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"Advanced tools for time-resolved imaging of tissue metabolism"

Abstract

In the last decades, the fast technological advances of solid-state image sensors have allowed in vivo molecular sensing methods to emerge. The application of these new technologies to medicine revolutionized diagnosis and treatment, greatly enhancing outcomes for patients. The use of optical imaging techniques in oncology adds detailed functional information on tissue microenvironment, which is mostly inaccessible with common medical devices. In this work, we develop in vivo time-resolved imaging method capable of recovering oxygen partial pressures and metabolism in real-time on a macro-scale, estimated from the delayed fluorescence (DF) lifetime of porphyrin dyes, such as protoporphyrin IX (PpIX). We apply our method to push the advances in two highly active medical research areas.

First, we utilize this imaging technique to elaborate on the biochemical origins of a novel and very promising ultra-high dose rate radiotherapy (FLASH-RT). FLASH-RT is a kind of radiotherapy that relies on a very high dose rate of > 40Gy/sec with sub-second temporal beam modulation. During FLASH-RT, it is hypothesized that oxygen is depleted in the targeted tissues, which yields normal tissue sparing while preserving the anti-tumor activity. Our time-gated imaging of PpIX can help us understand the complex dynamics of oxygen consumption, and thus elaborate on the origins of the FLASH effect.

Second, we use our oxygen-sensitive camera to develop a completely new surgical guidance method. In surgery, imaging of PpIX is performed to guide the resection of selected tumor types, such as gliomas, skin lesions, or bladder tumors. Unfortunately, the contrast is very low for the majority of other human tumors due to non-specific signals from the surrounding tissue. For the cases where regular fluorescence of PpIX shows nearly zero contrast, we demonstrate how PpIX DF indicates regions of tissue hypoxia with a very strong optical signal. Since this signal can be imaged and displayed to the surgeon in real-time, it has a great potential to be translated into clinical practice in the near future.

Thesis Committee

• Petr Bruza, PhD (Chair)
• Brian Pogue, PhD (Co-Chair)
• Rongxiao Zhang, PhD
• Guillem Pratx, PhD (Stanford University)

Contact

For more information, contact Theresa Fuller at theresa.d.fuller@dartmouth.edu.