Enhanced Vitreous Imaging in Healthy Eyes Using Swept Source Optical Coherence Tomography

Purpose To describe enhanced vitreous imaging for visualization of anatomic features and microstructures within the posterior vitreous and vitreoretinal interface in healthy eyes using swept-source optical coherence tomography (SS-OCT). The study hypothesis was that long-wavelength, high-speed, volumetric SS-OCT with software registration motion correction and vitreous window display or high-dynamic-range (HDR) display improves detection sensitivity of posterior vitreous and vitreoretinal features compared to standard OCT logarithmic scale display. Design Observational prospective cross-sectional study. Methods Multiple wide-field three-dimensional SS-OCT scans (500×500A-scans over 12×12 mm2) were obtained using a prototype instrument in 22 eyes of 22 healthy volunteers. A registration motion-correction algorithm was applied to compensate motion and generate a single volumetric dataset. Each volumetric dataset was displayed in three forms: (1) standard logarithmic scale display, enhanced vitreous imaging using (2) vitreous window display and (3) HDR display. Each dataset was reviewed independently by three readers to identify features of the posterior vitreous and vitreoretinal interface. Detection sensitivities for these features were measured for each display method. Results Features observed included the bursa premacularis (BPM), area of Martegiani, Cloquet's/BPM septum, Bergmeister papilla, posterior cortical vitreous (hyaloid) detachment, papillomacular hyaloid detachment, hyaloid attachment to retinal vessel(s), and granular opacities within vitreous cortex, Cloquet's canal, and BPM. The detection sensitivity for these features was 75.0% (95%CI: 67.8%–81.1%) using standard logarithmic scale display, 80.6% (95%CI: 73.8%–86.0%) using HDR display, and 91.9% (95%CI: 86.6%–95.2%) using vitreous window display. Conclusions SS-OCT provides non-invasive, volumetric and measurable in vivo visualization of the anatomic microstructural features of the posterior vitreous and vitreoretinal interface. The vitreous window display provides the highest sensitivity for posterior vitreous and vitreoretinal interface analysis when compared to HDR and standard OCT logarithmic scale display. Enhanced vitreous imaging with SS-OCT may help assess the natural history and treatment response in vitreoretinal interface diseases.Massachusetts Lions Eye Research Fund, Inc.Research to Prevent Blindness, Inc. (United States)United States. Air Force Office of Scientific Research (grant FA9550-1010551)United States. Air Force Office of Scientific Research (grant FA9550-12-1-0499)German Research Foundation (DFG-HO-1791/11-1)German Research Foundation (DFGGSC80-SAOT)German Research Foundation (DFG Research Training Group 1773)Champalimaud Foundation (Champalimaud Vision Award Fund)National Institutes of Health (U.S.) (R01- EY11289-28)National Institutes of Health (U.S.) (R01-CA075289-16)National Institutes of Health (U.S.) (R44-EY022864-01

