Myocardial remodeling in c-kit deficient mice - quantitative assessment by Magnetic Resonance Imaging and Mass Spectrometry Imaging
Final Report Abstract
Following myocardial infarction, cardiac tissue shows limited capacity of regeneration. Pluripotent stem cells are considered a promising approach to support healing of myocardial infarction. Bone barrow derived cells, which express the receptor tyrosine kinase c-kit, also known as the stem cells growth factor receptor SCFR, have been shown to drive myocardial healing by supporting neo-angiogenesis, modulating the inflammatory response to myocardial infarction, and promoting myofibroblast mediated repair of the murine infarct scar. Unfortunately, clinical trials applying c-kit+ bone marrow cells therapeutically could not reproduce those preclinical findings. Dedicated imaging techniques that track specific biological mechanisms of heart regeneration, non-invasively, in vivo and over time are therefore crucial to foster the development of novel therapeutic strategies to improve healing of myocardial infarction. In this project, we have successfully implemented a set of non-invasive imaging methods using either fluorescence mediated tomography, multispectral optoacoustic tomography, or MRI, for monitoring c-kit mediated effects of myocardial infarction healing. Each method was able to detect disturbed tissue healing in c-kit-deficient mice, due to alterations in the extracellular matrix or content of elastic fibres. Further, a novel metabolic MRI approach, based on the detection of glucose was implemented and used to characterize myocardial infarction. To obtain quantitative imaging biomarkers we combined in vivo MRI with both molecular and elemental ex vivo Mass Spectrometry Imaging, allowing for a quantitative readout of c-kit-dependent tissue alterations. Next Generation Sequencing of myocardial tissue confirmed extracellular matrix and elastic fibre-related gene expression as hallmark of c-kit-dependent healing deficiency. A number of immune cell-related gene modulations were discovered, some of which may offer novel targets for approaches to improve myocardial healing after an infarct.
Publications
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Spatially Resolved Quantification of Gadolinium(III)‐Based Magnetic Resonance Agents in Tissue by MALDI Imaging Mass Spectrometry after In Vivo MRI. Angewandte Chemie International Edition, 54(14), 4279-4283.
Aichler, Michaela; Huber, Katharina; Schilling, Franz; Lohöfer, Fabian; Kosanke, Katja; Meier, Reinhard; Rummeny, Ernst J.; Walch, Axel & Wildgruber, Moritz
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Characterization of Cardiac Dynamics in an Acute Myocardial Infarction Model by Four-Dimensional Optoacoustic and Magnetic Resonance Imaging. Theranostics, 7(18), 4470-4479.
Lin, Hsiao-Chun Amy; Déan-Ben, Xosé Luís; Ivankovic, Ivana; Kimm, Melanie A.; Kosanke, Katja; Haas, Helena; Meier, Reinhard; Lohöfer, Fabian; Wildgruber, Moritz & Razansky, Daniel
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Molecular imaging of myocardial infarction with Gadofluorine P – A combined magnetic resonance and mass spectrometry imaging approach. Heliyon, 4(4), e00606.
Lohöfer, Fabian; Hoffmann, Laura; Buchholz, Rebecca; Huber, Katharina; Glinzer, Almut; Kosanke, Katja; Feuchtinger, Annette; Aichler, Michaela; Feuerecker, Benedikt; Kaissis, Georgios; Rummeny, Ernst J.; Höltke, Carsten; Faber, Cornelius; Schilling, Franz; Botnar, René M.; Walch, Axel K.; Karst, Uwe & Wildgruber, Moritz
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Volumetric Optoacoustic Tomography Differentiates Myocardial Remodelling. Molecular Imaging and Biology, 22(5), 1235-1243.
Ivankovic, Ivana; Déan-Ben, Xosé Luís; Haas, Helena; Kimm, Melanie A.; Wildgruber, Moritz & Razansky, Daniel
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Corrections for Rabi oscillations in cardiac chemical exchange saturation transfer MRI under the influence of very short preparation pulses. NMR in Biomedicine, 37(4).
Schache, Daniel; Peddi, Ajay; Nahardani, Ali; Faber, Cornelius & Hoerr, Verena
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In-Vivo CEST MRI to assess and identify myocardial infarction by using natural D- glucose as a contrast agent. 2023 ISMRM & ISMRT Annual Meeting.
Peddi, Ajay; Schache, Daniel; Nahardani, Ali; Kuhlmann, Michael; Wildgruber, Moritz; Faber, Cornelius & Hoerr, Verena
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In-vivo CEST MRI with natural D-glucose as a contrast agent to evaluate and detect myocardial infarction in comparison to LGE. Proc. ESMRMB 2023
Ajay Peddi; Daniel Schache; Ali Nahardani; Michael Kuhlmann; Moritz Wildgruber; Cornelius Faber & Verena Hoerr
