Endoscopic biopsy apparatus, system and method

Information

  • Patent Grant
  • 9615748
  • Patent Number
    9,615,748
  • Date Filed
    Wednesday, January 20, 2010
    14 years ago
  • Date Issued
    Tuesday, April 11, 2017
    7 years ago
Abstract
Exemplary embodiments of apparatus, method and system for determining a position on or in a biological tissue can be provided. For example, using such exemplary embodiment, it is possible to control the focus of an optical imaging probe. In another exemplary embodiment, it is possible to implement a marking apparatus together with or into an optical imaging probe. According to one exemplary embodiment, it is possible (using one or more arrangements) to receive information associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique. Further, it is possible to, based on the information, cause a visible change on or in at least location of the portion(s) using at least one electro-magnetic radiation.
Description
FIELD OF THE DISCLOSURE

The present disclosure relates to exemplary embodiments of endoscopic biopsy systems that are guided by microscopic image information, and an associated method therefor.


BACKGROUND INFORMATION

The standard of care for the diagnosis of many epithelial precancerous and early cancer conditions is visual inspection of the patient directly or through an endoscope/laparoscope to identify abnormal tissue. Biopsies can then be obtained from these locations, processed, cut and stained with Hematoxylin and Eosin (H&E), and then observed under a microscope by a pathologist. A pathologist can view the slide at progressively increasing resolutions and renders a diagnosis by comparing its architectural and cellular patterns with his/her knowledge of patterns associated with different disease states.


For a number of cases, however, metaplasia, dysplasia, and early cancer may not be visually identified. In these situations, the only available option may be to obtain biopsies at random locations which are routinely conducted in the colon, esophagus, prostate, and bladder, among others. When the disease is focal or heterogeneously distributed within a much larger suspect area, a random biopsy procedure may be analogous to “finding a needle in a haystack,” resulting in poor diagnostic yields and uncertain patient management.


Since random biopsies may only facilitate the assessment of less than 0.1% of the potentially involved tissue, these procedures are usually fraught with significant sampling error and diagnostic uncertainty. Other tasks, such as the delineation of surgical tumor margins, can also be affected by this difficulty, resulting in all too frequent re-excisions or time-consuming frozen section analysis. Thus, there may be a need for providing an apparatus and a method for guiding biopsy that is superior to visual inspection and that can direct the physician to a location that is more likely to harbor the most severe disease.


Barrett's esophagus is a condition of the tubular esophagus, where the squamous epithelium changes to intestinal epithelium, termed specialized intestinal metaplasia (SIM). Thought to be precipitated by severe or longstanding gastroesophageal reflux disease (GERD), BE can undergo dysplastic progression, leading to esophageal adenocarcinoma. Current management of Barrett's esophagus can include endoscopic surveillance at regular time intervals, consisting of upper endoscopy with 4-quadrant random biopsy, to identify dysplasia or adenocarcinoma at an early stage. This method suffers from a low sensitivity, as it is compromised by the poor ability of endoscopists to identify SIM/dysplasia and the low fractional area of tissue sampled by biopsy.


In the past, in the field of biomedical optics, imaging methods have been developed to provide improved tissue diagnosis in vivo. These imaging methods can be generally categorized as macroscopic or microscopic techniques.


Macroscopic, e.g., wide field imaging methods including autofluorescence, fluorescence lifetime imaging, ALA-fluorescence, reflectance and absorption spectroscopic imaging, narrow-band imaging, and chromoendoscopy. These macroscopic methods can be used to quickly evaluate large regions of tissue. While many of these techniques are promising, the information provided is often quite different from that conventionally used in medicine for diagnosis.


Microscopic imaging, at times referred to as “optical biopsy,” is another approach that enables the visualization of tissues at a resolution scale that is more familiar to physicians and pathologists. In the past, the minimally-invasive endoscopic microscopy techniques that have been developed to visualize the architectural and cellular morphology required for histopathologic diagnosis in vivo facilitate a very small field of view, however, and the probes are usually manually manipulated to obtain images from discrete sites (“point-sampling”). As a result, such techniques suffer from substantially the same sampling limitations as excisional biopsy, and may not be well suited for guiding biopsy.


One such microscopic imaging technique, reflectance confocal microscopy (RCM), can be suited for non-invasive microscopy in patients as it offers imaging of cellular structures at ˜1 μm resolution, can measure microstructure without tissue contact, and does not require the administration of unapproved exogenous contrast agents.


RCM can reject or ignore multiply scattered light from tissue, and detects the singly backscattered photons that contain structural information by employing confocal selection of light reflected from a tightly focused beam. Most commonly, RCM can be implemented by rapidly scanning a focused beam in a plane parallel to the tissue surface, resulting in transverse or en face images of tissue. A large numerical aperture (NA) of RCM can yield a very high spatial resolution. Sensitive to the aberrations that arise as light propagates through inhomogeneous tissue; high-resolution imaging with RCM can typically be limited to a depth of 100-200 μm, which is sufficient for most epithelial disorders that manifest near a luminal surface.


While RCM has been demonstrated in the skin, the development of endoscopic confocal microscopy systems has taken longer due to technical challenges associated with miniaturizing a scanning microscope. One difficulty with such technique is providing a mechanism for rapidly raster-scanning the focused beam at the distal end of a small-diameter, flexible probe. A variety of approaches have been attempted to address this problem, including the use of distal micro electro mechanical systems (MEMS) beam scanning devices, and proximal scanning of single-mode fiber bundles.


Another challenge can be the miniaturization of high NA objectives used for optical sectioning. Possible solutions employing a gradient-index lens system, dual-axis objectives or custom designs of miniature objectives have been described. First, demonstrations of these technologies in patients are beginning to appear; detailed images of the morphology of cervical epithelium have been obtained in vivo using a fiber optic bundle coupled to a miniature objective lens and fluorescence based images of colorectal and esophageal lesions were shown using commercial instruments.


Even though endoscopic RCM has been demonstrated in patients, this technique is likely not currently optimized for biopsy guidance. One reason can be that such technique provides microscopic images only at discrete locations, the so-called “point sampling” approach problem mentioned above. Point sampling is inherent to RCM since it has an extremely limited field of view (e.g., 200-500 μm), which is less than that of an excisional biopsy. As a result, endoscopic RCM may likely have the same sampling errors and diagnostic yield limitations as excisional biopsy.


In order to use endoscopic RCM for biopsy guidance, the imaging paradigm may be shifted away from point sampling to microscopy with extremely large fields of view where every possible location within the tissue of interest is sampled. The output of this paradigm, which can be termed “Comprehensive Volumetric Microscopy (CVM),” can include microscopic images of entire organ or luminal surfaces in three-dimensions.


For CVM, imaging speeds of current techniques may need to be increased by at least an order of magnitude above video rate, due to the very high bandwidth of the microscopic information and the constraint of obtaining such data in a realistic procedural time (e.g., <20 min). In addition, catheter/endoscope technology can be developed to automatically scan the microscope over these large tissue surface areas rapidly and with a high degree of precision.


Recently, CVM has been implemented using a second-generation form of optical coherence tomography (OCT), called optical frequency domain imaging (OFDI), and rapid helically scanning catheters. This research has facilitated the acquisition of three-dimensional microscopic images of the entire distal esophagus in a few minutes and long segments of coronary arteries in patients in less than 5 seconds. (See Suter M. J. et al., “Comprehensive microscopy of the esophagus in human patients with optical frequency domain imaging”, Gastrointestinal endoscopy, 2008, Vol. 68(4), pp. 745-53; and Tearney G. J. et al., “Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging: First-in-human experience”, Journal of the American College of Cardiology, Imaging, 2008, pp. 1:752-61


While OFDI shows significant potential for certain clinical applications, its ˜10 μm resolution may not necessarily be sufficient for dysplasia and early cancer diagnosis, which can require knowledge of tissue morphology at both architectural and cellular levels. Thus, there may be a need to provide a new exemplary variant of RCM that is capable of rapidly obtaining high-resolution comprehensive volumetric images through an endoscopic probe.


One approach is to use spectrally encoded microscopy (“SECM”) technique(s). SECM's rapid imaging rate and its fiber-optic design can enable comprehensive volumetric RCM through an endoscopic probe. An SECM probe has been described which can scan an area equivalent to that of the distal esophagus (about 5.0 cm length, and about 2.5 cm diameter), at a single depth location, in approximately 1 minute. (See, e.g., Yelin D. et al., “Large area confocal microscopy”, Optics Letters, 2007; 32(9):1102-4).


Spectrally encoded confocal microscopy (“SECM”) is a single fiber-optic confocal microscopy imaging procedure, which uses a broad bandwidth light source and encodes one dimension of spatial information in the optical spectrum (as illustrated in the example of FIG. 1). As shown in FIG. 1, at the distal end of the probe, the output from the core of a single-mode or dual-clad fiber 110 is collimated by a collimation lens 115 and illuminates a transmission diffraction grating 120. An objective lens 130 focuses each diffracted wavelength to a distinct spatial location 141, 142, or 143 within the specimen, producing a transverse line focus 150 where each point on the line has a different wavelength or color. After reflection from the tissue, the light passes back through the lens 130, is recombined by the grating 120, and collected by the fiber 110. The aperture of the fiber 110 provides the spatial filtering mechanism to reject out-of-focus light. Outside the probe (within the system console) the spectrum of the returned light is measured and converted into confocal reflectance as a function of transverse displacement within the sample. Spectral decoding of this line in the image can be performed very rapidly, e.g., at rates of about 70 kHz, which can be approximately 10 times that of video rate confocal microscopy systems and up to about 100 times faster than some endoscopic RCM systems. The other transverse axes of the image can be obtained by relatively slow and straightforward mechanical actuation that may regularly employ for a wide variety of endoscopic probes. Images obtained by SECM demonstrate its capability to image subcellular-level microstructure relevant to the diagnosis of dysplasia and cancer (see FIG. 2). FIGS. 2A and 2B show exemplary SECM images of swine duodenum, obtained ex vivo, after compression of the bowel wall, showing the architecture of the duodenal villi and nuclear detail. Illustrated imaging depths are 50 μm and 100 μm shown in FIGS. 2A and 2B, respectively.


Accordingly, there may be a need to overcome at least some of the above-described issues and/or deficiencies.


SUMMARY OF EXEMPLARY EMBODIMENTS

Thus, at least some of these issues and/or deficiencies can be addressed with the exemplary embodiments of the apparatus, system and method according to the present disclosure.


Exemplary embodiments of the present disclosure provides mechanism and a methodology for automatically maintaining the foci at a desired tissue depth while scanning the spectrally encoded line across the sample. This exemplary advancement can compensate for patient motion and enables imaging at multiple depth locations. Further, in one exemplary embodiment, it is possible to conduct a large area confocal microscopy in patients by incorporating these technologies in an endoscopic probe suitable for human use.


According to another exemplary embodiment of the present disclosure, an apparatus can be provided. The apparatus can comprise at least one dispersive first arrangement which is configured to provide data associated with a signal received from at least one region of the sample(s). The exemplary apparatus can also comprise at least one focusing second arrangement which is configured to control a focal length and/or a focal position associated with first arrangement based on the data. According to an exemplary variant, at least one third arrangement can also be availed which is configured to provide further data associated with a further signal received from at least one further region of at least one sample. The region and the further region can at least partially overlap and/or be located at near one another. The focusing second arrangement(s) can be configured to control the focal length and/or the focal position associated with the first arrangement(s) based on the data and/or the further data. The dispersive and focusing arrangements can be provided in a balloon.


According to a further exemplary embodiment of the present disclosure, apparatus, method and system can be provided for imaging at least one portion of an anatomical tissue can also be provided. For example, with a dispersive arrangement, it is possible to provide at least one first electromagnetic radiation to the at least one portion to form a sample plane at an angle that is greater than 0 degrees and less than 90 degrees with respect to a plane of a surface of the portion(s). Further, at least one second electromagnetic radiation can be received from the sample plane which is associated with the first electromagnetic radiation(s) to generate information as a function the second electromagnetic radiation(s). A control signal can be generated based on the information so as to further control a location of a focal plane of the first electromagnetic radiation(s), or at least one three-dimensional image of the at least one portion can be generated as a function of the information.


In one exemplary variant, it is possible to generate the control signal based on a location of a surface of the sample using at least one portion of the at least one first electromagnetic radiation. It is also possible to separate the second electromagnetic radiation(s) into at least one first signal and at least one second signal. Further, the control signal can be generated based on the first signal(s), and at least one image associated with the sample can be generated as a function of the second signal(s).


In a further exemplary embodiment of the present disclosure, the SECM probe components can be incorporated into a transparent tube, e.g., having about 1.0 cm in diameter, with an approximately 2.5 cm diameter centering balloon and a rapid-exchange guide wire provision. Helical scanning can be accomplished by the use of a rotary junction and a pullback motor connected to the SECM optics via a wound cable through the tube. An exemplary arrangement in which an objective lens is angled relative to the surface of the sample can be used. This angled arrangement can be used to generate a feedback signal for controlling the focal plane of the objective lens and also provide three-dimensional image information through a single helical scan. The transverse resolution of the SECM optics can be, e.g., nominally about 1.6 μm and the autofocus mechanism can function, e.g., over a range of about ±500 μm. The SECM imaging system, operating at a center wavelength of 725 nm and capable of configured to obtain image data at about 70×106 pixels per second, can be enclosed in a portable arrangement, e.g., a cart.


