Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Giles Santyr

Abstract

Lung cancer is the largest contributor to cancer-related mortality worldwide. Only 20% of stage III non-small cell lung cancer patients survive after 5-years post radiation therapy (RT). Although RT is an important treatment modality for lung cancer, it is limited by Radiation-Induced Lung Injury (RILI). RILI develops in two phases: (i) the early phase (days-weeks) referred to radiation pneumonitis (RP), and (ii) the late phase (months). There is a strong interest in early detection of RP using imaging to improve outcomes of RT for lung cancer. This thesis describes a promising approach based on 129Xe gas as a contrast agent for Magnetic Resonance Imaging (MRI) of the lung airspace due to the large increase in signal possible by spin exchange optical pumping, or hyperpolarization (Hp). Additionally, 129Xe provides unique functional information due to its relatively high solubility and significant chemical shift in pulmonary tissue (PT) and red blood cell (RBC) compartments. In this thesis, a specialized Hp 129Xe MRI method was developed for detection of gas exchange abnormalities in the lungs associated with thoracic RT. In particular, the feasibility of quantifying the early phase of RILI is demonstrated in a rat model of RILI two weeks post-irradiation with a single fraction dose of 18 Gy. The challenge of low signal-to-noise ratio (SNR) in the dissolved phases was addressed in this work by development and construction of a Transmit-Only/Receive-Only radiofrequency coil. Another challenge addressed in the thesis was the lack of imaging techniques that provide sufficient spatial and temporal information for gas exchange. Therefore, a novel Hp 129Xe MRI technique was developed based on the multi-point IDEAL pulse sequence. The combination of these two developments enabled investigation of regional gas exchange changes associated with RP in the rat lung two weeks post-irradiation to assess the feasibility of early detection of RILI. Theoretical analysis of the gas exchange curves enabled measurements of average PT thickness (LPT) increases consistent with histology and relative blood volume (VRBC) reductions in the irradiated animal cohort compared to a non-irradiated cohort, and between irradiated right lungs compared to unirradiated left lungs in the irradiated cohort.