Preclinical Translation of Signal Amplification by Reversible Exchange for Next-Generation Hyperpolarized Metabolic Magnetic Resonance Imaging

• Applicant: Dr. Andreas Schmidt
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571352963

Hyperpolarized magnetic resonance enables signal enhancements of more than 10,000-fold compared to conventional MRI, allowing real-time observation of metabolic processes that are otherwise inaccessible. This has sparked growing interest and is currently being explored in over 50 clinical trials. However, to harvest the full biomedical potential of hyperpolarized MRI and enable widespread adoption in preclinical research and successful future clinical translation, robust, low-cost, user-friendly, safe, and high-throughput technologies are essential. This project investigates parahydrogen-based hyperpolarization as an alternative approach for metabolic MRI, with a focus on Signal Amplification by Reversible Exchange (SABRE). SABRE enables rapid and repeated hyperpolarization of biologically relevant molecules without chemical modification. Operating at room temperature and without cryogenics, it holds particular promise for high-throughput applications in preclinical research. We will explore SABRE's potential for biomedical imaging by studying polarization transfer in 13C-labeled metabolic agents, establishing methods to produce biocompatible, hyperpolarized solutions, and evaluating their performance in cell and animal models. Special focus will be placed on key known metabolic probes such as pyruvate, α-ketoglutarate, ketoisocaproate, fumarate, and pH-sensitive agents, including deuterated and esterified variants optimized for biomedical use, and selected combinations thereof. To enable these studies, we will investigate suited polarization methods and implement dedicated hardware including a novel SABRE polarizer and a continuous-flow bioreactor for real-time, repeated metabolic readouts in living cells. Through the unique combination with our rapid polarization methods, we will monitor complex metabolic properties longitudinally - for example to investigate dynamic changes in metabolism triggered by hypoxia or nutrient availability - with high temporal resolution. In vivo experiments in healthy mice will assess biodistribution, polarization lifetimes, and multi-agent injection feasibility with high throughput. Building on our recent demonstration of in vivo SABRE-based metabolic imaging and preliminary work, this project lays the foundation for studying a broad range of metabolic processes. It is key for future applications in disease models and research towards the clinical translation of the new methods.

• DFG Programme: Research Grants
• Major Instrumentation: Hochdurchsatz Parawasserstoff-Generator
• Co-Investigator: Professor Dr. Dominik von Elverfeldt