WO2011109818A2 - System, methods and computer- accessible medium which provide micoscopic images of at least one anatomical structure at a particular resolution - Google Patents
System, methods and computer- accessible medium which provide micoscopic images of at least one anatomical structure at a particular resolution Download PDFInfo
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- WO2011109818A2 WO2011109818A2 PCT/US2011/027421 US2011027421W WO2011109818A2 WO 2011109818 A2 WO2011109818 A2 WO 2011109818A2 US 2011027421 W US2011027421 W US 2011027421W WO 2011109818 A2 WO2011109818 A2 WO 2011109818A2
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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
- A61B5/06—Devices, other than using radiation, for detecting or locating foreign bodies ; determining position of probes within or on the body of the patient
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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
- A61B5/0059—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
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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
- A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
- A61B5/004—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
- A61B5/0044—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the heart
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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
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
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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
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
- A61B5/0084—Measuring 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
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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
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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
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/24—Coupling light guides
- G02B6/26—Optical coupling means
- G02B6/32—Optical coupling means having lens focusing means positioned between opposed fibre ends
Definitions
- the present disclosure relates to exemplary embodiments of imaging systems, apparatus and methods, and more specifically to methods, systems and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution.
- Topics relevant to the pathophysiology of CAD, such as the development and progression of coronary atherosclerotic lesions, plaque rupture and coronary thrombosis, and the arterial response to coronary device and pharmacologic therapies are therefore of great significance today.
- These biological processes can be mediated by molecular and cellular events that occur on a microscopic scale.
- OCT intracoronary optical coherence tomography
- OCT optical frequency domain imaging
- OFDI optical frequency domain imaging
- a flushing method has been developed which, in combination with the high frame rate of OFDI, can overcome at least some of the obstacles of blood interference with the OCT signal.
- a transverse resolution in OCT procedure(s) can be determined by the catheter's focal spot size.
- This conventional method neglects the intrinsic compromise between transverse resolution and depth of field in cross-sectional OCT images and results in images in which only a narrow depth range is resolved.
- An alternative approach can exploit the unique characteristics of Bessel, or "non- diffracting" beams to produce high transverse resolution over enhanced depths-of-field. Bessel beam illumination and detection of light reflected from the sample, however, can suffer from a significant reduction in contrast and detection efficiency. Thus, there may be a need to overcome at least some of the deficiencies associated with the conventional arrangements and methods described above.
- certain exemplary embodiments of the present disclosure can be associated and/or utilize analysis and manipulation of a coherent transfer function (CTF) of an exemplary OCT system.
- the current invention is instead based on an analysis and manipulation of the coherent transfer function (CTF) of an OCT system.
- the CTF can be considered a coherent extension of a modulation transfer function (MTF) and an optical transfer function (OTF).
- MTF modulation transfer function
- OTF optical transfer function
- the MTF or OTF can be manipulated and utilized according to certain exemplary embodiments.
- the quality of an optical system can be assessed by comparing its transfer function to that of a diffraction-limited optical system.
- Figure 1 shows a graph of coherent transfer functions (CTFs) for, e.g., a diffraction limited 2.5 ⁇ diameter spot and 2.5 ⁇ spot with an extended focal range of 2.0 mm, produced by Bessel beam illumination and detection.
- CTFs coherent transfer functions
- the transfer function of a Bessel beam illumination and detection 100 can have spatial frequencies that exceed a diffraction- limited system 110, although it likely sacrifices low- and mid-range spatial frequencies, possibly resulting in reduced contrast and detection sensitivity.
- one of the objects of the present disclosure is to provide exemplary embodiments of systems, methods and computer- accessible medium according to the present disclosure, which can provide microscopic images of at least one anatomical structure at a particular resolution.
- Another object of the present disclosure is to overcome a limited depth of focus limitations of conventional Gaussian beam and spatial frequency loss of Bessel beam systems for OCT procedures and/or systems and other forms of extended focal depth imaging.
- more than two imaging channels can illuminate/detect different Bessel and/or Gaussian beams.
- different transfer functions can be illuminated and/or detected.
- the exemplary combination of images obtained with such additional exemplary beams can facilitate the ⁇ CTF to be provided to the diffraction-limited case, and can also facilitate a depth-of-field extension even further.
- exemplary embodiments of apparatus, systems and methods can be provided for providing at least one electro-magnetic radiation to at least one sample.
- a plurality of wave-guiding arrangements can be provided which are configured to (i) provide the electro-magnetic radiation(s), and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each of the electro-magnetic radiation(s) to have a predetermined value.
- the exemplary apparatus can be part of a probe. Further the exemplary apparatus can include an interferometric arrangement provided in communication with the probe and/or be part of the probe.
- the wave-guiding arrangements can provide the radiation(s) in at least partially a circular pattern.
- At least one lens arrangement can be included which is configured to receive the electro-magnetic radiation(s) from the wave-guiding arrangements, and generate a further focus-spot radiation.
- the lens arrangement(s) can be configured to cause the further focus-spot radiation to have (i) an extended focal depth, and/or (ii) a diameter that is smaller than a diffraction limited spot on or in the sample.
- the diffraction limited spot can be a three-dimensional spot.
- the lens arrangement(s) can include a grin lens.
- At least one of the wave-guiding arrangements can be (i) a single-mode wave-guide, and/or (ii) composed a photo-polymer.
- a further wave-guiding arrangement can be provided, which is configured to provide a further electro-magnetic radiation to the sample, where the electro-magnetic radiation(s) and the further electro-magnetic radiation can be provided to at least partially overlapping portions of the sample.
- a housing can also be provided which at least partially encloses the wave-guiding aixangements, and/or a sheath can be provided which encloses the housing.
- a control arrangement can be provided which is configured to rotate and/or translate the housing.
- the lens arrangement(s) can include at least one optical element formed by and/or subjected to a photopolymer processing.
- the photopolymer processing can include irradiating a photopolymer so as to form the optical element(s).
- method and system can be provided for generating data associated with at least one portion of a sample.
- at least one first radiation can be forwarded to the portion(s) of the sample through at least one optical arrangement which is formed by or subjected to a photopolymer processing.
- At least one second radiation can be received from the portion(s) which can be based on the first radiation(s).
- the optical arrangement Based on an interaction between the optical arrangement(s) and the first radiation and/or the second radiation, the optical arrangement can have a first transfer function.
- at least one third radiation can be forwarded to the portion(s) through the optical arrangement.
- At least one fourth radiation can be received from the portion(s) which can be based on the third radiation(s).
- the optical arrangement(s) can have a second transfer function, where the first transfer function can be at least partially different from the second transfer function. Further, the data associated with the portion(s) can be generated based on the second and fourth radiations.
- method and system can be provided also for generating data associated with at least one portion of a sample.
- at least one first radiation can be forwarded to the portion(s) of the sample through at least one first optical arrangement which is formed by or subjected to a photopolymer processing.
- At least one second radiation can be received from the portion(s) which can be based on the first radiation(s).
- the first optical arrangement(s) can have a first transfer function.
- at least one third radiation can be forwarded to the portion(s) through at least one second optical arrangement.
- At least one fourth radiation can be received from the portion(s) which can be based on the third radiation(s).
- the second optical arrangement(s) Based on an interaction between the second optical arrangement(s) and the third radiation and/or the fourth radiation, the second optical arrangement(s) can have a second transfer function, where the first transfer function can be at least partially different from the second transfer function. Further, the data associated with the portion(s) can be generated based on the second and fourth radiations.
- the first optical arrangement(s) and/or the second optical arrangement(s) can be formed by or subjected to a photopolymer processing.
- Figure 1 is an exemplary graph of coherent transfer functions (CTFs) as a function of spatial frequencies produced by the prior Bessel beam illumination and detection;
- CTFs coherent transfer functions
- Figure 2 is an exemplary graph of coherent transfer functions (CTFs) as a function of spatial frequencies produced by an exemplary embodiment of a procedure and/or technique according to the present disclosure
- Figure 3 A is a first exemplary OCT image an exemplary OCT image of a cadaver coronary artery plaque obtained using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, whereas an exemplary Gauss-Gauss image contains low spatial frequency information;
- Figure 3B is a second exemplary OCT image of the cadaver coronary artery plaque using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, whereas an exemplary Bessel-Bessel image provides high-resolution but loses low and mid spatial frequencies;
- Figure 3C is a third exemplary OCT image of the cadaver coronary artery plaque using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, which provides a combined ⁇ OCT image (e.g., Gauss-Gauss+Gauss- Bessel+Bessel-Bessel), and images are normalized and displayed with the same brightness/contrast values;
- ⁇ OCT image e.g., Gauss-Gauss+Gauss- Bessel+Bessel-Bessel
- Figure 4A is a side cut-away view of a diagram of distal optics of a OCT catheter system according to an exemplary embodiment of the present disclosure
- Figure 4B is an exemplary graph of a polymer index profile generated using a Y- junction fan-out of the system the exemplary embodiment of shown in Figure 4 A;
- Figure 4C is an exemplary graph of an illumination profile generated using the Y- junction fan-out of the system the exemplary embodiment of shown in Figure 4A;
- Figure 4D is an exemplary graph of an simulated x-z PSF using the Y-junction fan-out of the system the exemplary embodiment of shown in Figure 4A;
- Figure 5A is a side cut-away view of a diagram of the distal optics of a OCT catheter system according to another exemplary embodiment of the present disclosure
- Figure 5B is an exemplary graph of an illumination profile generated using the distal optics con figuration of the system the exemplary embodiment of shown in Figure 5 A;
- Figure 5C is an exemplary graph of simulated x-z PSF generated using the distal optics con figuration of the system the exemplary embodiment of shown in Figure 5 A;
- Figure 6 is a schematic diagram of a system for generating one or more ⁇ images according to still a further exemplary embodiment of the present disclosure
- Figure 7 are side cut-away views of diagrams of the distal optics of the OCT catheter system according to still another exemplary embodiment of the present disclosure which includes axicon pair and a routing of a ring beam and a Gaussian beam of the distal optics configuration;
- Figure 8 is a side cut-away view of a diagram of the OCT catheter system according to yet further exemplary embodiment of the present disclosure which includes an exemplary optical pathlength incoding probe configuration that uses a single fiber and a single axicon lens;
- Figure 9 are side cut-away views of diagrams of the OCT catheter system according to a still further exemplary embodiment of the present disclosure which includes a further exemplary optical pathlength incoding probe configuration that uses a single fiber and a single axicon lens;
- Figure 10 are schematic views of diagrams of the distal optics of the OCT catheter system according to a further exemplary embodiment of the present disclosure which includes a single fiber multifocal lens probe configuration;
- Figure 11 is a side cut-away view of a diagram of the OCT catheter system according to a still further exemplary embodiment of the present disclosure which utilizes a mirror tunnel;
- Figure 12 is a side cut-away view of a diagram a portion of the OCT catheter system according to yet another exemplary embodiment of the present disclosure which utilizes a reflective achromatic phase mask and a ball lens;
- Figure 13 is a graph of a phase shift spectra of chromatic light upon reflection at glass-metal interface based on the exemplary embodiment of Figure 12;
- Figure 14A is an illustration of a Huygens diffraction pattern of lens with conventional focusing
- Figure 14B is an exemplary illustration of a Huygens diffraction pattern of lens with reflective achromatic phase mask and ball lens depicted in the exemplary embodiment of the system illustrated in Figure 13.
