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Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Background: Radiofrequency ablation (RFA) treatment outcomes vary for unknown reasons. One hypothesis is that variations in Barrett's epithelial thickness (BET) are associated with reduced RFA efficacy for thicker BET and strictures for thinner BET. Volumetric laser endomicroscopy (VLE) is an imaging modality that acquires high-resolution, depth-resolved images of BE. However, the attenuation of light by tissue and the lack of layering in Barrett's tissue challenge BET measurements and the study of relationships between thickness and RFA outcomes. We aimed to quantify BET and compared the reliability of standard and contrast-enhanced VLE images., Methods: Baseline VLE scans from BE patients without prior ablative therapy and a Prague (M) length of > 1 cm were obtained from the US VLE Registry. An algorithm was applied to the VLE images to flatten the mucosal surface and enhance the contrast of different esophageal wall layers. Subsequently, BET was measured by two independent VLE readers using both contrast- and non-contrast-enhanced datasets. In order to validate these adjusted images, intra- and interobserver agreements were calculated., Results: VLE scans from fifty-seven patients were included in this study. BET was measured at eight equidistant locations on the selected cross-sectional images at 0.5 cm intervals from the GEJ to the proximal-most extent of BE. The intra-observer coefficients of the two readers for the contrast-enhanced images were 0.818 (95% CI 0.798-0.836) and 0.890 (95% CI 0.878-0.900). The interobserver agreement for the contrast-enhanced images (0.880; 95% CI 0.867-0.891) was significantly better than for the original images (0.778; 95% CI 0.754-0.799)., Conclusion: We developed an algorithm that improves VLE visualization of the mucosal layers of the esophageal wall and enables rapid and reliable measurement of BET. Interobserver variability measurements were significantly reduced when using contrast enhancement. Studies are underway to correlate BET with treatment response.

Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.

A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging.

Understanding pediatric voice development and laryngeal pathology is predicated on a detailed knowledge of the microanatomy of the layered structure of the vocal fold. Our current knowledge of this microanatomy and its temporal evolution is limited by the lack of pediatric specimen availability. By providing the capability to image pediatric vocal folds in vivo, a noninvasive microscopy technique could greatly expand the existing database of pediatric laryngeal microanatomy and could furthermore make longitudinal studies possible. A variety of natural-contrast optical imaging technologies, including optical frequency domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and spectrally encoded confocal microscopy (SECM) have been recently developed for noninvasive diagnosis in adult patients. In this paper, we demonstrate the potential of these three techniques for laryngeal investigation by obtaining images of excised porcine vocal fold samples. In our study, OFDI allowed visualization of the vocal fold architecture deep within the tissue, from the superficial mucosa to the vocalis muscle. The micron-level resolution of SECM allowed investigation of cells and extracellular matrix fibrils from the superficial mucosa to the intermediate layer of the lamina propria (LP) (350 microm penetration depth). The large field of view (up to 700 microm), penetration depth (up to 500 microm), and resolution (2x2x1microm [XxYxZ]) of FF-OCM enabled comprehensive three-dimensional evaluation of the layered structure of the LP. Our results suggest that these techniques provide important and complementary cellular and structural information, which may be useful for investigating pediatric vocal fold maturation in vivo.

Spectral-domain optical coherence phase microscopy (SD-OCPM) measures minute phase changes in transparent biological specimens using a common path interferometer and a spectrometer based optical coherence tomography system. The Fourier transform of the acquired interference spectrum in spectral-domain optical coherence tomography (SD-OCT) is complex and the phase is affected by contributions from inherent random noise. To reduce this phase noise, knowledge of the probability density function (PDF) of data becomes essential. In the present work, the intensity and phase PDFs of the complex interference signal are theoretically derived and the optical path length (OPL) PDF is experimentally validated. The full knowledge of the PDFs is exploited for optimal estimation (Maximum Likelihood estimation) of the intensity, phase, and signal-to-noise ratio (SNR) in SD-OCPM. Maximum likelihood (ML) estimates of the intensity, SNR, and OPL images are presented for two different scan modes using Bovine Pulmonary Artery Endothelial (BPAE) cells. To investigate the phase accuracy of SD-OCPM, we experimentally calculate and compare the cumulative distribution functions (CDFs) of the OPL standard deviation and the square root of the Cramér-Rao lower bound (1/ square root 2SNR ) over 100 BPAE images for two different scan modes. The correction to the OPL measurement by applying ML estimation to SD-OCPM for BPAE cells is demonstrated.

