Novel Instrumentation for Optical Screening of Epithelial Dysplasia
Cancer, despite its status as the second leading cause of death worldwide, is often preventable given proper surveillance and timely intervention. In the esophagus, metaplastic changes linked to reflux disease lead to alterations in cellular DNA, abnormal growth, and eventually, metastatic cancer. Fortunately, this process takes place over a period of several years, during which treatment and eradication of the precancerous lesions is possible if discovered at a sufficiently early time.
Current protocols for surveillance of the esophagus are costly and limited. As an alternative, angle-resolved low-coherence interferometry (a/LCI) is an optical technique which enables depth-resolved measurements of nuclear morphology, a biomarker of precancer. a/LCI allows for real-time identification of precancerous lesions, which may be treated using radiofrequency ablation or related techniques.
In this dissertation, several advances in a/LCI technology are presented. Measurements of the nuclear refractive index, an important parameter for a/LCI inverse light scattering analysis, are offered to settle an important debate in the literature regarding the relative density of the cell nucleus. Instrumentational advances in a/LCI are demonstrated to address the need for implementing scanning capability, which is important for screening of larger tissues such as the cervix. The properties of commercially available fiber optic imaging bundles are investigated for their capacity to support coherence-based imaging, and when these are found to be lacking, an a/LCI device based on single-mode optical fibers is designed and validated using an array of pathlength-matched individual fibers, which exhibits significant advantages over previous image bundles. Computational analysis of a previous clinical a/LCI dataset is used to provide design guidance for this methodology. Finally, this new a/LCI device is combined with a rotational endoscopic optical coherence tomography (OCT) probe to create a multimodal imaging system for comprehensive evaluation of the esophageal epithelium. The complete system includes a paddle form factor which allows it to be affixed to the exterior of a commercial endoscope for clinical compatibility, similar to related endoscopic devices. These advances demonstrate the continued applicability of a/LCI for evaluating epithelial health, and present new and attractive options for surveillance and early intervention against cancer.
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