Multiparametric Immunoimaging Maps Inflammatory Signatures in Murine Myocardial Infarction Models.

In the past 2 decades, research on atherosclerotic cardiovascular disease has uncovered inflammation to be a key driver of the pathophysiological process. A pressing need therefore exists to quantitatively and longitudinally probe inflammation, in preclinical models and in cardiovascular disease patients, ideally using non-invasive methods and at multiple levels. Here, we developed and employed in vivo multiparametric imaging approaches to investigate the immune response following myocardial infarction. The myocardial infarction models encompassed either transient or permanent left anterior descending coronary artery occlusion in C57BL/6 and Apoe ^-/- mice. We performed nanotracer-based fluorine magnetic resonance imaging and positron emission tomography (PET) imaging using a CD11b-specific nanobody and a C-C motif chemokine receptor 2-binding probe. We found that immune cell influx in the infarct was more pronounced in the permanent occlusion model. Further, using ¹⁸ F-fluorothymidine and ¹⁸ F-fluorodeoxyglucose PET, we detected increased hematopoietic activity after myocardial infarction, with no difference between the models. Finally, we observed persistent systemic inflammation and exacerbated atherosclerosis in Apoe ^-/- mice, regardless of which infarction model was used. Taken together, we showed the strengths and capabilities of multiparametric imaging in detecting inflammatory activity in cardiovascular disease, which augments the development of clinical readouts.
Competing Interests: This work was supported by National Institute of Health grants R01HL143814 (to Dr Fayad), P01HL131478 (Drs Fayad and Mulder), P41EB025815 (Drs Liu and Gropler ), R35HL145212 (Dr Liu), and R35HL139598 (Dr Nahrendorf) and award K22CA226040 (Dr Rashidian). This work was also supported by an Innovation Research Fund Basic Research Award from the Dana-Farber Cancer Institute (Dr Rashidian). Dr Maier was supported by Deutsche Forschungsgemeinschaft grants (MA 7059/1 and MA 7059/3-1) and is part of SFB1425 funded by the Deutsche Forschungsgemeinschaft (project no. 422681845). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2023 The Authors.)