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.

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.

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 281OCT images and the corresponding bronchial biopsies were obtained.The histopathology of these areas includes 145 normal/hyperplasia, 61metaplasia, 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.Lung cancer is the most common cause of cancer death worldwide, with more than 1.3 million people dying of lung cancer annually (1). The 5-year survival rates after the diagnosis of lung cancer has improved only marginally in the last 3 decades (2). Although early detection and chemoprevention is effective in reducing the incidence and mortality of cancer of the breast, there is considerable skepticism in applying the same cancer control strategy in lung cancer. The most common criticism is the uncertain identity of intraepithelial neoplastic (IEN) lesions and the natural history of these lesions.There are unique challenges in detecting and treating IEN lesions in the lung compared with other organs. The lung is an internal organ consisting of a complex branching system of conducting airways leading to gas exchange units. Lung cancer consists of four major cell types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and neuroendocrine tumors (3). They are preferentially located in different parts of the bronchial tree. For example, squamous cell carcinoma and neuroendocrine tumors are more frequently found in the larger central airways compared with adenocarcinoma, which is more frequently found in the small peripheral airways and lung parenchyma. Au...

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.

We report a Doppler optical cardiogram gating technique for increasing the effective frame rate of Doppler optical coherence tomography (DOCT) when imaging periodic motion as found in the cardiovascular system of embryos. This was accomplished with a Thorlabs swept-source DOCT system that simultaneously acquired and displayed structural and Doppler images at 12 frames per second (fps). The gating technique allowed for ultra-high speed visualization of the blood flow pattern in the developing hearts of African clawed frog embryos (Xenopus laevis) at up to 1000 fps. In addition, four-dimensional (three spatial dimensions + temporal) Doppler imaging at 45 fps was demonstrated using this gating technique, producing detailed visualization of the complex cardiac motion and hemodynamics in a beating heart.

Advances in swept source laser technology continues to increase the imaging speed of swept-source optical coherence tomography (SS-OCT) systems. These fast imaging speeds are ideal for microvascular detection schemes, such as speckle variance (SV), where interframe motion can cause severe imaging artifacts and loss of vascular contrast. However, full utilization of the laser scan speed has been hindered by the computationally intensive signal processing required by SS-OCT and SV calculations. Using a commercial graphics processing unit that has been optimized for parallel data processing, we report a complete high-speed SS-OCT platform capable of real-time data acquisition, processing, display, and saving at 108,000 lines per second. Subpixel image registration of structural images was performed in real-time prior to SV calculations in order to reduce decorrelation from stationary structures induced by the bulk tissue motion. The viability of the system was successfully demonstrated in a high bulk tissue motion scenario of human fingernail root imaging where SV images (512 × 512 pixels, n = 4) were displayed at 54 frames per second.

Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution but has limited imaging depth. We report a novel, linear-scanning, needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system with a 19-guage (diameter of approximately 0.9 mm) echogenic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge, this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.

We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n = 28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm À2 for 25 minutes.High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R 2 = 0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle + light, no drug, n = 3) showed minimal microvascular changes or necrosis (4% F 1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients. [Cancer Res 2008;68(23):9987-95]