Title: ADVANCED TOOLS FOR TIME-RESOLVED IMAGING OF TISSUE METABOLISM

Committee: Petr Bruza (Chair), Brian Pogue (Co-Chair), Rongxiao Zhang, Guillem Pratx

Day: April 3^rd 2023

Time: 1pm EST

Location:  Dartmouth Health - room 571W or Zoom link

Abstract:

"Medical imaging is a crucial tool in diagnosing and treating diseases, and by far the most common set of tools used for point-of-care guidance between a physician and patient are optical devices. For example, visible light imaging has unique applications in endoscopy, dermatology, microscopy, and this range of devices utilize a wide range of optical signals for sensing the tissue.  Fluorescence imaging has become a niche but growing methodology in medical diagnostics and treatment because of its simplicity and the ability to integrate reporter molecules, that can reveal detailed information about cellular structures, metabolism, signaling, and other biomolecular features of cells and tissue components. Despite its scientific advantages, fluorescence imaging has limitations, including poor signal-to-background ratio, limited penetration depth, artifacts due to heterogeneity in tissue optical property distributions, and the presence of non-specific signals like autofluorescence.

This thesis investigates the application of several different time-domain imaging technologies, with the aim of improving imaging for clinical utility and developing fundamentally new tools in cases where signal is limited by tissue optical properties, intrinsic dye properties, or clinical workflow. Six distinct medical challenges are examined. The first two investigate deep tissue imaging potential using x-ray excited optical fluorescence, and the mechanisms underlying x-ray-induced fluorophore excitation. The next two sections of the work focus on improving surgical guidance techniques through depth sensing using LiDAR technology and on the development of a new contrast mechanism named pressure-enhanced sensing surgery (PRESS), providing a fundamentally new contrast based upon the biophysics of pressure applied to tissue and the response of the blood flow to this effect. The latter part of the thesis also includes the development and calibration of optical intracellular oxygen measurement methods, specifically to quantify oxygen depletion during ultra-high dose rate radiation therapy. These various phases of research have a commonality in discovery of how to improve imaging with fundamentally new approaches to signal capture."