动态增强MRI技术评价动脉粥样斑块的实验研究

Dynamic contrast-enhanced MRI examination of atherosclerotic plaques： an animal study using rabbit model

目的利用动态增强MRI探讨动脉粥样斑块Gd—DTPA强化的特点和强化机制。方法12只新西兰大白兔，通过高脂饮食联合内膜剥脱术在腹主动脉建立斑块模型。术后10—16周行动态增强MRI扫描。以71s为间隔获得35帧T1WI1并在第3次扫描开始的同时静脉注射Gd—DTPA。扫描结束后12h内取动脉斑块行HE和CD31免疫组织化学染色，计数新生血管。在MRI上测量斑块的时间-信号强度曲线，计算曲线的描述性参数，和新生血管计数进行Pearson相关性分析。以组织病理检查结果为参照，分析斑块强化特点。结果静脉注射Gd-DTPA后，动脉斑块明显强化，呈现“快进慢出”的特点。斑块内部强化程度不均匀，纤维成分强化较强，脂质和炎细胞聚集灶强化较弱。新生血管计数（117．7±93．3）和时间一信号强度曲线得到的峰值（1．05±0．30）、初始斜率（0．82±0．28）和7min曲线下面积（4．97±1．67）有显著正相关，相关系数r分别为：0．553（P〈0．01）、0．468（P〈0．05）、0．554（P〈0．01）。结论动脉粥样硬化斑块呈“快进慢出”的强化特点。新生血管生成、内膜通透性增加及细胞外基质增多可能是斑块被Gd—DTPA强化的原因。DEC—MRI定量分析斑块新生血管密度有一定的可行性。

Objective The enhanced patterns of atherosclerotic plaque on dynamic contrast- enhanced MRI have not been well studied. The aim of this study was to explore the patterns of plaque enhancement and their underlying mechanism by using dynamic contrast-enhanced MRI （DCE-MRI）. Methods Atherosclerotic plaques were induced in the aorta of 12 New Zealand White rabbits by a combination of endothelial denudation and high-cholesterol diet. Ten to sixteen weeks after surgery, DCE- MRI was performed with a fast spin echo T1 weighted sequence. Thirty-five phases of images were obtained at 71-second intervals. Gd-DTPA was injected coincident with the third scan via marginal ear vein. Specimens were harvested within 12 hours after imaging for HE staining and CD31 immunohistochemieal staining which was used to highlight neo-vessels. Plaque enhancement patterns were studied and compared with histological findings. Signal intensity of each plaque section was normalized to pre-contrast signal intensity of psoas muscle, after which signal intensity versus time curve was drawn. Pearson correlation coefficient was used to reveal association between histological neo-vessel count and descriptive parameters derived from signal intensity versus time curve. Results Plaques were significantly enhanced by Gd-DTPA. Enhancement patterns could be described as ＂fast-in and slow-out＂. Differences in patterns of enhancement were observed between tissues, with fibrous tissue enhanced more than lipid aggregation and leukocyte loci. Peak enhancement（ 1.05 ±0. 30）, initial slope（0. 82 ± 0. 28 ） and area under the curve at early phase（4. 97± 1.67） derived from signal intensity-time curve had significant correlations with neo-vessel count（ 117.7 ± 93.3） （r =0.553,0.468,0.554 respectively, P 〈0.05）. Conclusions The enhanced patterns of atherosclerotic plaque by Gd-DTPA were ＂fast- in and slow-out＂. Neovascularization, increased endothelial permeability and extracellular matrix may be the reasons for plaque enhancement by Gd-DTPA. DCE-MRI has the potential to quantify the extent of neo-vasculature formation within plaques.