COVID-19 Information

PhD Thesis Defense: Ethan Phillip LaRochelle

Thursday, April 9, 2020, 10:00am

Videoconference

For information on how to attend this videoconference, please email ethan.phillip.m.larochelle.TH@dartmouth.edu 

"Modeling broad-spectrum light sources in vivo for applications in cancer treatment and diagnostics"

Abstract

Electromagnetic photons in different forms, ranging from visible light to ionizing radiation, are used as the mechanism to trigger disruptive treatment pathways in cancer, and can simultaneously provide diagnostic information. The physical interactions these photons undergo is a complex stochastic process that is not easily simplified to analytical solutions. One approach for estimating clinically-actionable photon fluence is to develop Monte Carlo models of the system in question. The work presented in this thesis presents efficient methods to simulate these models and demonstrates applications in the fields of photodynamic therapy (PDT) and radiotherapy.

Dermatologic applications of PDT generally use the pro-drug aminolevulinic acid (ALA), which is selectively converted to the photosensitizer protoporphyrin IX (PpIX) within neoplastic cells. PpIX is commonly activated with both blue and red wavelengths of light in clinical treatment, but more recently broad-spectrum daylight has been investigated as an activation source. When broad-spectrum sunlight or lamps are used to activate PpIX, the dose planning becomes more complicated. Clinically, the effect of tissue optical properties is often overlooked. The first aim of this work presents a model-based method to estimate PDT dose at depth in tissue and proposes a simplified lookup table approach to improve clinical adoption of daylight or lamplight activation. The second aim refines this model based on clinical applications of daylight-PDT, time-correlated spectroradiometer, and weather forecast data to have broader planning and dosimetric utility.

During radiotherapy electrons are generated with sufficient energy to create broad-spectrum optical Cherenkov emissions in tissue, which can then be used to excite luminescent compounds. The third aim of this work investigates how models of both Cherenkov emissions and Cherenkov-excited luminescence can be used to determine limiting factors in optical detection. With a Cherenkov-excited, oxygen-sensitive, phosphorescent compound the partial pressure of oxygen (pO2) in the tumor microenvironment can be recorded non-invasively. The final aim experimentally demonstrates measurements of in vivo pO2 at high temporal resolution during fractionated radiotherapy treatments.

Thesis Committee

For more information, contact Daryl Laware at daryl.a.laware@dartmouth.edu.