- Figure 15A is a schematic diagram of an exemplary embodiment of a focusing arrangement that uses a refractive achromatic phase doublet mask in accordance with an exemplary embodiment of the present disclosure
- Figure 15B is an exemplary graph of transverse phase profiles of an exemplary mask illustrated in Figure 15 A;
- Figure 16 is a schematic diagram of the OCT system which includes a wavefront beam splitter and a common path interferometer, according to yet another exemplary embodiment of the present disclosure;
- an objective lens with a spherical aberration and a wavelength dependent focal shift
- Figure 17C is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses a broadband source (e.g., about 600 nm to 1050 nm) and an objective lens with spherical aberration and a wavelength dependent focal shift;
- a broadband source e.g., about 600 nm to 1050 nm
- an objective lens with spherical aberration and a wavelength dependent focal shift e.g., about 600 nm to 1050 nm
- Figure 17D is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses broadband source (e.g., 600 nm to 1050 nm), an objective lens with spherical aberration and a wavelength dependent focal shift, and an wavefront beam splitter;
- broadband source e.g., 600 nm to 1050 nm
- Figure 18 A is an exemplary ⁇ image of a coronary plaque showing multiple leukocytes (arrows);
- Figure 18B is an exemplary ⁇ image of a coronary plaque illustrating multiple leukocytes (arrows) of two different cell types, one smaller cell with scant cytoplasm, consistent with a lymphocyte (L) and another, larger cell with a highly scattering cytoplasm, indicative of a monocyte (M);
- Figure 18C is an exemplary ⁇ image of a coronary plaque illustrating a cell with an indented, bean-shaped nucleus (M) characteristic of a monocyte;
- Figure 18D is an exemplary ⁇ ( ⁇ image of a coronary plaque illustrating a leukocyte with a multi-lobed nucleus, which can indicate a neutrophil (N) attached to the endothelial surface;
- Figure 18E is an exemplary ⁇ image of the coronary plaque illustrating multiple leukocytes tethered to the endothelial surface by pseudopodia;
- Figure 18F is an exemplary ⁇ image of the coronary plaque illustrating cells with the morphology of monocytes (M) in a cross-section and an inset transmigrating through the endothelium;
- Figure 18G is an exemplary ⁇ image of multiple leukocytes distributed on the endothelial surface
- Figure 19A is an exemplary ⁇ image of platelets (P) adjacent to a leukocyte characteristic of a neutrophil (N), which is also attached to a small platelet;
- Figure 19B is an exemplary ⁇ image of fibrin (F) which is visible as linear strands bridging a gap in the coronary artery wall;
- Figure 19C is an exemplary ⁇ image of a cluster of leukocytes (L), adherent to the fibrin in an adjacent site to that illustrated in Figure 19B;
- Figure 19D is an exemplary ⁇ image of Fibrin thrombus (T) with multiple, entrapped leukocytes;
- Figure 19E is an exemplary ⁇ image of a more advanced thrombus (T) showing a leukocyte and fibrin strands;
- Figure 20A is a cross-sectional exemplary ⁇ OCT image of endothelial cells in culture
- Figure 20B is an en face exemplary ⁇ image of endothelial cells in culture;
- Figure 20C is an exemplary ⁇ image of a native swine coronary artery cross- section;
- Figure 20D is an exemplary three-dimensional rendering of the swine coronary artery, demonstrating endothelial "pavementing";
- Figure 21 is an exemplary ⁇ ( ⁇ image of microcalcifications which can be seen as bright densities within the ⁇ image of the fibrous cap;
- Figure 21B is an exemplary ⁇ image of the microcalcifications which can be seen as dark densities on the corresponding histology
- Figure 22A is an exemplary ⁇ image of a large calcium nodule, demonstrating disrupted intima/endothelium;
- Figure 22B is an expanded view of the region enclosed by a box illustrating microscopic tissue strands, consistent with fibrin (F), adjoining the unprotected calcium (white arrow) to the opposing detached intima;
- Figure 22C is an illustration of a corresponding histology of fibrin (F, black arrows) and denuded calcific surface (gray arrow);
- Figure 23A is an exemplary ⁇ ( ⁇ image of a large necrotic core (NC) fibroatheroma, demonstrating thick cholesterol crystals (CC), characterized by reflections from their top and bottom surfaces;
- NC large necrotic core
- CC thick cholesterol crystals
- Figure 23B is an exemplary ⁇ image of thin crystal (CC, gray arrow) piercing the cap of another necrotic core plaque (NC), shown in more detail in the inset;
- Figure 24 A is an exemplary ⁇ image of various smooth muscle cells appearing as low backscattering spindle-shaped cells (inset);
- Figure 24B is an exemplary ⁇ ( ⁇ image of smooth muscle cells producing collagen are spindle shaped, have a high backscattering interior (light gray arrow) and a "halo" of low backscattering (white arrow), which represents the cell body and collagen matrix, respectively (histology inset);
- Figure 25A is an exemplary ⁇ image of Taxus Liberie struts with/without polymer/drug, i.e., for polymer-coated struts, polymer reflection (PR), strut reflection (SR) and multiple reflections (MR1, MR2) can be seen;
- PR polymer reflection
- SR strut reflection
- MR1, MR2 multiple reflections
- Figure 25B is an exemplary ⁇ image of a cadaver coronary specimen with an implanted BMS shows struts devoid of polymer, covered by neointima;
- Figure 25 C is an exemplary ⁇ image of a cadaver coronary specimen with implanted DES struts from another cadaver showing polymer overlying the strut reflections (P, inset);
- Figure 26A is an exemplary ⁇ image showing tissue (light gray arrow) has separated the polymer off of the stent strut and the polymer has fractured (white arrow);
- Figure 26B is an exemplary ⁇ image illustrating a superficial leukocyte cluster (red arrow) and adjacent attached leukocytes overlying the site of the polymer fracture;
- Figure 26C is an exemplary ⁇ ( ⁇ image illustrating an inflammation at the edge of a strut (dashed region) from another patient;
- Figure 26D is an exemplary ⁇ OCT image illustrating an uncovered strut, completely devoid of overlying endothelium (inset);
- Figure 27A is a flow diagram of a process according to one exemplary embodiment of the present disclosure.
- Figure 27B is a flow diagram of the process according to another exemplary embodiment of the present disclosure.
- two or more imaging channels can be utilized, e.g., at least one which providing the Bessel beam illumination or detection and at least another one of which providing a Gaussian beam illumination or detection.
- This exemplary configuration can facilitate three or more unique and separable illumination-detection combinations (e.g., Bessel-Bessel, Bessel-Gaussian, Gaussian-Gaussian, etc.), where each combination can correspond to a different OCT image.
- coherent transfer functions (CTFs) for 2.5 ⁇ diameter spots are provided.
- Figure 2 illustrates a graphical comparison of a diffraction limit 200, extended focal range of 0.15 mm used in preliminary data 210, and the exemplary results of an exemplary embodiment of a procedure or technique according to the present disclosure, hereinafter termed ⁇ , with a focal range of 2.0 mm.
- ⁇ CTF can be generated, e.g., by combining Gaussian-Gaussian images 220, Bessel-Gaussian images 230, and Bessel-Bessel images 240.
- the exemplary ⁇ CTF procedure/technique can be used and/or provided over an axial focus range that can be, e.g., more than 0.5 mm, 1 mm, 2 mm, etc. (as well as others).
- the transverse FWHM spot diameters can be less than 5 ⁇ , 2 ⁇ , 1 ⁇ , etc. (as well as others).
- the depth of focus can be extended a factor of, e.g., approximately 2, 5, 10, 20, 50, 100, etc. (and possibly more) compared to the illumination with a plane wave or Gaussian beam.
- the high, low, and medium spatial frequency content in the image can be at least partially restored by combining images with different transfer functions.
- Figures 3 A-3C show exemplary OCT images of a cadaver coronary artery plaque obtained using an exemplary procedure/techniques according to exemplary embodiments of the present disclosure.
- an exemplary Gauss-Gauss image contains low spatial frequency information.
- an exemplary Bessel-Bessel image provides high-resolution but loses low and mid spatial frequencies.
- a combined ⁇ ( ⁇ image e.g., Gauss-Gauss+Gauss-Bessel+Bessel-Bessel
- images are normalized and displayed with the same brightness/contrast values.
- Figure 4A shows a side cut-away view of a diagram of a system which includes distal optics of a OCT catheter according to a first exemplary embodiment of the present disclosure.
- This exemplary system includes a Y-junction fan-out to produce the annulus (e.g., a darker shade in Figure 4A) and the Gaussian beam (e.g., a lighter shade in Figure 4A) of an exemplary distal optics design and/or configuration.
- This exemplary system of Figure 4A is provided to generate a diffraction-limited CTF and an axial focus range (e.g., a depth- of-focus) that can be more than, e.g., about 10 times longer than the diffraction-limited depth- of-focus.
- an exemplary output of a waveguide 400 can be transformed by a y-junction fan-out element410 to an array of spots that subtend a pattern such as a circle (as shown in an illustration of Figure 4C).
- the index profile of this element (as shown in an exemplary graph of Figure 4B) can be configured to be lossless and achromatic.
- the output of each spot can be individually collimated by a beam collimator in a collimator array 420.
- a Gaussian beam can be routed through a separate waveguide 430 in the center of the annular array.
- the exemplary output of the waveguide can be collimated by a collimator 440 located in the center of the collimator array 420.
- Exemplary collimated annular and Gaussian beams can be focused onto the sample using, e.g., one or more lenses, including but not limited to a gradient index (GRIN) lens 450, as shown in Figure 4A.
- GRIN gradient index
- such exemplary GRIN lens(es) 450 can be configured and/or structured to intentionally generate chromatic aberration, which can extend the axial focus yet further (as shown in an illustration of Figure 4D), and to possibly compensate for the aberrations induced by a transparent outer sheath 460.
- Electro-magnetic radiation e.g., light
- Figure 5A shows a second exemplary embodiment of distal optics of a OCT catheter system according to the present disclosure.
- the exemplary system of Figure 5 A illustrates an axicon arrangement (e.g., pair) and a routing of the annulus (shown in a darker shade in Figure 5A) and the Gaussian beam (shown in a darker shade in Figure 5A) of the distal optics design according to this exemplary embodiment.
- the exemplary system illustrate din Figure 5A can generate a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that can be more than, e.g., 10 times longer than the diffraction-limited depth-of-focus.
- the output of a waveguide 500 can be collimated by a collimator 510 located in a center of the exemplary catheter system.
- the collimated electromagnetic radiation e.g., light
- the axicons can be generated or produced using gradient index.
- a separate waveguide540 can be routed through the center of the annulus.
- the output of the waveguide can be collimated by a collimator 550 located in the center of the annulus. Simulated transverse intensity profiles of the collimated annular and Gaussian beams are shown in an illustration of Figure 5B.
- Collimated annular and Gaussian beams can be focused onto the sample using one or more lens, such as a GRIN lens 560.
- the GRIN lens 560 can be configured to intentionally generate chromatic aberration, which can extend the axial focus further (as shown in an illustration of Figure 4C), and to compensate the aberrations induced by the transparent outer sheath 570.
- the electro-magnetic radiation e.g., light
- FIG. 6 shows a schematic diagram of an imaging system for generating ⁇ images according to an exemplary embodiment of the present disclosure.
- an output of a source 600 providing electro-magnetic radiation(s) e.g., light radiation
- a linear polarizer 602 can be linearly polarized by a linear polarizer 602 and split into two or more beams by a beam splitter 604. At least one of the beams can be redirected to an input port of a switch 606.
- At least one of outputs of the switch 606 can be transmitted through a beam splitter 610, and coupled into a first light/electro-magnetic radiation guide 612. Another other of the outputs of the switch 606 can be attenuated by an attenuator 614, guided by a second light/electro-magnetic radiation guide 616 to a third beam splitter 618, and redirected to a reference reflector 620 through an attenuator 622, a third light/electro-magnetic radiation guide 624 and a dispersion compensation arrangement 626.
- An output of the light guide 612 can be connected to Bessel illumination and Bessel detection channel of a catheter 628.
- a further one of the outputs of the beam splitter 604 can be redirected to input port of a second three-port switch 630.
- One of the outputs of the switch 630 can be transmitted through a beam splitter 632, and coupled into a fourth light/electromagnetic radiation guide 634.
- Another one of the outputs of the switch 630 can be attenuated by an attenuator 635 guided by a fifth light guide 636 to a fourth beam splitter 638, and redirected to a reference reflector 640 through an attenuator 642, a fifth light guide 644 and a second dispersion compensation arrangement 646.
- the output of the light guide 634 can be connected to a Gaussian illumination and Gaussian detection channel of the catheter 628.
- the state of the switch 606 is 1, and the state of a fourth beam splitter 638 is 2, e.g., only the light/electro-magnetic radiation guide 612 can be illuminated so that the sample is illuminated by the Bessel illumination channel (see Table 1 of Figure 6).
- the back- scattered light from the sample can picked up by both, some or all of the Bessel and Gaussian detection channels of the catheter 628 (see Table 1 of Figure 6).
- the portion of electromagnetic radiation/light picked up by the Bessel detection channel can be guided by the first electro-magnetic radiation/light guide 612 to the beam splitter 610, where such radiation/light can be combined and interfered with the light from the reference reflector 620.
- At least part of the interference signal can be directed by the beam splitter 610 to a pinhole 648.
- An output of the pinhole 648 can be collimated and split by a polarizing beam splitter 650.
- One of outputs of the polarizing beam splitters 650 can be transmitted through a half wave plate 652, and detected by a spectrometer 654.
- Another of the outputs of the polarizing beam splitters 650 can be detected by a second spectrometer 656.
- a portion of the electro-magnetic radiation/light picked up by the Gaussian detection channel can be guided by the light guide 634 to the beam splitter 632, where it is combined and interfered with the light from the reference reflector 640.