The capability to image tissue motion such as blood flow through an endoscope could have many applications in medicine. Spectrally encoded endoscopy (SEE) is a recently introduced technique that utilizes a single optical fiber and miniature diffractive optics to obtain endoscopic images through small diameter probes. Using spectral-domain interferometry, SEE is furthermore capable of three-dimensional volume imaging at video rates. Here we show that by measuring relative spectral phases, this technology can additionally measure Doppler shifts. Doppler SEE is demonstrated in flowing Intralipid phantoms and vibrating middle ear ossicles.

We demonstrate a novel high-speed polarization-sensitive optical frequency domain imaging system employing high-speed polarization modulation. Rapid and continuous polarization modulation of light prior to illumination of the sample is accomplished by shifting the frequency of one polarization eigenstate by an amount equal to one quarter of the digitization sampling frequency. This approach enables polarization-sensitive imaging with a single detection channel and overcomes artifacts that may arise from temporal variations of the birefringence in fiber-optic imaging probes and spatial variation of birefringence in the sample.

Endoscopic imaging below tissue surfaces and through turbid media may provide improved diagnostic capabilities and visibility in surgical settings. Spectrally encoded endoscopy (SEE) is a recently developed method that utilizes a single optical fiber, miniature optics and a diffractive grating for high-speed imaging through small diameter, flexible endoscopic probes. SEE has also been shown to provide three-dimensional topological imaging capabilities. In this paper, we have configured SEE to additionally image beneath tissue surfaces, by increasing the system's sensitivity and acquiring the complex spectral density for each spectrally resolved point on the sample. In order to demonstrate the capability of SEE to obtain subsurface information, we have utilized the system to image a resolution target through intralipid solution, and conduct volumetric imaging of a mouse embryo and excised human middle-ear ossicles. Our results demonstrate that real-time subsurface imaging is possible with this miniature endoscopy technique.

Polarization sensitive optical coherence tomography (PS-OCT) provides a cross-sectional image of birefringence in biological samples that is complementary in many applications to the standard reflectance-based image. Recent ex vivo studies have demonstrated that birefringence mapping enables the characterization of collagen and smooth muscle concentration and distribution in vascular tissues. Instruments capable of applying these measurements percutaneously in vivo may provide new insights into coronary atherosclerosis and acute myocardial infarction. We have developed a polarization sensitive optical frequency domain imaging (PS-OFDI) system that enables high-speed intravascular birefringence imaging through a fiber-optic catheter. The novel design of this system utilizes frequency multiplexing to simultaneously measure reflectance of two incident polarization states, overcoming concerns regarding temporal variations of the catheter fiber birefringence and spatial variations in the birefringence of the sample. We demonstrate circular cross-sectional birefringence imaging of a human coronary artery ex vivo through a flexible fiber-optic catheter with an A-line rate of 62 kHz and a ranging depth of 6.2 mm.

A technique for increasing the ranging depth in optical frequency domain imaging utilizing frequency encoding is presented. Ranging depth is enhanced by using two interferometer reference arms with different path lengths and independent modulation frequencies (25 and 50 MHz). With this configuration, the sensitivity decreases by 6 dB over a depth range of 7 mm, approximately a threefold improvement over the conventional optical frequency domain imaging technique. We demonstrate that the reference arm frequency separation, tuning speed, center wavelength, and instantaneous coherence length determine the signal-to-cross-talk ratio.

