can be used to illustrate the exemplary apparatus, including the exemplary procedures performed thereby, and exemplary parts thereof.
  • a light source (or a source of electro-magnetic radiation) 100 for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 102.
  • the optical signal 102 can be transmitted to a spatial/temporal modulation unit/arrangement 104 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or mechanism 106, e.g., manually and/or by an automated unit/arrangement 108.
  • the optical signal 110 can then enter an interferometer, in which a beam splitter (BS) 112 can divide and/or separate the optical signal 102 into two paths, which can be referred to as a reference arm 114 and a sample arm 116.
  • BS beam splitter
  • the light or other electro-magnetic radiation can be focused using a lens 118 such as objective lens onto a reflective object 120 such as mirror.
  • the lens and reflective object are placed on a translating unit 122, which may be controlled via another control signal 124, e.g., manually and/or by an automated unit/arrangement 108.
  • the sample arm 116 the light and/or other electro-magnetic radiation can be focused using a lens 126, such as, e.g., an objective lens, onto a sample 128, such as tissue.
  • Back-reflected radiations from the sample arm 116 (e.g., reflected and/or provided from the sample 128) and the reference arm 114 can be transmitted back to the beamsplitter 112, where they can be recombined and directed to a collection lens 130.
  • the light other electro-magnetic radiation collected by the collection lens 130 can be focused onto a single -pixel photodetector 132 by such lens 130.
  • the photodetector 132 acquires such focused signal as an acquired signal 134, which is received by a data acquisition unit/arrangement 108 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG.6.
  • FIG. 2 shows a diagram of the compressive FFOCM system according to a second exemplary embodiment of the present disclosure, which utilizes an optical amplification enabling high detection sensitivity.
  • the second exemplary embodiment illustrated in FIG. 2 is similar to the exemplary system shown in FIG. 1, except that after the signals from the BS 212 (which is similar to the BS 112 of FIG.l) are recombined and directed to a collection lens 230, the collected light (or other electromagnetic radiation) can be focused onto an optical amplifier (e.g., semiconductor optical amplifiers, rare-Earth doped fiber amplifier, and/or optical parametric amplifier) 232, in which the image-encoded optical signal can be intensified to become a further signal 234.
  • an optical amplifier e.g., semiconductor optical amplifiers, rare-Earth doped fiber amplifier, and/or optical parametric amplifier
  • Such further signal 234 can be transmitted to the single-pixel photodetector 236, which acquires such signal, and transmits an additional signal 238.
  • additional signal 238 can be received by a data acquisition unit/arrangement/processor 208 for facilitating the compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6.
  • FIG. 3 shows a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure, which utilizes more than one photodetector such that the number of photodetectors is less than the number of pixels of at least one portion of one image of at least one anatomical structure.
  • FIG. 3 shows a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure, which utilizes more than one photodetector such that the number of photodetectors is less than the number of pixels of at least one portion of one image of at least one anatomical structure.
  • Such additional signal 334 can be received by a data acquisition unit/arrangement 308 for facilitating the compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6.
  • the number of photodetectors is less than a number of pixels of the reconstructed image.
  • FIG. 4 shows a diagram of the compressive FFOCM system provided in an endoscope according to another exemplary embodiment of the present disclosure.
  • a light source (or other electro-magnetic source) 400 for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 402 and can be controlled by a control signal or mechanism 404, e.g., manually and/or by an automated unit/arrangement/system 406.
  • the optical signal 402 can be transmitted to a spatial/temporal modulation unit/arrangement/system 408 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or mechanism 410, e.g., manually and/or by an automated unit/arrangement/system 406.
  • the optical signal 412 can be focused using at least one lens 414 into a waveguide (e.g., multi-mode fiber or fiber bundle) 416.
  • the waveguide 416 serves as a configuration to deliver the spatially-modulated light/electromagnetic-radiation to a luminal organ.
  • the imaging optics can be housed in a sheath 418, where such exemplary optics can receive the optical signal from the waveguide 416.