The exemplary system and probe can be configured to comprehensively image the entire human distal esophagus (about 2.5 cm diameter and about 5.0 cm length) at about 10 different focal locations, in approximately 10 minutes. Exemplary software can be provided and stored on a tangible computer-accessible medium (and executed by a processor or other computing arrangement(s)) a for convenient image data acquisition, display, and selection of sites to be marked for biopsy.


In yet another exemplary embodiments of the present disclosure, a laser marking apparatus, method and system can be provided according to the present disclosure. An approximately 400 mW, 1450 nm laser can be incorporated into the system and coupled into an endoscopic probe to create minute, visible superficial marks on tissue at selected image locations so that they may be subsequently biopsied by the endoscopist. For example, target sites, identified by SECM or OCT, can be marked so that the endoscopist can review and biopsy these locations. An exemplary embodiment of a laser marking apparatus, method and system can be provided for accomplishing this exemplary task. The exemplary laser marking technique can be incorporated into the exemplary embodiment of the apparatus, system and device according to the present disclosure.


According to one exemplary embodiment of the present disclosure, apparatus, method and system can be provided for determining a position on or in a biological tissue can be provided. For example, using such exemplary embodiment, it is possible (using one or more arrangements) to receive information associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique. Further, it is possible to, based on the information, cause a visible change on or in at least location of the portion(s) using at least one electro-magnetic radiation.


For example, the image(s) can include a volumetric image of the portion(s). The volumetric image can be a cylindrical image having a diameter of between about 10 mm to 100 mm and/or an extension of at most about 1 m. It is also possible (e.g., using a particular arrangement) to receive data associated with the visible change, and guide a visualization to the at least one portion based on the data. Further, it is possible to cause the visible change by ablating the portion(s). The ablation can be performed by irradiating the portion(s) with the electro-magnetic radiation(s).


In one exemplary embodiment of the present disclosure, the arrangement can be situated in a probe, and an ablation arrangement can be provided in the probe which is controlled by the arrangement to cause the visible change on or in one or more the portions. It is also possible to obtain the information via at least one wave-guiding arrangement, and the ablation arrangement can provides the electro-magnetic radiation(s) via the wave-guiding arrangement(s) to cause the visible change. In addition, the optical imaging technique can include a confocal microscopy technique, and the confocal microscopy technique can be a spectrally-encoded confocal microscopy technique. Further, the optical imaging technique can include an optical coherence tomography.


These advancements can achieve performance specifications that can be used for endoscopic use in patients. It is also possible to incorporate exemplary embodiments described herein in an endoscope and utilize the targeted biopsy technique, e.g., in clinical studies and in other scenarios.


The exemplary embodiment of the system and probe according to the present disclosure described herein can be used in patients undergoing upper endoscopy. While the application of the exemplary embodiments can be to a wide variety of epithelial cancers and other clinical applications such as tumor margin detection, one exemplary application can be for Barrett's esophagus (BE), as it is an area where these exemplary embodiments may have a high impact. Because the exemplary comprehensive SECM can sample the entire distal esophagus on a microscopic scale, the exemplary SECM-guided biopsy can yield a significantly higher sensitivity for the detection of dysplasia and early adenocarcinoma.


According to the exemplary embodiments of the present disclosure, it is possible to screening patients for Barrett's esophagus and improving the diagnostic capabilities of surveillance endoscopy. These advances can decrease the mortality associated with esophageal adenocarcinoma.


The image-guided biopsy according to the exemplary embodiments of the present disclosure is expected to be safe and well-tolerable, detect previously unattainable subcellular and architectural information over large epithelial surfaces of the esophagus, and provide an effective method for endoscopic biopsy targeting. The impact of these exemplary embodiments can be high, as it can provide clinicians with a powerful tool for improving the management of BE patients. While the broad goal of this invention is focused on reducing the mortality of esophageal adenocarcinoma, the exemplary SECM system and probe represent a new diagnostic platform that can be applied to dysplasia and cancer screening in other internal organ systems. The long term impact of the exemplary embodiments of the present disclosure can also affect treatment as it can enable less invasive surgical techniques such as RF ablation, photodynamic therapy, or endoscopic mucosal resection to be used at an earlier stage of disease progression.


According to the exemplary embodiments of the present disclosure, it is possible to screening patients for Barrett's esophagus and improving the diagnostic capabilities of surveillance endoscopy. These advances can decrease the mortality associated with esophageal adenocarcinoma.


To utilize comprehensive SECM to guide biopsy, additional exemplary procedures and/or steps can be taken. As an initial matter, the images are interpreted during the procedure. A comparison of SECM images of biopsy samples to corresponding histology can be performed that can describe an exemplary criteria for SECM diagnosis. Another exemplary embodiment of the system, device and method according to the present invention can be provided for obtaining information that is compatible with current morphologic methods for disease diagnosis. Advantages of this exemplary embodiment can include near-term clinical application and the potential for leveraging a large, existing database of clinic pathologic correlations. Further, it is likely that molecular imaging provide an impact in changing this paradigm in the future.


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 DRAWINGS

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 invention, in which:



FIG. 1 is a schematic diagram of an exemplary arrangement which utilizes spectrally-encoded confocal microscopy (SECM) techniques;



FIG. 2A is a SECM image of swine duodenum, obtained ex vivo, after compression of the bowel wall using the exemplary arrangement illustrated in FIG. 1 showing the architecture of the duodenal villi and nuclear detail at an imaging depth of about 50 μm;



FIG. 2B is another SECM image of swine duodenum, obtained ex vivo, after compression of the bowel wall using the exemplary arrangement illustrated in FIG. 1 showing the architecture of the duodenal villi and nuclear detail at an imaging depth of about 100 μm;



FIG. 3 is a schematic diagram and a photograph inset of an exemplary SECM arrangement/probe according to an exemplary embodiment of the present disclosure;



FIG. 4 is a schematic diagram of an exemplary spectrally encoded illumination on tissue using the exemplary embodiment of the arrangement/probe shown in FIG. 3;



FIG. 5A is an exemplary SECM image which can be utilized for focusing by the exemplary embodiment of the arrangement according to the present disclosure;



FIG. 5B is an exemplary graph of intensity versus pixel coordinate associated with the exemplary SECM image shown in FIG. 5A;



FIG. 6A is a cylindrical presentation of an exemplary image of a lens paper phantom obtained by an exemplary SECM bench-top probe without adaptive focusing;



FIG. 6B is a magnified view of the exemplary image shown in FIG. 6A;



FIG. 6C is a cylindrical presentation of an exemplary image of the lens paper phantom obtained by the exemplary SECM bench-top probe with adaptive focusing;



FIG. 6D is a magnified view of the exemplary image shown in FIG. 6C;



FIG. 6E is an illustration of an exemplary stack of SECM images of the lens paper phantom at a region of the sample over the imaging depth of 56 μm;



FIG. 7 is an exemplary SECM image of a human esophageal biopsy sample showing the gastroesophageal junction, squamous epithelium, and gastric cardia;



FIG. 8A is an exemplary SECM image of esophageal squamous epithelium showing intraepithelial eosinophils from a patient with presumed eosinophilic esophagitis;



FIG. 8B is an exemplary SECM image of a gastric body fundic type mucosa from the patient with presumed eosinophilic esophagitis imaged following 0.6% acetic acid;



FIG. 8C is an exemplary SECM image of Fundic gland polyp with columnar epithelium lining the cyst wall from the patient imaged following 0.6% acetic acid;



FIG. 9A is an exemplary SECM image of a specialized intestinal metaplasia obtained using the exemplary embodiment of the system and method according to the present disclosure was acquired following application of 0.6% acetic acid;



FIG. 9B is a magnification view of the image of FIG. 9A showing goblet cells;



FIG. 9C is an exemplary SECM image of a high grade dysplasia obtained using the exemplary embodiment of the system and method according to the present disclosure;



FIG. 9D is an exemplary SECM image according to the exemplary embodiments of the present disclosure demonstrating architectural and nuclear atypia;



FIG. 10 is an exemplary image flow diagram of the comprehensive microscopy guided biopsy platform with laser marking according to an exemplary embodiment of the method of the present disclosure;



FIG. 11 is an exemplary flow diagram of the SECM-guided biopsy process according to an exemplary embodiment of the present disclosure;



FIG. 12 is a schematic diagram of a side view of an exemplary SECM arrangement/probe according to an exemplary embodiment of the present disclosure;



FIG. 13 is a schematic diagram of an exemplary rotary junction of the exemplary embodiment of a system according to the present disclosure;



FIG. 14 is a schematic diagram of an exemplary SECM system of the exemplary embodiment according to the present disclosure;



FIG. 15 is a schematic diagram of an exemplary embodiment of an optoelectronic apparatus for generating the auto-focusing feedback signal according to the present disclosure





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

Exemplary embodiments of the systems, processes and arrangements according to the present disclosure includes, but not limited to (a) a SECM endoscopic probe, (b) diagnosis based on histopathologic features observed in SECM images, and/or (c) an image-guided laser marking system, etc. A description of each of these three exemplary embodiments is described in detail below, along with an exemplary embodiment of a clinically-viable SECM-guided biopsy system/probe according to the present disclosure.


Exemplary SECM Probe


Exemplary embodiments of the present disclosure which include certain arrangement/probe components facilitate comprehensive endoscopic SECM imaging of large luminal surfaces can be provided. As shown in the exemplary embodiment illustrated in FIG. 3, light from a broadband light source 310 (e.g., spectral bandwidth=about 30 nm; central wavelength=about 877 nm) can be coupled into a 50/50 fiber-optic beam splitter 320. Light from the fiber output port 110 of the beam splitter can be collimated by a collimation lens 115 (e.g., f=about 20 mm), and dispersed by a transmission holographic grating 120 (e.g., about 1700 lines/mm) into e.g., ˜350 resolvable points. The dispersed light can be focused onto the specimen 330 by an objective lens 130 (e.g., aspheric lens: f=about 4.5 mm; effective NA=about 0.53) through a thin-walled balloon 328 (e.g., diameter=about 20 mm; thickness=about 50 μm). The objective lens 130 can be angled so that the axial positions of the focused spots vary by e.g., about 50 μm across the imaging bandwidth. Helical scanning can be accomplished by rotating and translating the probe housing 320 by a motor 326 and a translation stage 327. A photo of the exemplary embodiment of the SECM probe is shown in the inset of FIG. 3. The size of the exemplary probe can be about 10 mm (W)×39 mm (L)×13 mm (H). The reflected light can be coupled back into the beam splitter and directed to a spectrometer comprising a collimation lens 341 (f=about 44 mm), a grating 342 (about 1800 lines/mm), a focusing lens 343 (f=about 200 mm), and a line scan camera 344 (e.g., Basler Sprint; pixel size=about 10 μm; 2048 pixels). The exemplary spectral resolution of the spectrometer can be about 0.04 nm.


To generate depth-resolved optical sections, each digitized spectrally-encoded line can be divided into, e.g., 8 segments where each segment corresponds to image information obtained at a different depth level. Exemplary image segments from the same depth level can be connected together to create a large-area optical section at each depth. In order to keep the focus of the high NA objective lens 130 within the sample 330, the objective lens 130 can also be scanned along the axial direction by a focusing mechanism 325, which can include a miniature linear guide and a piezoelectric transducer (PZT) actuator.



FIG. 4 shows a schematic diagram of the illumination beam from the objective lens 130 on the sample 330 through the balloon 328. Since the objective lens 130 is angled, each wavelength can image at a different depth of the sample 330. A spectral band 450 that images the balloon region 328 at a line scan can be used to locate the balloon surface in the field of view, which can be used to generate a feedback signal to control the focusing mechanism 325. for example, the remaining spectral band 440, together with the spectral band 450, can be used to generate line image of the sample 330. FIG. 5A shows an exemplary image that can be generated by the exemplary embodiment of the SECM arrangement/probe according to the present disclosure as shown in FIGS. 3 and 4. For example, the portion that visualizes the balloon 328 has higher signal level than that for the sample 330. The line profile along a line 530 (shown in FIG. 5B) illustrates a high intensity peak 540 at the balloon location, and such peak location can be used as a reference point to control the focusing mechanism (e.g., using a processing or computing device or arrangement).


Exemplary Experimental Results


The transverse resolution of the exemplary embodiment of the SECM arrangement/probe according to the present disclosure, measured by imaging the edge response function from bars on a 1951 USAF resolution chart, ranged from 1.25±0.13 μm to 1.45±0.33 μm, from the center to the edges of the spectral field of view, respectively. The axial resolution of the exemplary embodiment of the SECM arrangement/probe, obtained by z-scanning a mirror through the focus, was measured to be 10 μm and 4.4 μm for the edge and the center of the spectral FOV's, respectively. The adaptive focusing mechanism in the exemplary embodiment of the SECM arrangement/probe accurately tracked the sinusoidal motion of a moving mirror at rate of 1 Hz with displacement amplitude of about 250 μm. The exemplary mechanical design of the probe head and the software procedure used in this exemplary embodiment of the arrangement/probe was somewhat limited the speed and range of the adaptive focusing mechanism. It is possible to generate the feedback signal using a separate opto-electronic apparatus and it is possible to modify the probe housing, which can increase the response speed of the feedback loop and the focal range, respectively.



