Maier Alexander, Toner Yohana C, Munitz Jazz, Sullivan Nathaniel A T, Sakurai Ken, Meerwaldt Anu E, Brechbühl Eliane E S, Prévot Geoffrey, van Elsas Yuri, Maas Rianne J F, Ranzenigo Anna, Soultanidis Georgios, Rashidian Mohammad, Pérez-Medina Carlos, Heo Gyu Seong, Gropler Robert J, Liu Yongjian, Reiner Thomas, Nahrendorf Matthias, Swirski Filip K, Strijkers Gustav J, Teunissen Abraham J P, Calcagno Claudia, Fayad Zahi A, Mulder Willem J M, van Leent Mandy M T
BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Diagnostic, Molecular, and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
JACC Basic Transl Sci. 2023 Apr 5;8(7):801-816. doi: 10.1016/j.jacbts.2022.12.014. eCollection 2023 Jul.
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 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 Apoemice. 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 F-fluorothymidine and 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 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.
在过去20年中,对动脉粥样硬化性心血管疾病的研究发现炎症是病理生理过程的关键驱动因素。因此,迫切需要在临床前模型和心血管疾病患者中,理想情况下使用非侵入性方法并在多个层面上对炎症进行定量和纵向探究。在此,我们开发并采用多参数成像方法来研究心肌梗死后的免疫反应。心肌梗死模型包括在C57BL/6和Apo小鼠中短暂或永久性左冠状动脉前降支闭塞。我们使用CD11b特异性纳米抗体和C-C基序趋化因子受体2结合探针进行了基于纳米示踪剂的氟磁共振成像和正电子发射断层扫描(PET)成像。我们发现,在永久性闭塞模型中,梗死区免疫细胞流入更为明显。此外,使用F-氟胸苷和F-氟脱氧葡萄糖PET,我们检测到心肌梗死后造血活性增加,两种模型之间无差异。最后,我们观察到,无论使用哪种梗死模型,小鼠均存在持续性全身炎症和动脉粥样硬化加剧的情况。综上所述,我们展示了多参数成像在检测心血管疾病炎症活动方面的优势和能力,这有助于临床指标的发展。