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.