  • the output optical signal 420 can be focused using at least one lens 422, which then enters (or received by) an interferometer.
  • the interferometer can include a beam splitter 424 that can divide and/or separate the optical signal into two paths, which can be again referred to as a reference arm 426 and a sample arm 428.
  • the light or other electro-magnetic radiation can be reflected using a for example mirror 430, while the sample arm 428 is illuminated onto a sample (or at least one anatomical structure) 432.
  • Back-reflected radiations from the sample arm 428 (e.g., reflected and/or provided from the sample 432) and the reference arm 426 can be transmitted back to the beamsplitter 424, where they can be recombined and directed (alternatively, by means of a waveguide) to a photodetector (PD) arrangement 434.
  • PD photodetector
  • the photodetector 434 can acquire such optical signal as an acquired signal 436, which is received by a data acquisition unit/arrangement 406 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a compressive FFOCM in an endoscope procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6.
  • the compressive FFOCM endoscope can be spun and/or rotated to obtain circumferential information from the at least one luminal anatomical organ.
  • FIG. 5 shows a diagram of the compressive FFOCM system in a needle according to yet another exemplary embodiment of the present disclosure.
  • the imaging optics can be placed inside a bore of a needle.
  • a light source (or other electro-magnetic source) 500 for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 502, and can be controlled by a control signal or other mechanism 504, e.g., manually and/or by an automated unit/arrangement/system 506.
  • the optical signal 502 can be transmitted to a spatial/temporal modulation unit/arrangement/system 508 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or other mechanism 510, e.g., manually and/or by the automated unit/arrangement/system 506.
  • the optical signal 512 can be transmitted through a beamsplitter 514, and focused using at least one lens 516 (or a plurality of lenses) into a waveguide (e.g., multi-mode fiber, fiber bundle, etc.) 518.
  • a waveguide e.g., multi-mode fiber, fiber bundle, etc.
  • the imaging optics can be housed (either partially or entirely) inside the bore of a needle 520 (or in a catheter).
  • the output optical signal 522 can be focused onto an interferometer 526 (for example, a Mirau interferometer) using at least one lens 524 (or a plurality of lenses).
  • Back-reflected light or electromagnetic-radiation from the interferometer can be collected and transmitted back to the waveguide 518.
  • the reflected signal can be extracted and redirected using a beamsplitter 514 into a photodetector (PD) arrangement 530.
  • PD photodetector
  • the photodetector 530 can acquire such optical signal as an acquired signal 532, which can be received by a data acquisition unit/arrangement/system/processor/computer 506 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a FFOCM in a needle (and/or a small-diameter catheter) using, e.g., a compressive sensing procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6 (or other procedures).
  • FIG. 6 shows a hardware processing computer unit/arrangement 600 for facilitating the compressive FFOCM procedure according to various exemplary embodiments of the present disclosure.
  • This exemplary processing arrangement 600 can include a compressive sensing unit/arrangement 602, a cFFOCM processing unit/arrangement 604, a data acquisition unit/arrangement 606 (for example, consisting of a digitizer and digital processing unit), and an image display arrangement 608.
  • the compressive sensing unit/arrangement 602 can be configured to send and/or receive 610 commands and/or status updates to and/or from the light modulation unit/arrangement 612 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator).
  • the light modulation unit/arrangement 612 e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator.
  • the status of light modulation unit/arrangement 612 can be passed to the cFFOCM processing unit/arrangement 604.
  • the cFFOCM processing unit/arrangement 604 can send and/or receive 614 commands and/or status updates to and/or from the translating unit of the reference arm 616.
  • data containing image 618 are provided from the exemplary at least one photodetector 610 (as described herein), and received by the data acquisition unit/arrangement 606.
  • the acquired data 622 is provided to the cFFOCM processing unit single-pixel 604, where the image can be reconstructed using for example, pseudo-inverse, lo optimization, /; optimization, or greedy pursuit algorithms, and transmitted to the image display arrangement 608.

