| Currently, existing medical imaging modalities cannot provide quantitative assessment of subsurface microcirculation of human internal organs; however, high resolution blood flow imaging at the capillary level may have significant impact on applications such as neovasculature visualization and anti-angiogenesis therapies. This thesis focuses on the development of endoscopic Doppler optical coherence tomography (EDOCT), a novel non-invasive and quantitative technique using broadband near infrared light (1.3 mum) for imaging and quantifying microcirculation, and its diagnostic and therapeutic monitoring applications involving the microvasculature. An EDOCT system, that uses signal processing principles adopted from Doppler ultrasound imaging, was constructed and optimized for detecting subsurface microcirculation in the human gastrointestinal (GT) tract with 10--25 mum spatial resolution. This system was tested in a series of experiments including liquid phantoms of known optical and flow characteristics, and in vivo animal cardiac and tumor blood flow models, and demonstrated sensitivity to subsurface flow as low as 17 mum·sec-1. For diagnostic applications, this work demonstrates in a study of 22 patients that, for the first time, EDOCT is feasible in clinical GI endoscopy and can provide microstructural and microvascular details of normal and pathologic tissues. For therapeutic monitoring applications, we also demonstrate for the first time that Doppler OCT could detect and monitor tumor microcirculation changes induced by photodynamic therapy (PDT), in two tumor-xenograft animal models. These results suggest that EDOCT has potential clinical impact on both the diagnostic imaging of microcirculation and therapeutic monitoring of anti-vascular treatments. |
