Microscopic Image Guidance: Real-Time Thermal Therapy Monitoring for Epithelial Lesions

Abstract

Conventional image guidance is typically based on macroscopic clinical imaging modalities, such as magnetic resonance imaging, computed tomography and ultrasound imaging, which are limited in their ability to guide therapeutic interventions for epithelial lesions due to constraints on spatial resolution. Here, the notion of microscopic image guidance is introduced. The overall goal of this dissertation is to develop a framework for real-time guidance and monitoring of thermal therapy in epithelial lesions that seamlessly integrates optical frequency domain imaging (OFDI), which is a high-resolution (~10 microns), volumetric diagnostic imaging tool now used clinically in Barrett's esophagus patients. The first part of this dissertation investigates an approach to integrate OFDI into the conventional endoscopy workflow using a machine learning scheme after enriching the endoscopic scene with navigational landmarks through a noninvasive laser painting paradigm. The second part discusses an integrated approach that combines imaging, radiofrequency ablation (RFA), and monitoring in a single OFDI-RFA balloon catheter configuration. A label-free, noninvasive technique to monitor the thermal coagulation process at high resolution, based on complex difference variance, is first presented in a thulium laser benchtop setup. With proper noise calibration and non-uniform rotation distortion artifact correction, the precise delineation of the thermal coagulation zone is demonstrated in porcine esophagus ex vivo using the integrated OFDI-RFA catheter, as validated by NBTC histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to epithelial lesions and opens up the possibility of performing microscopic image-guided procedures in a vast array of epithelial applications beyond Barrett's esophagus in the future.