Abstract

Apparatus and process for facilitating a full-field microscopic imaging of at least one anatomical structure can be provided. For example, with an interferometric arrangement, it is possible (i) receive a first radiation from a reference arm and a second radiation from the anatomical structure(s), and (ii) generate a third radiation. For example, the first radiation and/or the second radiation can be modulated, and the third radiation can be a combination of the first and second radiations. Further, a single -pixel photodetector or multiple photodetectors arrangement can be used to receive and detect the third radiation for facilitating the full-field microscopic imaging of the anatomical structure(s).

Description

APPARATUS AND METHOD FOR HIGH-SPEED FULL FIELD OPTICAL
COHERENCE MICROSCOPY
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application relates to and claims priority from U.S. Patent Application No. 61/914,669, filed on December 1 1 , 2013, the entire disclosure of which is incorporated herein by reference.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates generally to exemplary methods and apparatus for providing optical coherence microscopy, and more particularly, to exemplary embodiments of methods and apparatus for providing and/or utilizing compressive sensing, single-pixel detectors, and optical image amplification for high-speed full-field optical coherence microscopy. BACKGROUND INFORMATION
[0003] Optical microscopy is an important technique/modality for probing living specimens with a subcellular resolution. Such imaging modality can facilitate a visualization of vital behavior and morphological details of cells in culture or in tissue. At a sub-cellular level, progress in understanding of their physics has been hindered by an apparent inability to observe the cellular structure and dynamics with fine three-dimensional spatial and/or temporal resolution.
[0004] Thus, a microscopy paradigm capable of providing fine three-dimensional spatial and temporal resolution in a highly scattering tissue can be of a high demand in medicine and biology.
[0005] Full-field optical coherence microscopy (FFOCM) modality is a wide-field high-resolution form of optical coherence tomography that can be useful for analyzing a microstructural morphology of biological specimen with a sub-cellular resolution deep within the tissue. Conventionally, FFOCM systems use a spatially incoherent source and an array detector, such as, e.g., a charge-coupled device (CCD) and complementary metal-oxide- semiconductor (CMOS) imaging sensors to generate en face image of sample under test. However, an exemplary image acquisition speed of the FFOCM systems can be limited by that of the imaging sensor. This possible limitation can be a result of the fundamental trade- off between detection sensitivity and frame rate. For example, at high frame rates, fewer photons are collected, thus likely leading to a lower sensitivity.
[0006] Accordingly, there may be a need to address at least some of the above- described deficiencies.
OBJECTS) AND SUMMARY OF EXEMPLARY EMBODIMENT(S)
[0007] It is one of the objects of the present disclosure to provide exemplary embodiments of systems, apparatus and methods which can perform high-speed FFOCM. In accordance with certain exemplary embodiments of the present disclosure, exemplary methods and apparatus can be provided, which can facilitate an implementation of the highspeed FFOCM using compressive sensing.
[0008] Another one of the objects of the present disclosure is to provide an endoscope-based approach to perform optical coherence microscopy. In accordance with certain exemplary embodiments of the present disclosure, exemplary methods and apparatus can be provided, which enable the implementation of full-field optical coherence microscopy of anatomical structures in an endoscope or a needle.
[0009] In order to perform the high-speed FFOCM, according to an exemplary embodiment of the present disclosure, it is possible to utilize a single -pixel detector and compressive sensing procedure. Thus, it is also possible to provide a microscopy paradigm, system, method and/or arrangement that can be based on or utilize principles of the FFOCM procedure(s) which can use a single-pixel detector and compressive sensing procedure to faciliate an optical image amplification, and thus can address and/or overcome the fundamental trade-off discussed above, achieving very high frame rates while maintaining a beneficial and improved isotropic spatial resolution.
[0010] In such exemplary embodiment, the illumination light or other electro- magentic radiation can be spatially and/or temporally modulated. The modulated light or other electro-magnetic radiation can enter the interferometer in which it is illuminated onto the tissue. Back-scattered light and/or the other electro-magnetic radiation can be collected using a single-pixel detector. For example, multiple acquisitions can be performed to reconstruct images.
