Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital and Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225, Düsseldorf, Germany.
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
J Cardiovasc Magn Reson. 2023 Oct 3;25(1):54. doi: 10.1186/s12968-023-00964-7.
BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by H and F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm. CONCLUSIONS: In this proof-of-concept study, F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.
背景：巨噬细胞在血管炎症中起着关键作用，并可预测心血管并发症。静脉内应用全氟碳的氟-19 磁共振成像（F MRI）可在实验性血管疾病小鼠模型中无背景地直接定量巨噬细胞丰度。最近，全氟辛基溴化物纳米乳液（PFOB-NE）已应用于使用临床 MRI 扫描仪在猪心肌梗死模型中有效成像巨噬细胞浸润。在本概念验证方法中，我们旨在使用 F MRI 非侵入性地成像颈动脉血管成形术后猪单核细胞/巨噬细胞浸润，以评估机械损伤后的早期炎症反应。
方法：在 8 头小型猪中，进行了两种不同类型的血管损伤：仅使用球囊过度扩张血管成形术（BA）的轻度损伤（n=4）和 BA 联合内皮剥脱（BA+ECDN）的严重损伤（n=4）。损伤后 3 天静脉内给予 PFOB-NE，然后进行 H 和 F MRI，以评估第 6 天的血管炎症负担。使用 X 射线血管造影、血管内超声和免疫组织化学在至少每根颈动脉 10 个节段验证机械损伤的血管反应。
结果：在所有 8 头猪中均成功诱导血管成形术。损伤后的反应特征为正性重塑，主要表现为外膜壁增厚，同时伴有单核细胞/巨噬细胞浸润。PFOB-NE 给药后未观察到严重不良反应。仅在 4 头 BA+ECDN 后猪中检测到体内 F 信号，其信噪比（SNR）为 14.7±4.8。离体分析显示 F SNR 与局部单核细胞/巨噬细胞细胞密度呈线性相关。浸润单核细胞/巨噬细胞的最小检测下限估计约为 410 个细胞/mm。
结论：在这项概念验证研究中，F MRI 能够定量检测血管损伤后的单核细胞/巨噬细胞浸润，具有足够的灵敏度。这可能为血管成形术后患者或甚至在动脉粥样硬化斑块中使用 MRI 进行血管炎症的非侵入性监测提供机会。
J Cardiovasc Magn Reson. 2023-10-3
Eur Heart J Cardiovasc Imaging. 2015-3-1
Int J Cardiovasc Imaging. 2011-12-27
J Cardiovasc Magn Reson. 2014-3-4
Mol Imaging Biol. 2020-6
Int J Mol Sci. 2025-3-10
J Funct Biomater. 2023-12-15
Zotero 插件
