PROJECT SUMMARY / ABSTRACT Hyperpolarized (HP) 13C pyruvate MRI is an emerging imaging modality that provides unique access to glucose metabolism in the brain, a pathway that is implicated in brain aging and neurodegeneration by 15O / 18F metabolic PET research studies from our group and others. Prior human HP 13C research has been restricted almost exclusively to scanners from a single vendor, because of need for specialized pulse sequences and hardware. In this R21 project, we propose to establish the feasibility and reproducibility of advanced HP 13C imaging of the human brain on a major underexplored clinical MRI platform (Siemens). Although we acknowledge that some prior HP 13C MR/MRI work has already been conducted on this platform, this will be the first study to use metabolite-specific echo-planar imaging (EPI) with spectral-spatial radiofrequency (RF) excitation, which is a highly advantageous approach for HP 13C studies and is the most popular method for human HP 13C MRI, according to a recent consensus review paper. This will also be the first HP 13C work in brain on Siemens. Thus we consider feasibility of state-of-the-art human HP 13C brain imaging on this platform as an important objective. In Aim 1, testing will first be conducted in vitro by imaging a human-scale 3D-printed Shepp-Logan bioreactor phantom that mimics the signal dynamics of human hyperpolarized 13C brain imaging studies. In Aim 2, we will evaluate the reproducibility of in vivo HP 13C pyruvate human brain imaging in a test group of cognitively unimpaired adults, recruited from our existing 15O / 18F metabolic PET study. Each subject will be scanned twice in succession during each imaging session, and regional and spatial comparisons will be made between runs. To clarify the overall focus of the project in this resubmission application, the main scientific objective is evaluating the reproducibility of HP 13C imaging of human brain in normal subjects, which has yet to be established. As an exploratory aim, topography of this pilot HP 13C pyruvate MRI data will also be compared against metabolic PET data from the same subjects, to help motivate future HP 13C pyruvate brain imaging research studies.