Quo Vadis Hyperpolarized 13C MRI?

Over the last two decades, hyperpolarized 13C MRI has gained significance in both preclinical and clinical studies, hereby relying on technologies like PHIP-SAH (ParaHydrogen-Induced Polarization-Side Arm Hydrogenation), SABRE (Signal Amplification by Reversible Exchange), and dDNP (dissolution Dynamic Nuclear Polarization), with dDNP being applied in humans. A clinical dDNP polarizer has enabled studies across 24 sites, despite challenges like high cost and slow polarization. Parahydrogen-based techniques like SABRE and PHIP offer faster, more cost-efficient alternatives but require molecule-specific optimization. The focus has been on imaging metabolism of hyperpolarized probes, which requires long T1, high polarization and rapid contrast generation. Efforts to establish novel probes, improve acquisition techniques and enhance data analysis methods including artificial intelligence are ongoing. Potential clinical value of hyperpolarized 13C MRI was demonstrated primarily for treatment response assessment in oncology, but also in cardiology, nephrology, hepatology and CNS characterization. In this review on biomedical hyperpolarized 13C MRI, we summarize important and recent advances in polarization techniques, probe development, acquisition and analysis methods as well as clinical trials. Starting from those we try to sketch a trajectory where the field of biomedical hyperpolarized 13C MRI might go.