Monitoring Response of Prostate Cancer to Ultrasound Thermal Therapy by Multi-Agent Hyperpolarized 13C Magnetic Resonance Imaging
Prostate cancer is the most frequently diagnosed invasive cancer and the third leading cause of cancer death in men. Traditionally, patients with localized low- or intermediate-risk prostate cancer were forced to decide between the passive but psychologically burdensome active surveillance and the aggressive treatment options, such as surgery or radiation. In recent years, ultrasound thermal therapy has become an alternative for such cases since it is minimally invasive and causes fewer side effects. During the two main types of thermal therapy (thermal ablation and hyperthermia), the targeted tissue is exposed to heat, which either causes immediate cell death or alters the metabolism and perfusion of the tissue, making it more susceptible to adjuvant therapies such as radiation and chemotherapy.
This dissertation focuses on monitoring the response of prostate cancer to thermal ablation and hyperthermia using the technique of hyperpolarized 13C MRI, which allows for non-invasive assessment of both tissue metabolism and perfusion with a single injection of the co-polarized 13C-labeled pyruvate and urea. These biomarkers successfully delineated the ablated regions of the tissues while providing insight into the changes in metabolism and perfusion in the tissues receiving sub-lethal heat dose. To further explore the effects of hyperthermia on prostate cancer, a compact MR-compatible ultrasound hyperthermia device was fabricated to perform hyperthermia on murine prostate tumors in a 14T preclinical MRI scanner (bore diameter = 4cm) with concurrent MR thermometry. The feasibility of monitoring the metabolic and perfusion changes in prostate cancer in vivo shortly after hyperthermia has been demonstrated. Ongoing murine studies will examine the significance of the treatment response. Noninvasive monitoring of the changes in metabolism and perfusion of prostate cancer upon thermal therapy is invaluable for determining the timing and dose of adjuvant therapies.