Metabolic Imaging in Clinical Applications using Hyperpolarised [1-13C]pyruvate

• Subject Area: Radiology ; Endocrinology, Diabetology, Metabolism ; Hematology, Oncology ; Nephrology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553593000

We aim to improve clinical imaging by capitalizing on the significant SNR enhancement afforded by hyperpolarization in the following: (a) Neuro-Oncology: [1-13C]pyruvate will be used to investigate tumor metabolism, targeting its central role in metabolic pathways. By probing unique tumor metabolic processes, we aim to provide real-time insights, surpassing conventional PET imaging limitations. Utilizing our world-renowned expertise in simultaneous MR-PET, a database of 10,000 patients studied with FET-PET and our tested AI methodology, we expect that [1-13C]pyruvate HP-MRI will provide critical insights. (b) Hyperpolarized 13C-MRI may play a significant role in elucidating the development and response of the ischemic penumbra in stroke. We will combine OEF measurements with lactate dehydrogenase (LDH) / pyruvate dehydrogenase (PDH) enzyme activity ratios as a possible indicator for the status of the ischemic and recovering brain. The ability of HP-MRI to rapidly assess [1-13C]pyruvate conversion to [1-13C]lactate production will be used to study cerebral ischaemia. We will characterize the kinetics of delivery, uptake, and enzymatic conversions of [1-13C]pyruvate in ischemic stroke patients to gain clinical insights into the critical treatment time window. (c) Brain energy metabolism is crucial for normal neuronal function and is implicated in various psychiatric disorders. Hyperpolarized 13C MRI (HP-MRI) can provide insights into the metabolic processes underlying these conditions. Changes in the lactate-to-bicarbonate ratio can indicate shifts between aerobic and anaerobic metabolism, often observed in mood disorders. Mitochondrial dysfunction is common to several psychiatric conditions, e.g. major depressive disorder (MDD) and schizophrenia. HP-MRI can non-invasively assess mitochondrial function by imaging the oxidative metabolism of [1-13C]pyruvate to bicarbonate via the PDH complex. This can provide valuable information about mitochondrial health and energy production in different brain regions implicated in psychiatric disorders. (d)Glucose is the main energy substrate for synaptic activity in the brain. Glucose PET has been used to study regional abnormalities in glucose utilization in neurodegenerative disease. We will use HP-MRI to investigate whether the diagnosis of Alzheimer's disease, fronto-temporal dementia or dementia with Lewy bodies can be made with high sensitivity and specificity using HP-MRI. (e) Outside the brain, we will use HP-MRI to investigate tumor differentiation, aggressiveness and treatment efficacy in the liver leading to personalized treatment based on metabolic signatures. (f) The rising incidence of diabetes, hypertension and obesity is contributing to an increase in chronic kidney disease (CKD). However, there is a significant lack of disease-specific non-invasive imaging biomarkers for kidney diseases. Our research will utilize HP-MRI to identify novel biomarkers and investigate kidney disease.

• DFG Programme: Major Instrumentation Initiatives
• Major Instrumentation: Headcoil ; Hyperpolariser ; Liver coil
• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Participating Institution: Forschungszentrum Jülich GmbH ; Institut für Neurowissenschaften und Medizin (INM) ; Physik der Medizinischen Bildgebung (INM-4)
• Leader: Professor Nadim Jon Shah, Ph.D.