Multiparametric Immunoimaging Maps Inflammatory Signatures in Murine Myocardial Infarction Models

Alexander Maier; Yohana C Toner; Jazz Munitz; Nathaniel A T Sullivan; Ken Sakurai; Anu E Meerwaldt; Eliane E S Brechbühl; Geoffrey Prévot; Yuri van Elsas; Rianne J F Maas; Anna Ranzenigo; Georgios Soultanidis; Mohammad Rashidian; Carlos Pérez-Medina; Gyu Seong Heo; Robert J Gropler; Yongjian Liu; Thomas Reiner; Matthias Nahrendorf; Filip K Swirski; Gustav J Strijkers; Abraham J P Teunissen; Claudia Calcagno; Zahi A Fayad; Willem J M Mulder; Mandy M T van Leent

doi:10.1016/j.jacbts.2022.12.014

Multiparametric Immunoimaging Maps Inflammatory Signatures in Murine Myocardial Infarction Models

JACC Basic Transl Sci. 2023 Apr 5;8(7):801-816. doi: 10.1016/j.jacbts.2022.12.014. eCollection 2023 Jul.

Authors

Alexander Maier^{1

2

3}, Yohana C Toner^{1

2

4}, Jazz Munitz^{1

2}, Nathaniel A T Sullivan^{1

2}, Ken Sakurai^{1

2}, Anu E Meerwaldt^{1

2

5}, Eliane E S Brechbühl^{1

2}, Geoffrey Prévot^{1

2}, Yuri van Elsas^{1

2

4}, Rianne J F Maas^{1

2

4}, Anna Ranzenigo^{1

2}, Georgios Soultanidis^{1

2}, Mohammad Rashidian^{6

7}, Carlos Pérez-Medina^{1

2

8}, Gyu Seong Heo⁹, Robert J Gropler⁹, Yongjian Liu⁹, Thomas Reiner¹⁰, Matthias Nahrendorf¹¹, Filip K Swirski¹², Gustav J Strijkers^{1

2

13}, Abraham J P Teunissen^{1

2

12

14}, Claudia Calcagno^{1

2}, Zahi A Fayad^{1

2}, Willem J M Mulder^{1

2

4

15}, Mandy M T van Leent^{1

2

12}

Affiliations

¹ BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
² Department of Diagnostic, Molecular, and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Department of Cardiology and Angiology I, Heart Center of Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
⁵ Biomedical Magnetic Resonance Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht/Utrecht University, Utrecht, the Netherlands.
⁶ Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁷ Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
⁹ Department of Radiology, Washington University, St Louis, Missouri, USA.
¹⁰ Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
¹¹ Center for Systems Biology, Massachusetts General Hospital Research Institute and Department of Radiology, Harvard Medical School, Boston, Massachusetts, USA.
¹² Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹³ Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
¹⁴ Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁵ Department of Chemical Biology, Eindhoven University of Technology, Eindhoven, the Netherlands.

PMID: 点击这里下载-->> 37547068
PMCID: 点击这里下载-->> PMC10401290
DOI: 点击这里下载-->> 10.1016/j.jacbts.2022.12.014

Abstract

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 ¹⁸F-fluorothymidine and ¹⁸F-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.

Keywords: MI; atherosclerosis; imaging; immunology; inflammation.

Abstract

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