Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Patients With Intracranial Metastasis Treated With (SRS)

This is a pilot prospective, single-institution study in both control participants, control participants with mild cognitive impairment and Alzheimer's disease and participants with evidence of intracranial metastases who will be planned for brain radiation therapy. Control participant accrual will be done through advertisements. For control participants with mild cognitive impairment, Alzheimer's disease and intracranial metastatic disease screening and accrual will be completed by a member of the participant's Circle of Care. Clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC) by the study's Qualified Investigator or medical designate. Eligible control participants must meet the study's inclusion and exclusion criteria and MRI eligibility. Intracranial metastatic participants must meet the study's inclusion and exclusion criteria, MRI eligibility will be undergoing radiation therapy (stereotactic radiotherapy).

The study will be divided into three parts:

Part I (Controls)

• Population: up to 146 study participants, ≥18 years of age
• Each participant in Groups A to G and J and K will undergo a single MRI sequence with a single hyperpolarized 13C pyruvate injection. Participants in group H, I, and M will undergo MRI sequences with two consecutive injections of hyperpolarized 13C pyruvate. The scans are expected to be of approximately 60 to 75 minutes in length.

Group A: up to 6 participants ≥ 18 years of age. Group B: up to 10 male participants between the age of 18-39 Group C: up to 10 female participants between the age of 18-39 Group D: up to 10 male participants between the age of 40-59 Group E: up to 10 female participants between the age of 40-59 Group F: up to 10 male participants ≥ 60 years of age Group G: up to 10 female participants ≥ 60 years of age Group H: up to 10 male or female participants ≥ 18 years of age Group I: up to 10 male or female participants ≥ 18 years of age Group J: up to 10 male or female participants ≥ 60 years of age with Mild Cognitive Impairment Group K: up to 10 male or female participants ≥ 60 years of age with Alzheimer's disease Group L: up to 10 male or female participants ≥18 years of age Group M: up to 30 male or female participants ≥18 years of age

Part II

• Population: up to 100 study participants from the Odette Cancer Centre, ≥18 years of age with demonstrated intracranial metastasis on imaging (CT or MRI), who have been referred to clinic for radiotherapy consideration.
• Procedure: Each participant will undergo additional MRI sequences (hyperpolarized 13C pyruvate MRS) with an additional length of approximately 30-60 minutes that will be performed on the day of or in advance of the participant's routine radiation planning scan prior to radiation treatment. No extra visits to the hospital, beyond routine clinical care, are anticipated.

Part III

• Population: up to 30 study participants from the Odette Cancer Centre, ≥18 years of age with demonstrated intracranial metastasis on imaging (CT or MRI), who have been referred to clinic for radiotherapy consideration.
• Procedure: Each participant will undergo additional MRI sequences (hyperpolarized 13C pyruvate MRS) with an additional length of approximately 30-60 minutes that will be performed on the day of or in advance of the participant's routine radiation planning scan prior to radiation treatment, or following treatment. In addition, if an adverse radiation effect is identified on post-SRS follow-up images by the qualified investigator, each participant will undergo non-routine MRI scans with a length of approximately 60-90 minutes. Participants who do not receive a pre-SRS hyperpolarized 13C pyruvate MRS scan, but that present with an ARE post-SRS, are also included in this population. The quantity of follow-up scans will be as deemed necessary by the qualified investigator.