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Multimodal Molecular Imaging

Final Report Summary - MUMI (Multimodal Molecular Imaging)

Multimodality molecular imaging was the research topic of the ERC grant MUMI at the Technische Universität München, Germany. The overall aim of this research program was to develop multimodality imaging strategies to quantitate biological processes in-vivo. The project includes two parts, one methodological part which aims at the construction of a novel PET insert to be used in combination of 7 T MR magnet for preclinical imaging of animal models. This PET insert includes several innovations. It is the first silicon photomultiplier (SiPM) technology PET insert for a 7 T magnet. The insert includes a single crystal read-out which is an innovation in comparison to the established block design of commercially available PET scanners. The insert operates with a dual layer of crystal read-outs and the insert ring structure employs a 3D printed structure. Completion of the PET insert was achieved in 2017 and it is currently being used for preclinical studies. The research includes innovative hardware, unique design, and novel electronics as well as reconstruction algorithm for processing of PET data. With the help of the ERC funding, a powerful team of young investigators could be formed. This methodological development is paralleled by the use of an integrated clinical whole-body PET/MR instrument, which includes avalanche photodiodes for PET detectors and a 3 T magnet for MR imaging. First studies compared this new instrumentation with conventional PET/CT imaging in order to document the accuracy of PET quantification using a newly developed attenuation correction provided by segmented MRimages. Further studies evaluated the clinical potential of PET/MR technology for applications in oncology, neurology and for cardiovascular diseases. Technology transfer from academia to industry is part of this research since the PET/MR instrumentation was sponsored by the German research foundation in close cooperation with Siemens medical systems.
First, clinical applications focused on the combined application of PET/MR for the characterization of ischemic injury in patients with acute myocardial infarction. Since PET provides specific markers of tissue viability while MR allows quantification of scaring after myocardial infarction, this combination provides unique characterization and prognostic workup of patients suffering from coronary artery disease. Specific focus is the delineation of inflammatory response to acute myocardial injury. Future studies will focus on the relationship of acute myocardial injury and ischemic inflammatory reaction occurring in most patients. The hypothesis to be followed is that PET multimodality imaging will provide biomarkers which can be used to predict and to therapeutically modify the inflammatory process following myocardial infarction. Besides cardiology, the use of PET/MR in patients with cancer was part of the ERC MUMI project. Especially the combination of multi-parametric MR imaging in patients with prostate cancer has provided promising results. The combination of MR diffusion weighted imaging and contrast enhanced MR imaging with radioactively labeled imaging probes has been proven to provide high sensitivity and specificity of detection of malignant tissue, not only in primary diagnosis, but also in the setting of recurrent disease. A major focus in the evaluation of PET/MR for oncology at TUM was related to prostate cancer. The addition of multiparametric MRI to tracer uptake as well as the higher soft-tissue contrast in MRI implies clear advances. The investigation was initially carried out comparing 11C-Choline PET/MR with PET/CT in different clinical scenarios. Later (since 2013) the use of the newly established 68Ga-PSMA-11 ligand was investigated in the background of different clinical questions.
Furthermore, the potential of PET/MR for the investigation of neurological diseases was evaluated. A neurobiological line of our research dealt with a simultaneous measurement of brain glucose metabolism and functional connectivity using resting state FDG-PET and fMRI, respectively. We also analyzed the performance of FDG-PET/MR in differential diagnosis of patients with suspected dementing disorders. The ERC funding has allowed the research group in Munich to accelerate the development as well as the validation of multimodality imaging in cardiovascular, oncological and neurological diseases. The funding allowed the generation of a powerful interdisciplinary research group which not only validates existing technology, but also develops innovative imaging instrumentation for the improved quantification of biology through in vivo imaging.