[0011] According to the exemplary embodiment of the present disclosure, the interfered signal from the output of the interferometer can be collected by a single-pixel photodetector. An exemplary signal processing procedure can be performed digitally to reconstruct an image. Use of the exemplary single-pixel detector can facilitate an optical amplification to be performed before the photodetection. Accordingly, such exemplary procedure(s) and/or configuration(s) can improve the sensitivity and frame rate, while maintaining a beneficial and/or improved isotropic high spatial resolution, and thus can address and/or overcome the fundamental trade-off discussed above, achieving high frame rates.
[0012] Another exemplary objects of the present disclosure is to provide exemplary method and apparatus to perform an optical signal amplification for a significant sensitivity enhancement in compressive FFOCM. For example, an optical amplifier (which can be modified according to an exemplary embodiment of the present disclosure) can be used to amplify the optical signal which contains the image, prior to the photodetection.
[0013] For example, apparatus and process for facilitating a full-field microscopic imaging of at least one anatomical structure according to an exemplary embodiment of the present disclosure can be provided. For example, with an interferometric arrangement, it is possible to (i) receive a first radiation from a reference arm and a second radiation from the anatomical structure(s), and (ii) generate a third radiation. For example, the first radiation and/or the second radiation can be modulated using at least one of a rotating diffuser, a spatial light modulator or a speckle -pattern modulator. The third radiation can be a combination of the first and second radiations. Further, a single -pixel photodetector arrangement can be used to receive and detect the third radiation for facilitating the full-field microscopic imaging of the anatomical structure(s).
[0014] According to another exemplary embodiment of the present disclosure, the apparatus can include a number of photodetectors that is less than a number of pixels of the at least one image of the at least one anatomical structure. In addition, a computer arrangement can be provided that can be configured to digitally construct at least one image of at least one portion of the anatomical structure(s) using data generated by the photodetectors arrangement. A modulation arrangement can be provided which can include at least one of a rotating diffuser, a spatial light modulator or a speckle-pattern modulator.
[0015] According to yet another exemplary embodiment of the present disclosure, the apparatus can include a signal amplification arrangement that can be configured to receive and amplify the third radiation. The signal amplification arrangement can be provided in a communication path between the interferometric arrangement and the photodetector arrangement, and can detect the amplified third radiation. In addition, a computer arrangement can be provided that can be configured to digitally construct at least one image of at least one portion of the anatomical structure(s) using data generated by the photodetector arrangement based on the amplified third radiation.
[0016] In another exemplary embodiment of the present disclosure, apparatus and process can be provided for imaging of at least one anatomical structure. For example, with an interferometric arrangement, it is possible to receive a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generate a third radiation at a first time and a fourth radiation at a second time. The first and/or second radiations can be spatially modulated, and each of the third and fourth radiations canbe a respective combination of the first and second radiations at the first and second times, respectively. In addition, e.g., with a photodetector arrangement, it is possible to receive and detect:
(i) the third radiation for imaging the anatomical structure(s) as a function of a first spatial modulation of the one(s) of the first and second radiations at the first time, and
(ii) the fourth radiation for imaging the anatomical structure(s) as a function of a second spatial modulation of the one(s) of the first and second radiations at the second time, where the first and second spatial modulations can be different from one another.
[0017] Further, with a pre-programmed computer arrangement, it is possible to generate the image(s) of the portion(s) of the anatomical structure(s) based on the third and fourth radiations.
[0018] According the exemplary embodiments of the present disclosure, a computer arrangement including data acquisition and compressive sensing procedure via, for example, pseudo-inverse, lo optimization, /; optimization, or greedy pursuit algorithms and/or procedures can be utilized to facilitate and reconstruct at least one portion of one image of at least one anatomical structure.
