Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Giles Santyr

Abstract

Lung cancer is the leading cause of cancer related death. Radiation therapy is a prominent treatment method but leads to adverse consequences. Radiation-Induced Lung Injury (RILI) is the primary adverse consequence that limits further radiation therapy and develops in 5-37% of the treated patients. RILI proceeds in two distinct phases: a) early and reversible Radiation Pneumonitis (RP), and b) late and irreversible radiation fibrosis. Clinically, Dose Volume Histogram (DVH) parameters derived from radiation therapy planning stage are used to determine outcome and severity of RP but have been demonstrated to possess a very low predictive power. Computed Tomography (CT) is the most commonly used modality for the imaging of RP, but often only detects very late RP that leaves little room for intervention to abort the progress to irreversible radiation fibrosis. Early detection of RP using imaging may allow for interventional treatment and management of the disease and the associated symptoms in a better manner. Improvement in Dynamic Nuclear Polarization (DNP) technology has led to advancement of hyperpolarized 13-Carbon-Magnetic Resonance Imaging (13C-MRI). In this thesis, we present the investigation of early detection of RP with 13C-MRI in an animal model with the use of hyperpolarized 13C-pyruvate. A pilot study demonstrated the proof of concept along with a qualitative histological confirmation. 13C-MRI data and histology data were collected 2 weeks post irradiation of whole thorax in rodents. In the subsequent study, regional and longitudinal 13C-MRI and quantitative histology data were analyzed to demonstrate the early organ-wide response of RP. These data were collected at day 5, 10, 15 and 25 post conformal irradiation of the right rodent lung. Finally, we demonstrate a novel approach to map pH using hyperpolarized 13C-bicarbonate with the use of spiral-Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) pulse sequence. Validation of this approach by comparison to Chemical Shift Imaging (CSI) pH measurement and standard pH measurement with the aid of phantoms along with hyperpolarized 13C-bicarbonate is presented. pH mapping may play a role in the staging and therapeutic intervention of cancer.

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