The Feasibility and Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Monitoring Patients With Intracranial Metastasis Treated With Stereotactic Radiosurgery (SRS)
Upwards of 40% of cancer patients will develop brain metastases during their illness, most of which become symptomatic. The burden of brain metastases impacts the quality and length of survival. Thus the management of brain metastases is a significant health care problem. Standard treatment options include stereotactic radiosurgery and/or whole brain radiation. There is a great interest in studying the association between the functional characteristics of tumors - such as tumour hypoxia and lactate accumulation - and clinical outcomes in order to guide management. These characteristics may predict future tumor behavior and stratify risk of therapy failure. Hyperpolarized 13C MR imaging is a novel functional imaging technique that uses 13C-labeled molecules, such as pyruvate, and MRS to image in vivo tissue metabolism. There is significant clinical heterogeneity in patients with brain metastasis due to differences in underlying tumour biology. Biochemical differences in tumour metabolism have been shown to correlate with response to therapy. While the significance of tissue hypoxia for radiosensitivity has been established for years, the impact of lactate accumulation on radiosensitivity has only recently been recognized. Studies have shown that tissue lactate levels correlate with radioresistance in several human tumours. Hyperpolarized 13C pyruvate MRS has been shown in numerous pre-clinical studies and a recent clinical study to have great potential as a metabolic imaging tool. Our study seeks to establish the role of hyperpolarized 13C MRS in characterizing the metabolic features of intracranial metastasis. The results of this study will provide insight into intracranial metastatic disease signatures with MR spectroscopy and determine if there is added benefit for incorporation of this new technique into future clinical MRI protocols. If the technique can accurately differentiate between aggressive and indolent tumours based on MR spectroscopic patterns, hyperpolarized 13C MRS may have wide-ranging utility in the future. In the era of personalized medicine, the ability of imaging tests to predict response to therapy would open the door for individualized treatment options specific to each patient's disease biology.
⁃ Part I (Controls) Group A
• Participants of all ethnic groups/race categories (≥18yrs old)
• Informed consent Group B
• Male participants of all ethnic groups/race categories (between the age of 18-39)
• Informed consent Group C
• Female participants of all ethnic groups/race categories (between the age of 18-39)
• Informed consent Group D
• Male participants of all ethnic groups/race categories (between the age of 40-59)
• Informed consent Group E
• Female participants of all ethnic groups/race categories (between the age of 40-59)
• Informed consent Group F
• Male participants of all ethnic groups/race categories (≥60 yrs old)
• Informed consent Group G
• Female participants of all ethnic groups/race categories (≥60 yrs old)
• Informed consent Group H and I
• Male or female participants of all ethnic groups/race categories (≥18 yrs old)
• Informed consent Group J
• Male or female participants of all ethnic groups/race categories (≥60 yrs old)
• Informed consent
• Diagnosed with mild cognitive impairment Group K
• Male or female participants of all ethnic groups/race categories (≥60 yrs old)
• Informed consent
• Diagnosed with mild Alzheimer's disease
⁃ Part II \& III
• Adult participants of all ethnic groups/race categories (age ≥18 yrs old)
• Radiographic diagnosis of brain metastases and pathological confirmation of a solid cancer primary
• At least 1 intracranial metastasis ≥1 cm in size
• Metastatic brain tumour amenable to Stereotactic radiosurgery or radiotherapy
• Participants on stable dexamethasone dose at the time of baseline MRI and 1-5 days post-SRS MRI
• Estimated survival more than 6 months
• Informed consent