Victor X. D. Yang

Speckle variance detection of microvasculature using swept-source optical coherence tomography

We report on imaging of microcirculation by calculating the speckle variance of optical coherence tomography (OCT) structural images acquired using a Fourier domain mode-locked swept-wavelength laser. The algorithm calculates interframe speckle variance in two-dimensional and three-dimensional OCT data sets and shows little dependence to the Doppler angle ranging from 75 degrees to 90 degrees . We demonstrate in vivo detection of blood flow in vessels as small as 25 microm in diameter in a dorsal skinfold window chamber model with direct comparison with intravital fluorescence confocal microscopy. This technique can visualize vessel-size-dependent vascular shutdown and transient vascular occlusion during Visudyne photodynamic therapy and may provide opportunities for studying therapeutic effects of antivascular treatments without on exogenous contrast agent.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part I): System design, signal processing, and performance

Improvements in real-time Doppler optical coherence tomography (DOCT), acquiring up to 32 frames per second at 250 x 512 pixels per image, are reported using signal processing techniques commonly employed in Doppler ultrasound imaging. The ability to measure a wide range of flow velocities, ranging from less than 20 microm/s to more than 10 cm/s, is demonstrated using an 1.3 microm DOCT system with flow phantoms in steady and pulsatile flow conditions. Based on full implementation of a coherent demodulator, four different modes of flow visualization are demonstrated: color Doppler, velocity variance, Doppler spectrum, and power Doppler. The performance of the former two, which are computationally suitable for real-time imaging, are analyzed in detail under various signal-to-noise and frame-rate conditions. The results serve as a guideline for choosing appropriate imaging parameters for detecting in vivo blood flow.

Optimized speckle variance OCT imaging of microvasculature

We optimize speckle variance optical coherence tomography (svOCT) imaging of microvasculature in high and low bulk tissue motion scenarios. To achieve a significant level of image contrast, frame rates must be optimized such that tissue displacement between frames is less than the beam radius. We demonstrate that higher accuracy estimates of speckle variance can enhance the detection of capillaries. These findings are illustrated in vivo by imaging the dorsal window chamber model (low bulk motion). We also show svOCT imaging of the nonstabilized finger (high bulk motion), using optimized imaging parameters, demonstrating better vessel detection than Doppler OCT.

Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation

Significant improvements are reported in the measurable velocity range and tissue motion artefact rejection of a phase-resolved optical coherence tomography and optical Doppler tomography system. Phase information derived from an in-phase and quadrature demodulator is used to estimate the mean blood flow velocity by the Kasai autocorrelation algorithm. A histogram-based velocity segmentation algorithm is used to determine block tissue movement and remove tissue motion artefacts that can be faster or slower in velocity than that of the microcirculation. The minimum detectable Doppler frequency is about 100 Hz, corresponding to a flow velocity resolution of 30 μm/s with an axial-line scanning frequency of 8.05 kHz and a mean phase change measured over eight sequential scans; the maximum detectable Doppler frequency is ±4 kHz (for bi-directional flow) before phase wrap-around.

In vivo Optical Coherence Tomography Imaging of Preinvasive Bronchial Lesions

Purpose: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy. Experimental Design: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation. Results: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P = 0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P = 0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions. Conclusion: Preliminary data suggest that autofluorescence bronchoscopy–guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part III): in vivo endoscopic imaging of blood flow in the rat and human gastrointestinal tracts

We previously described a fiber based Doppler optical coherence tomography system [1] capable of imaging embryo cardiac blood flow at 4~16 frames per second with wide velocity dynamic range [2]. Coupling this system to a linear scanning fiber optical catheter design that minimizes friction and vibrations, we report here the initial results of in vivo endoscopic Doppler optical coherence tomography (EDOCT) imaging in normal rat and human esophagus. Microvascular flow in blood vessels less than 100 microm diameter was detected using a combination of color-Doppler and velocity variance imaging modes, during clinical endoscopy using a mobile EDOCT system.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part II): Imaging in vivo cardiac dynamics of Xenopus laevis

We previously reported a Doppler optical coherence tomography (DOCT) system design [1] for high-speed imaging with wide velocity dynamic range (up to 28.5 dB when acquiring 8 frames per second), operating at 1.3 m with a coherence length of 13.5 m. Using a developmental biology model (Xenopus laevis), here we test the DOCT systems ability to image cardiac dynamics in an embryo in vivo, with a simple hand-held scanner at 4 ~ 16 frames per second. In particular, we show that high fidelity DOCT movies can be obtained by increasing the reference arm scanning rate (~8 kHz). Utilizing a combination of four display modes (B-mode, color-Doppler, velocity variance, and Doppler spectrum), we show that DOCT can detect changes in velocity distribution during heart cycles, measure the velocity gradient in the embryo, and distinguish blood flow Doppler signal from heart wall motions.

Optical coherence elastography: current status and future applications

Optical coherence tomography (OCT) has several advantages over other imaging modalities, such as angiography and ultrasound, due to its inherently high in vivo resolution, which allows for the identification of morphological tissue structures. Optical coherence elastography (OCE) benefits from the superior spatial resolution of OCT and has promising applications, including cancer diagnosis and the detailed characterization of arterial wall biomechanics, both of which are based on the elastic properties of the tissue under investigation. We present OCE principles based on techniques associated with static and dynamic tissue excitation, and their corresponding elastogram image-reconstruction algorithms are reviewed. OCE techniques, including the development of intravascular- or catheter-based OCE, are in their early stages of development but show great promise for surgical oncology or intravascular cardiology applications.

Review of speckle and phase variance optical coherence tomography to visualize microvascular networks

Abstract. High-resolution mapping of microvasculature has been applied to diverse body systems, including the retinal and choroidal vasculature, cardiac vasculature, the central nervous system, and various tumor models. Many imaging techniques have been developed to address specific research questions, and each has its own merits and drawbacks. Understanding, optimization, and proper implementation of these imaging techniques can significantly improve the data obtained along the spectrum of unique research projects to obtain diagnostic clinical information. We describe the recently developed algorithms and applications of two general classes of microvascular imaging techniques: speckle-variance and phase-variance optical coherence tomography (OCT). We compare and contrast their performance with Doppler OCT and optical microangiography. In addition, we highlight ongoing work in the development of variance-based techniques to further refine the characterization of microvascular networks.

Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience

BACKGROUND Expanding the current endoscopic optical coherence tomography (OCT) system with Doppler capability may augment this novel high-resolution cross-sectional imaging technique with functional blood flow information. The aim of this feasibility study was to assess the clinical feasibility of an endoscopic Doppler OCT (EDOCT) system in the human GI tract. METHODS During routine endoscopy, 22 patients were imaged by using a prototype EDOCT system, which provided color-Doppler and velocity-variance images of mucosal and submucosal blood flow at one frame per second, simultaneously with high-spatial-resolution (10-25 mum) images of tissue microstructure. The images were acquired from normal GI tract and pathologic tissues. OBSERVATIONS Subsurface microstructure and microcirculation images of normal and pathologic GI tissues, including Barretts esophagus, esophageal varices, portal hypertensive gastropathy, gastric antral vascular ectasia, gastric lymphoma, and duodenal adenocarcinoma, were obtained from 72 individual sites in vivo. Differences in vessel diameter, distribution, density, and blood-flow velocity were observed among the GI tissue pathologies imaged. CONCLUSIONS To our knowledge, this is the first study to demonstrate the feasibility of EDOCT imaging in the human GI tract during routine endoscopy procedures. EDOCT may detect the different microcirculation patterns exhibited by normal and diseased tissues, which may be useful for diagnostic imaging and treatment monitoring.