- At least part of the interference signal can be directed by the beam splitter 634 to a pinhole 658.
- An output of the pinhole 658 can be collimated and split by a polarizing beam splitter 660.
- At least one of outputs of the polarizing beam splitters 660 can be transmitted through a half wave plate 662, and detected by a third spectrometer 664.
- Another of the outputs of the polarizing beam splitters 660 can be detected by a fourth spectrometer 666.
- At least part of the interference signal can be directed by the beam splitter 610 to a pinhole 648.
- An output of the pinhole 648 can be collimated and split by a polarizing beam splitter 650.
- At least one of outputs of the polarizing beam splitters 650 can be transmitted through a half wave plate 652, and detected by a spectrometer 654.
- Another of the outputs of the polarizing beam splitters 650 can be detected by a second spectrometer 656.
- the portion of light picked up by the Gaussian detection channel is guided by the electro-magnetic radiation/light guide 634 to the beam splitter 632, where it is combined and interfere with the light/radiation from the reference reflector 640. At least part of the interference signal can be directed by the fourth electro-magnetic radiation/light guide 634 to a pinhole 658.
- the output of pinhole 658 is collimated and split by a polarizing beam splitter 660. AT least one of the two outputs of the polarizing beam splitters 660 can be transmitted through a half wave plate 662, and detected by a third spectrometer 664. Another of the outputs of the polarizing beam splitters 660 can be detected by a fourth spectrometer 666.
- Such exemplary polarization-diverse detection scheme/configuration shown in Figure 6 implemented by the combination of the polarizing beam splitter 650, the half wave plate 652 and the spectrometers 654, 656, and/or a combination of the polarizing beam splitter 660, the half wave plate 662 and the spectrometers 664, 666 can reduce and/or eliminate artifacts associated with tissue or optical fiber birefringence.
- the exemplary embodiment of the ⁇ catheter system according the present disclosure illustrated in Figure 6 can contain multiple waveguides that can, e.g., independently transmit and/or receive light/radiation from the catheter to waveguides 612 and 632.
- the detected signal can be digitized and transferred by a computer 668 via an image acquisition board 670. Data can be digitally displayed on or via a monitor 672, and/or stored in a storage device 674.
- the ⁇ detection technology can be implemented using, in one exemplary embodiment, a time domain OCT (TD-OCT) system, in another exemplary embodiment, a spectral-domain (SD-OCT) system, and, in yet another exemplary embodiment, an optical frequency domain interferometry (OFDI) system.
- TD-OCT time domain OCT
- SD-OCT spectral-domain
- OFDI optical frequency domain interferometry
- Complex images and/or real images from the different transfer function illumination and detection configurations can be acquired using the exemplary embodiment of the imaging system according to the present disclosure.
- such exemplary images can be filtered and recombined to generate a new image with an improved quality and a CTF that more closely approximates the diffraction limited CTF.
- the exemplary images with different transfer functions can be filtered or recombined incoherently and/or coherently to generate a new image with a CTF procedure/technique that more closely approximates the diffraction limited CTF procedure/technique.
- Figure 7 shows another exemplary embodiment of distal optics configuration of a OCT catheter according to the present disclosure for generating a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that can be more than, e.g., approximately 10 times longer than the diffraction-limited depth-of-focus.
- an output of a waveguide 700 can be collimated by a collimator 710.
- the waveguide 700 can be routed through the annular beam and is collimated Gaussian beam will be routed through the center of the annulus.
- the collimated light can be transformed into an annular beam through two or more axicons, such as, e.g., GRIN axicons 720, 730.
- a separate waveguide740 can be routed through a center of the annulus.
- An output of the waveguide 740 can be collimated by a collimator 750 located in the center of the annulus.
- the collimated annular and Gaussian beams can be focused onto the sample using one or more lens(es) 760, which can be, e.g., one or more GRIN lenses.
- the GRIN lens 760 can be configured and/or structured to intentionally generate chromatic aberration(s), which can extend the axial focus further and compensate for the aberrations induced by a transparent outer sheath.
- the light/radiation can be directed to the artery wall by a deflector 770.
- Figure 8 shows another exemplary embodiment of the distal optics configuration of the OCT catheter according to the present disclosure.
- Such exemplary configuration can be used to generate a diffraction-limited CTF and depth of focus that is, e.g., more than 10 times longer than the diffraction-limited depth-of-focus.
- An output of a waveguide 800 can be collimated by a collimator 810.
- a pupil aperture created by the collimator 810 can be split into two or more beams, i.e., central circular beam(s) and an annular beam.
- One or more lenses 820 such as an objective lens, achromat lens , aplanat lens, or GRIN lens, that has an aperture substantially the similar as or identical to a central zone can focus a low NA Gaussian beam into the tissue or the sample.
- the annular beam can be transmitted through a spacer 830, and focused into the sample by an annular axicon lens 840 with an aperture that is substantially similar or identical to the annular beam.
- the beams can be directed to the sample by a deflector 850.
- the optical pathlength of the lens 820 can be configured to be different from that of the spacer 830 so that each of, e.g., four images generated can be pathlength encoded.
- the different images can be detected, and their CTF can be combined as per the exemplary methods and/or procedures described herein.
- Figure 9 shows another exemplary embodiment of the distal optics configuration of the OCT catheter system according to the present disclosure, which can be used for generating a diffraction-limited CTF and a depth of focus that is longer than the diffraction- limited depth-of-focus.
- the output of a waveguide 900 can be collimated by a collimator 910.
- a pupil aperture created by the collimator 910 can be split into two or more zones by a circular glass window 920 positioned at the center of the objective lens aperture, e.g., (i) a central circular zone that is transmitted through the circular glass window 920, and (ii) an annular zone.
- the central circular beam can be focused as a low NA Gaussian beam into the tissue and/or sample, and the annular beam can be focused into a Bessel beam focus in the tissue by the lens 930.
- a glass window can have a higher refractive index than air, and the thickness of the window can be so chosen such that the light/radiation field that undergoes different channel can be path-length separated and/or encoded.
- Figure 10 shows a further exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and a depth of focus that can be longer than the diffraction-limited depth-of-focus.
- An output of a waveguide 1000 can be collimated by a collimator 1010.
- a pupil aperture created by the collimator 1010 can be split into a number of concentric zones 1020, 1030, 1040.
- a multifocal lens such as, e.g., a GRIN lens, can be used so that the beam in each zone can be focused to a different axial focal position.
- the scattered light/radiation from each zone can be optical pathlength-encoded so that such scattered beams do not interfere with each other.
- the different images can be detected, and their CTF combined pursuant to the exemplary methods and procedures described herein.
- Figure 11 shows yet another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that is longer than the diffraction-limited depth-of- focus.
- an output of a point object 1100 can be transformed by a mirror tunnel device 11 10 to multiple orders of light/radiation beams, e.g., zeroth order beam 1 120, -1st order beam 1130, and -2nd order beam 1140, etc.
- each order of rays can contain a unique band of spatial frequency of the illumination/detection CTF of the focusing device.
- These orders can, in yet another exemplary embodiment, be path length-encoded so that images generated therein can be detected, and their CTF combined using the different images corresponding to the different orders as per the exemplary CTF combination methods and/or procedures described herein.
- Figures 12 shows another exemplary embodiment of the distal optics configuration of the OCT catheter system according to the present disclosure for generating a diffraction-limited CTF and a depth of focus that is longer than the diffraction-limited depth- of-focus.
- an output of a waveguide 1200 can be focused by a half ball lens 1210.
- a planar surface of the half ball lens 1210 can have a binary phase pattern 1220.
- the depth of the pattern can be configured to produce a small phase shift, e.g., such as a pattern depth of 198 nm ( ⁇ phase shift at 850 nm).
- the top surface can be coated with a reflecting coating, such as Au, and a bottom surface can be coated with the same and/or another coating such as Al, with the final phase shift being given by a curve 1300 shown in a graph of Figure 13, which illustrates an optical phase length difference of the glass mask (e.g., no metal coating) and a total phase shift (e.g., mask + coating).
- a reflecting coating such as Au
- a bottom surface can be coated with the same and/or another coating such as Al, with the final phase shift being given by a curve 1300 shown in a graph of Figure 13, which illustrates an optical phase length difference of the glass mask (e.g., no metal coating) and a total phase shift (e.g., mask + coating).
- a curve 1310 and a curve 1320 of the graph of Figure 13 can have a wavelength-dependent phase change of the p-polarized light upon reflection at BK7-A1 and BK7-Au, respectively, with an incident angle of 45 degrees.
- the curve 1330 can be the wavelength dependent phase shift of the light caused by, e.g., 198 nm height difference upon 45 degree reflection at BK7-air interface.
- a binary phase mask can be optimized to produce an extended axial focus (as shown in an illustration of Figure 14b) compared with the diffraction limited axial focus (as shown in an illustration of Figure 14a).
- the light/radiation transmitted from the surfaces with different phase shifts can generate different transfer functions, which can be detected and combined to create a new image with a different CTF pursuant to the exemplary methods and/or procedures described herein.
- Figure 15A shows a side-cut-away view of a diagram of another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and an depth of focus longer than the diffraction-limited depth-of- focus.
- the system of Figure 15A generates the results by a factor of, e.g., approximately 2, 5, 10, 20, 10, 100, etc.
- An output of a waveguide 1500 can be collimated by one or more lens(es) 1510.
- the collimated beam can be spatially modulated by a phase doublet 1520, which can include a positive phase plate and a negative phase plate with the same or similar phase pattern.
- Figure 15B shows an exemplary graph of transverse phase profiles of an exemplary mask (e.g., BK7-SNPH2 phase doublet mask) illustrated in Figure 15A
- an exemplary mask e.g., BK7-SNPH2 phase doublet mask
- the spatially modulated beam can be focused into an extended axial focus by an objective lens 1530.
- Figure 16 shows still another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and depth of focus according to the present disclosure that is longer than the diffraction-limited depth- of- focus, by a factor of preferably approximately 2, 5, 10, 20, 10, 100, etc..
- An output of a light source 1600 can be split by a beam splitter 1610.
- the beam aperture of at least one of the outputs of the beam splitter can be split or separated by a rod mirror 1620 into two or more regions.
- the rod mirror 1620 can redirect the central part of the beam to a reference reflector 1630 through an objective lens 1640.
- the annular beam can be focused into the sample by a second objective lens 1660 that can be substantially similar or identical to one or more lens(es) 1640 into a Bessel focus featured with extended axial focus and super-resolution in transverse direction (as shown in the exemplary ⁇ images of Figure 18D).
- the light back-scattered from the sample is combined with the light reflected from the reference reflector through the rod mirror at a pinhole 1660.
- the output of the pinhole 1660 is detected by a spectrometer 1670.
- the objective lens 1650 is configured to intentionally generate chromatic aberration and spherical aberration, which extend the axial focus further (as shown in the exemplary ⁇ images of Figures 18C and 18D).
- Figure 18A shows an exemplary ⁇ image of a coronary plaque showing multiple leukocytes (arrows).
- Figure 18B shows an exemplary ⁇ image of a coronary plaque illustrating multiple leukocytes (arrows) of two different cell types, one smaller cell with scant cytoplasm, consistent with a lymphocyte (L) and another, larger cell with a highly scattering cytoplasm, indicative of a monocyte (M).
- L lymphocyte
- M monocyte
- Figure 18A illustrates an exemplary ⁇ image of a coronary plaque showing multiple leukocytes 1800 which has been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 18B illustrates an exemplary ⁇ image of a coronary plaque showing multiple leukocytes of two different cell types, one smaller cell 1810 with scant cytoplasm, consistent with a lymphocyte and another, larger cell 1820 with a highly scattering cytoplasm, suggestive of a monocyte.
- Figure 18C illustrates an exemplary ⁇ image of a coronary plaque showing a cell 1830 with an indented, bean-shaped nucleus characteristic of a monocyte.
- Figure 18D illustrates an exemplary ⁇ ( ⁇ image of a coronary plaque showing a leukocyte 1840 with a multi-lobed nucleus, suggestive of a neutrophil attached to the endothelial surface.
- Figure 18E illustrates an exemplary ⁇ image of a coronary plaque showing multiple leukocytes 1850, tethered to the endothelial surface by pseudopodia 1860.
- Figure 18F illustrates an exemplary ⁇ ( ⁇ image of a coronary plaque showing cells 1870 with the morphology of monocytes in this cross-section and inset transmigrating through the endothelium 1880.
- Figure 18G illustrates an exemplary ⁇ image of multiple leukocytes 1890 distributed on the endothelial surface.