FIGS. 6A-6E show exemplary SECM images and data for a substantially complete exemplary pullback image of, e.g., a 2.0 cm phantom without adaptive focusing (see FIGS. 6A and 6B) and with adaptive focusing (see FIGS. 6C and 6D). The exemplary phantom consists of lens paper affixed to the outer surface of the balloon (diameter=about 20 mm). The exemplary embodiment of the SECM arrangement/probe according to the present disclosure was scanned using a rotation rate of about 20 rpm; a total of about 400 circumferential scans were acquired in 20 minutes, limited primarily by the speed of the method used to generate the control signal. Since the length of a single spectrally-encoded line was 400 μm, the longitudinal step size of 50 μm provided 8 different depth levels. At low magnification (shown in FIGS. 6A and 6C), the macroscopic structure of the paper, including folds and voids, can be visualized. When regions of this data set are shown at higher magnifications, individual fibers and fiber microstructure can be clearly resolved (as shown in FIGS. 6B and 6D—see inset).


By utilizing the automatic focusing mechanism (the image produced by which is shown in FIGS. 6C and 6D), the entire dataset remained in focus and information can be acquired from all optical sections within the approximately 50 μm range, even when the exemplary arrangement/probe was not centered. In contrast, when the focusing mechanism was off, only small portions of the phantom were in focus and visible (as shown in FIGS. 6A and 6B). A stack of exemplary SECM images at a region of the sample through different imaging depths is shown in FIG. 6E. This exemplary image stack provides three-dimensional information over the depth of about 56 μm at 8 different focal planes. Feature changes are well noticed between the images from the different imaging planes including the white dotted circular region. These exemplary results demonstrate the technical feasibility of comprehensive exemplary SECM for luminal organs.


Histopathologic Features Visualized by Exemplary SECM Techniques


An exemplary SECM system with similar optical specifications as that described herein above for the exemplary embodiment of the endoscopic SECM probe can be utilized, e.g., to image entire human biopsy samples (as described in, e.g., Kang D. et al., “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy”, Gastrointest Endosc. 2009). This exemplary SECM system can utilize a wavelength-swept source (e.g., central wavelength=1320 nm; bandwidth=70 nm; repetition rate=5 kHz) and a 0.7 NA objective lens. A single-mode illumination and multi-mode detection imaging configuration can be used to reduce laser speckle noise, a method that can also be employed in the exemplary arrangement/probe described herein above. The resolutions of such exemplary SECM system can be, e.g., 2.3 μm and 9.7 μm along the transverse and axial directions, respectively. FIG. 7 shows an exemplary image of one of the first data sets that have been acquired from an exemplary biopsy study, demonstrating the architectural morphology of, e.g., a normal gastroesophageal junction.


Exemplary SECM images of other esophageal tissue types can also be obtained, including squamous mucosa with scattered eosinophils gastric fundic body type mucosa and a fundic gland polyp (see FIGS. 8A, 8B and 8C). Images of Barrett's esophagus (see FIGS. 9A and 9B) appear to be distinct from gastric cardia (as shown in FIG. 7) and high-grade dysplasia (as shown in FIG. 9C). For example, an application of 0.6% acetic acid (vinegar) for enhancing nuclear contrast can be performed on, e.g., the majority of the biopsy samples. Further clinical study of SECM imaging on a larger set of biopsy samples can deliver diagnostic criteria of SECM imaging and evaluate its accuracy. The diagnostic criteria can be used in the SECM-guided biopsy to identify and locate diseased regions automatically or manually by clinicians or image readers.


Exemplary Laser Marking for Guiding Biopsy


To utilize endoscopic microscopy techniques to guide biopsy, regions of dysplasia and early carcinoma identified by the imaging system can be marked so that they can be visible by traditional endoscopy.



FIG. 10 shows an image progress diagram of an exemplary embodiment of a method of image-guided biopsy that uses laser marking of the superficial esophageal mucosa according to the present disclosure. To demonstrate the feasibility of laser marking targeted biopsy, this exemplary technique has been tested in swine in vivo (n=4) through a balloon catheter with OFDI imaging modality. For each animal, the balloon catheter and inner optical imaging probe were positioned within the esophagus. A 400 mW, 1450 nm laser was used to mark the esophagus through a fiber-optic probe, focused to a spot diameter of approximately 30 μm. A total of 68 randomly located 8-second targets 1021 were created in the swine esophagus. A comprehensive microscopy dataset 1010 of the distal 5.0 cm of the esophagus was then obtained and used 1020 to locate the targets 1021. After locating a target on the endoscopic microscopy image, smaller 2-second laser marks 1041 were made on either side of the target to serve as a guide for biopsy 1030 (see FIG. 10). Following laser marking, the balloon catheter was removed and the esophagus was visualized by conventional endoscopy 1040. An inspection of the esophagus 1040 revealed that both marks surrounding 1041 each target 1021 were visible by endoscopy for about 97% of the targets. Histopathological analysis 1050 of the marks showed that both the 8- and 2-second marks caused only minor injury to the mucosa, extending to the superficial submucosa, which healed after two days. These exemplary results demonstrate that laser marking is a viable approach for facilitating biopsy guided by endoscopic microscopy. Although OFDI imaging modality was used for this experiment, SECM can also be utilized through a balloon catheter to guide biopsy.


For various internal organ systems, random biopsy can be the standard of care for the diagnosis of epithelial metaplasia, dysplasia, and early cancer. SECM-guided biopsy can change this paradigm and improve outcomes for patients who undergo regular surveillance for these conditions. SECM may be capable of identifying architectural and cellular microstructure relevant to esophageal diagnosis. Certain exemplary technical components can be preferred for implementing SECM-guided biopsy in an endoscopic probe. It is possible to provide an exemplary embodiment of a clinically viable SECM system and endoscopic probe. The exemplary system/device can obtain RCM data at multiple depths over the entire distal esophagus, and can facilitate the physician to identify and mark suspect locations in the tissue so that they can be subsequently biopsied.


Exemplary SECM-Guided Biopsy



FIG. 11 illustrates a flow diagram of exemplary embodiment of the procedures according to the present disclosure for conducting the exemplary SECM-guided biopsy. For example, a centering balloon probe can be inserted over a guide wire (block 1120) that has been previously placed endoscopically (block 1110). When the balloon probe is in place, the balloon can be inflated in block 1130, and comprehensive SECM can be performed using a helical scan pattern in block 1140. In the endoscopic suite, the exemplary SECM dataset can be analyzed, and biopsy targets may be selected on the image in block 1150. The SECM probe can then automatically return to those locations in the patient and can place laser marks on either side of the targets in block 1160. Following such exemplary laser marking, the balloon can be deflated and removed in block 1170. The endoscopist can then obtain biopsies from the marked sites in block 1180. Although SECM is used in the exemplary procedures shown in FIG. 11, other microscopic imaging technologies including OCT can be also used to guide the biopsy.


Exemplary Endoscopic Probe


A clinical exemplary SECM-guided biopsy device can comprise, e.g., three components: a) the probe, b) the probe-console interface, and c) the console. An exemplary schematic diagram of an exemplary embodiment of the SECM arrangement/probe is shown in FIG. 12. The exemplary SECM arrangement/probe can comprise a double-clad fiber (DCF) 1211 which can transceive the imaging light, and also transmit the laser marking beam. To reduce speckle noise, imaging can be accomplished by illuminating the sample through the core of the DCF, and by receiving the light remitted from the sample through both the core and inner cladding. The fiber can be contained within a wound cable 1212 that rotates, and can translate within a transparent 1.0 cm diameter sheath 1232.


Rotating and translating the wound cable at its proximal end can facilitate an exemplary helical imaging to take place over the entire extent of the balloon 328. During imaging, a control signal, derived from the reflection from the balloon surface (see FIGS. 4 and 5), can be used to generate an input to the focusing mechanism 325 to adaptively change the focal location. The wound cable 1212 and DCF 1211 can be attached to the housing 320 of the exemplary SECM arrangement/probe, which can contain a collimation lens 115, a grating 120, an objective lens 130, and the focusing mechanism 325. A 6.0 cm long, 2.5 cm diameter transparent centering balloon 328, can be affixed to the transparent sheath 1232. The distal end of the exemplary arrangement/probe can be terminated by a guide wire provision 1231.


Exemplary Probe Optics.


It is possible to reduce the size of the exemplary arrangement/probe further by developing customized optical and mechanical components. In order to minimize or reduce the rigid length, the collimation lens 115 can be fabricated to decrease the distance between the DCF 1211 and the lens 115. The grating 120 (e.g., Holographix, Hudson, Mass.) can be provided to have, e.g., maximum diffraction efficiency for the 2nd order at 725 nm and for the 1st order at about 1450 nm. The exemplary objective lens 130 (e.g., NA=0.4) can be provided (e.g., ZEMAX, Bellevue, Wash.) and produced (e.g., Optimax Systems Inc., Ontario) to have diffraction-limited performance throughout the optical sectioning depth range of about 100 μm in tissue. The objective lens 130 can be achromatic at 725 nm and 1450 nm, and can have a cylindrical surface to compensate for the astigmatism induced by the transparent catheter's sheath 1232.


Exemplary Wound Cable.


It is possible to utilize exemplary multi-layer wound drive shafts to scan distal optics within the patient for other imaging modalities. A custom wound cable 1212 can be fabricated (e.g., Asahi Intec, USA) and tested for the motion transduction accuracy and repeatability through the catheter.


Exemplary Balloon-Centering Catheter.


An exemplary balloon-centering catheter utilizing a transparent polycarbonate sheath 1232 (e.g., diameter=about 10 mm) and a transparent plastic balloon 328 (e.g., Advanced Polymers, Salem, N.H.; inflated diameter=about 25 mm) can be provided to house the probe optics and wound cable (e.g., Device company; Innovative Medical Design, Tyngsboro, Mass.). The exemplary catheter can be tested for transparency, flexibility, and trackability to ensure that it is suitable for intraesophageal imaging.


Exemplary Probe-Console Interface


An exemplary rotary junction (shown in an exemplary embodiment of the arrangement of FIG. 13) can be provided to couple light from the console to/from the probe and rotate the exemplary SECM arrangement/probe within the transparent sheath. In contrast to the exemplary OCT rotary junctions, the exemplary SECM optical rotary junction can transmit the imaging light from the light source 310 into the core 1351 of a double clad fiber (“DCF”). The inner cladding 1352 of the DCF can transmit laser marking light 1380, and can deliver imaging light returned from the sample to a spectrometer 1370.


To accomplish a separation of single- from multi-mode light, the exemplary rotary junction can contain two focusing lenses 1320, 1360 and a single-mode/multi-mode splitter, e.g., comprise a mirror 1330 with a central transparent aperture and a relay lens 1340 (see FIG. 13). The exemplary rotary junction can rotate the wound cable 1212 at 70 rpm. In addition to coupling light from a static system to rotating catheter optics, the exemplary rotary junction can also transmit low electrical current to control the focusing mechanism. Further, the entire exemplary rotary junction can be affixed to a linearly scanning pullback stage, translating at a rate of about 0.1 mm/s, to enable helical scanning of the SECM probe optics. Motor encoder output from both rotational and linear motors can be digitized synchronously with the image signal to facilitate the exemplary SECM probe to return to any given image location in the patient for laser marking.


The exemplary optical rotary junction can be provided in Solid Works and simulated in ZEMAX. Exemplary design(s) can be optimized for maximum throughput and ease of manufacturing and tolerancing. The exemplary design(s) can be custom-machined, assembled and tested for single and double-passed throughput and rotational uniformity. The exemplary rotary junction can additionally be designed to fit within the standard motorized pull back trays.


Exemplary Console


An exemplary console (an example of a schematic diagram of which is shown in FIG. 14) can comprise the light sources and detectors used to image, mark, and can also be used to generate a feedback signal to control the focal location of the probe's objective lens. For imaging, light from a broadband light source 310 (e.g., Fianium SC450-6) can be filtered by a filter 1411 to have a broadband NIR spectrum 1421 of 725±30 nm. This exemplary wavelength range can be chosen so as to provide an appropriate compromise between resolution, penetration depth, and detector sensitivity. In addition, the center wavelength can be half that of the wavelength of the laser marking beam 1448 (e.g., about 1450 nm) from the high power laser 1380. By diffracting the imaging beam through the grating of the probe's second order and the marking laser through the first order, both can illuminate the same location on the sample.


Optical components, including the dichroic mirror 1441 and the mirror 1442 in the console, can route the single-mode imaging laser and multi-mode marking laser to the exemplary SECM probe 1430 through the rotary junction 1420. Remitted confocal light from the rotary junction 1420 can be divided by a dichroic mirror 1443 into two beams; the imaging beam 1446 that is directed to a spectrometer 1370 and the focusing beam 1447 that can be coupled to an optoelectronic apparatus 1460 for generating the auto-focusing feedback signal. The imaging beam 1446 and the focusing beam 1447 can cover different spectral regions. Each line in the image can be detected using a line-scan camera (e.g., SPL2048-140k, Basler) in the spectrometer 1380; exemplary digital image data can be transferred to the computer 1480 at a line rate of about 70 kHz and saved to a data recording system (e.g., Signatec DR-400) in real-time. The computer generates the control signal for the focusing mechanism in the SECM probe 1430.