Noninvasive measurements of the scattering coefficients of optically turbid media using angle-resolved optical frequency-domain imaging (OFDI) are demonstrated. It is shown that, by incoherently averaging OFDI reflectance signals acquired at different backscattering angles, speckle noise is reduced, allowing scattering coefficients to be extracted from a single A-line with much higher accuracy than with measurements from conventional OFDI and optical coherence tomography systems. Modeling speckle as a random phasor sum, the relationship between the measurement accuracy and the number of compounded angles is derived. The sensitivity analysis is validated with measurements from a tissue phantom.

We present a novel method for rapidly acquiring optical coherence tomography (OCT) images at multiple backscattering angles. By angularly compounding these images, high levels of speckle reduction were achieved. Signal-to-noise ratio (SNR) improvements of 3.4 dB were obtained from a homogeneous tissue phantom, which was in good agreement with the predictions of a statistical model of speckle that incorporated the optical parameters of the imaging system. In addition, the fast acquisition rate of the system (10 kHz A-line repetition rate) allowed angular compounding to be performed in vivo without significant motion artifacts. Speckle-reduced OCT images of human dermis show greatly improved delineation of tissue microstructure.

Imaging large tissue areas with microscopic resolution in vivo may offer an alternative to random excisional biopsy. We present an approach for performing confocal imaging of large tissue surface areas using spectrally encoded confocal microscopy (SECM). We demonstrate a single-optical-fiber SECM apparatus, designed for imaging luminal organs, that is capable of imaging with a transverse resolution of 2.1 microm over a subsurface area of 16 cm2 in less than 1 min. Due to the unique probe configuration and scanning geometry, the speed and resolution of this new imaging technology are sufficient for comprehensively imaging large tissues areas at a microscopic scale in times that are appropriate for clinical use.

Recently, we have experimentally demonstrated a new form of cross-sectional, coherence-gated fluorescence imaging referred to as SD-FCT ('spectral-domain fluorescence coherence tomography'). Imaging in SD-FCT is accomplished by spectrally detecting self-interference of the spontaneous emission of fluorophores, thereby providing depth-resolved information on the axial positions of fluorescent probes. Here, we present a theoretical investigation of the factors affecting the detected SD-FCT signal through scattering media. An imaging equation for SD-FCT is derived that includes the effects of defocusing, numerical-aperture, and the optical properties of the medium. A comparison between the optical sectioning capabilities of SD-FCT and confocal microscopy is also presented. Our results suggest that coherence gating in fluorescence imaging may provide an improved approach for depth-resolved imaging of fluorescently labeled samples; high axial resolution (a few microns) can be achieved with low numerical apertures (NA<0.09) while maintaining a large depth of field (a few hundreds of microns) in a relatively low scattering medium (6 mean free paths), whereas moderate NA's can be used to enhance depth selectivity in more highly scattering biological samples.

Full-field optical coherence microscopy (FFOCM) utilizes coherence gating to obtain high-resolution optical sections in thick tissues. FFOCM is an attractive technology for endoscopic microscopy at the cellular level since it does not require a high NA objective lens or beam scanning and is therefore particularly amenable to miniaturization. In this manuscript, we present a novel scheme for conducting FFOCM that utilizes spectrally modulated, spatially incoherent illumination and a static Linnik interferometer. This approach is advantageous for endoscopic microscopy since it allows FFOCM to be conducted through a single multimode fiber optic imaging bundle and does not require moving parts in the endoscope probe. Images acquired from biological samples in free space demonstrate that this new method provides the same detailed microscopic structure as that of conventional FFOCM. High-resolution images were also obtained through a multimode fiber bundle, further supporting the potential of this method for endoscopic microscopy.

Speckle noise significantly limits the information content provided by coherent optical imaging methods such as optical coherence tomography and its recent derivative, optical frequency-domain imaging (OFDI). In this paper, we demonstrate a novel OFDI system that simultaneously acquires hundreds of angularly resolved images, which can be compounded to reduce speckle noise. The system comprises an InGaAs line-scan camera and an interferometer, configured so that the elements of the detector array simultaneously capture light spanning a backscattering angular range of 32 degrees. On successive read-outs of the array, the wavelength of the laser source was stepped through a range of 130 nm centered at 1295 nm to concurrently generate 400 angle-resolved OFDI images. A theory of angle-resolved OFDI and the design equations of the system are presented. Incoherent averaging of the angle-resolved data is shown to yield substantial speckle reduction (as high as an 8 dB SNR improvement) in images of a tissue phantom and esophageal tissue ex vivo.

