Quantitative Sodium MRI of Prostate Cancer

Josephine L. Tan, Western University

Abstract

Sodium (²³Na) magnetic resonance imaging (MRI) has emerged as a promising molecular imaging modality to evaluate imbalances in tissue sodium concentration (TSC), a hallmark of many tumour types including prostate cancer (PCa). Changes in TSC arise from compromised cell membrane integrity and have been implicated in promoting cancer cell invasion, migration, and immune evasion. However, ²³Na MRI studies of PCa are under-documented and typically performed with an endorectal coil, which introduce challenges (e.g., a non-uniform sensitivity profile, limited prostate coverage, patient discomfort) that hinder its clinical translation. In this thesis, a framework for quantitative ²³Na MRI of PCa using an external ²³Na transmit/receive coil at 3 Tesla is described, focusing on ²³Na image sensitivity correction and TSC quantification throughout the whole prostate gland. The framework was first applied in a study of 20 participants with biopsy-proven PCa, which demonstrated significantly lower TSC in PCa lesions relative to surrounding noncancerous prostate tissue. Clinical multiparametric MRI (mpMRI) similarly measured significantly lower apparent diffusion coefficient (ADC) values, suggesting that low TSC in lesions is due in part to their high cell density. Then, to investigate whether ²³Na MRI can detect PCa treatment response, ²³Na MRI was performed alongside mpMRI and prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) in 20 PCa participants before and after 3 months of androgen deprivation therapy. Following treatment, a significant increase in TSC, no change in ADC, and a significant decrease in PSMA uptake were observed in PCa lesions, implying a multifaceted biological response to hormone therapy. Finally, the findings of ²³Na MRI, mpMRI, and PSMA-PET were validated in PCa lesions defined by whole-mount histopathology. Across 4 PCa participants, intra- and interpatient heterogeneity was observed in TSC, ADC, and PSMA uptake between lesions and normal prostate tissue, revealing the benefit of using multiple imaging modalities to detect and characterize lesions. Overall, this thesis establishes a novel, quantitative framework for external ²³Na MRI of PCa, offering a non-invasive, clinically integrable approach to assess whole-prostate sodium homeostasis.