Exemplary Adaptive Focusing Optoelectronics.


An exemplary optoelectronic apparatus for generating the adaptive focus feedback signal according to the present disclosure can be provided (an exemplary diagram of which is shown in FIG. 15). As shown in FIG. 15, the focusing beam 1447 from the exemplary SECM probe (shown in FIG. 5) can be optically separated from the imaging beam 1446 (as shown in the diagram of FIG. 14), and a grating 1520 can be used to disperse its spectrum onto a position-sensitive detector 1530 (PSD; e.g., quadrant photodetector). The electrical signals from the individual cells in the PSD 1530 can be algebraically or mathematically processed (e.g., using a computing or processing arrangement) to provide the peak wavelength, which can correspond to the position of the inner surface of the balloon.


The balloon surface position can then be converted into a control signal that can drive the focusing mechanism and move the objective lens in the SECM probe. The output signal 1540 from the PSD 1530 can be fed to an analogue electric feedback circuit that controls the focusing mechanism directly or can be routed to the computer 1540 to be used for control purpose. By making this feedback/control independent of the imaging data acquisition, its response time can be much faster than that of the exemplary SECM arrangement/probe described herein above with reference to FIG. 3, resulting in an increase in imaging speed by more than a factor of, e.g., 4.


Exemplary Laser Marking for Guided Biopsy.


For example, two exemplary diode lasers (e.g., wavelength=about 1450 nm, power=about 200 mW each) can be polarization-multiplexed and integrated into the SECM system to create marks for guiding biopsy. Light from the diode lasers can be transmitted through a shutter and coupled into the inner cladding of the SECM probe through the rotary junction. A computer or other processing device(s) can control the intensities and exposure durations of the diode lasers. For safety reasons, e.g., the laser shutter can be configured to only allow a maximum of, e.g., about 10 seconds per exposure at any given site.


Exemplary System Integration.


Exemplary imaging and marking lasers can be tested for power and spatial coherence. Some or all optics can be tested for throughput and efficiency. The optical layout can be assembled on a small breadboard for incorporation into the cart. The imaging spectrometer can be fabricated and its spectral resolution and light throughput can be tested using standard techniques. Following assembly of the exemplary individual components, the exemplary system can be integrated into a portable, medical-grade cart. Software can be provided to control the rotary junction, the adaptive focusing mechanism, and the marking lasers using one or more computers. Existing software to facilitate the navigation of the image in a manner similar to that done with Google™ Earth, where pan and zoom quickly enable the viewer to focus on a precisely located area of interest, can be adapted for SECM datasets. Additional software user-interface inputs can be provided to allow the observer to quickly switch between different optical sections, delineate the target sites, and initiate laser marking.


Exemplary Specifications and Performance Expectations


Table 1 (below) depicts the exemplary specifications and objective performance targets (OPT) for the exemplary SECM arrangement/probe and system according to the present disclosure. The exemplary OPTs can be based on the preferences of comprehensive endoscopic confocal microscopy and prior experience with centering-balloon imaging of the esophagus. Meeting such exemplary OPTs can furthermore provide beneficial imaging performance. The exemplary arrangement/probe can have a deflated diameter of about 1.0 cm and a rigid length of about 4.5 cm—specifications that match that of commercially available, over-the-wire endoscopic ultrasound devices. Transverse and axial resolutions, governed by the number of modes transmitted through the inner cladding of the DCF can be better than critically sampled in the circumferential direction and Nyquist sampled along the longitudinal dimension. The longitudinal interval of about 72 μm between neighboring circumferential scans can provide optical sections at about 10 discrete depth locations and up to about 100 μm beyond the surface of the balloon. The exemplary marking beam can have a spot size of about 30 μm on the sample, which is sufficient for producing endoscopically visible marks on the esophageal surface in, e.g., about 2 seconds.












TABLE 1








Value




















Specification





Balloon diameter
2.5
cm



Scan length
5.0
cm



Sheath diameter
1.0
cm



Rigid length
4.5
cm



Center wavelength
725
nm



Objective lens NA
0.4




Pixels/scan
1024




Line rate
70
kHz



Rotation speed
70
RPM



Pullback speed
0.1
mm/s



Imaging duration
10
min



OPT





Single pass insertion loss
5
dB



Transverse resolution
1.6
μm



Axial resolution
10
μm



Spectral FOV
720
μm



Sectioning depth range
100
μm



Dynamic focusing range
±500
μm



Dynamic response of adaptive focusing
2
Hz



Marking beam diameter
30
μm










The image-guided biopsy according to the exemplary embodiments of the present disclosure is expected to be safe and well-tolerable, detect previously unattainable subcellular and architectural information over large epithelial surfaces of the esophagus, and provide an effective method for endoscopic biopsy targeting. The long term impact of the exemplary embodiments of the present disclosure can also affect treatment as it can enable less invasive surgical techniques such as RF ablation, photodynamic therapy, or endoscopic mucosal resection to be used at an earlier stage of disease progression.


The foregoing merely illustrates the principles of the invention. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention can be used with imaging systems, and for example with those described in International Patent Publication WO 2005/047813 published May 26, 2005, U.S. Patent Publication No. 2006/0093276, published May 4, 2006, U.S. Patent Publication No. 2005/0018201, published Jan. 27, 2005 and U.S. Patent Publication No. 2002/0122246, published May 9, 2002, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. 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 affecting a biological tissue, comprising: a radiation disperser arrangement which is configured to encode spatial information in an optical spectrum, and disperse first radiation and second radiation which have different spectral bands from one another;at least one detector arrangement which is configured to receive and detect the first radiation; andat least one structural computer arrangement which is configured to: receive first data associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique, wherein the optical imaging technique includes a confocal microscopy technique that encodes spatial information in an optical spectrum, and wherein the first data is associated with the first radiation,based on the first data, forward the second radiation to the radiation disperser arrangement to cause a visible change that includes at least one endoscopically-visible marking on or in at least one location that is outside of and adjacent to the at least one portion, andcause a removal or a destruction of at least part of the at least one portion using image second data for the visible change on or in the at least one location.
  • 2. The apparatus according to claim 1, wherein the at least one image for which the first data is received includes a volumetric image of the at least one portion.
  • 3. The apparatus according to claim 2, wherein the volumetric image is a cylindrical image having a diameter of between about 10 mm to 100 mm.
  • 4. The apparatus according to claim 2, wherein the volumetric image is a cylindrical image having an extension of at most about 1 m.
  • 5. The apparatus according to claim 2, wherein the at least one structural computer arrangement is further configured to obtain data associated with the visible change, and guide a visualization to the at least one portion based on the data.
  • 6. The apparatus according to claim 1, further comprising an ablation arrangement which is configured to ablate the at least one portion.
  • 7. The apparatus according to claim 6, wherein the ablation of the at least one portion is performed by irradiating the at least one portion with the at least one electro-magnetic radiation using the ablation arrangement.
  • 8. The apparatus according to claim 1, wherein the at least one computer arrangement is situated in a probe, and further comprising an ablation arrangement provided in the probe which is controlled by the at least one computer arrangement to cause the visible change on or in the at least one portion.
  • 9. The apparatus according to claim 8, wherein the at least one computer arrangement is configured to obtain the information via at least one wave-guiding arrangement, and the ablation arrangement provides the at least one electro-magnetic radiation via the at least one wave-guiding arrangement to cause the visible change.
  • 10. The apparatus according to claim 1, wherein the optical imaging technique includes an optical coherence tomography.
  • 11. The apparatus according to claim 1, wherein the at least one computer arrangement is configured to cause a change to a superficial section of the at least one portion.
  • 12. The apparatus according to claim 1, further comprising a biopsy arrangement which is configured to remove at least one section of the at least one portion that is substantially near or at a location of the visible change.
  • 13. The apparatus according to claim 1, wherein the radiation disperser arrangement includes a grating.
  • 14. A method for affecting a biological tissue, comprising: encoding spatial information in an optical spectrum;dispersing first radiation and second radiation which have different spectral bands from one another;receiving and detecting the first radiation;receiving first data associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique, wherein the optical imaging technique includes a confocal microscopy technique that encodes spatial information in an optical spectrum, and wherein the first data is associated with the first radiation; andbased on the first data, forwarding the second radiation to be dispersed so as to cause a visible change that includes at least one endoscopically-visible marking on or in at least one location that is outside of and adjacent to of the at least one portion; andusing imaging second data for the visible change on or in the at least one location, causing a removal or a destruction of at least part of the at least one portion.
  • 15. An apparatus for affecting a biological tissue, comprising: a radiation disperser arrangement which is configured to encode spatial information in an optical spectrum, and disperse first radiation and second radiation which have different spectral bands from one another;at least one detector arrangement which is configured to receive and detect the first radiation; andat least one computer arrangement which is configured to: receive first data associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique, wherein the optical imaging technique includes a confocal microscopy technique that encodes spatial information in an optical spectrum, and wherein the first data is associated with the first radiation, andbased on the information, forward the second radiation to the dispersive arrangement to cause a visible change that includes at least one endoscopically-visible marking on or in at least one location that is outside of and adjacent to of the at least one portion.
  • 16. The apparatus according to claim 15, wherein the radiation disperser arrangement includes a grating.
CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is based upon and claims the benefit of priority from U.S. Patent Application Ser. No. 61/145,914, filed on Jan. 20, 2009, and from U.S. Patent Application Ser. No. 61/184,180, filed on Jun. 4, 2009, the entire disclosures of which are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

The invention was made with the U.S. Government support under Grant Nos. CA122161, RR019768 and EY014975 awarded by the National Institutes of Health and Grant No. W81XWH-07-2-0011 awarded by the U.S. Army Medical Research. Thus, the U.S. Government has certain rights in this invention.

