Dynamic ¹³C-MRI of Branched-Chain Amino Acid Metabolism Using Hyperpolarized [1-¹³C]2-Ketoisocaproate: A Multiband IDEAL Spiral Approach in Rodents and Pigs

Purpose: To develop and validate a dynamic ¹³C-MRI acquisition strategy for imaging branched-chain amino acid (BCAA) metabolism catalyzed by branched-chain aminotransferase (BCAT) using hyperpolarized [1-¹³C]2-ketoisocaproate (KIC), and to assess its scalability to a large-animal model.

Methods: A multiband spectral-spatial excitation was combined with IDEAL spiral imaging at 3 T to capture conversion of KIC to [1-¹³C]leucine. Hyperpolarized KIC was produced by dissolution dynamic nuclear polarization (dDNP). The method was validated in phantoms mimicking in vivo conditions and applied in mouse brains, where BCAT activity is well characterized. To assess translational feasibility, the protocol was adapted for pig kidneys, a well-perfused organ with renal physiology and BCAT expression similar to humans. 

Results: Phantom studies confirmed spectral separation and accurate spatial localization. In mice, the multiband IDEAL spiral sequence generated metabolic maps comparable to chemical-shift imaging but with higher SNR. Dynamic imaging at 1 s temporal resolution captured reproducible KIC-to-leucine conversion across six animals. In pigs, 2 s-resolution imaging revealed KIC uptake in renal vasculature and cortex followed by cortical leucine accumulation and efflux into the vena cava, reflecting localized metabolism and transport. 

Conclusion: The presented ¹³C-MRI strategy enables efficient spectral separation and high-temporal-resolution imaging of KIC metabolism in rodents and pigs, establishing a translatable framework for noninvasive studies of BCAA metabolism.