Temporal dynamics of monocyte migration after myocardial infarction with 19F-MRI

• Applicants: Professor Dr. Michael Bock; Dr. Alexander Maier
• Subject Area: Cardiology, Angiology ; Medical Physics, Biomedical Technology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 492563001

After myocardial infarction (MI), the imbalance of the monocytes’ inflammatory and reparative response leads to aggravated myocardial damage and suboptimal tissue repair which results in worse long-term patient outcomes. Currently, novel therapeutic strategies are investigated that modulate monocyte migration and response to MI to limit ischemic damage and promote healing. Thus, there is an urgent clinical need to develop and validate new in vivo readouts of monocyte migration and response after MI as a potential prognostic marker of cardiac outcomes, or to characterize the efficacy of new immune-modulating compounds. 19F-MRI has successfully been applied in small animals to study myeloid cell uptake and migration after MI, but only few reports are published where 19F-MRI has been used in human-size models such as pigs. The transfer of 19F MRI into large animals is crucial for both the method validation and the development of clinical applications. In this research project 19F-MRI will be realized in a pig model concentrating on MRI of the spleen during MI to detect myeloid cell egress, and assess early inflammatory responses. For the imaging studies in pigs new RF coils will be developed that enable highly sensitive 19F/1H image acquisitions in the spleen of a pig, and MRI acquisition methods will be implemented to overcome the low signal-to-noise ratio in non-proton MRI by incorporating 1H image information. With these instruments, at first myeloid cells in the spleen that are labeled with 19F nano¬particles will be visualized with MRI. MI will be induced under interventional MRI guidance in combination with 19F MRI of the spleen. The egress of 19F labeled myeloid cells from the spleen will then be monitored during MI, and egress inhibition by Angiotensin-converting enzyme inhibition will be tested. 19F-MRI with labeled myeloid cells has the potential of a prognostic marker and translation into humans using PFC carriers, which are already approved for human application.

• DFG Programme: Research Grants