US Referenced Citations (358)
Number Name Date Kind
3090753 Matuszak et al. May 1963 A
3872407 Hughes Mar 1975 A
4030831 Gowrinathan Jun 1977 A
4140364 Yamashita et al. Feb 1979 A
4224929 Furihata Sep 1980 A
4479499 Alfano et al. Oct 1984 A
4585349 Gross et al. Apr 1986 A
4601036 Faxvog et al. Jul 1986 A
4639999 Daniele Feb 1987 A
4650327 Ogi Mar 1987 A
4734578 Horikawa Mar 1988 A
4744656 Moran et al. May 1988 A
4751706 Rohde et al. Jun 1988 A
4763977 Kawasaki et al. Aug 1988 A
4827907 Tashiro et al. May 1989 A
4834111 Khanna et al. May 1989 A
4890901 Cross, Jr. Jan 1990 A
4905169 Buican et al. Feb 1990 A
4909631 Tan et al. Mar 1990 A
4940328 Hartman Jul 1990 A
4966589 Kaufman Oct 1990 A
4984888 Tobias et al. Jan 1991 A
4998972 Chin et al. Mar 1991 A
5085496 Yoshida et al. Feb 1992 A
5121983 Lee Jun 1992 A
5177488 Wang et al. Jan 1993 A
5197470 Helfer et al. Mar 1993 A
5202931 Bacus et al. Apr 1993 A
5208651 Buican May 1993 A
5212667 Tomlinson et al. May 1993 A
5214538 Lobb May 1993 A
5217456 Narciso, Jr. Jun 1993 A
5241364 Kimura et al. Aug 1993 A
5250186 Dollinger et al. Oct 1993 A
5251009 Bruno Oct 1993 A
5275594 Baker Jan 1994 A
5281811 Lewis Jan 1994 A
5283795 Fink Feb 1994 A
5302025 Kleinerman Apr 1994 A
5304173 Kittrell et al. Apr 1994 A
5317389 Hochberg et al. May 1994 A
5318024 Kittrell et al. Jun 1994 A
5333144 Liedenbaum et al. Jul 1994 A
5348003 Caro Sep 1994 A
5394235 Takeuchi et al. Feb 1995 A
5400771 Pirak et al. Mar 1995 A
5404415 Mori et al. Apr 1995 A
5414509 Veligdan May 1995 A
5424827 Horwitz et al. Jun 1995 A
5479928 Cathignoal et al. Jan 1996 A
5522004 Djupsjobacka et al. May 1996 A
5555087 Miyagawa et al. Sep 1996 A
5565983 Barnard et al. Oct 1996 A
5565986 Knuttel Oct 1996 A
5566267 Neuberger Oct 1996 A
5628313 Webster, Jr. May 1997 A
5635830 Itoh Jun 1997 A
5649924 Everett et al. Jul 1997 A
5701155 Wood et al. Dec 1997 A
5730731 Mollenauer et al. Mar 1998 A
5748318 Maris et al. May 1998 A
5752518 McGee et al. May 1998 A
5785651 Baker et al. Jul 1998 A
5801831 Sargoytchev et al. Sep 1998 A
5810719 Toida Sep 1998 A
5817144 Gregory et al. Oct 1998 A
5829439 Yokosawa et al. Nov 1998 A
5836877 Zavislan et al. Nov 1998 A
5840031 Crowley Nov 1998 A
5910839 Erskine et al. Jun 1999 A
5912764 Togino Jun 1999 A
5926592 Harris et al. Jul 1999 A
5955737 Hallidy et al. Sep 1999 A
5975697 Podoleanu et al. Nov 1999 A
5994690 Kulkarni et al. Nov 1999 A
5995223 Power Nov 1999 A
6007996 McNamara et al. Dec 1999 A
6010449 Selmon et al. Jan 2000 A
6016197 Krivoshlykov Jan 2000 A
6020963 Dimarzio et al. Feb 2000 A
6025956 Nagano et al. Feb 2000 A
6037579 Chan et al. Mar 2000 A
6045511 Ott et al. Apr 2000 A
6052186 Tsai Apr 2000 A
6078047 Mittleman et al. Jun 2000 A
6094274 Yokoi Jul 2000 A
6107048 Goldenring et al. Aug 2000 A
6111645 Tearney et al. Aug 2000 A
6245026 Campbell et al. Jun 2001 B1
6249381 Suganuma Jun 2001 B1
6249630 Stock et al. Jun 2001 B1
6272268 Miller et al. Aug 2001 B1
6297018 French et al. Oct 2001 B1
6301048 Cao et al. Oct 2001 B1
6341036 Tearney et al. Jan 2002 B1
6374128 Toida et al. Apr 2002 B1
6377349 Fercher Apr 2002 B1
6396941 Bacus et al. May 2002 B1
6437867 Zeylikovich et al. Aug 2002 B2
6441892 Xiao et al. Aug 2002 B2
6441959 Yang et al. Aug 2002 B1
6445485 Frigo et al. Sep 2002 B1
6445939 Swanson et al. Sep 2002 B1
6475159 Casscells et al. Nov 2002 B1
6475210 Phelps et al. Nov 2002 B1
6477403 Eguchi et al. Nov 2002 B1
6485413 Boppart et al. Nov 2002 B1
6501551 Tearney et al. Dec 2002 B1
6516014 Sellin et al. Feb 2003 B1
6517532 Altshuler et al. Feb 2003 B1
6538817 Farmer et al. Mar 2003 B1
6540391 Lanzetta et al. Apr 2003 B2
6549801 Chen et al. Apr 2003 B1
6560259 Hwang et al. May 2003 B1
6567585 Harris May 2003 B2
6593101 Richards-Kortum et al. Jul 2003 B2
6611833 Johnson et al. Aug 2003 B1
6654127 Everett et al. Nov 2003 B2
6657730 Pfau et al. Dec 2003 B2
6658278 Gruhl Dec 2003 B2
6692430 Adler Feb 2004 B2
6701181 Tang et al. Mar 2004 B2
6721094 Sinclair et al. Apr 2004 B1
6725073 Motamedi et al. Apr 2004 B1
6738144 Dogariu et al. May 2004 B1
6741884 Freeman et al. May 2004 B1
6757467 Rogers Jun 2004 B1
6790175 Furusawa et al. Sep 2004 B1
6831781 Tearney et al. Dec 2004 B2
6839496 Mills et al. Jan 2005 B1
6882432 Deck Apr 2005 B2
6900899 Nevis May 2005 B2
6909105 Heintzmann et al. Jun 2005 B1
6949072 Furnish et al. Sep 2005 B2
6961123 Wang et al. Nov 2005 B1
6996549 Zhang et al. Feb 2006 B2
7006232 Rollins et al. Feb 2006 B2
7019838 Izatt et al. Mar 2006 B2
7027633 Foran et al. Apr 2006 B2
7061622 Rollins et al. Jun 2006 B2
7072047 Westphal et al. Jul 2006 B2
7075658 Izatt et al. Jul 2006 B2
7099358 Chong et al. Aug 2006 B1
7113288 Fercher Sep 2006 B2
7113625 Watson et al. Sep 2006 B2
7130320 Tobiason et al. Oct 2006 B2
7139598 Hull et al. Nov 2006 B2
7142835 Paulus Nov 2006 B2
7148970 De Boer Dec 2006 B2
7177027 Hirasawa et al. Feb 2007 B2
7190464 Alphonse Mar 2007 B2
7230708 Lapotko et al. Jun 2007 B2
7236637 Sirohey et al. Jun 2007 B2
7242480 Alphonse Jul 2007 B2
7267494 Deng et al. Sep 2007 B2
7272252 De La Torre-Bueno et al. Sep 2007 B2
7304798 Izumi et al. Dec 2007 B2
7330270 O'Hara et al. Feb 2008 B2
7336366 Choma et al. Feb 2008 B2
7342659 Horn et al. Mar 2008 B2
7355716 De Boer et al. Apr 2008 B2
7355721 Quadling et al. Apr 2008 B2
7359062 Chen et al. Apr 2008 B2
7365858 Fang-Yen et al. Apr 2008 B2
7366376 Shishkov et al. Apr 2008 B2
7382809 Chong et al. Jun 2008 B2
7391520 Zhou et al. Jun 2008 B2
7458683 Chernyak et al. Dec 2008 B2
7530948 Seibel et al. May 2009 B2
7539530 Caplan et al. May 2009 B2
7609391 Betzig Oct 2009 B2
7630083 de Boer et al. Dec 2009 B2
7643152 de Boer et al. Jan 2010 B2
7643153 de Boer et al. Jan 2010 B2
7646905 Guittet et al. Jan 2010 B2
7649160 Colomb et al. Jan 2010 B2
7664300 Lange et al. Feb 2010 B2
7733497 Yun et al. Jun 2010 B2
7782464 Mujat et al. Aug 2010 B2
7799558 Dultz Sep 2010 B1
7805034 Kato et al. Sep 2010 B2
7911621 Motaghiannezam et al. Mar 2011 B2
7969578 Yun et al. Jun 2011 B2
7973936 Dantus Jul 2011 B2
8315282 Huber et al. Nov 2012 B2
20010020126 Swanson et al. Sep 2001 A1
20010036002 Tearney et al. Nov 2001 A1
20010055462 Seibel Dec 2001 A1
20020024015 Hoffmann et al. Feb 2002 A1
20020037252 Toida et al. Mar 2002 A1
20020048025 Takaoka Apr 2002 A1
20020048026 Isshiki et al. Apr 2002 A1
20020052547 Toida May 2002 A1
20020057431 Fateley et al. May 2002 A1
20020068853 Adler Jun 2002 A1
20020086347 Johnson et al. Jul 2002 A1
20020091322 Chaiken et al. Jul 2002 A1
20020109851 Deck Aug 2002 A1
20020113965 Roche et al. Aug 2002 A1
20020122182 Everett et al. Sep 2002 A1
20020140942 Fee et al. Oct 2002 A1
20020158211 Gillispie Oct 2002 A1
20020166946 Iizuka et al. Nov 2002 A1
20020168158 Furusawa et al. Nov 2002 A1
20020183623 Tang et al. Dec 2002 A1
20030001071 Mandella et al. Jan 2003 A1
20030013973 Georgakoudi et al. Jan 2003 A1
20030025917 Suhami Feb 2003 A1
20030028114 Casscells, III et al. Feb 2003 A1
20030030816 Eom et al. Feb 2003 A1
20030043381 Fercher Mar 2003 A1
20030053673 Dewaele et al. Mar 2003 A1
20030067607 Wolleschensky et al. Apr 2003 A1
20030082105 Fischman et al. May 2003 A1
20030097048 Ryan et al. May 2003 A1
20030103212 Westphal et al. Jun 2003 A1
20030108911 Klimant et al. Jun 2003 A1
20030120137 Pawluczyk et al. Jun 2003 A1
20030137669 Rollins et al. Jul 2003 A1
20030165263 Hamer et al. Sep 2003 A1
20030174339 Feldchtein et al. Sep 2003 A1
20030191392 Haldeman Oct 2003 A1
20030220749 Chen et al. Nov 2003 A1
20030236443 Cespedes et al. Dec 2003 A1
20040002650 Mandrusov et al. Jan 2004 A1
20040039252 Koch Feb 2004 A1
20040039298 Abreu Feb 2004 A1
20040054268 Esenaliev et al. Mar 2004 A1
20040072200 Rigler et al. Apr 2004 A1
20040075841 Van Neste et al. Apr 2004 A1
20040076940 Alexander et al. Apr 2004 A1
20040077949 Blofgett et al. Apr 2004 A1
20040085540 Lapotko et al. May 2004 A1
20040110206 Wong et al. Jun 2004 A1
20040126048 Dave et al. Jul 2004 A1
20040126120 Cohen et al. Jul 2004 A1
20040150830 Chan Aug 2004 A1
20040152989 Puttappa et al. Aug 2004 A1
20040165184 Mizuno Aug 2004 A1
20040188148 Chen et al. Sep 2004 A1
20040189999 De Groot et al. Sep 2004 A1
20040204651 Freeman et al. Oct 2004 A1
20040239938 Izatt Dec 2004 A1
20040246490 Wang Dec 2004 A1
20040246583 Mueller et al. Dec 2004 A1
20040247268 Ishihara et al. Dec 2004 A1
20040254474 Seibel et al. Dec 2004 A1
20040258106 Araujo et al. Dec 2004 A1
20040263843 Knopp et al. Dec 2004 A1
20050004453 Tearney et al. Jan 2005 A1
20050018133 Huang et al. Jan 2005 A1
20050018201 De Boer et al. Jan 2005 A1
20050035295 Bouma et al. Feb 2005 A1
20050036150 Izatt et al. Feb 2005 A1
20050046837 Izumi et al. Mar 2005 A1
20050049488 Homan Mar 2005 A1
20050057680 Agan Mar 2005 A1
20050057756 Fang-Yen et al. Mar 2005 A1
20050059894 Zeng et al. Mar 2005 A1
20050065421 Burckhardt et al. Mar 2005 A1
20050119567 Choi et al. Jun 2005 A1
20050128488 Yelin et al. Jun 2005 A1
20050165303 Kleen et al. Jul 2005 A1
20050171438 Chen et al. Aug 2005 A1
20050190372 Dogariu et al. Sep 2005 A1
20050197530 Wallace et al. Sep 2005 A1
20050221270 Connelly et al. Oct 2005 A1
20050251116 Steinke et al. Nov 2005 A1
20050254059 Alphonse Nov 2005 A1
20050254061 Alphonse et al. Nov 2005 A1
20060033923 Hirasawa et al. Feb 2006 A1
20060039004 De Boer et al. Feb 2006 A1
20060093276 Bouma et al. May 2006 A1
20060103850 Alphonse et al. May 2006 A1
20060106375 Werneth et al. May 2006 A1
20060146339 Fujita et al. Jul 2006 A1
20060164639 Horn et al. Jul 2006 A1
20060167363 Bernstein et al. Jul 2006 A1
20060171503 O'Hara et al. Aug 2006 A1
20060184048 Saadat et al. Aug 2006 A1
20060189928 Camus et al. Aug 2006 A1
20060193352 Chong et al. Aug 2006 A1
20060224053 Black et al. Oct 2006 A1
20060244973 Yun et al. Nov 2006 A1
20060279742 Tearney Dec 2006 A1
20070002435 Ye et al. Jan 2007 A1
20070019208 Toida et al. Jan 2007 A1
20070024860 Tobiason et al. Feb 2007 A1
20070035743 Vakoc et al. Feb 2007 A1
20070038040 Cense et al. Feb 2007 A1
20070048818 Rosen et al. Mar 2007 A1
20070070496 Gweon et al. Mar 2007 A1
20070076217 Baker et al. Apr 2007 A1
20070081236 Tearney et al. Apr 2007 A1
20070086013 De Lega et al. Apr 2007 A1
20070086017 Buckland et al. Apr 2007 A1
20070091317 Freischlad et al. Apr 2007 A1
20070133002 Wax et al. Jun 2007 A1
20070179487 Tearney et al. Aug 2007 A1
20070188855 Shishkov et al. Aug 2007 A1
20070203404 Zysk et al. Aug 2007 A1
20070208400 Nadkarni et al. Sep 2007 A1
20070223006 Tearney et al. Sep 2007 A1
20070233056 Yun Oct 2007 A1
20070236700 Yun et al. Oct 2007 A1
20070253901 Deng et al. Nov 2007 A1
20070258094 Izatt et al. Nov 2007 A1
20070263226 Kurtz et al. Nov 2007 A1
20070291277 Everett et al. Dec 2007 A1
20080002197 Sun et al. Jan 2008 A1
20080007734 Park et al. Jan 2008 A1
20080013960 Tearney et al. Jan 2008 A1
20080021275 Tearney et al. Jan 2008 A1
20080027429 Oyatsu Jan 2008 A1