Recent results have demonstrated unprecedented wavelength-tuning speed and repetition rate performance of semiconductor ring lasers incorporating scanning filters. However, several unique operational characteristics of these lasers have not been adequately explained, and the lack of an accurate model has hindered optimization. We numerically investigated the characteristics of these sources, using a semiconductor optical amplifier (SOA) traveling-wave Langevin model, and found good agreement with experimental measurements. In particular, we explored the role of the SOA refractive-index nonlinearities in determining the intracavity frequency-shift-broadening and the emitted power dependence on scan speed and direction. Our model predicts both continuous-wave and pulse operation and shows a universal relationship between the output power of lasers that have different cavity lengths and the filter peak frequency shift per round trip, therefore revealing the advantage of short cavities for high-speed biomedical imaging.

A novel optical frequency-domain imaging system is demonstrated that employs a passive optical demodulation circuit and a chirped digital acquisition clock derived from a voltage-controlled oscillator. The demodulation circuit allows the separation of signals from positive and negative depths to better than 50 dB, thereby eliminating depth degeneracy and doubling the imaging depth range. Our system design is compatible with dual-balanced and polarization-diverse detection, important techniques in the practical biomedical application of optical frequency-domain imaging.

Full-field optical coherence microscopy (FFOCM) is an interferometric technique for obtaining wide-field microscopic images deep within scattering biological samples. FFOCM has primarily been implemented in the 0.8 mum wavelength range with silicon-based cameras, which may limit penetration when imaging human tissue. In this paper, we demonstrate FFOCM at the wavelength range of 0.9 - 1.4 mum, where optical penetration into tissue is presumably greater owing to decreased scattering. Our FFOCM system, comprising a broadband spatially incoherent light source, a Linnik interferometer, and an InGaAs area scan camera, provided a detection sensitivity of 86 dB for a 2 sec imaging time and an axial resolution of 1.9 mum in water. Images of phantoms, tissue samples, and Xenopus Laevis embryos were obtained using InGaAs and silicon camera FFOCM systems, demonstrating enhanced imaging penetration at longer wavelengths.

We present ultra-high resolution optical coherence tomography (OCT) structural intensity and optical Doppler tomography (ODT) flow velocity images of the human retina in vivo. The ultra-high speed OCT system is based on Spectral Domain or Fourier Domain technology, which provides a sensitivity advantage over conventional OCT of more than 2 orders of magnitude. This sensitivity improvement allows video rate OCT and ODT cross sectional imaging of retinal structures. Images will be presented with axial resolutions of 6 and 3.5 microns. We observed small features in the inner and outer plexiform layers, which are believed to be small blood vessels. Flow velocity images will be presented showing pulsatile flow in retinal arteries and veins.

We demonstrate an ultrahigh-speed wavelength-swept semiconductor laser using a polygon-based wavelength scanning filter. With a polygon rotational speed of 900 revolutions per second, a continuous wavelength tuning rate of 9200 nm/ms and a tuning repetition rate of 115 kHz were achieved. The wavelength tuning range of the laser was 80 nm centered at 1325 nm, and the average polarized output power was 23 mW.

We present a novel heterodyne approach for performing fast, three-dimensional spectrally encoded imaging. Volumetric data of a volunteer's finger and of coin surfaces were acquired at a rate of 5 volume sets per second with a depth resolution of 145 microm.

We demonstrate a wide tuning range high-speed wavelength-swept semiconductor laser based on a polygon scanning filter that is common to two laser cavities. Linear wavelength tuning was achieved over 145 nm around 1310 nm at a tuning repetition rate of 20 kHz. The wavelength tuning filter is expandable to accommodate multiple semiconductor optical amplifiers for further widening of the laser wavelength tuning range.