[0019] These and other objects, features and advantages of the exemplary embodiments of the present disclosure will become apparent upon reading the following detailed description of the exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS [0020] Further objects, features and advantages of the present disclosure will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present disclosure, in which:
[0021] FIG. 1 is a diagram of a compressive FFOCM system according to an exemplary embodiment of the present disclosure;
[0022] FIG. 2 is a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure which utilizes an optical amplification enabling high detection sensitivity;
[0023] FIG. 3 is a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure in which a number of photodetectors that is less than a number of pixels is utilized;
[0024] FIG. 4 is a diagram of the compressive FFOCM system in an endoscope according to yet another exemplary embodiment of the present disclosure;
[0025] FIG. 5 is a schematic diagram of the compressive FFOCM system in a needle according to an exemplary embodiment of the present disclosure; and
[0026] FIG. 6 shows a block diagram of a processing arrangement for facilitating a compressive FFOCM procedure according to an exemplary embodiment of the present disclosure.
[0027] Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the subject disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope and spirit of the subject disclosure as defined by the appended claims.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0028] Referring more specifically to the drawings, for illustrative purposes, apparatus and methods according to the exemplary embodiments of the present disclosure are generally illustrated in FIGS. 1-6. It will be appreciated that there may be other exemplary configurations of the apparatus and parts thereof, and that the exemplary methods (including the steps and sequences thereof) according to the exemplary embodiments of the present disclosure may vary, without departing from the exemplary concepts as described herein. [0029] In general, the exemplary embodiments of the present disclosure relate to devices, systems, apparatus and methods for the high-speed high-resolution imaging in one, two, three, etc. dimensions that can facilitate the image acquisition of, e.g., a deep turbid tissue. The exemplary embodiments of the apparatus shown in FIGS. 1-6 can be used to illustrate the exemplary apparatus, including the exemplary procedures performed thereby, and exemplary parts thereof.
[0030] For example, as shown in the diagram of FIG. 1, a light source (or a source of electro-magnetic radiation) 100, for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 102. The optical signal 102 can be transmitted to a spatial/temporal modulation unit/arrangement 104 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or mechanism 106, e.g., manually and/or by an automated unit/arrangement 108. The optical signal 110 can then enter an interferometer, in which a beam splitter (BS) 112 can divide and/or separate the optical signal 102 into two paths, which can be referred to as a reference arm 114 and a sample arm 116.
[0031] In the reference arm 114, the light or other electro-magnetic radiation can be focused using a lens 118 such as objective lens onto a reflective object 120 such as mirror. The lens and reflective object are placed on a translating unit 122, which may be controlled via another control signal 124, e.g., manually and/or by an automated unit/arrangement 108. In the sample arm 116, the light and/or other electro-magnetic radiation can be focused using a lens 126, such as, e.g., an objective lens, onto a sample 128, such as tissue. Back-reflected radiations from the sample arm 116 (e.g., reflected and/or provided from the sample 128) and the reference arm 114 can be transmitted back to the beamsplitter 112, where they can be recombined and directed to a collection lens 130. The light other electro-magnetic radiation collected by the collection lens 130 can be focused onto a single -pixel photodetector 132 by such lens 130. The photodetector 132 acquires such focused signal as an acquired signal 134, which is received by a data acquisition unit/arrangement 108 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG.6.
[0032] FIG. 2 shows a diagram of the compressive FFOCM system according to a second exemplary embodiment of the present disclosure, which utilizes an optical amplification enabling high detection sensitivity. Indeed, such system according to the second exemplary embodiment illustrated in FIG. 2 is similar to the exemplary system shown in FIG. 1, except that after the signals from the BS 212 (which is similar to the BS 112 of FIG.l) are recombined and directed to a collection lens 230, the collected light (or other electromagnetic radiation) can be focused onto an optical amplifier (e.g., semiconductor optical amplifiers, rare-Earth doped fiber amplifier, and/or optical parametric amplifier) 232, in which the image-encoded optical signal can be intensified to become a further signal 234. Then, such further signal 234 can be transmitted to the single-pixel photodetector 236, which acquires such signal, and transmits an additional signal 238. Such additional signal 238 can be received by a data acquisition unit/arrangement/processor 208 for facilitating the compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6.