20080049220 Izzia et al. Feb 2008 A1
20080070323 Hess et al. Mar 2008 A1
20080094613 de Boer et al. Apr 2008 A1
20080094637 de Boer et al. Apr 2008 A1
20080097225 Tearney et al. Apr 2008 A1
20080097709 de Boer et al. Apr 2008 A1
20080100837 de Boer et al. May 2008 A1
20080139906 Bussek et al. Jun 2008 A1
20080152353 de Boer et al. Jun 2008 A1
20080154090 Hashimshony Jun 2008 A1
20080201081 Reid Aug 2008 A1
20080204762 Izatt et al. Aug 2008 A1
20080218696 Mir Sep 2008 A1
20080226029 Weir et al. Sep 2008 A1
20080228086 Ilegbusi Sep 2008 A1
20080234560 Nomoto et al. Sep 2008 A1
20080252901 Shimizu Oct 2008 A1
20080265130 Colomb et al. Oct 2008 A1
20080297806 Motachiannezam Dec 2008 A1
20080308730 Vizi et al. Dec 2008 A1
20090004453 Murai et al. Jan 2009 A1
20090005691 Huang Jan 2009 A1
20090011948 Uniu et al. Jan 2009 A1
20090012368 Banik et al. Jan 2009 A1
20090012369 Robinson et al. Jan 2009 A1
20090044799 Qiu Feb 2009 A1
20090051923 Zuluaga Feb 2009 A1
20090131801 Suter et al. May 2009 A1
20090192358 Jaffer et al. Jul 2009 A1
20090196477 Cense et al. Aug 2009 A1
20090209834 Fine Aug 2009 A1
20090273777 Yun et al. Nov 2009 A1
20090290156 Popescu et al. Nov 2009 A1
20090305309 Chien et al. Dec 2009 A1
20090306520 Schmitt et al. Dec 2009 A1
20090323056 Yun et al. Dec 2009 A1
20100086251 Xu et al. Apr 2010 A1
20100094576 de Boer et al. Apr 2010 A1
20100145145 Shi et al. Jun 2010 A1
20100150467 Zhao et al. Jun 2010 A1
20100261995 Mckenna et al. Oct 2010 A1
20110028967 Rollins et al. Feb 2011 A1
20110160681 Dacey, Jr. et al. Jun 2011 A1
20110218403 Tearney et al. Sep 2011 A1
Foreign Referenced Citations (159)
Number Date Country
1550203 Dec 2004 CN
10351319 Jun 2005 DE
102005034443 Feb 2007 DE
0617286 Feb 1994 EP
0697611 Feb 1996 EP
0728440 Aug 1996 EP
1324051 Jul 2003 EP
2149776 Feb 2010 EP
2738343 Aug 1995 FR
2298054 Aug 1996 GB
6073405 Apr 1985 JP
361040633 Mar 1986 JP
62-188001 Jun 1989 JP
04-056907 Feb 1992 JP
20040056907 Feb 1992 JP
5509417 Nov 1993 JP
H8-136345 May 1996 JP
H08-160129 Jun 1996 JP
9-10213 Jan 1997 JP
9-230248 Sep 1997 JP
10-213485 Aug 1998 JP
10-267631 Oct 1998 JP
10-267830 Oct 1998 JP
2259617 Oct 1999 JP
2000-023978 Jan 2000 JP
2000-046729 Feb 2000 JP
2000-121961 Apr 2000 JP
2000-504234 Apr 2000 JP
2000-126116 May 2000 JP
2000-131222 May 2000 JP
2001-4447 Jan 2001 JP
2001-500026 Jan 2001 JP
2001-104315 Apr 2001 JP
2001-174404 Jun 2001 JP
2001-174744 Jun 2001 JP
2001-507251 Jun 2001 JP
2001-508340 Jun 2001 JP
2007-539336 Jun 2001 JP
2001-212086 Jul 2001 JP
2001-212086 Aug 2001 JP
2008-533712 Aug 2001 JP
2001-264246 Sep 2001 JP
2001-515382 Sep 2001 JP
2001-525580 Dec 2001 JP
2002-503134 Jan 2002 JP
2002-035005 Feb 2002 JP
2002-205434 Feb 2002 JP
2002-095663 Apr 2002 JP
2002-113017 Apr 2002 JP
2002-148185 May 2002 JP
2002-516586 Jun 2002 JP
2002-214127 Jul 2002 JP
2002-214128 Jul 2002 JP
2002214127 Jul 2002 JP
2003-014585 Jan 2003 JP
2003-504627 Feb 2003 JP
20030035659 Feb 2003 JP
2003-512085 Apr 2003 JP
2003-513278 Apr 2003 JP
2003-516531 May 2003 JP
2004-028970 Jan 2004 JP
2004-037165 Feb 2004 JP
2004-057652 Feb 2004 JP
2004-089552 Mar 2004 JP
2004-113780 Apr 2004 JP
2004-514920 May 2004 JP
2004-258144 Sep 2004 JP
2004-317437 Nov 2004 JP
2005-062850 Mar 2005 JP
2005-110208 Apr 2005 JP
2005-510323 Apr 2005 JP
2005-156540 Jun 2005 JP
2005-516187 Jun 2005 JP
2005-195485 Jul 2005 JP
2005-241872 Sep 2005 JP
2006-015134 Jan 2006 JP
2006-015134 Jan 2006 JP
2006-237359 Sep 2006 JP
2007-500059 Jan 2007 JP
2007-075403 Mar 2007 JP
2007-83053 Apr 2007 JP
2007-524455 Aug 2007 JP
2007271761 Oct 2007 JP
2003-102672 Apr 2012 JP
2149464 May 2000 RU
2209094 Jul 2003 RU
2213421 Sep 2003 RU
2242710 Dec 2004 RU
2255426 Jun 2005 RU
2108122 Jun 2006 RU
79008941 Oct 1979 WO
9201966 Feb 1992 WO
9216865 Oct 1992 WO
9216865 Oct 1993 WO
96-02184 Feb 1996 WO
96-04839 Feb 1996 WO
9800057 Jan 1998 WO
98-35203 Aug 1998 WO
9848846 Nov 1998 WO
9944089 Feb 1999 WO
99-28856 Jun 1999 WO
99-45838 Sep 1999 WO
99-45338 Oct 1999 WO
00-42906 Jul 2000 WO
00-43730 Jul 2000 WO
01-04828 Jan 2001 WO
0101111 Jan 2001 WO
0127679 Apr 2001 WO
01-33215 May 2001 WO
01-38820 May 2001 WO
01-42735 Jun 2001 WO
01-82786 Nov 2001 WO
02-37075 May 2002 WO
0237075 May 2002 WO
02-45572 Jun 2002 WO
02-68853 Jun 2002 WO
02-054027 Jul 2002 WO
02053050 Jul 2002 WO
02-083003 Oct 2002 WO
02084263 Oct 2002 WO
03-003903 Jan 2003 WO
03-012405 Feb 2003 WO
03-013624 Feb 2003 WO
03013624 Feb 2003 WO
03046495 Jun 2003 WO
03046636 Jun 2003 WO
03053226 Jul 2003 WO
03062802 Jul 2003 WO
03-088826 Oct 2003 WO
03105678 Dec 2003 WO
2004-037068 May 2004 WO
2004-043251 May 2004 WO
2004057266 Jul 2004 WO
2004-073501 Sep 2004 WO
2004-100789 Nov 2004 WO
2004-105598 Dec 2004 WO
2005-045362 May 2005 WO
2005-047813 May 2005 WO
2005047813 May 2005 WO
2005082225 Sep 2005 WO
2006004743 Jan 2006 WO
2006-020605 Feb 2006 WO
2006-058187 Feb 2006 WO
2006038876 Apr 2006 WO
2006039091 Apr 2006 WO
2006-050320 May 2006 WO
2006-058187 Jun 2006 WO
2006059109 Jun 2006 WO
2006124860 Nov 2006 WO
2006-131859 Dec 2006 WO
2007-030835 Mar 2007 WO
2007028531 Mar 2007 WO
WO 2007041376 Apr 2007 WO
WO 2007041376 Apr 2007 WO
2007083138 Jul 2007 WO
2007084995 Jul 2007 WO
2009-033064 Mar 2009 WO
2011-055376 May 2011 WO
2011-080713 Jul 2011 WO
Non-Patent Literature Citations (226)
Entry
R. Haggitt et al., “Barrett's Esophagus Correlation Between Mucin Histochemistry, Flow Cytometry, and Histological Diagnosis for Predicting Increased Cancer Risk,” Apr. 1988, American Journal of Pathology, vol. 131, No. 1, pp. 53-61.
R.H. Hardwick et al., (1995) “c-erbB-2 Overexpression in the Dysplasia/Carcinoma Sequence of Barrett's Oesophagus,” Journal of Clinical Pathology, vol. 48, No. 2, pp. 129-132.
W. Polkowski et al, (1998) Clinical Decision making in Barrett's Oesophagus can be supported by Computerized Immunoquantitation and Morphometry of Features Associated with Proliferation and Differentiation, Journal of pathology, vol. 184, pp. 161-168.
J.R. Turner et al., MN Antigen Expression in Normal Preneoplastic, and Neoplastic Esophagus: A Clinicopathological Study of a New Cancer-Associated Biomarker,: Jun. 1997, Human Pathology, vol. 28, No. 6, pp. 740-744.
D.J. Bowery et al., (1999) “Patterns of Gastritis in Patients with Gastro-Oesophageal Reflux Disease,”, Gut, vol. 45, pp. 798-803.
O'Reich et al., (2000) “Expression of Oestrogen and Progesterone Receptors in Low-Grade Endometrial Stromal Sarcomas,”, British Journal of Cancer, vol. 82, No. 5, pp. 1030-1034.
M.I. Canto et al., (1999) “Vital Staining and Barrett's Esophagus,” Gastrointestinal Endoscopy, vol. 49, No. 3, Part 2, pp. S12-S16.
S. Jackle et al., (2000) “In Vivo Endoscopic Optical Coherence Tomography of the Human Gastrointestinal Tract—Toward Optical Biopsy,” Encoscopy, vol. 32, No. 10, pp. 743-749.
E. Montgomery et al., “Reproducibility of the Diagnosis of Dysplasia in Barrett Esophagus: A Reaffirmation,” Apr. 2001, Human Pathology, vol. 32, No. 4, pp. 368-378.
H. Geddert et al., “Expression of Cyclin B1 in the Metaplasia-Dysphasia-Carcinoma Sequence of Barrett Esophagus,” Jan. 2002, Cancer, vol. 94, No. 1, pp. 212-218.
P. Pfau et al., (2003) “Criteria for the Diagnosis of Dysphasia by Endoscopic Optical Coherence Tomography,” Gastrointestinal Endoscopy, vol. 58, No. 2, pp. 196-2002.
R. Kiesslich et al., (2004) “Confocal Laser Endoscopy for Diagnosing Intraepithelial Neoplasias and Colorectal Cancer in Vivo,” Gastroenterology, vol. 127, No. 3, pp. 706-713.
X. Qi et al., (2004) “Computer Aided Diagnosis of Dysphasia in Barrett's Esophagus Using Endoscopic Optical Coherence Tomography,” SPIE, Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine VIII. Proc. of Conference on., vol. 5316, pp. 33-40.
Seltzer et al., (1991) “160 nm Continuous Tuning of a MQW Laser in an External Cavity Across the Entire 1.3 μm Communications Window,” Electronics Letters, vol. 27, pp. 95-96.
Office Action dated Jan. 25, 2010 for U.S. Appl. No. 11/537,048.
International Search Report dated Jan. 27, 2010 for PCT/US2009/050553.
International Search Report dated Jan. 27, 2010 for PCT/US2009/047988.
International Search Report dated Feb. 23, 2010 for U.S. Appl. No. 11/445,131.
Office Action dated Mar. 18, 2010 of U.S. Appl. No. 11/844,454.
Office Action dated Apr. 8, 2010 of U.S. Appl. No. 11/414,564.
Japanese Office Action dated Apr. 13, 2010 for Japanese Patent application No. 2007-515029.
International Search Report dated May 27, 2010 for PCT/US2009/063420.
Office Action dated May 28, 2010 for U.S. Appl. No. 12/015,642.
Office Action dated Jun. 2, 2010 for U.S. Appl. No. 12/112,205.
Liptak David C. et al., (2007) “On the Development of a Confocal Rayleigh-Brillouin Microscope” American Institute of Physics vol. 78, 016106.
Office Action mailed Oct. 1, 2008 for U.S. Appl. No. 11/955,986.
Invitation of Pay Additional Fees mailed Aug. 7, 2008 for International Application No. PCT/US2008/062354.
Invitation of Pay Additional Fees mailed Jul. 20, 2008 for International Application No. PCT/US2007/081982.
International Search Report and Written Opinion mailed Mar. 7, 2006 for PCT/US2005/035711.
International Search Report and Written Opinion mailed Jul. 18, 2008 for PCT/US2008/057533.
Aizu, Y et al. (1991) “Bio-Speckle Phenomena and Their Application to the Evaluation of Blood Flow” Optics and Laser Technology, vol. 23, No. 4, Aug. 1, 1991.
Richards G.J. et al. (1997) “Laser Speckle Contrast Analysis (LASCA): A Technique for Measuring Capillary Blood Flow Using the First Order Statistics of Laser Speckle Patterns” Apr. 2, 1997.
Gonick, Maria M., et al (2002) “Visualization of Blood Microcirculation Parameters in Human Tissues by Time Integrated Dynamic Speckles Analysis” vol. 972, No. 1, Oct. 1, 2002.
International Search Report and Written Opinion mailed Jul. 4, 2008 for PCT/US2008/051432.
Jonathan, Enock (2005) “Dual Reference Arm Low-Coherence Interferometer-Based Reflectometer for Optical Coherence Tomography (OCT) Application” Optics Communications vol. 252.
Motaghian Nezam, S.M.R. (2007) “increased Ranging Depth in optical Frequency Domain Imaging by Frequency Encoding” Optics Letters, vol. 32, No. 19, Oct. 1, 2007.
Office Action dated Jun. 30, 2008 for U.S. Appl. No. 11/670,058.
Office Action dated Jul. 7, 2008 for U.S. Appl. No. 10/551,735.
Australian Examiner's Report mailed May 27, 2008 for Australian patent application No. 2003210669.
Notice of Allowance mailed Jun. 4, 2008 for U.S. appl. No. 11/174,425.
European communication dated May 15, 2008 for European patent application No. 05819917.5.
International Search Report and Written Opinion mailed Jun. 10, 2008 for PCT/US2008/051335.
Oh. W.Y. et al (2006) “Ultrahigh-Speed Optical Frequency Domain Imaging and Application to laser Ablation Monitoring” Applied Physics Letters, vol. 88.
Office Action dated Aug. 21, 2008 for U.S. Appl. No. 11/505,700.
