Dynamic Hyperpolarized MRI for Imaging ¹³C-Ketoisocaproate Metabolism in an Alzheimer’s Disease model

Motivation: With hyperpolarized 13C-MRI, α-keto-[1-13C]isocaproate (KIC) conversion to leucine can be probed in vivo. While static imaging has shown potential, dynamic acquisitions may enhance metabolic investigations. Goal(s): Our goal was to develop and validate a dynamic imaging strategy to assess cerebral KIC metabolism in vivo, using an animal model of Alzheimer's Disease (AD). Approach: Transgenic 5xFAD (n=3) and wild-type (n=3) mice received KIC injections. Dynamic imaging of KIC's conversion to leucine was conducted using an IDEAL spiral CSI acquisition-method. Results: The results demonstrated rapid leucine accumulation in the brain, with a significantly higher cerebral metabolic conversion to leucine in AD mice compared to controls. Impact: We introduce a dynamic method to measure BCAT activity in vivo, with initial results indicating increased activity in a preclinical Alzheimer's model. By enabling real-time tracking of KIC metabolism, we provide a tool for investigating metabolic alterations in neurological disorders.