Ultrasound-modulated optical tomography is a dual-wave sensing technique in which diffusive light in a turbid medium interacts with an imposed acoustic field. A phase-modulated photon field emanates from the interaction region and carries with it information about the optomechanical properties of the medium. We present a technique for detection of ultrasound-induced optical phase modulation using an adaptive, photorefractive-crystal-based interferometry system. Experimental results are presented demonstrating detection of ultrasound-modulated signals in highly scattering media by use of pulsed ultrasound insonation.

A two-axis scanning catheter was developed for 3D endoscopic imaging with spectral domain optical coherence tomography (SD-OCT). The catheter incorporates a micro-mirror scanner implemented with microelectromechanical systems (MEMS) technology: the micro-mirror is mounted on a two-axis gimbal comprised of folded flexure hinges and is actuated by magnetic field. The scanner can run either statically in both axes or at the resonant frequency (>= 350Hz) for the fast axis. The assembled catheter has an outer diameter of 2.8 mm and a rigid part of 12 mm in length. Its scanning range is ± 20˚ in optical angle in both axes with low voltages (1~3V), resulting in a scannable length of approximately 1 mm at the surface in both axes, even with the small catheter size. The catheter was incorporated with a multi-functional SD-OCT system for 3D endoscopic imaging. Both intensity and polarization-sensitive images could be acquired simultaneously at 18.5K axial scans/s. In vivo 3D images of human fingertips and oral cavity tissue are presented as a demonstration. Fujimoto, "Scanning single-mode fiber optic catheter-endoscope for optical coherence tomography," Opt. Lett. 21, 543-545 (1996). 26. B. E. Bouma and G. J. Tearney, "Power-efficient nonreciprocal interferometer and linear-scanning fiberoptic catheter for optical coherence tomography," Opt. Lett. 24, 531-533 (1999).

IMPORTANCE The limited tissue sampling of a biopsy can lead to an incomplete assessment of basal cell carcinoma (BCC) subtypes and depth. Reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT) imaging may enable real-time, noninvasive, comprehensive three-dimensional sampling in vivo, which may improve the diagnostic accuracy and margin assessment of BCCs.OBJECTIVE To determine the accuracy of a combined RCM-OCT device for BCC detection and deep margin assessment. DESIGN, SETTING, AND PARTICIPANTSThis pilot study was carried out on 85 lesions from 55 patients referred for physician consultation or Mohs surgery at Memorial Sloan Kettering Skin Cancer Center in Hauppauge, New York. These patients were prospectively and consecutively enrolled in the study between January 1, 2017, and December 31, 2017. Patients underwent imaging, with the combined RCM-OCT probe, for previously biopsied, histopathologically confirmed BCCs and lesions clinically or dermoscopically suggestive of BCC. Only patients with available histopathologic examination after imaging were included. MAIN OUTCOMES AND MEASURESImprovements in sensitivity, specificity, and diagnostic accuracy for BCC using the combined RCM-OCT probe as well as the correlation between OCT-estimated depth and histopathologically measured depth were investigated. RESULTSIn total, 85 lesions from 55 patients (27 [49%] were female and 28 [51%] were male with a median [range] age of 59 [21-90] years) were imaged. Imaging was performed on 25 previously biopsied and histopathologically confirmed BCCs and 60 previously nonbiopsied but clinically or dermoscopically suspicious lesions. Normal skin and BCC features were correlated and validated with histopathologic examination. In previously biopsied lesions, residual tumors were detected in 12 of 25 (48%) lesions with 100% sensitivity (95% CI, 73.5%-100%) and 23.1% specificity (95% CI, 5.0%-53.8%) for combined RCM-OCT probe. In previously nonbiopsied and suspicious lesions, BCCs were diagnosed in 48 of 60 (80%) lesions with 100% sensitivity (95% CI, 92.6%-100%) and 75% specificity (95% CI, 42.8%-94.5%). Correlation was observed between depth estimated with OCT and depth measured with histopathologic examination: the coefficient of determination (R 2 ) was 0.75 (R = 0.86; P < .001) for all lesions, 0.73 (R = 0.85; P < .001) for lesions less than 500 μm deep, and 0.65 (R = 0.43; P < .001) for lesions greater than 500 μm deep. CONCLUSIONS AND RELEVANCECombined RCM-OCT imaging may be prospectively used to comprehensively diagnose lesions suggestive of BCC and triage for treatment. Further validation of this device must be performed on a larger cohort.

Progression of retinal degeneration in a mouse model was studied in vivo with high-resolution spectral-domain optical coherence tomography (SD-OCT). Imaging in 3D with high depth resolution (<3 mum), SD-OCT resolved all the major layers of the retina of control C57BL/6J mice. Images of transgenic mice having a null mutation of the rhodopsin gene revealed the anatomical consequences of retinal degeneration: thinning of the outer retina, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and inner and outer segments (IS/OS). We monitored the progression of retinal degeneration in rd1 mice (C3H/HeJ) by periodically imaging the same mice from the time the pups opened their eyes on P13 to P34. SD-OCT images showed that the outer retina (OPL, ONL, IS/OS) had already thinned by 73% (100 to 27 mum) at eye opening. The retina continued to degenerate, and by P20 the outer retina was not resolvable. The thickness of entire retina decreased from 228 mum (control) to 152 mum on P13 and to 98 mum by P34, a 57% reduction with the complete loss in the outer retina. In summary, we show that SD-OCT can monitor the progression of retinal degeneration in transgenic mice.

The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm × 6 mm × 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.

We present a hand-held implementation and preliminary evaluation of a combined optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) probe for detecting and delineating the margins of basal cell carcinomas (BCCs) in human skin

Abstract:We report the development of a novel otoscopy probe for assessing middle ear anatomy and function. Video imaging and phasesensitive optical coherence tomography are combined within the same optical path. A sound stimuli channel is incorporated as well to study middle ear function. Thus, besides visualizing the morphology of the middle ear, the vibration amplitude and frequency of the eardrum and ossicles are retrieved as well. Preliminary testing on cadaveric human temporal bone models has demonstrated the capability of this instrument for retrieving middle ear anatomy with micron scale resolution, as well as the vibration of the tympanic membrane and ossicles with sub-nm resolution. Duker, and J. G. Fujimoto, "Phase-sensitive swept-source optical coherence tomography imaging of the human retina with a vertical cavity surface-emitting laser light source," Opt. Lett. 38(3), 338-340 (2013).

We present in-vivo 3D human vocal fold images with polarization sensitive optical coherence tomography (PS-OCT). Characterizing the extent and location of vocal fold lesions provides useful information in guiding surgeons during phonomicrosurgery. Previous studies showed that PS-OCT imaging can distinguish vocal fold lesions from normal tissue, but these studies were limited to 2D cross-sectional imaging and were susceptible to sampling error. In-vivo 3D endoscopic imaging was performed by using a recently developed 2-axis MEMS scanning catheter and a spectral domain OCT (SD-OCT), running at 18.5 frames/s. Imaging was performed in the operating room with patients under general anesthesia and 3D images were acquired either by 2D scanning of the scanner on the sites of interest or by combining 1D scanning and manual sliding to capture whole length of the vocal fold. Vocal fold scar, polyps, nodules, papilloma and malignant lesions were imaged and characteristics of individual lesions were analyzed in terms of spatial distribution and variation of tissue structure and birefringence. The 3D large sectional PS-OCT imaging showed that the spatial extent of vocal fold lesions can be found non-invasively with good contrast from normal tissue.