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Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Collaborative Specialization

Molecular Imaging

Supervisor

Scholl, Timothy J.

Affiliation

Robarts Research Institute

Abstract

Glioblastoma (GBM) is an aggressive cancer which presents significant challenges for disease management and treatment. Tissue sodium concentration (TSC) is a sensitive indicator of disease and changes in TSC can be used as a potential biomarker for treatment response. A longitudinal orthotopic C6 GBM model was used to study changes in TSC due to cancer. Animals were imaged with contrast enhanced T1-weighted, T2-weighted and sodium MRI and were either un-treated or received temozolomide (TMZ) treatment. Accurate assessment of TSC was possible for tumour volumes greater than 150mm3 using 3mm isotropic imaging voxels. TSC increased with tumour growth for all animals. However, there were no differences in TSC changes between treated and non-treated animals. Ultimately TSC at endpoint was lower for treated animals, however this difference was not significant. This study demonstrates the feasibility of preclinical sodium MRI at 3T and highlights future potential challenges to overcome for this modality.

Summary for Lay Audience

Glioblastoma (GBM) is an aggressive brain cancer which presents significant challenges for disease management and treatment. Tissue sodium concentration (TSC) is a sensitive indicator of disease and observing changes in TSC can provide additional information about tumour biology. Magnetic resonance imaging (MRI) is a powerful non-invasive imaging modality which uses the physics underlying magnetism to obtain images of the body. MRI can capture the differences between soft tissues and provide detailed structural and morphological information about internal areas of the body. Standard MRI relies on the hydrogen atoms found in the body – particularly in the water to capture these images. Sodium MRI applies the same principles used in standard MRI but instead on sodium atoms found throughout the body, providing TSC information. In this study, C6 rats were implanted with GBM brain tumours and imaged longitudinally using standard MRI techniques and sodium MRI. Animals were either untreated, or received treatment using temozolomide (TMZ) – the chemotherapy drug used to treat GBM. Accurate assessment of TSC was possible for tumour volumes greater than 150mm3 using 3mm isotropic imaging voxels. TSC increased with tumour growth for all animals. However, there were no differences in TSC changes between treated and non-treated animals. Ultimately TSC at endpoint was lower for treated animals, however this difference was not significant. This study demonstrates the feasibility of preclinical sodium MRI at 3T and highlights future potential challenges to overcome for this modality.

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