Endoscopes employing a single optical fiber may have advantages over conventional fiber-bundle or CCD array imaging techniques, including the potential for greater flexibility and miniaturization. Although single-mode fibers can provide superior resolution compared with multimode fibers, they are prone to increased speckle noise and suffer from limited optical throughput and reduced depth of field. We demonstrate the use of a double-clad fiber for single-mode illumination and multimode detection to achieve high-resolution, reduced-speckle imaging with high optical throughput and a large depth of field.

We demonstrate a compact high-power rapidly swept wavelength tunable laser source based on a semiconductor optical amplifier and an extended-cavity grating filter. The laser produces excellent output characteristics for biomedical imaging, exhibiting >4-mW average output power, <0.06-nm instantaneous linewidth, and >80-dB noise extinction with its center wavelength swept over 100 nm at 1310 nm at variable repetition rates up to 500 Hz.

A method for three-dimensional surface measurements with phase-sensitive spectrally encoded imaging is demonstrated. Both transverse and depth information is transmitted through a single-mode optical fiber, allowing this scheme to be incorporated into a miniature probe. This approach is demonstrated by measurement of the profile of a lens surface and by three-dimensional imaging of the face of a small doll.

Ultrahigh-speed tuning of an extended-cavity semiconductor laser is demonstrated. The laser resonator comprises a unidirectional fiber-optic ring, a semiconductor optical amplifier as the gain medium, and a novel scanning filter based on a polygonal scanner. Variable tuning rates up to 1150 nm/ms (15.7-kHz repetition frequency) are demonstrated over a 70-nm wavelength span centered at 1.32 microm. This tuning rate is more than an order of magnitude faster than previously demonstrated and is facilitated in part by self-frequency shifting in the semiconductor optical amplifier. The instantaneous linewidth of the source is <0.1 nm for 9-mW cw output power and a low spontaneous-emission background of -80 dB.

Speckle, the dominant factor reducing image quality in optical coherence tomography (OCT), limits the ability to identify cellular structures that are essential for diagnosis of a variety of diseases. We describe a new high-speed method for implementing angular compounding by path length encoding (ACPE) for reducing speckle in OCT images. By averaging images obtained at different incident angles, with each image encoded by path length, ACPE maintains high-speed image acquisition and requires minimal modifications to OCT probe optics. ACPE images obtained from tissue phantoms and human skin in vivo demonstrate a qualitative improvement over traditional OCT and an increased SNR that correlates well with theory.

Background: Conventional contrast cineangiography and intravascular ultrasound (IVUS) provide a limited definition of vessel microstructure and are unable to evaluate dissection, tissue prolapse, and stent apposition on a size scale less than 100 micro m., Objective: To evaluate the use of intravascular optical coherence tomography (OCT) to assess the coronary arteries in patients undergoing coronary stenting., Methods: OCT was employed in patients having percutaneous coronary interventions. Images were obtained before initial balloon dilatation and following stent deployment, and were evaluated for vessel dissection, tissue prolapse, stent apposition, and stent asymmetry. IVUS images were obtained before OCT, using an automatic pull back device., Results: 42 stents were imaged in 39 patients without complications. Dissection, prolapse, and incomplete stent apposition were observed more often with OCT than with IVUS. Vessel dissection was identified in eight stents by OCT and two by IVUS. Tissue prolapse was identified in 29 stents by OCT and 12 by IVUS; the extent of the prolapse (mean (SD)) was 242 (156) microm by OCT and 400 (100) microm by IVUS. Incomplete stent apposition was observed in seven stents by OCT and three by IVUS. Irregular strut separation was identified in 18 stents by both OCT and IVUS., Conclusions: Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS.

A method for performing miniature endoscopy with a high number of resolvable points is presented. This approach, spectrally encoded endoscopy (SEE), uses a broad-bandwidth light source and a diffraction grating to simultaneously detected the reflectivity at multiple points along a transverse line within the sample. As opposed to images from miniature optical fiber bundle endoscopes, the number of resolvable points in SEE images is dependent on the spectral width and the groove density of the diffraction grating. We acquired images of a human finger in vivo, using a 550-mu;m -diameter SEE system to demonstrate the feasibility of this technique.