- Figure 19A-19E show exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 19A illustrates an exemplary ⁇ image of platelets 1900 (P) adjacent to a leukocyte characteristic of a neutrophil 1910 (N), which is also attached to a small platelet 1920 (yellow arrow).
- Figure 19B illustrates an exemplary ⁇ image of fibrin 1930 (F) which is visible as linear strands bridging a gap in the coronary artery wall.
- Figure 19C illustrates an exemplary ⁇ image of a cluster of leukocytes 1940 (L), adherent to the fibrin in an adjacent site to Figure 19B .
- Figure 19D illustrates an exemplary ⁇ image of Fibrin thrombus 1950 (T) with multiple, entrapped leukocytes.
- Figure 19E an ⁇ image of a more advanced thrombus 1960 (T) showing a leukocyte 1970 (arrow) and fibrin strands 1980(inset, F).
- Figures 20A-20D show further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 20A illustrates a cross-sectional exemplary ⁇ image of endothelial cells 2000 in culture.
- Figure 20B shows an en face exemplary ⁇ image of endothelial cells 2010 in culture.
- Figure 20C illustrates an exemplary ⁇ image of native swine coronary artery cross-section 2020.
- Figure 20D shows a three-dimensional rendering of the swine coronary artery, demonstrating endothelial "pavementing" 2030 ⁇
- Figures 20A-20D show further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 21 A shows an exemplary ⁇ image of microcalcifications which are seen as bright densities within the ⁇ image of the fibrous cap 2100.
- Figure 2 IB illustrates an exemplary ⁇ image of microcalcifications which are seen as purple densities on the corresponding histology 2110.
- Figures 20A-20D illustrate further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 22A shows an exemplary ⁇ image of a large calcium nodule, demonstrating disrupted intima/endothelium 2200.
- Figure 22B shows an expanded view of an exemplary region enclosed by the red box shows microscopic tissue strands, consistent with fibrin 2210, adjoining the unprotected calcium 2220 to the opposing detached intima.
- Figure 22C shows a corresponding histology illustrating fibrin 2230 and denuded calcific surface 2240.
- Figures 23A-26C illustrate further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure.
- Figure 23A shows an exemplary ⁇ ( ⁇ image of a large necrotic core 2300 fibroatheroma, demonstrating thick cholesterol crystals 2310, characterized by reflections from their top and bottom surfaces.
- Figure 23B shows an exemplary ⁇ image of thin crystal 2320, piercing the cap of another necrotic core plaque 2330, shown in more detail in the inset.
- Figure 24A shows an exemplary ⁇ image of many smooth muscle cells 2400 appear as low backscattering spindle-shaped cells (inset).
- Figure 24B shows an exemplary ⁇ image of smooth muscle cells producing collagen are spindle shaped, have a high backscattering interior 2410 and a "halo" of low backscattering 2420, which can represent the cell body 2430 and collagen matrix 2440, respectively (e.g., histology inset).
- Figure 25 A shows an exemplary ⁇ image of Taxus Liberie (Boston Scientific, Natick, MA) struts without polymer 2500, with polymer without drug 2510, and with polymer with drug 2520.
- polymer reflection 2530, strut reflection 2540 and multiple reflections 2550 and 2560 can be seen.
- Figure 25B shows an exemplary ⁇ 1 image of a cadaver coronary specimen with an implanted BMS 2570 shows struts devoid of polymer, covered by neointima 2580.
- Figure 25C shows an exemplary ⁇ image of a cadaver coronary specimen with implanted DES struts 2590 from another cadaver showing polymer overlying the strut reflections 2595 (inset).
- Figure 26A shows an exemplary ⁇ image showing tissue 2600 has separated the polymer 2610 off of the stent strut 2620 and the polymer has fractured 2630.
- Figure 26B shows an exemplary ⁇ image showing superficial leukocyte cluster 2640 and adjacent attached leukocytes 2650 overlying the site of the polymer fracture 2660.
- Figure 26C shows an exemplary ⁇ image showing inflammation 2670 at the edge of a strut 2680 from another patient.
- Figure 26D shows an exemplary ⁇ image showing uncovered strut 2690, completely devoid of overlying endothelium.
- the optical elements for the exemplary ⁇ OCT system/probe can be fabricated by irradiating a photopolymer with a tightly focused beam, whose position can be controlled in three- dimensions with nm-level precision.
- the photopolymer can respond to a variable refractive index that can be proportional to an optical energy deposited, facilitating a miniature, solid volume to implement complex optical functionality.
- Such exemplary method and procedure previously generated miniature fiber couplers, tapered waveguides, waveguide arrays, lenses, diffractive optical elements, and complex optical assemblies, all within a monolithic, polymer component, for example.
- This exemplary embodiment facilitates the exemplary ⁇ probe to be a stable, monolithic element that can provide the extended focal depth functionality described herein, than can be incorporated into, e.g., miniaturized ⁇ catheters and endoscopes.
- One advantage of this exemplary embodiment is that the photopolymer-derived optical element/arrangement can be made repeatedly with a high precision, and can be mass-produced at relatively low cost.
- Figure 27A shows a flow diagram of a method for providing data associated with at least one portion of at least one sample according to one exemplary embodiment of the present disclosure.
- procedure 2710 at least one first radiation is forwarded to at least one portion of the sample through at least one optical arrangement (e.g., as described in various exemplary embodiments herein), and at least one second radiation is received from the portion which is based on the first radiation.
- the optical arrangement Based on an interaction between the optical arrangement and the first radiation and/or the second radiation, the optical arrangement has a first transfer function.
- at least one third radiation is forwarded to the portion through such optical arrangement, and at least one fourth radiation is received from the portion which is based on the third radiation.
- the optical arrangement Based on an interaction between this optical arrangement and the third radiation and/or the fourth radiation, the optical arrangement has a second transfer function.
- the first transfer function can be at least partially different from the second transfer function.
- the data associated with the portion(s) can be generated based on the second and fourth radiations.
- Figure 27B shows a flow diagram of the method for providing data associated with at least one portion of at least one sample according to another exemplary embodiment of the present disclosure.
- procedure 2760 at least one first radiation is forwarded to at least one portion of the sample through at least one first optical arrangement (e.g., as described in various exemplary embodiments herein), and at least one second radiation is received from the portion which is based on the first radiation.
- the first optical arrangement Based on an interaction between the first optical arrangement and the first radiation and/or the second radiation, the first optical arrangement has a first transfer function.
- procedure 2770 at least one third radiation is forwarded to the portion through at least one second optical arrangement, and at least one fourth radiation is received from the portion which is based on the third radiation.
- the optical arrangement Based on an interaction between the second optical arrangement and the third radiation and/or the fourth radiation, the optical arrangement has a second transfer function.
- the first transfer function can be at least partially different from the second transfer function.
- the data associated with the portion(s) can be generated based on the second and fourth radiations.
Abstract
Exemplary embodiments of apparatus, systems and methods can be provided for providing at least one electro-magnetic radiation to at least one sample. For example, a plurality of wave-guiding arrangements can be provided which are configured to (i) provide the electro-magnetic radiation(s), and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each of the electro-magnetic radiation(s) to have a predetermined value. The exemplary apparatus can be part of a probe. Further the exemplary apparatus can include an interferometric arrangement provided in communication with the probe and/or be part of the probe.
Description
SYSTEMS, METHODS AND COMPUTER-ACCESSIBLE MEDIUM WHICH PROVIDE MICROSCOPIC IMAGES OF AT LEAST ONE ANATOMICAL STRUCTURE AT A PARTICULAR RESOLUTION
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is based upon and claims the benefit of priority from U.S. Patent Application Serial Nos. 61/311,171 and 61/311,272, both filed March 5, 2010, the entire disclosures of which are incorporated herein by reference.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to exemplary embodiments of imaging systems, apparatus and methods, and more specifically to methods, systems and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution.
BACKGROUND INFORMATION
[0003] Coronary artery disease (CAD) and its clinical manifestations, including heart attack or acute myocardial infarction (AMI), is the number one cause of mortality in the US, claiming nearly 500,000 lives and costing approximately $400B per year. Topics relevant to the pathophysiology of CAD, such as the development and progression of coronary atherosclerotic lesions, plaque rupture and coronary thrombosis, and the arterial response to coronary device and pharmacologic therapies are therefore of great significance today. These biological processes can be mediated by molecular and cellular events that occur on a microscopic scale. Certain progress in understanding, diagnosing, and treating CAD has been hindered by the fact that it has been difficult or impossible to interrogate the human coronary wall at cellular-level resolution in vivo.
[0004] Over the past decade, intracoronary optical coherence tomography (OCT) has been developed, which is a catheter-based technique that obtains cross-sectional images of reflected light from the coronary wall. Intracoronary OCT has a spatial resolution of 10 μιη, which is an order of magnitude better than that of the preceding coronary imaging method, intravascular ultrasound (IVUS). In the parent R01, a second-generation form of OCT has been developed, i.e., termed optical frequency domain imaging (OFDI), that has very high image acquisition rates, making it possible to conduct high-resolution, three-dimensional imaging of the coronary vessels. In addition, a flushing method has been developed which, in combination with the high frame rate of OFDI, can overcome at least some of the obstacles of blood interference with the OCT signal. As a direct result, it may be preferable to perform intracoronary OCT procedures in the clinical setting. Indeed, certain interventional cardiology applications for OCT have emerged, and growing the field exponentially. It is believed that OCT can become a significant imaging modality for guiding coronary interventions worldwide.
[0005] Since the technology developed in the parent R01 has been translated and facilitated for a clinical practice through the distribution of commercial OFDI imaging systems, it may be preferable to review macromolecules and cells involved in the pathogenesis of CAD.
[0006] For example, a transverse resolution in OCT procedure(s) can be determined by the catheter's focal spot size. To improve the resolution, it is possible to increase the numerical aperture of the lens that focuses light into the sample. This conventional method, however, neglects the intrinsic compromise between transverse resolution and depth of field in cross-sectional OCT images and results in images in which only a narrow depth range is resolved.
[0007] An alternative approach can exploit the unique characteristics of Bessel, or "non- diffracting" beams to produce high transverse resolution over enhanced depths-of-field. Bessel beam illumination and detection of light reflected from the sample, however, can suffer from a significant reduction in contrast and detection efficiency. Thus, there may be a need to overcome at least some of the deficiencies associated with the conventional arrangements and methods described above.
[0008] As briefly indicated herein above, certain exemplary embodiments of the present disclosure can be associated and/or utilize analysis and manipulation of a coherent transfer function (CTF) of an exemplary OCT system. The current invention is instead based on an analysis and manipulation of the coherent transfer function (CTF) of an OCT system. The CTF can be considered a coherent extension of a modulation transfer function (MTF) and an optical transfer function (OTF). Thus, for example, for non-interferometric systems, the MTF or OTF can be manipulated and utilized according to certain exemplary embodiments. In general, the quality of an optical system can be assessed by comparing its transfer function to that of a diffraction-limited optical system. Figure 1 shows a graph of coherent transfer functions (CTFs) for, e.g., a diffraction limited 2.5 μιτι diameter spot and 2.5 μπι spot with an extended focal range of 2.0 mm, produced by Bessel beam illumination and detection. As illustrated in Figure 1, the transfer function of a Bessel beam illumination and detection 100 can have spatial frequencies that exceed a diffraction- limited system 110, although it likely sacrifices low- and mid-range spatial frequencies, possibly resulting in reduced contrast and detection sensitivity.
[0009] Thus, there may be a need to overcome at least some of the deficiencies associated with the conventional arrangements and methods described above. SUMMARY OF EXEMPLARY EMBODIMENTS OF THE DISCLOSURE
[0010] To address and/or overcome such deficiencies, one of the objects of the present disclosure is to provide exemplary embodiments of systems, methods and computer- accessible medium according to the present disclosure, which can provide microscopic images of at least one anatomical structure at a particular resolution. Another object of the present disclosure is to overcome a limited depth of focus limitations of conventional Gaussian beam and spatial frequency loss of Bessel beam systems for OCT procedures and/or systems and other forms of extended focal depth imaging.
[0011] According to another exemplary embodiment of the present disclosure, more than two imaging channels can illuminate/detect different Bessel and/or Gaussian beams. In yet a further exemplary embodiment, different transfer functions can be illuminated and/or detected. The exemplary combination of images obtained with such additional exemplary beams can facilitate the μΟ^Τ CTF to be provided to the diffraction-limited case, and can also facilitate a depth-of-field extension even further.
