Optical polarimetry for noninvasive glucose sensing enabled by Sagnac interferometry.

Optical polarimetry is used in pharmaceutical drug testing and quality control for saccharide-containing products (juice, honey). More recently, it has been proposed as a method for noninvasive glucose sensing for diabetic patients. Sagnac interferometry is commonly used in optical gyroscopes, measuring minute Doppler shifts resulting from mechanical rotation. In this work, we demonstrate that Sagnac interferometers are also sensitive to optical rotation, or the rotation of linearly polarized light, and are therefore useful in optical polarimetry. Results from simulation and experiment show that Sagnac interferometers are advantageous in optical polarimetry as they are insensitive to net linear birefringence and alignment of polarization components.

Laparoscopic optical coherence tomography imaging of human ovarian cancer.

OBJECTIVES: Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. METHODS: A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. RESULTS: Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. CONCLUSIONS: We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.

An automatic algorithm for detecting stent endothelialization from volumetric optical coherence tomography datasets.

Recent research has suggested that endothelialization of vascular stents is crucial to reducing the risk of late stent thrombosis. With a resolution of approximately 10 microm, optical coherence tomography (OCT) may be an appropriate imaging modality for visualizing the vascular response to a stent and measuring the percentage of struts covered with an anti-thrombogenic cellular lining. We developed an image analysis program to locate covered and uncovered stent struts in OCT images of tissue-engineered blood vessels. The struts were found by exploiting the highly reflective and shadowing characteristics of the metallic stent material. Coverage was evaluated by comparing the luminal surface with the depth of the strut reflection. Strut coverage calculations were compared to manual assessment of OCT images and epi-fluorescence analysis of the stented grafts. Based on the manual assessment, the strut identification algorithm operated with a sensitivity of 93% and a specificity of 99%. The strut coverage algorithm was 81% sensitive and 96% specific. The present study indicates that the program can automatically determine percent cellular coverage from volumetric OCT datasets of blood vessel mimics. The program could potentially be extended to assessments of stent endothelialization in native stented arteries.

Assessment of blood vessel mimics with optical coherence tomography.

Optical coherence tomography (OCT) is an imaging modality that enables assessment of tissue structural characteristics. Studies have indicated that OCT is a useful method to assess both blood vessel morphology and the response of a vessel to a deployed stent. We evaluated the ability of OCT to visualize the cellular lining of a tissue-engineered blood vessel mimic (BVM) and the response of this lining to a bare metal stent. We develop a side-firing endoscope that obtains intraluminal, longitudinal scans within the sterile bioreactor environment, enabling time-serial assessment. Seventeen BVMs are imaged with the endoscopic OCT system. The BVMs are then evaluated via fluorescence microscopy and/or standard histologic techniques. We determine that (1) the OCT endoscope can be repeatedly inserted without visible damage to the BVM cellular lining, (2) OCT provides a precise measure of cellular lining thickness with good correlation to measurements obtained from histological sections, and (3) OCT is capable of monitoring the accumulation of cellular material in response to a metallic stent. Our studies indicate that OCT is a useful technique for monitoring the BVM cellular lining, and that OCT may facilitate the use of BVMs for early stage device assessment.

Tissue-engineered vascular grafts as in vitro blood vessel mimics for the evaluation of endothelialization of intravascular devices.

The accelerating use of minimally invasive procedures for the treatment of cardiovascular disease, and the commensurate development of intravascular devices such as stents, has lead to a high demand for preclinical assessment techniques. A 3-dimensional in vitro blood vessel mimic (BVM) would be ideal for device testing before animal or clinical studies. This is possible based on current capabilities for the creation of tissue-engineered vascular grafts (TEVGs). Using an established method of pressure-sodding human endothelial cells onto a polymer scaffold, a BVM was created in an in vitro bioreactor system under flow. Scanning electron microscopy and immunohistochemistry verified a cellular lining and revealed a luminal monolayer of endothelial cells. After BVM development, bare metal stents were deployed. Stented and unstented BVMs were evaluated using fluorescent nuclear staining and optical coherence tomography (OCT). En face and cross-sectional evaluation of bisbenzimide-stained nuclei revealed cellular coverage of the stent surfaces. Cross-sectional evaluation using OCT also illustrated a cellular layer developing over the stent struts. These data support the use of TEVGs as in vitro BVMs for pre-clinical evaluation of the endothelial cell response to stents and endovascular devices.

Novel focused OCT-LIF endoscope.

Combined optical coherence tomography (OCT) and laser-induced fluorescence (LIF) endoscopy has shown higher sensitivity and specificity for distinguishing normal tissue from adenoma when compared to either modality alone. Endoscope optical design is complicated by the large wavelength difference between the two systems. A new high-resolution endoscope 2 mm in diameter is presented that can create focused beams from the ultraviolet to near-infrared. A reflective design ball lens operates achromatically over a large wavelength range, and employs TIR at two faces and reflection at a third internal mirrored face. The 1:1 imaging system obtains theoretically diffraction-limited spots for both the OCT (1300 nm) and LIF (325 nm) channels.

A concentric three element radial scanning optical coherence tomography endoscope.

We have developed a 2.1 mm outer diameter optical coherence tomography endoscope that provides radial scans of luminal structures. The endoscope consists of three elements: (1) a stationary central core containing the fibers and focusing elements, (2) a rotating intermediate tube with a distal rod prism, and (3) a stationary sterilized glass cover. This design enables radial and spiral scanning and allows adjustment of the axial focal distance. Additionally, this design is capable of focusing light from multiple fibers into tissue. The performance of the endoscope was demonstrated in a study of tissue engineered blood vessels imaged at various time points during development.

Using optical coherence tomography to evaluate skin sun damage and precancer.

BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) is a depth resolved imaging modality that may aid in identifying sun damaged skin and the precancerous condition actinic keratosis (AK). STUDY DESIGN/MATERIALS AND METHODS: OCT images were acquired of 112 patients at 2 sun protected and 2 sun exposed sites, with a subsequent biopsy. Each site received a dermatological evaluation, a histological diagnosis, and a solar elastosis (SE) score. OCT images were examined visually and statistically analyzed. RESULTS: Characteristic OCT image features were identified of sun protected, undiseased, sun damaged, and AK skin. A statistically significant difference (P<0.0001) between the average attenuation values of skin with minimal and severe solar elastosis was observed. Significant differences (P<0.0001) were also found between undiseased skin and AK using a gradient analysis. Using image features, AK could be distinguished from undiseased skin with 86% sensitivity and 83% specificity. CONCLUSION: OCT has the potential to guide biopsies and provide non-invasive measures of skin sun damage and disease state, possibly increasing efficiency of chemopreventive agent trials.