[0033] FIG. 3 shows a diagram of the compressive FFOCM system according to another exemplary embodiment of the present disclosure, which utilizes more than one photodetector such that the number of photodetectors is less than the number of pixels of at least one portion of one image of at least one anatomical structure. Indeed, such system according to this exemplary embodiment illustrated in FIG. 3 is similar to the exemplary system shown in FIG. 1, except that multiple photodetectors 332 are used to detect the signal. Such additional signal 334 can be received by a data acquisition unit/arrangement 308 for facilitating the compressive FFOCM procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6. In this embodiment, the number of photodetectors is less than a number of pixels of the reconstructed image.
[0034] FIG. 4 shows a diagram of the compressive FFOCM system provided in an endoscope according to another exemplary embodiment of the present disclosure. In this exemplary embodiment, a light source (or other electro-magnetic source) 400, for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 402 and can be controlled by a control signal or mechanism 404, e.g., manually and/or by an automated unit/arrangement/system 406. The optical signal 402 can be transmitted to a spatial/temporal modulation unit/arrangement/system 408 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or mechanism 410, e.g., manually and/or by an automated unit/arrangement/system 406. The optical signal 412 can be focused using at least one lens 414 into a waveguide (e.g., multi-mode fiber or fiber bundle) 416. The waveguide 416 serves as a configuration to deliver the spatially-modulated light/electromagnetic-radiation to a luminal organ.
[0035] The imaging optics can be housed in a sheath 418, where such exemplary optics can receive the optical signal from the waveguide 416. The output optical signal 420 can be focused using at least one lens 422, which then enters (or received by) an interferometer. The interferometer can include a beam splitter 424 that can divide and/or separate the optical signal into two paths, which can be again referred to as a reference arm 426 and a sample arm 428.
[0036] In the reference arm 426, e.g., the light or other electro-magnetic radiation can be reflected using a for example mirror 430, while the sample arm 428 is illuminated onto a sample (or at least one anatomical structure) 432. Back-reflected radiations from the sample arm 428 (e.g., reflected and/or provided from the sample 432) and the reference arm 426 can be transmitted back to the beamsplitter 424, where they can be recombined and directed (alternatively, by means of a waveguide) to a photodetector (PD) arrangement 434. The photodetector 434 can acquire such optical signal as an acquired signal 436, which is received by a data acquisition unit/arrangement 406 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a compressive FFOCM in an endoscope procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6. According to an exemplary embodiment of the present disclosure, the compressive FFOCM endoscope can be spun and/or rotated to obtain circumferential information from the at least one luminal anatomical organ.
[0037] FIG. 5 shows a diagram of the compressive FFOCM system in a needle according to yet another exemplary embodiment of the present disclosure. In this exemplary embodiment, the imaging optics can be placed inside a bore of a needle. A light source (or other electro-magnetic source) 500, for example, Arc lamp, supercontinuum source, laser diode, or light emitting diode can generate an optical signal 502, and can be controlled by a control signal or other mechanism 504, e.g., manually and/or by an automated unit/arrangement/system 506. The optical signal 502 can be transmitted to a spatial/temporal modulation unit/arrangement/system 508 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator) that can be controlled by a control signal or other mechanism 510, e.g., manually and/or by the automated unit/arrangement/system 506. The optical signal 512 can be transmitted through a beamsplitter 514, and focused using at least one lens 516 (or a plurality of lenses) into a waveguide (e.g., multi-mode fiber, fiber bundle, etc.) 518. [0038] According the exemplary embodiment illustrated in FIG. 5, the imaging optics can be housed (either partially or entirely) inside the bore of a needle 520 (or in a catheter). The output optical signal 522 can be focused onto an interferometer 526 (for example, a Mirau interferometer) using at least one lens 524 (or a plurality of lenses). Back-reflected light or electromagnetic-radiation from the interferometer can be collected and transmitted back to the waveguide 518. Subsequently, the reflected signal can be extracted and redirected using a beamsplitter 514 into a photodetector (PD) arrangement 530. The photodetector 530 can acquire such optical signal as an acquired signal 532, which can be received by a data acquisition unit/arrangement/system/processor/computer 506 for processing and image reconstruction, as shown in an exemplary embodiment of the processing arrangement for facilitating a FFOCM in a needle (and/or a small-diameter catheter) using, e.g., a compressive sensing procedure according to an exemplary embodiment of the present disclosure that is shown in FIG. 6 (or other procedures).