[0012] Accordingly, exemplary embodiments of apparatus, systems and methods can be provided for providing at least one electro-magnetic radiation to at least one sample. For example, a plurality of wave-guiding arrangements can be provided which are configured to (i) provide the electro-magnetic radiation(s), and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each of the electro-magnetic radiation(s) to have a predetermined value. The exemplary apparatus can be part of a probe. Further the exemplary apparatus can include an interferometric arrangement provided in communication with the probe and/or be part of the probe.
[0013] In another exemplary embodiment of the present disclosure, the wave-guiding arrangements can provide the radiation(s) in at least partially a circular pattern. At least one lens arrangement can be included which is configured to receive the electro-magnetic radiation(s) from the wave-guiding arrangements, and generate a further focus-spot radiation.
The lens arrangement(s) can be configured to cause the further focus-spot radiation to have (i) an extended focal depth, and/or (ii) a diameter that is smaller than a diffraction limited spot on or in the sample. The diffraction limited spot can be a three-dimensional spot. In addition or alternatively, The lens arrangement(s) can include a grin lens.
[0014] According to yet another exemplary embodiment of the present disclosure, at least one of the wave-guiding arrangements can be (i) a single-mode wave-guide, and/or (ii) composed a photo-polymer. Additionally, a further wave-guiding arrangement can be provided, which is configured to provide a further electro-magnetic radiation to the sample, where the electro-magnetic radiation(s) and the further electro-magnetic radiation can be provided to at least partially overlapping portions of the sample. A housing can also be provided which at least partially encloses the wave-guiding aixangements, and/or a sheath can be provided which encloses the housing. Further, a control arrangement can be provided which is configured to rotate and/or translate the housing. The lens arrangement(s) can include at least one optical element formed by and/or subjected to a photopolymer processing. The photopolymer processing can include irradiating a photopolymer so as to form the optical element(s).
[0015] In a further exemplary embodiment of the present disclosure, method and system can be provided for generating data associated with at least one portion of a sample. For example, at least one first radiation can be forwarded to the portion(s) of the sample through at least one optical arrangement which is formed by or subjected to a photopolymer processing. At least one second radiation can be received from the portion(s) which can be based on the first radiation(s). Based on an interaction between the optical arrangement(s) and the first radiation and/or the second radiation, the optical arrangement can have a first transfer function. Then, at least one third radiation can be forwarded to the portion(s) through the optical arrangement. At least one fourth radiation can be received from the
portion(s) which can be based on the third radiation(s). Based on an interaction between the optical arrangement(s) and the third radiation and/or the fourth radiation, the optical arrangement(s) can have a second transfer function, where the first transfer function can be at least partially different from the second transfer function. Further, the data associated with the portion(s) can be generated based on the second and fourth radiations.
[0016] According to yet further exemplary embodiment of the present disclosure, method and system can be provided also for generating data associated with at least one portion of a sample. For example, at least one first radiation can be forwarded to the portion(s) of the sample through at least one first optical arrangement which is formed by or subjected to a photopolymer processing. At least one second radiation can be received from the portion(s) which can be based on the first radiation(s). Based on an interaction between the first optical arrangement(s) and the first radiation and/or the second radiation, the first optical arrangement(s) can have a first transfer function. Then, at least one third radiation can be forwarded to the portion(s) through at least one second optical arrangement. At least one fourth radiation can be received from the portion(s) which can be based on the third radiation(s). Based on an interaction between the second optical arrangement(s) and the third radiation and/or the fourth radiation, the second optical arrangement(s) can have a second transfer function, where the first transfer function can be at least partially different from the second transfer function. Further, the data associated with the portion(s) can be generated based on the second and fourth radiations. The first optical arrangement(s) and/or the second optical arrangement(s) can be formed by or subjected to a photopolymer processing.
[0017] These and other objects, features and advantages of the exemplary embodiment 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 DRAWING(S)
[0018] Further objects, features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present disclosure, in which:
[0019] Figure 1 is an exemplary graph of coherent transfer functions (CTFs) as a function of spatial frequencies produced by the prior Bessel beam illumination and detection;
[0020] Figure 2 is an exemplary graph of coherent transfer functions (CTFs) as a function of spatial frequencies produced by an exemplary embodiment of a procedure and/or technique according to the present disclosure;
[0021] Figure 3 A is a first exemplary OCT image an exemplary OCT image of a cadaver coronary artery plaque obtained using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, whereas an exemplary Gauss-Gauss image contains low spatial frequency information;
[0022] Figure 3B is a second exemplary OCT image of the cadaver coronary artery plaque using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, whereas an exemplary Bessel-Bessel image provides high-resolution but loses low and mid spatial frequencies;
[0023] Figure 3C is a third exemplary OCT image of the cadaver coronary artery plaque using an exemplary procedure/techniques according to an exemplary embodiment of the present disclosure, which provides a combined μOCT image (e.g., Gauss-Gauss+Gauss- Bessel+Bessel-Bessel), and images are normalized and displayed with the same brightness/contrast values;
[0024] Figure 4A is a side cut-away view of a diagram of distal optics of a OCT catheter system according to an exemplary embodiment of the present disclosure;
[0025] Figure 4B is an exemplary graph of a polymer index profile generated using a Y- junction fan-out of the system the exemplary embodiment of shown in Figure 4 A;
[0026] Figure 4C is an exemplary graph of an illumination profile generated using the Y- junction fan-out of the system the exemplary embodiment of shown in Figure 4A;
[0027] Figure 4D is an exemplary graph of an simulated x-z PSF using the Y-junction fan-out of the system the exemplary embodiment of shown in Figure 4A;
[0028] Figure 5A is a side cut-away view of a diagram of the distal optics of a OCT catheter system according to another exemplary embodiment of the present disclosure;
[0029] Figure 5B is an exemplary graph of an illumination profile generated using the distal optics con figuration of the system the exemplary embodiment of shown in Figure 5 A;
[0030] Figure 5C is an exemplary graph of simulated x-z PSF generated using the distal optics con figuration of the system the exemplary embodiment of shown in Figure 5 A;
[0031] Figure 6 is a schematic diagram of a system for generating one or more μΟΟΤ images according to still a further exemplary embodiment of the present disclosure;
[0032] Figure 7 are side cut-away views of diagrams of the distal optics of the OCT catheter system according to still another exemplary embodiment of the present disclosure which includes axicon pair and a routing of a ring beam and a Gaussian beam of the distal optics configuration;
[0033] Figure 8 is a side cut-away view of a diagram of the OCT catheter system according to yet further exemplary embodiment of the present disclosure which includes an exemplary optical pathlength incoding probe configuration that uses a single fiber and a single axicon lens;
[0034] Figure 9 are side cut-away views of diagrams of the OCT catheter system according to a still further exemplary embodiment of the present disclosure which includes a
further exemplary optical pathlength incoding probe configuration that uses a single fiber and a single axicon lens;
[0035] Figure 10 are schematic views of diagrams of the distal optics of the OCT catheter system according to a further exemplary embodiment of the present disclosure which includes a single fiber multifocal lens probe configuration;
[0036] Figure 11 is a side cut-away view of a diagram of the OCT catheter system according to a still further exemplary embodiment of the present disclosure which utilizes a mirror tunnel;
[0037] Figure 12 is a side cut-away view of a diagram a portion of the OCT catheter system according to yet another exemplary embodiment of the present disclosure which utilizes a reflective achromatic phase mask and a ball lens;
[0038] Figure 13 is a graph of a phase shift spectra of chromatic light upon reflection at glass-metal interface based on the exemplary embodiment of Figure 12;
[0039] Figure 14A is an illustration of a Huygens diffraction pattern of lens with conventional focusing;
[0040] Figure 14B is an exemplary illustration of a Huygens diffraction pattern of lens with reflective achromatic phase mask and ball lens depicted in the exemplary embodiment of the system illustrated in Figure 13.
[0041] Figure 15A is a schematic diagram of an exemplary embodiment of a focusing arrangement that uses a refractive achromatic phase doublet mask in accordance with an exemplary embodiment of the present disclosure;
[0042] Figure 15B is an exemplary graph of transverse phase profiles of an exemplary mask illustrated in Figure 15 A;
[0043] Figure 16 is a schematic diagram of the OCT system which includes a wavefront beam splitter and a common path interferometer, according to yet another exemplary embodiment of the present disclosure;
[0044] Figure 17A is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses a monochromatic light source (e.g.., λ = 825 nm) and a spherical aberration free objective lens;
[0045] Figure 17B is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses a monochromatic light source (e.g., λ = 825 nm) and an objective lens with a spherical aberration and a wavelength dependent focal shift;
[0046] Figure 17C is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses a broadband source (e.g., about 600 nm to 1050 nm) and an objective lens with spherical aberration and a wavelength dependent focal shift;
[0047] Figure 17D is an exemplary simulated PSF illustration of generated by the exemplary OCT system shown in Figure 16 that uses broadband source (e.g., 600 nm to 1050 nm), an objective lens with spherical aberration and a wavelength dependent focal shift, and an wavefront beam splitter;
[0048] Figure 18 A is an exemplary μΟΟΤ image of a coronary plaque showing multiple leukocytes (arrows);
[0049] Figure 18B is an exemplary μΟΟΤ image of a coronary plaque illustrating multiple leukocytes (arrows) of two different cell types, one smaller cell with scant cytoplasm, consistent with a lymphocyte (L) and another, larger cell with a highly scattering cytoplasm, indicative of a monocyte (M);
[0050] Figure 18C is an exemplary μΟΟΎ image of a coronary plaque illustrating a cell with an indented, bean-shaped nucleus (M) characteristic of a monocyte;
[0051] Figure 18D is an exemplary μ(^Τ image of a coronary plaque illustrating a leukocyte with a multi-lobed nucleus, which can indicate a neutrophil (N) attached to the endothelial surface;
[0052] Figure 18E is an exemplary μΟ^Τ image of the coronary plaque illustrating multiple leukocytes tethered to the endothelial surface by pseudopodia;
[0053] Figure 18F is an exemplary μΟ^Τ image of the coronary plaque illustrating cells with the morphology of monocytes (M) in a cross-section and an inset transmigrating through the endothelium;
[0054] Figure 18G is an exemplary μΟΟΓ image of multiple leukocytes distributed on the endothelial surface;
[0055] Figure 19A is an exemplary μΟΟΎ image of platelets (P) adjacent to a leukocyte characteristic of a neutrophil (N), which is also attached to a small platelet;
[0056] Figure 19B is an exemplary μΟΟΎ image of fibrin (F) which is visible as linear strands bridging a gap in the coronary artery wall;
[0057] Figure 19C is an exemplary μΟΟΎ image of a cluster of leukocytes (L), adherent to the fibrin in an adjacent site to that illustrated in Figure 19B;
[0058] Figure 19D is an exemplary μΟΟΎ image of Fibrin thrombus (T) with multiple, entrapped leukocytes;
[0059] Figure 19E is an exemplary μΟΟΓ image of a more advanced thrombus (T) showing a leukocyte and fibrin strands;
[0060] Figure 20A is a cross-sectional exemplary μOCT image of endothelial cells in culture;
[0061] Figure 20B is an en face exemplary μΟΟΊ image of endothelial cells in culture;
[0062] Figure 20C is an exemplary μΟΟΎ image of a native swine coronary artery cross- section;
[0063] Figure 20D is an exemplary three-dimensional rendering of the swine coronary artery, demonstrating endothelial "pavementing";
[0064] Figure 21 is an exemplary μ(^Τ image of microcalcifications which can be seen as bright densities within the μΟ^Γ image of the fibrous cap;
[0065] Figure 21B is an exemplary μΟ^Γ image of the microcalcifications which can be seen as dark densities on the corresponding histology;
[0066] Figure 22A is an exemplary μΟΟΓ image of a large calcium nodule, demonstrating disrupted intima/endothelium;
[0067] Figure 22B is an expanded view of the region enclosed by a box illustrating microscopic tissue strands, consistent with fibrin (F), adjoining the unprotected calcium (white arrow) to the opposing detached intima;
[0068] Figure 22C is an illustration of a corresponding histology of fibrin (F, black arrows) and denuded calcific surface (gray arrow);
[0069] Figure 23A is an exemplary μ(^Τ image of a large necrotic core (NC) fibroatheroma, demonstrating thick cholesterol crystals (CC), characterized by reflections from their top and bottom surfaces;
[0070] Figure 23B is an exemplary μΟΟΎ image of thin crystal (CC, gray arrow) piercing the cap of another necrotic core plaque (NC), shown in more detail in the inset;
[0071] Figure 24 A is an exemplary μΟΟΓ image of various smooth muscle cells appearing as low backscattering spindle-shaped cells (inset);
[0072] Figure 24B is an exemplary μ(^Τ image of smooth muscle cells producing collagen are spindle shaped, have a high backscattering interior (light gray arrow) and a
"halo" of low backscattering (white arrow), which represents the cell body and collagen matrix, respectively (histology inset);
[0073] Figure 25A is an exemplary μΟΟΎ image of Taxus Liberie struts with/without polymer/drug, i.e., for polymer-coated struts, polymer reflection (PR), strut reflection (SR) and multiple reflections (MR1, MR2) can be seen;
[0074] Figure 25B is an exemplary μΟΟΓ image of a cadaver coronary specimen with an implanted BMS shows struts devoid of polymer, covered by neointima;
[0075] Figure 25 C is an exemplary μΟΟΎ image of a cadaver coronary specimen with implanted DES struts from another cadaver showing polymer overlying the strut reflections (P, inset);
[0076] Figure 26A is an exemplary μΟΟΤ image showing tissue (light gray arrow) has separated the polymer off of the stent strut and the polymer has fractured (white arrow);
[0077] Figure 26B is an exemplary μΟΟΓ image illustrating a superficial leukocyte cluster (red arrow) and adjacent attached leukocytes overlying the site of the polymer fracture;
[0078] Figure 26C is an exemplary μ(^Τ image illustrating an inflammation at the edge of a strut (dashed region) from another patient;
[0079] Figure 26D is an exemplary μOCT image illustrating an uncovered strut, completely devoid of overlying endothelium (inset);
[0080] Figure 27A is a flow diagram of a process according to one exemplary embodiment of the present disclosure; and
[0081] Figure 27B is a flow diagram of the process according to another exemplary embodiment of the present disclosure.