Sticker, Markus (2002) En Face Imaging of Single Cell layers by Differential Phase-Contrast Optical Coherence Microscopy) Optics Letters, col. 27, No. 13, Jul. 1, 2002.
International Search Report and Written Opinion dated Jul. 17, 2008 for International Application No. PCT/US2008/057450.
International Search Report and Written Opinion dated Aug. 11, 2008 for International Application No. PCT/US2008/058703.
US National Library of Medicine (NLM), Bethesda, MD, US; Oct. 2007 (Oct. 2007), “Abstracts of the 19th Annual Symposium of Transcatheter Cardiovascular Therapeutics, Oct. 20-25, 2007, Washington, DC, USA.”
International Search Report and Written Opinion dated May 26, 2008 for International Application No. PCT/US2008/051404.
Office Action dated Aug. 25, 2008 for U.S. Appl. No. 11/264,655.
Office Action dated Sep. 11, 2008 for U.S. Appl. No. 11/624,334.
Office Action dated Aug. 21, 2008 for U.S. Appl. No. 11/956,079.
Gelikono, V. M. et al. Oct. 1, 2004 “Two-Wavelength Optical Coherence Tomography” Radio physics and Quantum Electronics, Kluwer Academic Publishers-Consultants. vol. 47, No. 10-1.
International Search Report and Written Opinion for PCT/US2007/081982 dated Oct. 19, 2007.
Database Compendex Engineering Information, Inc., New York, NY, US; Mar. 5, 2007, Yelin, Dvir et al: “Spectral-Domain Spectrally-Encoded Endoscopy”.
Database Biosis Biosciences Information Service, Philadelphia, PA, US; Oct. 2006, Yelin D. et al: “Three-Dimensional Miniature Endoscopy”.
International Search Report and Written Opinion mailed Mar. 14, 2005 for PCT/US2004/018045.
Notification of the international Preliminary Report on Patentability mailed Oct. 21, 2005.
Shim M.G. et al., “Study of Fiber-Optic Probes for In vivo Medical Raman Spectroscopy” Applied Spectroscopy. vol. 53, No. 6, Jun. 1999.
Bingid U. et al., “Fibre-Optic Laser-Assisted Infrared Tumour Diagnostics (FLAIR); Infrared Tomour Diagnostics” Journal of Physics D. Applied Physics, vol. 38, No. 15, Aug. 7, 2005.
Jun Zhang et al. “Full Range Polarization-Sensitive Fourier Domain Optical Coherence Tomography” Optics Express, vol. 12, No. 24. Nov. 29, 2004.
Yonghua et al., “Real-Time Phase-Resolved Functional Optical Hilbert Transformation” Optics Letters, vol. 27, No. 2, Jan. 15, 2002.
Siavash et al., “Self-Referenced Doppler Optical Coherence Tomography” Optics Letters, vol. 27, No. 23, Dec. 1, 2002.
International Search Report and Written Opinion dated Dec. 20, 2004 for PCT/US04/10152.
Notification Concerning Transmittal of International Preliminary Report on Patentability dated Oct. 13, 2005 for PCT/US04/10152.
International Search Report and Written Opinion dated Mar. 23, 2006 for PCT/US2005/042408.
International Preliminary Report on Patentability dated Jun. 7, 2007 for PCT/US2005/042408.
International Search Report and Written Opinion dated Feb. 28, 2007 for International Application No. PCT/US2006/038277.
International Search Report and Written Opinion dated Jan. 30, 2009 for International Application No. PCT/US2008/081834.
Fox, J.A. et al; “A New Galvanometric Scanner for Rapid tuning of C02 Lasers” New York, IEEE, US vol. Apr. 7, 1991.
Motaghian Nezam, S.M. et al: “High-speed Wavelength-Swept Semiconductor laser using a Diffrection Grating and a Polygon Scanner in Littro Configuration” Optical Fiber Communication and the National Fiber Optic Engineers Conference Mar. 29, 2007.
International Search Report and Written Opinion dated Feb. 2, 2009 for International Application No. PCT/US2008/071786.
Bilenca A et al: “The Role of Amplitude and phase in Fluorescence Coherence Imaging: From Wide Filed to Nanometer Depth Profiling”, Optics IEEE, May 5, 2007.
Inoue, Yusuke et al: “Varible Phase-Contrast Fluorescence Spectrometry for Fluorescently Strained Cells”, Applied Physics Letters, Sep. 18, 2006.
Bernet, S et al: “Quantitative Imaging of Complex Samples by Spiral Phase Contrast Microscopy”, Optics Express, May 9, 2006.
International Search Report and Written Opinion dated Jan. 15, 2009 for International Application No. PCT/US2008/074863.
Office Action dated Feb. 17, 2009 for U.S. Appl. No. 11/211,483.
Notice of Reasons for Rejection mailed Dec. 2, 2008 for Japanese patent application No. 2000-533782.
International Search Report and Written Opinion dated Feb. 24, 2009 for PCT/US2008/076447.
European Official Action dated Dec. 2, 2008 for EP 07718117.0.
Barfuss et al (1989) “Modified Optical Frequency Domain Reflectometry with High spatial Resolution for Components of integrated optic Systems”, Journal of Lightwave Technology, IEEE vol. 7., No. 1.
Yun et al., (2004) “Removing the Depth-Degeneracy in Optical Frequency Domain Imaging with Frequency Shifting”, Optics Express, vol. 12, No. 20.
International Search Report and Written Opinion dated Jun. 10, 2009 for PCT/US08/075456.
European Search Report issued May 5, 2009 for European Application No. 01991471.2.
Motz, J.T. et al: “Spectral- and Frequency-Encoded Fluorescence Imaging” Optics Letters, OSA, Optical Society of America, Washington, DC, US, vol. 30, No. 20, Oct. 15, 2005, pp. 2760-2762.
Japanese Notice of Reasons for Rejection dated Jul. 14, 2009 for Japanese Patent application No. 2006-503161.
Office Action dated Aug. 18, 2009 for U.S. Appl. No. 12/277,178.
Office Action dated Aug. 13, 2009 for U.S. Appl. No. 10/136,813.
Office Action dated Aug. 6, 2009 for U.S. Appl. No. 11/624,455.
Office Action dated May 15, 2009 for U.S. Appl. No. 11/537,123.
Office Action dated Apr. 17, 2009 for U.S. Appl. No. 11/537,343.
Office Action dated Apr. 15, 2009 for U.S. Appl. No. 12/205,775.
Office Action dated Dec. 9, 2008 for U.S. Appl. No. 09/709,162.
Office Action dated Dec. 23, 2008 for U.S. Appl. No. 11/780,261.
Office Action dated Jan. 9, 2010 for U.S. Appl. No. 11/624,455.
Office Action dated Feb. 18, 2009 for U.S. Appl. No. 11/285,301.
Beddow et al, (May 2002) “Improved Performance Interferomater Designs for Optical Coherence Tomography”, IEEE Optical Fiber Sensors Conference, pp. 527-530.
Yaqoob et al., (Jun. 2002) “High-Speed Wavelength-Multiplexed Fiber-Optic Sensors for Biomedicine,” Sensors Proceedings of the IEEE, pp. 325-330.
Office Action dated Feb. 18, 2009 for U.S. Appl. No. 11/697,012.
Zhang et al, (Sep. 2004), “Fourier Domain Functional Optical Coherence Tomography”, Saratov Fall Meeting 2004, pp. 8-14.
Office Action dated Feb. 23, 2009 for U.S. Appl. No. 11/956,129.
Office Action dated Mar. 16, 2009 for U.S. Appl. No. 11/621,694.
Office Action dated Oct. 1, 2009 for U.S. Appl. No. 11/677,278.
Office Action dated Oct. 6, 2009 for U.S. Appl. No. 12/015,642.
Lin, Stollen et al., (1977) “A CW Tunable Near-infrared (1.085-1.175-um) Raman Oscillator,” Optics Letters, vol. 1, 96.
Summons to attend Oral Proceedings dated Oct. 9, 2009 for European patent application No. 06813365.1.
Office Action dated Dec. 15, 2009 for U.S. Appl. No. 11/549,397.
Office Action dated Jul. 7, 2010 for U.S. Appl. No. 11/624,277.
Montag Ethan D., “Parts of the Eye” online textbook for JIMG 774: Vision & Psycophysics, download on Jun. 23, 2010 from http://www.cis.rit.edu/people/faculty/montag/vandplite/pages/chap—8/ch8p3.html.
Office Action dated Jul. 16, 2010 for U.S. Appl. No. 11/445,990.
Office Action dated Jul. 20, 2010 for U.S. Appl. No. 11/625,135.
Office Action dated Aug. 5, 2010 for U.S. Appl. No. 11/623,852.
Chinese office action dated Aug. 4, 2010 for CN 200780005949.9.
Chinese office action dated Aug. 4, 2010 for CN 200780016266.3.
Zhang et al., “Full Range Polarization-Sensitive Fourier Domain Optical Coherence Tomography” Optics Express, Nov. 29, 2004, vol. 12, No. 24.
Office Action dated Aug. 27, 2010 for U.S. Appl. No. 11/569,790.
Office Action dated Aug. 31, 2010 for U.S. Appl. No. 11/677,278.
Office Action dated Sep. 3, 2010 for U.S. Appl. No. 12/139,314.
Yong Zhao et al: “Virtual Data Grid Middleware Services for Data-Intensive Science”, Concurrency and Computation: Practice and Experience, Wiley, London, GB, Jan. 1, 2000, pp. 1-7, pp. 1532-0626.
Swan et al., “Toward Nanometer-Scale Resolution in Fluorescence Microscopy using Spectral Self-Inteference” IEEE Journal. Selected Topics in Quantum Electronics 9 (2) 2003, pp. 294-300.
Moiseev et al., “Spectral Self-Interfence Fluorescence Microscopy”, J. Appl. Phys. 96 (9) 2004, pp. 5311-5315.
Hendrik Verschueren, “Interference Reflection Microscopy in Cell Biology”, J. Cell Sci. 75, 1985, pp. 289-301.
Park et al., “Diffraction Phase and Fluorescence Microscopy”, Opt. Expr. 14 (18) 2006, pp. 8263-8268.
Swan et al, “High Resolution Spectral Self-Interference Fluorescence Microscopy”, Proc. SPIE 4621, 2002, pp. 77-85.
Sanchez et al., “Near-Field Fluorscence Microscopy Based on Two-Photon Excvitation with Metal Tips”, Phys. Rev. Lett. 82 (20) 1999, pp. 4014-4017.
Wojtkowski, Maciej, Ph.D. “Three-Dimensional Retinal Imaging with High-Speed Ultrahigh-Resolution Optical Coherence Tomography” Ophthalmology, Oct. 2005, 112(10): 1734-1746.
Vaughan, J.M. et al., “Brillouin Scattering, Density and Elastic Properties of the Lens and Cornea of the Eye”, Nature, vol. 284, Apr. 3, 1980, pp. 489-491.
Hess, S.T. et al. “Ultra-high Resolution Imaging by Fluorescence Photoactivation Localization Microscopy” Biophysical Journal vol. 91, Dec. 2006, 4258-4272.
Fernandez-Suarez, M. et al., “Fluorescent Probes for Super-Resolution Imaging in Living Cells” Nature Reviews Molecular Cell Biology vol. 9, Dec. 2008.
Extended European Search Report mailed Dec. 14, 2010 for EP 10182301.1.
S. Hell et al., “Breaking the diffraction resolution limit by stimulated-emission—stimulated-emission-depletion fluorescence microscopy,” Optics Letters. 19:495 (1995) and Ground State Depletion (GSD).
S. Hell et al. “Ground-State-Depletion fluorescence microscopy—a concept for breaking the diffraction resolution limit,” Applied Physics B. 60:780 (1994)) fluorescence microscopy, photo-activated localization microscopy (PALM).
E. Betzig et al. “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313:1642 (2006), stochastic optical reconstruction microscopy (STORM).
M. Rust et al. “Sub-diffraction-limited imaging by stochastic optical reconstruction microscopy (STORM),” Nature Methods 3:783 (2006), and structured illumination microscopy (SIM).
B. Bailey et al. “Enhancement of Axial Resolution in Fluorescence Microscopy by Standing-Wave Excitation,” Nature 366:44 (1993).
M. Gustafsson “Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy,” Journal of Microscopy 198:82 (2000).
M. Gustafsson “Nonlinear structured illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution,” PNAS 102:13081 (2005)).
R. Thompson et al. “Precise nanometer localization analysis for individual fluorescent probes,” Biophysical Journal 82:2775 (2002).
K. Drabe et al. “Localization of Spontaneous Emission in front of a mirror,” Optics Communications 73:91 (1989).