Background and Aims: Optical coherence tomography (OCT) is an imaging technique that produces high-resolution cross-sectional images in vivo. The aim of this study was to establish the sensitivity and specificity of OCT for diagnosing specialized intestinal metaplasia (SIM)., Methods: OCT was used to image the stomach and esophagus of 121 patients. A total of 288 biopsy-correlated OCT images were acquired. OCT criteria for SIM were formulated by analyzing 75 images of SIM. The SIM image criteria were retrospectively tested by applying them to images of gastric, squamous, SIM, and cardiac epithelium. The criteria were then tested prospectively to determine the sensitivity and specificity of OCT for diagnosing SIM., Results: OCT images of SIM are characterized by (1) absence of the layered structure of normal squamous epithelium and the vertical "pit and crypt" morphology of gastric mucosa, (2) disorganized architecture with inhomogeneous tissue contrast and an irregular mucosal surface, and (3) presence of submucosal glands. These criteria were 100% sensitive and 93% specific for SIM when applied retrospectively and 97% sensitive and 92% specific when tested prospectively., Conclusions: OCT is highly sensitive and specific for SIM and may aid in the diagnosis and surveillance of this preneoplastic lesion.

Background: Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively., Methods: In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands., Results: Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P <.00001) in normal glands (average, 23.0% +/- 10.9%) and adenomatous glands (average, 0.4% +/- 0.7%)., Conclusions: CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use.

Optical coherence tomography (OCT) is a high-resolution, cross-sectional optical imaging technique that allows in situ imaging of tissue by measuring back-reflected light. OCT provides images in real time with a resolution approaching that of conventional histopathology, but without the need for tissue removal. OCT imaging can be performed endoscopically to visualize gastrointestinal tissue using a fiberoptic catheter passed through the instrument channel of a conventional endoscope. The resolution of OCT allows visualization of the different layers of gastrointestinal epithelium and the differentiation of Barrett's epithelium from normal gastric and squamous mucosa. OCT has also been used to image esophageal adenocarcinoma and colonic polyps. Recent developments include Doppler OCT, spectroscopic OCT, and ultrahigh-resolution OCT, which can visualize nuclei within single cells. Although still in its infancy as a clinical tool, OCT currently provides high-resolution images over the same imaging depth as conventional mucosal biopsy, and may prove to be a useful and minimally invasive technique for evaluating gastrointestinal tissue, particularly for early neoplastic changes.

Objective: A high-resolution coronary artery imaging modality has the potential to address important diagnostic and management problems in cardiology. Optical coherence tomography (OCT) is a promising new optical imaging technique with a resolution of approximately 10 microm. The purpose of this study was to use a new OCT catheter to demonstrate the feasibility of performing OCT imaging of normal coronary arteries, intimal dissections, and deployed stents in vivo., Methods and Results: Normal coronary arteries, intimal dissections, and stents were imaged in five swine with OCT and compared with intravascular ultrasound (IVUS). In the normal coronary arteries, visualization of all of the layers of the vessel wall was achieved with a saline flush, including the intima which was not identified by IVUS. Following dissection, detailed layered structures including intimal flaps, intimal defects, and disruption of the medial wall were visualized by OCT. IVUS failed to show clear evidence of intimal and medial disruption. Finally, the microanatomic relationships between stents and the vessel walls were clearly identified only by OCT., Conclusions: In this preliminary experiment, we have demonstrated that in vivo OCT imaging of normal coronary arteries, intimal dissections, and deployed stents is feasible, and allows identification of clinically relevant coronary artery morphology with high-resolution and contrast.