[0082] 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 exemplary embodiments without departing from the true scope and spirit of the subject disclosure as defined by the appended claims.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0083] According to one exemplary embodiment of the present disclosure, two or more imaging channels can be utilized, e.g., at least one which providing the Bessel beam illumination or detection and at least another one of which providing a Gaussian beam illumination or detection. This exemplary configuration can facilitate three or more unique and separable illumination-detection combinations (e.g., Bessel-Bessel, Bessel-Gaussian, Gaussian-Gaussian, etc.), where each combination can correspond to a different OCT image. As shown in the exemplary graph of Figure 2, coherent transfer functions (CTFs) for 2.5 μπι diameter spots are provided.
[0084] For example, Figure 2 illustrates a graphical comparison of a diffraction limit 200, extended focal range of 0.15 mm used in preliminary data 210, and the exemplary results of an exemplary embodiment of a procedure or technique according to the present disclosure, hereinafter termed μΟ^Τ, with a focal range of 2.0 mm. According to one exemplary embodiment of the present disclosure he μΟΟΓ CTF can be generated, e.g., by combining Gaussian-Gaussian images 220, Bessel-Gaussian images 230, and Bessel-Bessel images 240.
[0085] In another exemplary embodiment of the present disclosure, the exemplary μΟΟΤ CTF procedure/technique can be used and/or provided over an axial focus range that can be, e.g., more than 0.5 mm, 1 mm, 2 mm, etc. (as well as others). According to additional exemplary embodiments of the present disclosure, the transverse FWHM spot diameters can
be less than 5 μηι, 2 μη , 1 μηι, etc. (as well as others). In still further exemplary embodiments of the present disclosure, the depth of focus can be extended a factor of, e.g., approximately 2, 5, 10, 20, 50, 100, etc. (and possibly more) compared to the illumination with a plane wave or Gaussian beam. In yet another exemplary embodiment of the present disclosure, the high, low, and medium spatial frequency content in the image can be at least partially restored by combining images with different transfer functions.
[0086] Figures 3 A-3C show exemplary OCT images of a cadaver coronary artery plaque obtained using an exemplary procedure/techniques according to exemplary embodiments of the present disclosure. For example, in Figure 3A an exemplary Gauss-Gauss image contains low spatial frequency information. In Figure 3B, an exemplary Bessel-Bessel image provides high-resolution but loses low and mid spatial frequencies. Further, in Figure 3C, a combined μ(^Τ image (e.g., Gauss-Gauss+Gauss-Bessel+Bessel-Bessel) is provided, and images are normalized and displayed with the same brightness/contrast values.
[0087] Figure 4A shows a side cut-away view of a diagram of a system which includes distal optics of a OCT catheter according to a first exemplary embodiment of the present disclosure. This exemplary system includes a Y-junction fan-out to produce the annulus (e.g., a darker shade in Figure 4A) and the Gaussian beam (e.g., a lighter shade in Figure 4A) of an exemplary distal optics design and/or configuration. This exemplary system of Figure 4A is provided to generate a diffraction-limited CTF and an axial focus range (e.g., a depth- of-focus) that can be more than, e.g., about 10 times longer than the diffraction-limited depth- of-focus. As shown in Figure 4A, an exemplary output of a waveguide 400 can be transformed by a y-junction fan-out element410 to an array of spots that subtend a pattern such as a circle (as shown in an illustration of Figure 4C). The index profile of this element (as shown in an exemplary graph of Figure 4B) can be configured to be lossless and
achromatic. The output of each spot can be individually collimated by a beam collimator in a collimator array 420.
[0088] As show in Figure 4A, a Gaussian beam can be routed through a separate waveguide 430 in the center of the annular array. The exemplary output of the waveguide can be collimated by a collimator 440 located in the center of the collimator array 420. Exemplary collimated annular and Gaussian beams can be focused onto the sample using, e.g., one or more lenses, including but not limited to a gradient index (GRIN) lens 450, as shown in Figure 4A. In addition to focusing two beams, such exemplary GRIN lens(es) 450 can be configured and/or structured to intentionally generate chromatic aberration, which can extend the axial focus yet further (as shown in an illustration of Figure 4D), and to possibly compensate for the aberrations induced by a transparent outer sheath 460. Electro-magnetic radiation (e.g., light) can be directed to an anatomical structure480 by a deflector 470.
[0089] Figure 5A shows a second exemplary embodiment of distal optics of a OCT catheter system according to the present disclosure. For example, the exemplary system of Figure 5 A illustrates an axicon arrangement (e.g., pair) and a routing of the annulus (shown in a darker shade in Figure 5A) and the Gaussian beam (shown in a darker shade in Figure 5A) of the distal optics design according to this exemplary embodiment. In particular, the exemplary system illustrate din Figure 5A can generate a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that can be more than, e.g., 10 times longer than the diffraction-limited depth-of-focus. The output of a waveguide 500 can be collimated by a collimator 510 located in a center of the exemplary catheter system. The collimated electromagnetic radiation (e.g., light) can be transformed into an annular beam using two or more axicons 520, 530. According to another exemplary embodiment, the axicons can be generated or produced using gradient index.
[0090] As shown in Figure 5A, a separate waveguide540 can be routed through the center of the annulus. The output of the waveguide can be collimated by a collimator 550 located in the center of the annulus. Simulated transverse intensity profiles of the collimated annular and Gaussian beams are shown in an illustration of Figure 5B. Collimated annular and Gaussian beams can be focused onto the sample using one or more lens, such as a GRIN lens 560. In addition to focusing two or more beams, the GRIN lens 560 can be configured to intentionally generate chromatic aberration, which can extend the axial focus further (as shown in an illustration of Figure 4C), and to compensate the aberrations induced by the transparent outer sheath 570. The electro-magnetic radiation (e.g., light) can be directed to the artery wall by a deflector 580.
[0091] Figure 6 shows a schematic diagram of an imaging system for generating μΟΟΎ images according to an exemplary embodiment of the present disclosure. As provided in the exemplary embodiment of Figure 6, an output of a source 600 providing electro-magnetic radiation(s) (e.g., light radiation) can be linearly polarized by a linear polarizer 602, and split into two or more beams by a beam splitter 604. At least one of the beams can be redirected to an input port of a switch 606.
[0092] At least one of outputs of the switch 606 can be transmitted through a beam splitter 610, and coupled into a first light/electro-magnetic radiation guide 612. Another other of the outputs of the switch 606 can be attenuated by an attenuator 614, guided by a second light/electro-magnetic radiation guide 616 to a third beam splitter 618, and redirected to a reference reflector 620 through an attenuator 622, a third light/electro-magnetic radiation guide 624 and a dispersion compensation arrangement 626. An output of the light guide 612 can be connected to Bessel illumination and Bessel detection channel of a catheter 628.
[0093] As shown in Figure 6, a further one of the outputs of the beam splitter 604 can be redirected to input port of a second three-port switch 630. One of the outputs of the switch
630 can be transmitted through a beam splitter 632, and coupled into a fourth light/electromagnetic radiation guide 634. Another one of the outputs of the switch 630 can be attenuated by an attenuator 635 guided by a fifth light guide 636 to a fourth beam splitter 638, and redirected to a reference reflector 640 through an attenuator 642, a fifth light guide 644 and a second dispersion compensation arrangement 646. The output of the light guide 634 can be connected to a Gaussian illumination and Gaussian detection channel of the catheter 628.
[0094] When the state of the switch 606 is 1, and the state of a fourth beam splitter 638 is 2, e.g., only the light/electro-magnetic radiation guide 612 can be illuminated so that the sample is illuminated by the Bessel illumination channel (see Table 1 of Figure 6). The back- scattered light from the sample can picked up by both, some or all of the Bessel and Gaussian detection channels of the catheter 628 (see Table 1 of Figure 6). The portion of electromagnetic radiation/light picked up by the Bessel detection channel can be guided by the first electro-magnetic radiation/light guide 612 to the beam splitter 610, where such radiation/light can be combined and interfered with the light from the reference reflector 620.
[0095] Further, as illustrated in Figure 6, at least part of the interference signal can be directed by the beam splitter 610 to a pinhole 648. An output of the pinhole 648 can be collimated and split by a polarizing beam splitter 650. One of outputs of the polarizing beam splitters 650 can be transmitted through a half wave plate 652, and detected by a spectrometer 654. Another of the outputs of the polarizing beam splitters 650 can be detected by a second spectrometer 656. A portion of the electro-magnetic radiation/light picked up by the Gaussian detection channel can be guided by the light guide 634 to the beam splitter 632, where it is combined and interfered with the light from the reference reflector 640. At least part of the interference signal can be directed by the beam splitter 634 to a pinhole 658. An output of the pinhole 658 can be collimated and split by a polarizing beam splitter 660. At least one of outputs of the polarizing beam splitters 660 can be transmitted through a half wave plate 662,
and detected by a third spectrometer 664. Another of the outputs of the polarizing beam splitters 660 can be detected by a fourth spectrometer 666.
[Θ096] When the state of the switch 606 is 2 and the state of the switch 638 is 1, e.g., only the fourth electro-magnetic radiation/light guide 634 can be illuminated, so that the sample is illuminated by Gaussian illumination channel (shown in Table 1 of Figure 6). The back- scattered electro-magnetic radiation/light from the sample can be picked up by both Bessel and Gaussian detection channels of the catheter 630 (shown in Table 1 of Figure 6). At least one portion of the electro-magnetic radiation/light picked up by the Bessel detection channel is guided by the electro-magnetic radiation/light guide 612 to the beam splitter 610, where it can be combined and interfered with the light from the reference reflector 620. At least part of the interference signal can be directed by the beam splitter 610 to a pinhole 648. An output of the pinhole 648 can be collimated and split by a polarizing beam splitter 650. At least one of outputs of the polarizing beam splitters 650 can be transmitted through a half wave plate 652, and detected by a spectrometer 654. Another of the outputs of the polarizing beam splitters 650 can be detected by a second spectrometer 656.
[0097] The portion of light picked up by the Gaussian detection channel is guided by the electro-magnetic radiation/light guide 634 to the beam splitter 632, where it is combined and interfere with the light/radiation from the reference reflector 640. At least part of the interference signal can be directed by the fourth electro-magnetic radiation/light guide 634 to a pinhole 658. The output of pinhole 658 is collimated and split by a polarizing beam splitter 660. AT least one of the two outputs of the polarizing beam splitters 660 can be transmitted through a half wave plate 662, and detected by a third spectrometer 664. Another of the outputs of the polarizing beam splitters 660 can be detected by a fourth spectrometer 666.
[0098] Such exemplary polarization-diverse detection scheme/configuration shown in Figure 6 implemented by the combination of the polarizing beam splitter 650, the half wave
plate 652 and the spectrometers 654, 656, and/or a combination of the polarizing beam splitter 660, the half wave plate 662 and the spectrometers 664, 666 can reduce and/or eliminate artifacts associated with tissue or optical fiber birefringence. The exemplary embodiment of the μΟΟΤ catheter system according the present disclosure illustrated in Figure 6 can contain multiple waveguides that can, e.g., independently transmit and/or receive light/radiation from the catheter to waveguides 612 and 632. The detected signal can be digitized and transferred by a computer 668 via an image acquisition board 670. Data can be digitally displayed on or via a monitor 672, and/or stored in a storage device 674.