Development Of Optical Coherence Tomography For Tissue Diagnostics

Microvasculature can be found in almost every part of the human body, including the internal organs. Importantly, abnormal changes in microvasculature are usually related to pathological development of the tissue cells. Monitoring of changes in blood flow properties in microvasculature, therefore, provides useful diagnostic information about pathological conditions in biological tissues as exemplified in glaucoma, diabetes, age related macular degeneration, port wine stains, burn-depth, and potentially skin cancer. However, the capillary network is typically only one cell in wall thickness with 5 to 10 microns in diameter and located in the dermis region of skin. Therefore, a non-invasive flow imaging technique that is capable of depth sectioning at high resolution and high speed is demanded. Optical coherence tomography (OCT), particularly after its advancement in frequency domain OCT (FD-OCT), is a promising tool for non-invasive high speed, high resolution, and high sensitivity depth-resolved imaging of biological tissues. Over the last ten years, numerous efforts have been paid to develop OCTbased flow imaging techniques. An important effort is the development of phase-resolved Doppler OCT (PR-DOCT). Phase-resolved Doppler imaging using FD-OCT is particularly of interest because of the direct access to the phase information of the depth profile signal. Furthermore, the high speed capability of FD-OCT is promising for real time flow monitoring as well as 3D flow segmentation applications. However, several challenges need to be addressed; 1) Flow in biological samples exhibits a wide dynamic range of flow velocity caused by, for example, the iv variation in the flow angles, flow diameters, and functionalities. However, the improvement in imaging speed of FD-OCT comes at the expense of a reduction in sensitivity to slow flow information and hence a reduction in detectable velocity range; 2) A structural ambiguity socalled \u27mirror image\u27 in FD-OCT prohibits the use of maximum sensitivity and imaging depth range; 3) The requirement of high lateral resolution to resolve capillary vessels requires the use of an imaging optics with high numerical aperture (NA) that leads to a reduction in depth of focus (DOF) and hence the imaging depth range (i.e. less than 100 microns) unless dynamic focusing is performed. Nevertheless, intrinsic to the mechanism of FD-OCT, dynamic focusing is not possible. In this dissertation, the implementation of PR-DOCT in a high speed swept-source based FD-OCT is investigated and optimized. An acquisition scheme as well as a processing algorithm that effectively extends the detectable velocity dynamic range of the PR-DOCT is presented. The proposed technique increased the overall detectable velocity dynamic range of PR-DOCT by about five times of that achieved by the conventional method. Furthermore, a novel technique of mirror image removal called ‘Dual-Detection FD-OCT’ (DD-FD-OCT) is presented. One of the advantages of DD-FD-OCT to Doppler imaging is that the full-range signal is achieved without manipulation of the phase relation between consecutive axial lines. Hence the full-range DD-FDOCT is fully applicable to phase-resolved Doppler detection without a reduction in detectable velocity dynamic range as normally encountered in other full-range techniques. In addition, PRDOCT can utilize the maximum SNR provided by the full-range capability. This capability is particularly useful for imaging of blood flow that locates deep below the sample surface, such as v blood flow at deep posterior human eye and blood vessels network in the dermis region of human skin. Beside high speed and functional imaging capability, another key parameter that will open path for optical diagnostics using OCT technology is high resolution imaging (i.e. in a regime of a few microns or sub-micron). Even though the lateral resolution of OCT can be independently improved by opening the NA of the imaging optics, the high lateral resolution is maintained only over a short range as limited by the depth of focus that varies inversely and quadratically with NA. Recently developed by our group, ‘Gabor-Domain Optical Coherence Microscopy’ (GD-OCM) is a novel imaging technique capable for invariant resolution of about 2-3 m over a 2 mm cubic field-of-view. This dissertation details the imaging protocol as well as the automatic data fusion method of GD-OCM developed to render an in-focus high-resolution image throughout the imaging depth of the sample in real time. For the application of absolute flow measurement as an example, the precise information about flow angle is required. GDOCM provides more precise interpretation of the tissue structures over a large field-of-view, which is necessary for accurate mapping of the flow structure and hence is promising for diagnostic applications particularly when combined with Doppler imaging. Potentially, the ability to perform high resolution OCT imaging inside the human body is useful for many diagnostic applications, such as providing an accurate map for biopsy, guiding surgical and other treatments, monitoring the functional state and/or the post-operative recovery process of internal organs, plaque detection in arteries, and early detection of cancers in the gastrointestinal tract. Endoscopic OCT utilizes a special miniature probe in the sample arm to vi access tubular organs inside the human body, such as the cardiovascular system, the lung, the gastrointestinal tract, the urinary tract, and the breast duct. We present an optical design of a dynamic focus endoscopic probe that is capable of about 4 to 6 m lateral resolution over a large working distance (i.e. up to 5 mm from the distal end of the probe). The dynamic focus capability allows integration of the endoscopic probe to GD-OCM imaging to achieve high resolution endoscopic tomograms. We envision the future of this developing technology as a solution to high resolution, minimally invasive, depth-resolved imaging of not only structure but also the microvasculature of in vivo biological tissues that will be useful for many clinical applications, such as dermatology, ophthalmology, endoscopy, and cardiology. The technology is also useful for animal study applications, such as the monitoring of an embryo’s heart for the development of animal models and monitoring of changes in blood circulation in response to external stimulus in small animal brains

Doctor of Philosophy

dissertationWhile boundary representations, such as nonuniform rational B-spline (NURBS) surfaces, have traditionally well served the needs of the modeling community, they have not seen widespread adoption among the wider engineering discipline. There is a common perception that NURBS are slow to evaluate and complex to implement. Whereas computer-aided design commonly deals with surfaces, the engineering community must deal with materials that have thickness. Traditional visualization techniques have avoided NURBS, and there has been little cross-talk between the rich spline approximation community and the larger engineering field. Recently there has been a strong desire to marry the modeling and analysis phases of the iterative design cycle, be it in car design, turbulent flow simulation around an airfoil, or lighting design. Research has demonstrated that employing a single representation throughout the cycle has key advantages. Furthermore, novel manufacturing techniques employing heterogeneous materials require the introduction of volumetric modeling representations. There is little question that fields such as scientific visualization and mechanical engineering could benefit from the powerful approximation properties of splines. In this dissertation, we remove several hurdles to the application of NURBS to problems in engineering and demonstrate how their unique properties can be leveraged to solve problems of interest