Background: Optical coherence tomography is a new, high spatial-resolution, cross-sectional imaging technique. We investigated the ability of optical coherence tomography to provide detailed images of subsurface structures in the upper gastrointestinal (GI) tract., Methods: Optical coherence tomography was performed during routine upper GI endoscopy on 32 patients including 20 patients with Barrett's esophagus. An endoscopic mucosal biopsy was obtained immediately after imaging and was used for histopathologic correlation., Results: Optical coherence tomography provided clear delineation of layers of the normal human esophagus extending from the epithelium to the longitudinal muscularis propria. Gastric mucosa was differentiated from esophageal mucosa, Barrett's esophagus was differentiated from normal esophageal mucosa, and esophageal adenocarcinoma was distinguished from normal esophagus and Barrett's esophagus., Conclusions: Optical coherence tomography allows visualization of the subsurface architectural morphology of the upper GI tract. The diagnostic information provided by this new imaging modality suggests that it may be a useful adjunct to endoscopy.

Background: Optical coherence tomography (OCT) is a new method of catheter based micron scale imaging. OCT is analogous to ultrasound, measuring the intensity of backreflected infrared light rather than sound waves., Objective: To demonstrate the ability of OCT to perform high resolution imaging of arterial tissue in vivo., Methods: OCT imaging of the abdominal aorta of New Zealand white rabbits was performed using a 2.9 F OCT imaging catheter. Using an ultrashort pulse laser as a light source for imaging, an axial resolution of 10 micrometer was achieved., Results: Imaging was performed at 4 frames/second and data were saved in either super VHS or digital format. Saline injections were required during imaging because of the signal attenuation caused by blood. Microstructure was sharply defined within the arterial wall and correlated with histology. Some motion artefacts were noted at 4 frames/second., Conclusions: In vivo imaging of the rabbit aorta was demonstrated at a source resolution of 10 micrometer, but required the displacement of blood with saline. The high resolution of OCT allows imaging to be performed near the resolution of histopathology, offering the potential to have an impact both on the identification of high risk plaques and the guidance of interventional procedures.

A nonreciprocal fiber-optic interferometer is demonstrated in an optical coherence tomography (OCT) system. The increased power efficiency of this system provides a 4.1-dB advantage over standard Michelson implementations. In addition, a new linear-scanning fiber-optic catheter is demonstrated that avoids the rotary optical junction that is required in circumferential scanning systems. These advancements have permitted the clinical implementation of OCT imaging in the human gastrointestinal tract.

An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique.

Purpose: To evaluate three-dimensional optical coherence tomography (OCT) for use in the assessment of the microsurgical anastomoses of vessels and nerves., Materials and Methods: OCT is an optical analogue of ultrasonography and is capable of imaging nontransparent biologic tissue by detecting backscattered infrared light. Cross-sectional in vitro images of rabbit and human vessels and nerves were obtained in as little as 125 msec at 10-micron resolution by using a solid-state laser as a light source. A surgical microscope was integrated with OCT to perform simultaneous imaging with en face visualization. Cross-sectional images were assembled to produce three-dimensional reconstructions of microsurgical specimens., Results: Three-dimensional OCT reconstructions depicted the structure within an arterial anastomosis and helped identify sites of luminal obstruction. The longitudinal spatial orientation of individual nerve fascicles was tracked in three dimensions to identify changes in position. In vitro human arteries and nerves embedded in highly scattering tissue and not visible at microscopy were located and imaged with OCT at eight frames per second., Conclusion: The three-dimensional, micrometer-scale, diagnostic imaging capabilities of OCT permit rapid feedback for assessment of microsurgical procedures. OCT technology can be readily integrated with surgical microscopes and has potential for intraoperative monitoring to improve patient outcome.

Optical coherence tomography (OCT) is a new technique for performing high-resolution, cross-sectional tomographic imaging in human tissue. OCT is analogous to ultrasound B mode imaging except that it uses light rather than acoustical waves. As a result, OCT has over 10 times the resolution of currently available clinical high-resolution cross-sectional imaging technologies. In this work, we investigate the capability of OCT to differentiate the architectural morphology of pancreatobiliary tissues. Normal pancreatobiliary tissues, including the gallbladder, common bile duct, pancreatic duct, and pancreas were taken postmortem and imaged using OCT. Images were compared to corresponding histology to confirm tissue identity. Microstructure was delineated in different tissues, including tissue layers, glands, submucosal microvasculature, and pancreatic islets of Langerhans. The ability of OCT to provide high-resolution imaging of pancreatobiliary architectural morphology suggests the feasibility of using OCT as a powerful diagnostic endoscopic imaging technology to image early stages of pancreatobiliary disease.

