MRI and Blood Biomarkers for the Prediction of Neurocognitive Decline Following Brain Radiation

This study determines whether non-invasive evaluation using repeated magnetic resonance imaging (MRI) scans and repeated blood biomarker measurements can be used to predict changes in a person's mental functions that result from radiation exposure to the brain. This study may let researchers monitor patient responses to treatment and the disease better and possibly make changes to patient treatment, if needed.

PRIMARY OBJECTIVE:

I. To describe changes of image features on conventional T1- and T2- weighted imaging, and quantitative changes on multiparametric MRI including apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), fractional volume of the extravascular, extracellular space (ve) and Ktrans (transfer constant that characterizes the diffusive transport of low-molecular weight gadolinium across the capillary endothelium) associated with neurocognitive changes following radiation.

SECONDARY OBJECTIVES:

I. To identify biofluid biomarkers at baseline and dynamics of biomarkers after radiation exposure that are associated with neurocognitive changes.

II. To model a composite early biomarker (baseline or within 3 weeks of the start of radiotherapy) that incorporates the most promising imaging and biofluid biomarkers to predict for later neurocognitive decline.

III. To evaluate the relationship between the delivered radiation dosimetry to brain subregions and patterns of neurocognitive decline in order to inform potential subregions of focus for future pre-clinical and clinical investigation.

IV. To evaluate the relationship between quantitative changes on multiparametric MRI including apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), fractional volume of the extravascular, extracellular space (ve) and Ktrans (transfer constant that characterizes the diffusive transport of low-molecular weight gadolinium across the capillary endothelium) with radiation dosimetry.

EXPLORATORY OBJECTIVE:

I. To explore changes on advanced MR measurements of structural connectomics, functional connectomics, working memory network, cerebrovascular reactivity (CVR), cerebral blood flow (CBF) and brain metabolism associated with neurocognitive changes following radiation.

OUTLINE:

Patients undergo multiparametric MRI with contrast at baseline, 3 weeks during radiotherapy, and at 1, 3, 6, 12, and 24 months post-radiotherapy. Patients undergo multiparametric MRI without contrast at 1, 2, 4, 5, and 6 weeks during radiotherapy. Patients may undergo functional MRI at baseline and 6 months post-radiotherapy. Patients also complete questionnaires and undergo collection of blood samples at baseline, weekly through week 6 during radiotherapy, and at 1, 3, 6, 12, and 24 months post radiotherapy.

Eligibility Criteria:
Inclusion Criteria:

* Patients must be age \>= 18 years
* Patients must be planned for fractionated radiotherapy that will be delivered over at least 5 weeks and that will expose the brain to radiation
* Patients must have Karnofsky performance status (KPS) \>= 80
* Patients must be able to obtain an MRI scan with gadolinium contrast
* Female patients of childbearing age must not be pregnant as determined with a serum beta human chorionic gonadotropin (HCG) no greater than 14 days prior to study registration, or breast-feeding. (The exclusion is made because gadolinium may be teratogenic in pregnancy). Pregnancy tests are part of standard of care routine if a patient is receiving radiation treatment
* Patient must be fluent enough in English to complete neurocognitive testing
* Education of \>= 12 years (high school graduate or equivalent) by patient self-report
* Patient is able to complete an in-person and electronic neurocognitive assessments (i.e. is alert and has the ability to comprehend and complete the assessments)
* Patient has no history of psychiatric or medical conditions that would result in an inability to complete serial neurocognitive tests, severe claustrophobia, prior cerebrovascular event(s), degenerative neurological diagnoses (e.g., dementia, Parkinson's, multiple sclerosis \[MS\]) or severe psychiatric illness (e.g., schizophrenia) that may impact neurocognitive and imaging assessments

Exclusion Criteria:

* Previous brain radiation without comprehensive dosimetry records
* Concurrent chemotherapy
* Psychiatric or medical conditions that would result in inability to complete serial neurocognitive tests
* Severe claustrophobia requiring sedative medications for the MRI
* Prior cerebrovascular event(s) or degenerative neurological diagnoses (e.g., dementia, Parkinson's, MS)
* Contraindication to gadolinium-based contrast administration for MRI (i.e. allergy to gadolinium or severe chronic kidney disease defined by estimated glomerular filtration rate \[eGFR\] \< 30 mL/min/1.73 m\^2, as per institutional policy)