Gopi Maguluri

Detection of ultrasound-modulated photons in diffuse media using the photorefractive effect.

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.

Computations of the acoustically induced phase shifts of optical paths in acoustophotonic imaging with photorefractive-based detection.

Acoustophotonic imaging uses ultrasound-modulated scattered light to improve the quality of optical imaging in diffusive media. Experiments that use photorefractive-crystal-based detection have shown that there is a large dc shift in the acoustically modulated or ac optical signal, which could be utilized to further improve optical imaging resolution. We report that photon paths in a diffusive medium were generated by a Monte Carlo simulation, and the optical phase shifts of the various photons induced by the presence of a realistic focused ultrasound beam were calculated. Quantities that characterize the ac and dc signal components were evaluated by use of the calculated phase shifts. It was confirmed that the dc component dominates owing to coherent summation of the contributions from all the photons.

Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

Abstract. We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ∼1  μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ∼7  μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ∼600  μm, and agreement with histology was within about ±50  μm.

Handheld optical coherence tomography–reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins

Abstract. 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 in vivo. A standard OCT approach (spectrometer-based) with a central wavelength of 1310 nm and 0.11 numerical aperture (NA) was combined with a standard RCM approach (830-nm wavelength and 0.9 NA) into a common path hand-held probe. Cross-sectional OCT images and enface RCM images are simultaneously displayed, allowing for three-dimensional microscopic assessment of tumor morphology in real time. Depending on the subtype and depth of the BCC tumor and surrounding skin conditions, OCT and RCM imaging are able to complement each other, the strengths of each helping overcome the limitations of the other. Four representative cases are summarized, out of the 15 investigated in a preliminary pilot study, demonstrating how OCT and RCM imaging may be synergistically combined to more accurately detect BCCs and more completely delineate margins. Our preliminary results highlight the potential benefits of combining the two technologies within a single probe to potentially guide diagnosis as well as treatment of BCCs.

Investigation of middle ear anatomy and function with combined video otoscopy-phase sensitive OCT

We report the development of a novel otoscopy probe for assessing middle ear anatomy and function. Video imaging and phase-sensitive 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.

Enhanced detection of acousto-photonic scattering using a photorefractive crystal

Acousto-photonic imaging (API) is a dual-wave sensing technique in which a diffusive photon wave in a turbid medium interacts with an imposed acoustic field that drives scatterers to coherent periodic motion. A phase-modulated photon field emanates from the interaction region and carries with it information about the local opto-mechanical properties of the insonated media. A technological barrier to API has been sensitivity - the flux of phase-modulated photons is very small and the incoherence of the resulting speckle pattern reduces the modulation of the scattered light leading to low sensitivity. We report preliminary results from a new detection scheme in which a photorefractive crystal is used to mix the diffusively scattered laser light with a reference beam. The crystal serves as a dynamic holographic medium where the signal beam interferes with the reference beam, creating a photorefractive grating from which beams diffract. In addition, the phase modulation is converted to an amplitude modulation so that the API signal can be detected. Measurements of the API signal are presented for gel phantoms with polystyrene beads used as scatterers, showing a qualitative agreement with a simple theoretical model developed.

Hand scanning optical coherence tomography imaging using encoder feedback

We present a new method for generating micron-scale OCT images of interstitial tissue with a hand scanning probe and a linear optical encoder that senses probe movement relative to a fixed reference point, i.e., tissue surface. Based on this approach, we demonstrate high resolution optical imaging of biological tissues through a very long biopsy needle. Minor artifacts caused by tissue noncompliance are corrected using a software algorithm which detects the simple repetition of the adjacent A-scans. This hand-scanning OCT imaging approach offers the physician the freedom to access imaging sites of interest repeatedly.

Modeling of optoacoustic signal generation for high resolution near-surface imaging with experimental verification

Optoacoustic systems making use of optical detection probes are potentially advantageous over contact transducers for noncontact, noninvasive high-resolution near surface imaging applications. In this work, an interferometer is used for high-frequency optoacoustic microscopy. The limitations of this system in terms of both sensitivity and resolution are discussed. A theoretical model has been developed for two-dimensional excitation source geometries, which can be used to predict the optoacoustic signal from a target material with an arbitrary through-thickness optical absorption distribution. The model incorporates the temporal and spatial profile of the excitation laser pulse, and is used to predict the actual out-of-plane displacement at the target surface. An adaptive, photorefractive crystal-based interferometry system has been used to measure the optically induced displacement on the surface of target materials, and the results show reasonable quantitative agreement with theory. The detection system has a 200 MHz bandwidth allowing for high-resolution imaging, and the use of optical probes for both generation and detection allows for the probes to be easily co-aligned on the sample surface. Preliminary experimental results are presented demonstrating the feasibility of using all-optical optoacoustic microscopy for near surface imaging of small-scale spatial variations in optical absorption.

Simultaneous Multi-Channel AOSLO Imaging for Visualizing Inner Retina Structures

A new detection scheme was demonstrated for multiple channels simultaneous imaging that provides isotropic images of inner retina structures free of directionality artifacts. The channels can be combined to reveal additional structural and functional details.

Evaluation of a Combined Reflectance Confocal Microscopy–Optical Coherence Tomography Device for Detection and Depth Assessment of Basal Cell Carcinoma

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 Participants This 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 Measures Improvements 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. Results In 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 (R2) was 0.75 (R = 0.86; P < .001) for all lesions, 0.73 (R = 0.85; P < .001) for lesions less than 500 &mgr;m deep, and 0.65 (R = 0.43; P < .001) for lesions greater than 500 &mgr;m deep. Conclusions and Relevance Combined 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.