Chemical exchange sensitive MRI as biomarker of early therapeutic response in glioma patients

• Applicant: Privatdozent Dr. Daniel Paech
• Subject Area: Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445704496

Early therapy response assessment in brain tumor patients following radiochemotherapy is one of today’s major clinical challenges in neuro-oncology, since clinical routine gadolinium contrast-enhanced magnetic resonance imaging (MRI) cannot safely distinguish between therapy associated changes and tumor progression. This diagnostic uncertainty considerably reduces the therapeutic window for patient-individualized treatment strategies, which is particularly problematic since many patients suffer from early progression.Chemical exchange (CE)-sensitive MRI has recently emerged as a novel type of contrast mechanism that allows obtaining information on a molecular level with an image resolution comparable to standard MRI. Particularly, CE-sensitive MRI of endogenous proteins and exogenously administered glucose has been shown to have great potential to improve the diagnostic management of cancer patients.Over the last years, our group has made key developments in the field of CE-sensitive MRI approaches at 7.0 Tesla (7T) that enabled in vivo imaging of proteins with increased specificity. Pilot studies in glioma patients after radiochemotherapy revealed early treatment-related protein signal changes associated with therapy repsonse of these patients. Furthermore, our group was the first to investigate intravenously administered glucose as exogenous CE-sensitive contrast agent in a cohort of glioma patients at 7T.However, these pilot studies were carried out at ultra-high field MRI, which is why so far the diagnostic potential of the CE-sensitive MRI approaches could not be investigated and clinical evidence is still missing. Therefore, the main objective of this proposal is to translate these techniques to a clinical field strength (3T) and to investigate CE-sensitive MRI as a biomarker of early therapeutic response in glioma patients. The first major goal of this proposal is to integrate the previously established CE-sensitive protein MRI approach at 3T into the standard brain tumor protocol in order to conduct a prospective clinical cohort investigation of early therapy response in glioma patients (n=200) following radiochemotherapy. Further, the established glucose-enhanced CE-sensitive MRI approach at 7T will be employed to carry out hypothesis-generating pilot studies of early therapy response assessment in glioma patients. The second major goal is to translate the glucose-enhanced CE-sensitive MRI approach to 3T including a systematic optimization of contrast-to-noise ratio and the robustness of the method.The information on tumor protein content and glucose uptake provided by CE-sensitive MRI is expected to allow early stratification of treatment responders and non-responders to radiochemotherapy. This considerable gain of time to start individualized therapies would in turn improve follow-up management and prognosis of glioma patients.

• DFG Programme: Research Grants
• Co-Investigators: Dr. Steffen Görke; Professor Dr. Mark E. Ladd; Professor Dr. Heinz-Peter Schlemmer