Raman Subha V, Winner Marshall W, Tran Tam, Velayutham Murugesan, Simonetti Orlando P, Baker Peter B, Olesik John, McCarthy Beth, Ferketich Amy K, Zweier Jay L
Davis Heart and Lung Research Institute and Heart Center, The Ohio State University, Columbus, Ohio 43210, USA.
JACC Cardiovasc Imaging. 2008 Jan;1(1):49-57. doi: 10.1016/j.jcmg.2007.09.002.
We investigated the role of iron deposition in atherosclerotic plaque instability using a novel approach of in vivo plaque characterization by a noninvasive, noncontrast magnetic resonance-based T2* measurement. This approach was validated using ex vivo plaque analyses to establish that T2* accurately reflects intraplaque iron composition.
Iron catalyzes free radical production, a key step for lipid peroxidation and atherosclerosis development. The parameter T2* measures tissue magnetic susceptibility, which historically has been used to quantify hepatic and myocardial iron. The T2* measurement has not been used for in vivo plaque characterization in patients with atherosclerosis.
Thirty-nine patients referred for carotid endarterectomy were prospectively enrolled to undergo preoperative carotid magnetic resonance imaging (MRI) and postoperative analysis of the explanted plaque. Clinical history of any symptoms attributable to each carotid lesion was recorded. We could not complete MRI in 4 subjects because of their claustrophobia, and 3 patients scanned before the institution of a neck stabilizer had motion artifact, precluding quantification.
Symptomatic patients had significantly lower plaque T2* values (20.0 +/- 1.8 ms) compared with asymptomatic patients (34.4 +/- 2.7 ms, p < 0.001). Analytical methods demonstrated similar total iron (138.6 +/- 36.5 microg/g vs. 165.8 +/- 48.3 microg/g, p = NS) but less low molecular weight Fe(III) (7.3 +/- 3.8 microg/g vs. 17.7 +/- 4.0 microg/g, p < 0.05) in the explanted plaques of symptomatic versus asymptomatic patients, respectively, which is consistent with a shift in iron from Fe(III) to greater amounts of T2*-shortening forms of iron. Mass spectroscopy also showed significantly lower calcium (37.5 +/- 10.8 mg/g vs. 123.6 +/- 19.3 mg/g, p < 0.01) and greater copper (3.2 +/- 0.5 microg/g vs. 1.7 +/- 0.1 microg/g, p < 0.01) in plaques from symptomatic patients.
In vivo measurement of intraplaque T2* using MRI is feasible and distinguishes symptom-producing from non-symptom-producing plaques in patients with carotid artery atherosclerosis. Symptom-producing plaques demonstrated characteristic changes in iron forms by ex vivo analysis, supporting the dynamic presence of iron in the microenvironment of atherosclerotic plaque.
我们采用基于非侵入性、无对比剂磁共振的T2测量这一新型体内斑块特征分析方法，研究铁沉积在动脉粥样硬化斑块不稳定性中的作用。通过离体斑块分析对该方法进行验证，以确定T2能准确反映斑块内铁成分。
铁催化自由基生成，这是脂质过氧化和动脉粥样硬化发展的关键步骤。T2参数测量组织磁敏感性，历史上一直用于量化肝脏和心肌中的铁。T2测量尚未用于动脉粥样硬化患者的体内斑块特征分析。
前瞻性纳入39例因颈动脉内膜切除术而就诊的患者，术前行颈动脉磁共振成像（MRI）检查，并在术后对切除的斑块进行分析。记录每个颈动脉病变所致任何症状的临床病史。4名受试者因幽闭恐惧症无法完成MRI检查，3名在颈部固定器使用前扫描的患者存在运动伪影，无法进行量化分析。
有症状患者的斑块T2值（20.0±1.8毫秒）显著低于无症状患者（34.4±2.7毫秒，p<0.001）。分析方法显示，有症状患者与无症状患者的离体斑块中总铁含量相似（分别为138.6±36.5微克/克和165.8±48.3微克/克，p=无显著差异），但有症状患者斑块中低分子量Fe(III)含量较少（分别为7.3±3.8微克/克和17.7±4.0微克/克，p<0.05），这与铁从Fe(III)向更多缩短T2形式的铁转变一致。质谱分析还显示，有症状患者斑块中的钙含量显著较低（分别为37.5±10.8毫克/克和123.6±19.3毫克/克，p<0.01），铜含量较高（分别为3.2±0.5微克/克和1.7±0.1微克/克，p<0.01）。
使用MRI对斑块内T2*进行体内测量是可行的，并且能够区分颈动脉粥样硬化患者中产生症状的斑块和不产生症状的斑块。通过离体分析，产生症状的斑块在铁的形式上表现出特征性变化，支持了铁在动脉粥样硬化斑块微环境中的动态存在。