[0099] According the present disclosure, the μΟΟΤ detection technology can be implemented using, in one exemplary embodiment, a time domain OCT (TD-OCT) system, in another exemplary embodiment, a spectral-domain (SD-OCT) system, and, in yet another exemplary embodiment, an optical frequency domain interferometry (OFDI) system. Complex images and/or real images from the different transfer function illumination and detection configurations can be acquired using the exemplary embodiment of the imaging system according to the present disclosure. In one exemplary embodiment, such exemplary images can be filtered and recombined to generate a new image with an improved quality and a CTF that more closely approximates the diffraction limited CTF. The exemplary images with different transfer functions can be filtered or recombined incoherently and/or coherently to generate a new image with a CTF procedure/technique that more closely approximates the diffraction limited CTF procedure/technique.
[00100] Figure 7shows another exemplary embodiment of distal optics configuration of a OCT catheter according to the present disclosure for generating a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that can be more than, e.g., approximately 10 times longer than the diffraction-limited depth-of-focus.
[00101] For example, an output of a waveguide 700 can be collimated by a collimator 710. Indeed, the waveguide 700 can be routed through the annular beam and is collimated Gaussian beam will be routed through the center of the annulus. The collimated light can be transformed into an annular beam through two or more axicons, such as, e.g., GRIN axicons 720, 730. A separate waveguide740 can be routed through a center of the annulus. An output of the waveguide 740 can be collimated by a collimator 750 located in the center of the annulus. The collimated annular and Gaussian beams can be focused onto the sample using one or more lens(es) 760, which can be, e.g., one or more GRIN lenses. In addition to focusing the beams, the GRIN lens 760 can be configured and/or structured to intentionally generate chromatic aberration(s), which can extend the axial focus further and compensate for the aberrations induced by a transparent outer sheath. The light/radiation can be directed to the artery wall by a deflector 770.
[00102] Figure 8 shows another exemplary embodiment of the distal optics configuration of the OCT catheter according to the present disclosure. Such exemplary configuration can be used to generate a diffraction-limited CTF and depth of focus that is, e.g., more than 10 times longer than the diffraction-limited depth-of-focus. An output of a waveguide 800 can be collimated by a collimator 810. A pupil aperture created by the collimator 810 can be split into two or more beams, i.e., central circular beam(s) and an annular beam. One or more lenses 820, such as an objective lens, achromat lens , aplanat lens, or GRIN lens, that has an aperture substantially the similar as or identical to a central zone can focus a low NA Gaussian beam into the tissue or the sample.
[Θ01Θ3] The annular beam can be transmitted through a spacer 830, and focused into the sample by an annular axicon lens 840 with an aperture that is substantially similar or identical to the annular beam. The beams can be directed to the sample by a deflector 850. There can be four images generated from four channels, e.g., central illumination/central detection,
central illumination/annular detection, annular illumination/annular detection, annular illumination/central detection. The optical pathlength of the lens 820 can be configured to be different from that of the spacer 830 so that each of, e.g., four images generated can be pathlength encoded. In this exemplary embodiment, the different images can be detected, and their CTF can be combined as per the exemplary methods and/or procedures described herein.
[0Θ104] Figure 9 shows another exemplary embodiment of the distal optics configuration of the OCT catheter system according to the present disclosure, which can be used for generating a diffraction-limited CTF and a depth of focus that is longer than the diffraction- limited depth-of-focus. For example, as illustrated in Figure 9, the output of a waveguide 900 can be collimated by a collimator 910. A pupil aperture created by the collimator 910 can be split into two or more zones by a circular glass window 920 positioned at the center of the objective lens aperture, e.g., (i) a central circular zone that is transmitted through the circular glass window 920, and (ii) an annular zone. The central circular beam can be focused as a low NA Gaussian beam into the tissue and/or sample, and the annular beam can be focused into a Bessel beam focus in the tissue by the lens 930. A glass window can have a higher refractive index than air, and the thickness of the window can be so chosen such that the light/radiation field that undergoes different channel can be path-length separated and/or encoded. In each A line, there can be three or more segments of signal coming from the (e.g., 4) channels: central illumination/central detection, central illumination/annular detection, annular illumination/annular detection, annular illumination/central detection.
[00105] Figure 10 shows a further exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and a depth of focus that can be longer than the diffraction-limited depth-of-focus. An output of a waveguide 1000 can be collimated by a collimator 1010. A pupil aperture created by the
collimator 1010 can be split into a number of concentric zones 1020, 1030, 1040. A multifocal lens, such as, e.g., a GRIN lens, can be used so that the beam in each zone can be focused to a different axial focal position. The scattered light/radiation from each zone can be optical pathlength-encoded so that such scattered beams do not interfere with each other. In this exemplary embodiment, the different images can be detected, and their CTF combined pursuant to the exemplary methods and procedures described herein.
[00106] Figure 11 shows yet another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and an axial focus range (e.g., depth-of-focus) that is longer than the diffraction-limited depth-of- focus. For example, an output of a point object 1100 can be transformed by a mirror tunnel device 11 10 to multiple orders of light/radiation beams, e.g., zeroth order beam 1 120, -1st order beam 1130, and -2nd order beam 1140, etc. When a focusing device 1150 is employed so that most or all the order of rays are focused at the same focal position in the sample, each order of rays can contain a unique band of spatial frequency of the illumination/detection CTF of the focusing device. These orders can, in yet another exemplary embodiment, be path length-encoded so that images generated therein can be detected, and their CTF combined using the different images corresponding to the different orders as per the exemplary CTF combination methods and/or procedures described herein.
[00107] Figures 12 shows another exemplary embodiment of the distal optics configuration of the OCT catheter system according to the present disclosure for generating a diffraction-limited CTF and a depth of focus that is longer than the diffraction-limited depth- of-focus. As illustrated in Figure 12, an output of a waveguide 1200 can be focused by a half ball lens 1210. A planar surface of the half ball lens 1210 can have a binary phase pattern 1220. In one further exemplary embodiment, the depth of the pattern can be configured to produce a small phase shift, e.g., such as a pattern depth of 198 nm (π phase shift at 850 nm).
In another exemplary embodiment, the top surface can be coated with a reflecting coating, such as Au, and a bottom surface can be coated with the same and/or another coating such as Al, with the final phase shift being given by a curve 1300 shown in a graph of Figure 13, which illustrates an optical phase length difference of the glass mask (e.g., no metal coating) and a total phase shift (e.g., mask + coating).
[00108] A curve 1310 and a curve 1320 of the graph of Figure 13 can have a wavelength- dependent phase change of the p-polarized light upon reflection at BK7-A1 and BK7-Au, respectively, with an incident angle of 45 degrees. The curve 1330 can be the wavelength dependent phase shift of the light caused by, e.g., 198 nm height difference upon 45 degree reflection at BK7-air interface. A binary phase mask can be optimized to produce an extended axial focus (as shown in an illustration of Figure 14b) compared with the diffraction limited axial focus (as shown in an illustration of Figure 14a). The light/radiation transmitted from the surfaces with different phase shifts can generate different transfer functions, which can be detected and combined to create a new image with a different CTF pursuant to the exemplary methods and/or procedures described herein.
[00109] Figure 15A shows a side-cut-away view of a diagram of another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and an depth of focus longer than the diffraction-limited depth-of- focus. For example, the system of Figure 15A generates the results by a factor of, e.g., approximately 2, 5, 10, 20, 10, 100, etc. An output of a waveguide 1500 can be collimated by one or more lens(es) 1510. The collimated beam can be spatially modulated by a phase doublet 1520, which can include a positive phase plate and a negative phase plate with the same or similar phase pattern. By matching Abbe number of the positive phase plate and the negative phase plate, the wavelength dependent phase error can be canceled or reduced. Figure 15B shows an exemplary graph of transverse phase profiles of an exemplary mask
(e.g., BK7-SNPH2 phase doublet mask) illustrated in Figure 15A For example, by choosing Ohara S-NPH2 (Vd = 18.896912, Nd = 1.922860) and Schott BK7 (Vd = 64.167336, Nd = 1.5168), with depth 7.2554 um and 13.4668 um respectively, the phase profile is shown in Figure 15B. The spatially modulated beam can be focused into an extended axial focus by an objective lens 1530.
[00110] Figure 16 shows still another exemplary embodiment of the distal optics configuration of the OCT catheter system for generating a diffraction-limited CTF and depth of focus according to the present disclosure that is longer than the diffraction-limited depth- of- focus, by a factor of preferably approximately 2, 5, 10, 20, 10, 100, etc.. An output of a light source 1600 can be split by a beam splitter 1610. The beam aperture of at least one of the outputs of the beam splitter can be split or separated by a rod mirror 1620 into two or more regions. For example, the rod mirror 1620 can redirect the central part of the beam to a reference reflector 1630 through an objective lens 1640. The annular beam can be focused into the sample by a second objective lens 1660 that can be substantially similar or identical to one or more lens(es) 1640 into a Bessel focus featured with extended axial focus and super-resolution in transverse direction (as shown in the exemplary μΟΟΓ images of Figure 18D). The light back-scattered from the sample is combined with the light reflected from the reference reflector through the rod mirror at a pinhole 1660. The output of the pinhole 1660 is detected by a spectrometer 1670. The objective lens 1650 is configured to intentionally generate chromatic aberration and spherical aberration, which extend the axial focus further (as shown in the exemplary μΟΟΎ images of Figures 18C and 18D). Figure 18A shows an exemplary μΟΟΓ image of a coronary plaque showing multiple leukocytes (arrows). In addition, Figure 18B shows an exemplary μΟΟΤ image of a coronary plaque illustrating multiple leukocytes (arrows) of two different cell types, one smaller cell with scant
cytoplasm, consistent with a lymphocyte (L) and another, larger cell with a highly scattering cytoplasm, indicative of a monocyte (M).
[00111] Indeed, Figure 18A illustrates an exemplary μΟΟΊ image of a coronary plaque showing multiple leukocytes 1800 which has been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. Figure 18B illustrates an exemplary μΟΟΓ image of a coronary plaque showing multiple leukocytes of two different cell types, one smaller cell 1810 with scant cytoplasm, consistent with a lymphocyte and another, larger cell 1820 with a highly scattering cytoplasm, suggestive of a monocyte. Figure 18C illustrates an exemplary μΟΟΓ image of a coronary plaque showing a cell 1830 with an indented, bean-shaped nucleus characteristic of a monocyte. Figure 18D illustrates an exemplary μ(^Τ image of a coronary plaque showing a leukocyte 1840 with a multi-lobed nucleus, suggestive of a neutrophil attached to the endothelial surface. Figure 18E illustrates an exemplary μΟΟΎ image of a coronary plaque showing multiple leukocytes 1850, tethered to the endothelial surface by pseudopodia 1860. Figure 18F illustrates an exemplary μ(^Τ image of a coronary plaque showing cells 1870 with the morphology of monocytes in this cross-section and inset transmigrating through the endothelium 1880. Further, Figure 18G illustrates an exemplary μΟΟΤ image of multiple leukocytes 1890 distributed on the endothelial surface.
[00112] Figure 19A-19E show exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. For example Figure 19A illustrates an exemplary μΟ^Τ image of platelets 1900 (P) adjacent to a leukocyte characteristic of a neutrophil 1910 (N), which is also attached to a small platelet 1920 (yellow arrow). Figure 19B illustrates an exemplary μΟΟΤ image of fibrin 1930 (F) which is visible as linear strands bridging a gap in the coronary artery wall. Figure 19C illustrates an exemplary μΟΟΤ image of a cluster of leukocytes 1940 (L),
adherent to the fibrin in an adjacent site to Figure 19B .Figure 19D illustrates an exemplary μΟΟΓ image of Fibrin thrombus 1950 (T) with multiple, entrapped leukocytes. Figure 19E an μΟΟΤ image of a more advanced thrombus 1960 (T) showing a leukocyte 1970 (arrow) and fibrin strands 1980(inset, F).
