Fast hydrogenation and hyperpolarization for repetitive, highly sensitive, metabolic magnetic resonance imaging

• Applicant: Dr. Andreas Schmidt
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 458556701

Mechanistic information on mammalian metabolism in vivo and dynamic metabolic changes are difficult to access with typical analytical tools because either the spatial, chemical, or temporal resolution is insufficient. Magnetic resonance imaging (MRI) is one of the most powerful diagnostic methods in medicine. In principle, it can also be used for non-invasive, radiation-free imaging of metabolism. However, its low sensitivity typically hinders MRI to detect metabolites other than some of the most abundant ones (often with concentrations higher than 1 millimolar). This limitation can be addressed by improving the sensitivity of MRI: Through hyperpolarization (HP) nuclear spins of molecules get strongly aligned in the magnetic field, increasing the MRI signal by 4-5 orders of magnitude. This way, metabolically active, hyperpolarized tracers for MRI can be produced, the conversion of which can be tracked in vivo to visualize metabolic pathways of the tracers. The enormous potential of HP for diagnosis and therapy planning, for example in the case of tumors, has already been demonstrated in preclinical and human studies.We recently demonstrated that HP tracers can be produced directly in the MRI system and applied in vivo within seconds. Since no transfer of the tracer to the MRI scanner is necessary, a larger proportion of the short-lived signal amplification (~minutes) can be used for imaging. In addition, we recently have succeeded in repeatedly producing HP tracers in no more than 15 seconds.Probably, the greatest challenge of HP is its short lifetime, as it decays with the longitudinal relaxation time T1 (for carbon-13 (13C) in deuterium labeled molecules often ~1 min; the T1 of protons (1H) is typically shorter) - 13C-HP tracers can often be measured for no more than 2 - 3 min in vivo.In this project, we will significantly extend this acquisition window for the first time. For this purpose, we enable tracers to be produced and administered in vivo in high concentrations and with high HP repeatedly. We show the potential of this approach in healthy-animal experiments and observe dynamic changes in the uptake and metabolism of lactate in tissue, while we increase the blood concentration through repeated injections of a lactate tracer. Lactate is a metabolite for energy production and its concentration in the blood is an important parameter in clinical diagnostics. For instance, in intensive care the mortality of patients is highly elevated under severe hyperlactatemia (>10 millimol/L lactate in the blood) especially if there is no prominent clearance within 12 h. A better understanding of lactate clearance in vivo will help us to better investigate and interpret pathological changes of the lactate concentration in blood in the future.

• DFG Programme: Research Grants