King's College London, Division of Imaging Sciences and Biomedical Engineering, London, UK.
Atherosclerosis. 2012 May;222(1):43-9. doi: 10.1016/j.atherosclerosis.2012.01.008. Epub 2012 Jan 10.
Molecular magnetic resonance imaging (MRI) has emerged as a promising non-invasive modality to characterize atherosclerotic vessel wall changes on a morphological and molecular level. Intraplaque and endothelial fibrin has recently been recognized to play an important role in the progression of atherosclerosis. This study aimed to investigate the feasibility of intraplaque and endothelial fibrin detection using a fibrin-targeted contrast-agent, FTCA (EPIX Pharmaceuticals, Lexington, MA), in a mouse model of atherosclerosis.
Male apolipoproteinE-knockout mice (ApoE(-/-)) were fed a high fat diet (HFD) for one to three months. MRI of the brachiocephalic artery was performed prior to and 90 min after the administration of FTCA (n=8 per group). Contrast to noise ratios (CNR) and longitudinal relaxation rates (R1) of plaques were determined and compared to ex vivo fibrin density measurements on immunohistological sections stained with a fibrin-specific antibody and gadolinium concentrations measured by inductively coupled mass spectroscopy (ICP-MS).
Molecular MRI after FTCA administration demonstrated a significant increase (p<0.05) in contrast agent uptake in brachiocephalic artery plaques. In vivo CNR measurements were in good agreement with ex vivo fibrin density measurements on immunohistochemistry (y=2.4x+11.3, R(2)=0.82) and ICP-MS (y=0.95x+7.1, R(2)=0.70). Late stage atherosclerotic plaques displayed the strongest increase in CNR, R1, ex vivo fibrin staining and gadolinium concentration (p<0.05).
This study demonstrated the feasibility of intraplaque and endothelial fibrin imaging using FTCA. Direct in vivo fibrin detection and quantification could be useful for characterization and staging of coronary and carotid atherosclerotic lesions, which may aid diagnosis and intervention.
分子磁共振成像（MRI）已成为一种很有前途的非侵入性方法，可以在形态学和分子水平上对动脉粥样硬化血管壁变化进行特征描述。斑块内和血管内皮纤维蛋白最近被认为在动脉粥样硬化的进展中起着重要作用。本研究旨在探讨使用纤维蛋白靶向对比剂 FTCA（EPIX 制药公司，列克星敦，马萨诸塞州）在动脉粥样硬化小鼠模型中检测斑块内和血管内皮纤维蛋白的可行性。
雄性载脂蛋白 E 基因敲除（ApoE(-/-)）小鼠喂食高脂肪饮食（HFD）1-3 个月。在给予 FTCA 之前和之后 90 分钟，对肱动脉进行 MRI 检查（每组 8 只）。测定斑块的对比噪声比（CNR）和纵向弛豫率（R1），并与用纤维蛋白特异性抗体染色的免疫组织化学切片上的纤维蛋白密度测量值和通过电感耦合质谱（ICP-MS）测量的钆浓度进行比较。
FTCA 给药后的分子 MRI 显示肱动脉斑块内对比剂摄取显著增加（p<0.05）。体内 CNR 测量值与免疫组织化学纤维蛋白密度测量值（y=2.4x+11.3，R(2)=0.82）和 ICP-MS（y=0.95x+7.1，R(2)=0.70）具有良好的一致性。晚期动脉粥样硬化斑块的 CNR、R1、体外纤维蛋白染色和钆浓度增加最强（p<0.05）。
本研究证明了使用 FTCA 进行斑块内和血管内皮纤维蛋白成像的可行性。直接的体内纤维蛋白检测和定量可能有助于冠状动脉和颈动脉粥样硬化病变的特征描述和分期，这可能有助于诊断和干预。