[0Θ113] Figures 20A-20D show further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. For example, Figure 20A illustrates a cross-sectional exemplary μΟΟΎ image of endothelial cells 2000 in culture. Figure 20B shows an en face exemplary μΟ^Τ image of endothelial cells 2010 in culture. Figure 20C illustrates an exemplary μΟϋΎ image of native swine coronary artery cross-section 2020. Figure 20D shows a three-dimensional rendering of the swine coronary artery, demonstrating endothelial "pavementing" 2030Λ
[00114] Figures 20A-20D show further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. Figure 21 A shows an exemplary μΟΰΤ image of microcalcifications which are seen as bright densities within the μΟΟΓ image of the fibrous cap 2100. Figure 2 IB illustrates an exemplary μΟϋΤ image of microcalcifications which are seen as purple densities on the corresponding histology 2110.
[00115] Further, Figures 20A-20D illustrate further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. For example, Figure 22A shows an exemplary μΟ^Τ image of a large calcium nodule, demonstrating disrupted intima/endothelium 2200. Figure 22B shows an expanded view of an exemplary region enclosed by the red box shows microscopic tissue strands, consistent with fibrin 2210, adjoining the unprotected calcium 2220 to the opposing detached intima. Figure 22C shows a corresponding histology illustrating fibrin 2230 and denuded calcific surface 2240.
[00116] In addition, Figures 23A-26C illustrate further exemplary images which have been generated using the exemplary embodiment(s) of the methods, systems and apparatus according to the present disclosure. For example, Figure 23A shows an exemplary μ(^Τ image of a large necrotic core 2300 fibroatheroma, demonstrating thick cholesterol crystals 2310, characterized by reflections from their top and bottom surfaces. Figure 23B shows an exemplary μθα image of thin crystal 2320, piercing the cap of another necrotic core plaque 2330, shown in more detail in the inset. Figure 24A shows an exemplary μΟΟΎ image of many smooth muscle cells 2400 appear as low backscattering spindle-shaped cells (inset). Figure 24B shows an exemplary μΟΰΤ image of smooth muscle cells producing collagen are spindle shaped, have a high backscattering interior 2410 and a "halo" of low backscattering 2420, which can represent the cell body 2430 and collagen matrix 2440, respectively (e.g., histology inset).
[00117] Figure 25 A shows an exemplary μΟ^Τ image of Taxus Liberie (Boston Scientific, Natick, MA) struts without polymer 2500, with polymer without drug 2510, and with polymer with drug 2520. For polymer-coated struts, polymer reflection 2530, strut reflection 2540 and multiple reflections 2550 and 2560 can be seen. Figure 25B shows an exemplary μΟΟ1 image of a cadaver coronary specimen with an implanted BMS 2570 shows struts devoid of polymer, covered by neointima 2580. Figure 25C shows an exemplary μΟΟΓ image of a cadaver coronary specimen with implanted DES struts 2590 from another cadaver showing polymer overlying the strut reflections 2595 (inset).
[00118] In addition, Figure 26A shows an exemplary μΟΟΓ image showing tissue 2600 has separated the polymer 2610 off of the stent strut 2620 and the polymer has fractured 2630. Figure 26B shows an exemplary μΟΰΤ image showing superficial leukocyte cluster 2640 and adjacent attached leukocytes 2650 overlying the site of the polymer fracture 2660. Figure 26C shows an exemplary μΟΟΓ image showing inflammation 2670 at the edge of a
strut 2680 from another patient. Figure 26D shows an exemplary μΟΟΤ image showing uncovered strut 2690, completely devoid of overlying endothelium.
[00119] In still another exemplary embodiment of the present disclosure, the optical elements for the exemplary μOCT system/probe can be fabricated by irradiating a photopolymer with a tightly focused beam, whose position can be controlled in three- dimensions with nm-level precision. The photopolymer can respond to a variable refractive index that can be proportional to an optical energy deposited, facilitating a miniature, solid volume to implement complex optical functionality. (See, e.g., Sullivan AC, Grabowski MW and McLeod RR, "Three-dimensional direct-write lithography into photopolymer", Applied Optics 2007; 46: 295-301; and Scott TF, Kowalski BA, Sullivan AC, Bowman CN and McLeod RR, "Two-Color Single-Photon Photoinitiation and Photoinhibition for Subdiffraction Photolithography", Science 2009; 324: 913-7; also see U.S. Patent Publicaton Nos. 2009/0218519 and 2006/0193579).
[00120] Such exemplary method and procedure previously generated miniature fiber couplers, tapered waveguides, waveguide arrays, lenses, diffractive optical elements, and complex optical assemblies, all within a monolithic, polymer component, for example. This exemplary embodiment facilitates the exemplary μΟΟΤ probe to be a stable, monolithic element that can provide the extended focal depth functionality described herein, than can be incorporated into, e.g., miniaturized μΟΟΤ catheters and endoscopes. One advantage of this exemplary embodiment is that the photopolymer-derived optical element/arrangement can be made repeatedly with a high precision, and can be mass-produced at relatively low cost.
[00121] Figure 27A shows a flow diagram of a method for providing data associated with at least one portion of at least one sample according to one exemplary embodiment of the present disclosure. For example, in procedure 2710, at least one first radiation is forwarded to at least one portion of the sample through at least one optical arrangement (e.g., as
described in various exemplary embodiments herein), and at least one second radiation is received from the portion which is based on the first radiation. Based on an interaction between the optical arrangement and the first radiation and/or the second radiation, the optical arrangement has a first transfer function. Then, in procedure 2720, at least one third radiation is forwarded to the portion through such optical arrangement, and at least one fourth radiation is received from the portion which is based on the third radiation. Based on an interaction between this optical arrangement and the third radiation and/or the fourth radiation, the optical arrangement has a second transfer function. The first transfer function can be at least partially different from the second transfer function. Further, in procedure 2730, the data associated with the portion(s) can be generated based on the second and fourth radiations.
[0Θ122] Figure 27B shows a flow diagram of the method for providing data associated with at least one portion of at least one sample according to another exemplary embodiment of the present disclosure. For example, in procedure 2760, at least one first radiation is forwarded to at least one portion of the sample through at least one first optical arrangement (e.g., as described in various exemplary embodiments herein), and at least one second radiation is received from the portion which is based on the first radiation. Based on an interaction between the first optical arrangement and the first radiation and/or the second radiation, the first optical arrangement has a first transfer function. Then, in procedure 2770, at least one third radiation is forwarded to the portion through at least one second optical arrangement, and at least one fourth radiation is received from the portion which is based on the third radiation. Based on an interaction between the second optical arrangement and the third radiation and/or the fourth radiation, the optical arrangement has a second transfer function. The first transfer function can be at least partially different from the second transfer
function. Further, in procedure 2780, the data associated with the portion(s) can be generated based on the second and fourth radiations.
[00123] The foregoing merely illustrates the principles of the present disclosure. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. For example, more than one of the described exemplary arrangements, radiations and/or systems can be implemented to implement the exemplary embodiments of the present disclosure Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention 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), U.S. Patent Application No. 10/861,179 filed June 4, 2004, 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), U.S. Patent Application No. 11/445,990 filed June 1, 2006, International Patent Application PCT/US2007/066017 filed April 5, 2007, and U.S. Patent Application No. 11/502,330 filed August 9, 2006, 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 methods which, although not explicitly shown or described herein, embody the principles of the present disclosure and are thus within the spirit and scope of the present disclosure. In addition, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly being incorporated herein in its entirety. All publications referenced herein above are incorporated herein by reference in their entireties.
Claims
1. An apparatus for providing at least one electro-magnetic radiation to at least one sample, comprising:
a plurality of wave-guiding arrangements configured to (i) provide the at least one electro-magnetic radiation, and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each of the at least one electro-magnetic radiation to have a predetermined value.
2. The apparatus according to claim 1, wherein the wave-guiding arrangements provide the at least one radiation in at least partially a circular pattern.
3. The apparatus according to claim 1, further comprising at least one lens arrangement which is configured to receive the at least one electro-magnetic radiation from the wave- guiding arrangements, and generate a further focus-spot radiation.
4. The apparatus according to claim 3, wherein the at least one lens arrangement is configured to cause the further focus-spot radiation to have an extended focal depth.
5. The apparatus according to claim 3, wherein the at least one lens arrangement is configured to cause the further focus-spot radiation to have a diameter that is smaller than a diffraction limited spot on or in the sample.
6. The apparatus according to claim 5, wherein the diffraction limited spot is a three- dimensional spot.
7. The apparatus according to claim 3, wherein the at least one lens arrangement includes a grin lens.
8. The apparatus according to claim 1, wherein at least one of the wave-guiding
arrangements is a single-mode wave-guide.
9. The apparatus according to claim 1, wherein at least one of the wave-guiding
arrangements is composed of a photo-polymer.
10. The apparatus according to claim 1, further comprising a further wave-guiding arrangement is configured to provide a further electro-magnetic radiation to the sample, wherein the at least one electro-magnetic radiation and the further electro-magnetic radiation are provided to at least partially overlapping portions of the sample.
11. The apparatus according to claim 1, further comprising a housing which at least partially encloses the wave-guiding arrangements.
12. The apparatus according to claim 11, further comprising a sheath enclosing the housing.
13. The apparatus according to claim 11, further comprising a control arrangement which is configured to at least one of rotate or translate the housing.
14. The apparatus according to claim 1, wherein the at least one lens arrangement includes at least one optical element which is at least one formed by or subjected to a photopolymer processing.
15. The apparatus according to claim 14, wherein the photopolymer processing includes irradiating a photopolymer so as to form the at least one optical element.
16. A probe for providing at least one electro-magnetic radiation to at least one sample, comprising:
a plurality of wave-guiding arrangements configured to (i) provide the at least one electro-magnetic radiation, and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each electro-magnetic radiations to have a predetermined value.
17. A system for imaging at least one sample, comprising:
a probe comprising a plurality of wave-guiding arrangements configured to (i) provide at least one electro-magnetic radiation to the at least one sample, and (ii) at a point of emission of each of the wave guiding arrangements, cause a phase of each electro-magnetic radiations to have a predetermined value;
an interferometric arrangement provided in communication with the probe.
18. The system according to claim 17, wherein the interferometric aiTangement is part of the probe.
19. A method for generating data associated with at least one portion of a sample, comprising:
forwarding at least one first radiation at to the at least one portion through at least one optical arrangement which is formed by or subjected to a photopolymer processing, and receiving at least one second radiation from the at least one portion which is based on the at least one first radiation, wherein, based on an interaction between the at least one optical arrangement and at least one of the first radiation or the second radiation, the at least one optical arrangement has a first transfer function;
forwarding at least one third radiation to the at least one portion through the at least one optical arrangement, and receiving at least one fourth radiation from the at least one portion which is based on the at least one third radiation, wherein, based on an interaction between the at least one optical arrangement and at least one of the third radiation or the fourth radiation, the at least one optical arrangement has a second transfer function, and wherein the first transfer function is at least partially different from the second transfer function; and
generating the data based on the second and fourth radiations.
20. An apparatus for generating data associated with at least one portion of a sample, comprising:
at least one optical arrangement which is (i) formed by or subjected to a photopolymer processing, and (ii) configured to:
i. forward at least one first radiation at to the at least one portion through at least one optical arrangement, and receiving at least one second radiation from the at least one portion which is based on the at least one first radiation, wherein, based on an interaction between the at least one optical arrangement and at least one of the first radiation or the second radiation, the at least one optical arrangement has a first transfer function,
ii. forward at least one third radiation to the at least one portion through the at least one optical arrangement, and receiving at least one fourth radiation from the at least one portion which is based on the at least one third radiation, wherein, based on an interaction between the at least one optical arrangement and at least one of the third radiation or the fourth radiation, the at least one optical arrangement has a second transfer function, and wherein the first transfer function is at least partially different from the second transfer function; and
at least one further arrangement configured to generate the data based on the second and fourth radiations.
21. An apparatus for generating data associated with at least one portion of a sample, comprising:
at least one first optical arrangement configured to forward at least one first radiation at to the at least one portion through at least one optical arrangement, and receiving at least one second radiation from the at least one portion which is based on the at least one first radiation, wherein, based on an interaction between the at least one first optical arrangement and at least one of the first radiation or the second radiation, the at least one first optical arrangement has a first transfer function,
at least one second optical arrangement configured to forward at least one third radiation to the at least one portion through the at least one second optical arrangement, and receiving at least one fourth radiation from the at least one portion which is based on the at least one third radiation, wherein, based on an interaction between the at least one second optical arrangement and at least one of the third radiation or the fourth radiation, the at least one second optical arrangement has a second transfer function, and wherein the first transfer function is at least partially different from the second transfer function; and
at least one third arrangement configured to generate the data based on the second and fourth radiations,
wherein at least one of the at least one first optical arrangement or the at least one second optical arrangement is formed by or subjected to a photopolymer processing.
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