[0039] FIG. 6 shows a hardware processing computer unit/arrangement 600 for facilitating the compressive FFOCM procedure according to various exemplary embodiments of the present disclosure. This exemplary processing arrangement 600 can include a compressive sensing unit/arrangement 602, a cFFOCM processing unit/arrangement 604, a data acquisition unit/arrangement 606 (for example, consisting of a digitizer and digital processing unit), and an image display arrangement 608. The compressive sensing unit/arrangement 602 can be configured to send and/or receive 610 commands and/or status updates to and/or from the light modulation unit/arrangement 612 (e.g., a spatial light modulation device, a rotating diffuse device and/or a speckle pattern generator). The status of light modulation unit/arrangement 612 can be passed to the cFFOCM processing unit/arrangement 604. The cFFOCM processing unit/arrangement 604 can send and/or receive 614 commands and/or status updates to and/or from the translating unit of the reference arm 616. Further, data containing image 618 are provided from the exemplary at least one photodetector 610 (as described herein), and received by the data acquisition unit/arrangement 606. The acquired data 622 is provided to the cFFOCM processing unit single-pixel 604, where the image can be reconstructed using for example, pseudo-inverse, lo optimization, /; optimization, or greedy pursuit algorithms, and transmitted to the image display arrangement 608.
[0040] The foregoing merely illustrates the principles of the disclosure. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present disclosure can be used with and/or implement any OCT system, OFDI system, SD-OCT system or other imaging systems, and for example with those described in International Patent Application PCT/US2004/029148, filed September 8, 2004 which published as International Patent Publication No. WO 2005/047813 on May 26, 2005, U.S. Patent Application No. 11/266,779, filed November 2, 2005 which published as U.S. Patent Publication No. 2006/0093276 on May 4, 2006, and U.S. Patent Application No. 10/501,276, filed July 9, 2004 which published as U.S. Patent Publication No. 2005/0018201 on January 27, 2005, and U.S. Patent Publication No. 2002/0122246, published on May 9, 2002, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements, and procedures which, although not explicitly shown or described herein, embody the principles of the disclosure and can be thus within the spirit and scope of the disclosure. In addition, all publications and references referred to above can be incorporated herein by reference in their entireties. It should be understood that the exemplary procedures described herein can be stored on any computer accessible medium, including a hard drive, RAM, ROM, removable disks, CD-ROM, memory sticks, etc., and executed by a processing arrangement and/or computing arrangement which can be and/or include a hardware processors, microprocessor, mini, macro, mainframe, etc., including a plurality and/or combination thereof. In addition, certain terms used in the present disclosure, including the specification, drawings and claims thereof, can be used synonymously in certain instances, including, but not limited to, e.g., data and information. It should be understood that, while these words, and/or other words that can be synonymous to one another, can be used synonymously herein, that there can be instances when such words can be intended to not be used synonymously. Further, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it can be explicitly being incorporated herein in its entirety. All publications referenced above can be incorporated herein by reference in their entireties.

Claims

WHAT IS CLAIMED IS:
1. An apparatus for imaging at least one anatomical structure, comprising:
an interferometric arrangement configured to receive a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generate a third radiation, wherein at least one of the first and second radiations are spatially modulated, and the third radiation is a combination of the first and second radiations; and
a photodetector arrangement configured to receive and detect the third radiation for facilitating a full-field microscopic imaging of the at least one anatomical structure.