A need exists in respiratory medicine for a technology capable of identifying airway pathology on a micron scale. This study has demonstrated the feasibility of optical coherence tomography (OCT) for ultrahigh resolution imaging of the upper respiratory tract by in vitro studies of human tissue. OCT is a relatively new technique that can be used to noninvasively collect tomographic images of tissue microstructure with micron-scale resolution. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. Samples throughout the upper respiratory tract, from the epiglottis to the secondary bronchi, were imaged. The resulting images were compared with histopathology and verified the ability of OCT to delineate relevant structures such as the epithelium, mucosa, cartilage and its sublayers, and glands at a resolution higher than any clinical imaging technology. The ability of OCT to generate image resolution in the range close to that of histopathology in real time, as well as easy integration with small, relatively inexpensive endoscopes, low cost, and lack of a need for a transducing medium, supports the hypothesis that this optical technology could become a powerful modality in the diagnosis and management of a wide range of clinical respiratory pathology.

A need exists in medicine for a technology capable of 'optical biopsy,' imaging at or near the resolution of histopathology without the need for excisional biopsy. Optical coherence tomography (OCT) is a recently developed imaging technology that uses infrared light to generate cross-sectional images on a micron scale. In this work, the feasibility of OCT for optical biopsy was confirmed with in vitro tissue from the skeletal and male reproductive systems. This work supports the hypothesis that OCT is an attractive technology for in vivo optical biopsy.

Optical coherence tomography (OCT) is an optical imaging technique that is capable of performing micron-scale, cross-sectional imaging of internal microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light rather than sound and performs imaging by measuring the back-scattered intensity of light from structures in tissue. We describe recent advances in OCT technology including the application of short pulse solid state lasers based on Ti: Al2O3 and Cr: Mg2SiO4 to enable high-resolution, high-speed imaging as well as the development of OCT catheter/endoscope delivery to permit imaging of internal organ systems. OCT enables the nonexcisional, in situ, real-time imaging of tissue microstructure and is thus a powerful and promising technique for optical biopsy.

We demonstrate two short-coherence-length, rare-earth-doped fiber optical sources for performing optical coherence tomography (OCT) in human tissue. The first source is a stretched-pulse, mode-locked Er-doped fiber laser with a center wavelength of 1.55 μm, a power of 100 mW, and a bandwidth of 80 nm. The second is a Tm-doped silica fiber fluorescent source emitting up to 7 mW of power at 1.81 μm with a bandwidth of 80 nm. The OCT imaging depth of penetration in in vitro human aorta is compared using these sources and conventional 1.3-μm sources. © 1998 Society of Photo-Optical Instrumentation Engineers.

A rapid-scanning optical delay line that employs phase control has several advantages, including high speed, high duty cycle, phase- and group-delay independence, and group-velocity dispersion compensation, over existing optical delay methods for interferometric optical ranging applications. We discuss the grating-based phase-control delay line and its applications to interferometric optical ranging and measurement techniques such as optical coherence domain reflectometry and optical coherence tomography. The system performs optical ranging over an axial range of 3 mm with a scanning rate of 6m/s and a repetition rate of 2 kHz. The device is especially well suited for applications such as optical coherence tomography that require high-speed, repetitive, linear delay line scanning with a high duty cycle.

We present a cw chromium-doped forsterite laser that permits rapid wavelength tuning over a broad bandwidth and demonstrate the application of this source to frequency-domain ranging and optical tomography. The entire tuning range of 1200 to 1275 nm can be swept in less than 500 micros . This permits frequency-domain ranging to be performed with a scan rate of 2 kHz and an axial resolution of 15 microm .