Swan et al. “Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference,” IEEE Quantum Electronics 9:294 (2003).
C. Joo, et al. “Spectral Domain optical coherence phase and multiphoton microscopy,” Optics Letters 32:623 (2007).
Virmani et al., “Lesions from sudden coronary death: A comprehensive morphological classification scheme for atherosclerotic lesions,” Arterioscler. Thromb. Vase. Bio., 20:1262-75 (2000).
Gonzalez, R.C. and Wintz, P., “Digital Image Processing” Addison-Wesley Publishing Company, Reading MA, 1987.
V. Tuchin et al., “Speckle interferometry in the measurements ofbiotissues vibrations,” SPIE, 1647: 125 (1992).
A.A. Bednov et al., “Investigation of Statistical Properties of Lymph Flow Dynamics Using Speckle-Microscopy,” SPIE, 2981: 181-90 (1997).
Feng et al., “Mesocopic Conductors and Correlations in Laser Speckle Patters” Science, New Series, vol. 251, No. 4994, pp. 633-639 (Feb. 8, 1991).
Lee et al., “The Unstable Atheroma,” Arteriosclerosis, Thrombosis & Vascular Biology, 17:1859-67 (1997).
International Search report dated Apr. 29, 2011 for PCT/US2010/051715.
International Search report dated Sep. 13, 2010 for PCT/US2010/023215.
European Search Report daled Jun. 25, 2012 for EP 10733985.5.
Wieser, Wolfgang et al., “Multi-Megahertz OCT: High Quality 3D Imaging at 20 million A-Scans and 4.5 Gvoxels per Second” Jul. 5, 2010, vol. 18, No. 14, Optics Express.
International Search Report and Written Opinion mailed Aug. 30, 2012 for PCT/US2012/035234.
Japanese Notice of Reasons for Rejection dated Oct. 2, 2012 for 2007-543626.
Yoden, K. et al. “An Approach to Optical Reflection Tomograpyhy Along the Geometrial Thickness,” Optical Review, vol. 7, No. 5, Oct. 1, 2000.
The First Office Action for Japanese Patent Application No. 2013-263754 dated Sep. 30, 2014.
The Office Action for Japanese Patent Application 2013-263754 dated on Jun. 2, 2015.
The Office Action for Japanese Patent Application No. 2011-546443 dated Feb. 3, 2015.
Poneros er al: “Optical Coherence Tomography of the Biliary Tree During ERCP”, Gastrointestinal Endoscopy, Elsevier, NL, vol. 55, No. 1, Jan. 1, 2002, pp. 84-88.
Fu L e tal: Double-Clad Photonic Crystal Fiber Coupler for compact Nonlinear Optical Microscopy Imaging, Optics Letters, OSA, Optical Society of America, vol. 31, No. 10, May 15, 2006, pp. 1471-1473.
Japanese language Appeal Decision dated Jan. 10, 2012 for JP 2006-503161.
Japanese Notice of Grounds for Rejection dated Oct. 28, 2011 for JP2009-294737.
Japanese Notice of Grounds for Rejection dated Dec. 28, 2011 for JP2008-535793.
Japanese Notice of Reasons for Rejection dated Dec. 12, 2011 for JP 2008-533712.
International Search Report and Written Opinion mailed Feb. 9, 2012 based on PCT/US2011/034810.
Japanese Notice of Reasons for Rejection dated Mar. 27, 2012 for JP 2003-102672.
Japanese Notice of Reasons for Rejection dated May 8, 2012 for JP 2008-533727.
Korean Office Action dated May 25, 2012 for KR 10-2007-7008116.
Japanese Notice of Reasons for Rejection dated May 21, 2012 for JP 2008-551523.
Japanese Notice of Reasons for Rejection dated Jun. 20, 2012 for JP 2009-546534.
European Official Communication dated Aug. 1, 2012 for EP 10193526.0.
European Search Report dated Jun. 23, 2012 for EP 10733985.5.
Wieser, Wolfgang et al., “Multi-Metahertz OCT: High Quality 3D Imaging at 20 million A-Scans and 4.5 Gvoxels per Second” Jul. 5, 2010, vol. 18, No. 14, Optics Express.
European Communication Pursuant to EPC Article 94(3) for EP 07845206.7 dated Aug. 30, 2012.
International Search Report and Written Opinion mailed Aug. 30, '2012 for PCT/US2012/035234.
Giuliano, Scarcelli et al., “Three-Dimensional Brillouin Confocal Microscopy”. Optical Society of American, 2007, CtuV5.
Giuliano, Scarcelli et al., “Confocal Brillouin Microscopy for Three-Dimensional Mechanical Imaging.” Nat Photonis, Dec. 9, 2007.
Japanese Notice of Reasons for Rejections dated Oct. 10, 2012 for 2008-553511.
W.Y. Oh et al: “High:Speed Polarization Sensitive Optical Frequency Domain Imaging with Frequency Multiplexing”, Optics Express, vol. 16, No. 2, Jan. 1, 2008.
Athey, B.D. et al., “Development and Demonstration of a Networked Telepathology 3-D Imaging, Databasing, and Communication System”, 1998 (“C2”) , pp. 5-17.
D'Amico, A.V., et al., “Optical Coherence Tomography as a Method for Indentifying Benign and Maliganat Microscopic Structures in the Prostrate Gland”, Urology, vol. 55, Isue 5, May 2000 (“C3”), pp. 783-787.
Tearney, G.J. et al., “In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography”, Science, vol. 276, No. 5321, Junl. 27, 1997 (“C6”), pp. 2037-2039.
Japanese Notice of Reasons for Rejections dated Oct. 2, 2012 for 2007-543626.
Canadian Office Action dated Oct. 10, 2012 for 2,514,189.
Japanese Notice of Reasons for Rejections dated Nov. 9, 2012 for JP 2007-530134.
Japanese Notice of Reasons for Rejections dated Nov. 27, 2012 for JP 2009-554772.
Japanese Notice of Reasons for Rejections dated Oct. 11, 2012 for JP 2008-533712.
Yoden, K. et al. “An Approach to Optical Reflection Tomography Along the Geometrial Thickness,” Optical Review, vol. 7, No. 5, Oct. 1, 2000.
International Search Report and Written Opinion mailed Oct. 25, 2012 for PCT/US2012/047415.
Joshua, Fox et al: “Measuring Primate RNFL Thickness with OCT”, IEEE Journal of Selected Topics in Quantum Electronics, IEEE Service Center, Piscataway, NJ, US, vol. 7,No. 6, Nov. 1, 2001.
European Official Communication dated Feb. 6, 2013 for 04822169.1.
International Search Report mailed Jan. 31, 2013 for PCT/US2012/061135.
Viliyam K. Pratt. Lazernye Sistemy Svyazi. Moskva, Izdatelstvo “Svyaz”, 1972. p. 68-70.
International Search Report and Written Opinion mailed Jan. 31, 2013 for PCT/US2012/060843.
European Search Report mailed on Mar. 11, 2013 doe EP 10739129.4.
Huber, R et al: “Fourier Domain Mode Locked Lasers for OCT Imaging at up to 290 kHz Sweep Rates”, Proceedings of SPIE, SPIE—International Society for Optical Engineering, US, vol. 5861, No. 1, Jan. 1, 2005.
M. Kourogi et al: “Programmable High Speed (1MHz) Vernier-mode-locked Frequency-Swept Laser for OCT Imaging”, Proceedings of SPIE, vol. 6847, Feb. 7, 2008.
Notice of Reasons for Rejection dated Feb. 5, 2013 for JP 2008-509233.
Notice of Reasons for Rejection dated Feb. 19, 2013 for JP 2008-507983.
European Extended Search Report mailed Mar. 26, 2013 for EP 09825421.1.
Masahiro, Yamanari et al: “polarization-Sensitive Swept-Source Optical Coherence Tomography with Continuous Source Polarization Modulation”, Optics Express, vol. 16, No. 8, Apr. 14, 2008.
European Extended Search Report mailed on Feb. 1, 2013 for EP 12171521.3.
Nakamura, Koichiro et al., “A New Technique of Optical Ranging by a Frequency-Shifted Feedback Laser”, IEEE Phontonics Technology Letters, vol. 10, No. 12, pp. 1041-1135, Dec. 1998.
Lee, Seok-Jeong et al., “Ultrahigh Scanning Speed Optical Coherence Tomography Using Optical Frequency Comb Generators”, The Japan Soceity of Applied Physics, vol. 40 (2001).
Kinoshita, Masaya et al., “Optical Frequency-Domain Imaging Microprofilmetry with a Frequency-Tunable Liquid-Crystal Fbry-Perot Etalon Device” Applied Optics, vol. 38, No. 34, Dec. 1, 1999.
Notice of Reasons for Rejection mailed on Apr. 16, 2013 for JP 2009-510092.
Bachmann A.H. et al: “Heterodyne Fourier Domain Optical Coherence Tomography for Full Range Probing with High Axial Resolution”, Optics Express, OSA, vol. 14, No. 4, Feb. 20, 2006.
European Search Report for 12194876.4 dated Feb. 1, 2013.
International Search Report and Written Opinion for PCT/US2013/022136.
Thomas J. Flotte: “Pathology Correlations with Optical Biopsy Techniques”, Annals of the New York Academy of Sciences, Wiley-Blackwell Publishing, Inc. SU, vol. 838, No. 1, Feb. 1, 1998, pp. 143-149.
Constance R. Chu et al: Arthroscopic Microscopy of Articular Cartilage Using Optical Coherence Tomography, American Journal of Sports Medicine, American Orthopedic Society for Sports Medicine, Waltham, MA, Vo. 32, No. 9, Apr. 1, 2004.
Bouma B E et al: Diagnosis of Specialized Intestinal Metaplasia of the Esophagus with Optical Coherence Tomography, Conference on Lasers and Electro-Optics. Technical Digest. OSA, US, vol. 56, May 6, 2001.
Shen et al: “Ex Vivo Histology-Correlated Optical Coherence Tomography in the Detection of Transmural Inflammation in Crohn's Disease”, Clinical Gastroenterology and Heptalogy, vol. 2, No. 9, Sep. 1, 2004.
Shen et al: “In Vivo Colonscopic Optical Coherence Tomography for Transmural Inflammation in Inflammatory Bowel Disease”, Clinical Gastroenterology and Hepatology, American Gastroenterological Association, US, vol. 2, No. 12, Dec. 1, 2004.
Ge Z et al: “Identification of Colonic Dysplasia and Neoplasia by Diffuse Reflectance Spectroscopy and Pattern Recognition Techniques”, Applied Spectroscopy, The Society for Applied Spectroscopy, vol. 52, No. 6, Jun. 1, 1998.
Elena Zagaynova et al: “Optical Coherence Tomography: Potentialities in Clinical Practice”, Proceedings of SPIE, Aug. 20, 2004.
Westphal et al: “Correlation of Endoscopic Optical Coherence Tomography with Histology in the Lower-GI Tract”, Gastrointestinal Endoscopy, Elsevier, NL, vol. 61, No. 4, Apr. 1, 2005.
Haggitt et al: “Barrett's Esophaagus, Dysplasia, and Adenocarcinoma”, Human Pathology, Saunders, Philadelphia, PA, US, vol. 25, No. 10, Oct. 1, 1994.
Gang Yao et al. “Monte Carlo Simulation of an Optical Coherence Tomography Signal in Homogenous Turbid Media,” Physics in Medicine and Biology, 1999.
Murakami, K. “A Miniature Confocal Optical Scanning Microscopy for Endscopes”, Proceedings of SPIE, vol. 5721, Feb. 28, 2005, pp. 119-131.
Seok, H. Yun et al: “Comprehensive Volumetric Optical Microscopy in Vivo”, Nature Medicine, vol. 12, No. 12, Jan. 1, 2007.
Baxter: “Image Zooming”, Jan. 25, 2005, Retrieved from the Internet.
Qiang Zhou et al: “A Novel Machine Vision Application for Analysis and Visualization of Confocal Microscopic Images” Machine Vision and Applications, vol. 16, No. 2, Feb. 1, 2005.
Igor Gurov et al: (2007) “Full-field High-Speed Optical Coherence Tomography System for Evaluting Multilayer and Random Tissues”, Proc. of SPIE, vol. 6618.
Igor Gurov et al: “High-Speed Signal Evaluation in Optical Coherence Tomography Based on Sub-Nyquist Sampling and Kalman Filtering Method” AIP Coherence Proceedings, vol. 860, Jan. 1, 2006.
Groot De P et al: “Three Dimensional Imaging by Sub-Nyquist Sampling of White-Light Interferograms”, Optics Letters, vol. 18, No. 17, Sep. 1, 1993.
Silva et al: “Extended Range, Rapid Scanning Optical Delay Line for Biomedical Interferometric Imaging”, Electronics Letters, IEE Stevenage, GB vol. 35, No. 17, Aug. 19, 1999.
Related Publications (1)
Number Date Country
20100210937 A1 Aug 2010 US
Provisional Applications (2)
Number Date Country
61145914 Jan 2009 US
61184180 Jun 2009 US