Project Details
Projekt
Concurrent tracking of the trafficking of individual immune cell populations after myocardial infarction (MI) by ‘multicolor’ 1H/19F MRI
Subject Area
Medical Physics, Biomedical Technology
Cardiology, Angiology
Cardiology, Angiology
Term
from 2017 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 330470715
19F MRI has proven to be an excellent tool for background-free imaging of inflammation. For this, emulsified perfluorocarbons (PFCs) are injected, which are preferentially phagocytized by circulating monocytes that can be detected by 1H/19F MRI after infiltration into inflammatory foci. However, also B-cells, dendritic cells or neutrophils can internalize PFCs under certain conditions and small-sized PFCs may passively diffuse into inflammatory lesions via a leaky endothelium. Thus, the detected 19F signal is derived from a complex mixture of cells which were labelled in the bloodstream and/or locally internalized the PFCs. Lately, we advanced the 19F MRI approach by directing ligand-equipped PFCs to specific epitopes enabling an active targeting of individual cell populations. Furthermore, we developed an imaging technique for concurrent detection of different PFCs with distinct spectral signatures allowing the simultaneous visualization of several targets. To overcome the described limitations, this proposal is aimed at expanding the current approach for:1) Specific targeting of neutrophils, classical/non-classical monocytes and CD4+ T-cells: For this, we will generate PFCs to specifically label the distinct cell types within the bloodstream and implement a ‘multicolor’ 19F compressed sensing technique to enhance the detection thresholds. We already revealed a targeting peptide for neutrophils and will identify novel ligands against both monocyte subsets using phage display screening. CD4+ T-cells will be targeted by anti-CD4 mAb/mAb-derivatives and/or by a novel transgenic mouse with specific PFC internalization properties of CD4+ T-cells. 2) Tracking sequential immune cell infiltration and alterations in tissue texture after MI: Monitoring the infiltration of neutrophils, classical/non-classical monocytes and CD4+ T-cells into the heart after MI will enable a precise mapping of the quality of the current inflammatory state. In combination with multiparametric 1H MRI (T1, T2, CEST), this allows a comprehensive characterization of local inflammation and associated alterations in tissue textures. To address interorgan crosstalk also bone marrow, spleen, kidney and lung are included into the imaging protocol which will provide insight in the overall immune cell trafficking after MI. With this approach, we will furthermore investigate how an altered immunological predisposition will impact on the outcome after MI. In summary, this approach will permit (i) locoregional discrimination of the sequential infiltration of distinct immune cell populations together with in-depths characterization of tissue properties and (ii) to monitor the effect of MI on immune cell recruitment to other major target organs. In the long run, this approach might also be transferred to the clinical setting for identification of individual inflammation patterns in patients to tailor adequate therapy regimes for precision medicine.
DFG Programme
Research Grants