2. The apparatus according to claim 1, further comprising a signal amplification arrangement configured to receive and amplify the third radiation, and provided in a communication path between the interferometric arrangement and the photodetector arrangement, wherein the photodetector arrangement detects the amplified third radiation.
3. The apparatus according to claim 2, further comprising a computer arrangement which is configured to digitally construct at least one image of at least one portion of the at least one anatomical structure using data generated by the photodetector arrangement based on the amplified third radiation.
4. The apparatus according to claim 2, wherein the photodetector arrangement includes a number of the photodetectors that is less than a number of pixels of the at least one image of the at least one anatomical structure.
5. The apparatus according to claim 1, wherein the photodetector arrangement is a single-pixel photodetector arrangement.
6. The apparatus according to claim 1, further comprising a modulation arrangement which includes at least one of a rotating diffuser, a spatial light modulator or a speckle- pattern modulator.
7. An apparatus for imaging of at least one anatomical structure, comprising: an interferometric arrangement configured to receive a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generate a third radiation at a first time and a fourth radiation at a second time, wherein at least one of the first and second radiations are spatially modulated, and each of the third and fourth radiations is a respective combination of the first and second radiations at the first and second times, respectively;
a photodetector arrangement configured to receive and detect:
(i) the third radiation for imaging the at least one anatomical structure as a
function of a first spatial modulation of the at least one of the first and second radiations at the first time, and
(ii) the fourth radiation for imaging the at least one anatomical structure as a
function of a second spatial modulation of the at least one of the first and second radiations at the second time, wherein the first and second spatial modulations are different from one another; and
a computer arrangement which is configured to generate the at least one image of the at least one portion of the at least one anatomical structure based on the third and fourth radiations.
8. The apparatus according to claim 7, wherein the photodetector arrangement includes a number of the photodetectors that is less than a number of pixels of the at least one image of the at least one anatomical structure.
9. The apparatus according to claim 7, wherein the computer arrangement generates the at least one image that is a full-field optical coherence tomography image or a full-field optical coherence microscopy image.
10. The apparatus according to claim 7, further comprising a modulation arrangement which includes at least one of a rotating diffuser, a spatial light modulator or a speckle- pattern modulator.
11. The apparatus according to claim 7, wherein the computer arrangement generates the at least one image based on a compressive sensing procedure.
12. The apparatus according to claim 7, further comprising a signal amplification arrangement configured to receive and amplify the third and fourth radiations, and provided in a communication path between the interferometric arrangement and the photodetector arrangement, wherein the photodetector arrangement detects the amplified third and fourth radiations.
13. The apparatus according to claim 12, further comprising a computer arrangement which is configured to digitally construct the at least one image using data generated by the photodetector arrangement based on the amplified third and fourth radiations.
14. The apparatus according to claim 7, wherein the photodetector arrangement is a single-pixel photodetector arrangement.
15. A process for imaging at least one anatomical structure, comprising:
with an interferometric arrangement, receiving a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generating a third radiation, wherein at least one of the first and second radiations are spatially modulated, and the third radiation is a combination of the first and second radiations; and
with a photodetector arrangement, receiving and detecting the third radiation for facilitating a full-field microscopic imaging of the at least one anatomical structure.
16. A method for imaging of at least one anatomical structure, comprising:
with an interferometric arrangement, receiving a first radiation from a reference arm and a second radiation from the at least one anatomical structure, and generating a third radiation at a first time and a fourth radiation at a second time, wherein at least one of the first and second radiations are spatially modulated, and each of the third and fourth radiations is a respective combination of the first and second radiations at the first and second times, respectively;
with a photodetector arrangement, receiving and detecting:
(i) the third radiation for imaging the at least one anatomical structure as a
function of a first spatial modulation of the at least one of the first and second radiations at the first time, and (ii) the fourth radiation for imaging the at least one anatomical structure as a function of a second spatial modulation of the at least one of the first and second radiations at the second time, wherein the first and second spatial modulations are different from one another; and
with a pre-programmed computer arrangement, generating the at least one image of the at least one portion of the at least one anatomical structure based on the third and fourth radiations.
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