OBJECTIVE: To innovatively developed a macrophage-target nanoparticle based contrast-enhanced high-resolution magnetic resonance vessel wall imaging (HR-VWI) strategy to characterize the plaques vulnerable features on rabbits.<break><break> <break><break>BACKGROUND: Lacking of sensitive and specific image-marker of HR-VWI leads this technique depending upon the plaque morphological characteristics. Nanoparticle-based contrast agents modified with targeting ligands allow amplifying MR signals of the interested components. The key to successful translation is the requirement that conducting studies in larger animals to provide reasonable diagnostic readouts.<break><break> <break><break>METHODS: The HR-VWI enhanced with macrophage-targeted PP1-Au@GSH@Gd (GdMG) nanoclusters (NCs) and the conventional Gadovist were utilized for the plaque vulnerability evaluation by a systematic histogram analysis in atherosclerosis (AS) rabbit model.<break><break> <break><break>RESULTS: Due to the compelling targeting capacity of GdMG NCs to foamy macrophages, the contrast-to-noise ratio (CNR) from pre-injection baseline dramatically raised from 6.50 to 36.91 (p<0.001), with an increment of 1.39-fold higher than that of the Gadovist approach. Spearman s correlation test confirmed that the coefficient of variation (CV) derived from the histogram analysis based on GdMG NCs HR-VWI was indeed positively linearly correlated with pathology vulnerability index (VIP) significantly (p < 0.05) with adjusted R2 = 0.775. Finally, mathematic formulas with histogram-derived parameters as variables were fitted to quantitatively calculate the histogram vulnerability index (VIH) with the strength of the adjusted R2 = 0.952 (p<0.001), and Area under the curve (AUC) of 0.875 (p<0.001) to realize the in vivo and quantitative calculation of the plaque vulnerability.<break><break> <break><break>CONCLUSION: Profiting from the splendid inflammation targeted capacity and excellent MRI performance of GdMG NCs, as well as the highly quantitative characteristics of histogram analysis, we disclosed that our established imaging protocol was able to identify the plaques vulnerability index that were comparable to pathological examinations in both retrospective and prospective experiments.

中文翻译：

---

兔纳米团簇致敏血管壁成像剖面对颈动脉斑块易损性的精密预测

目的：创新地开发一种基于巨噬细胞靶向纳米颗粒的对比增强高分辨率磁共振血管壁成像 (HR-VWI) 策略，以表征兔子的斑块易损特征。<break><break> <break><break>背景： HR-VWI 缺乏灵敏和特定的图像标记导致这项技术取决于斑块形态特征。用靶向配体修饰的基于纳米颗粒的造影剂可以放大感兴趣成分的 MR 信号。成功翻译的关键是要求对大型动物进行研究以提供合理的诊断读数。<break><break> <break><break>方法：以巨噬细胞为目标的 PP1-Au@GSH@Gd (GdMG) 纳米团簇 (NCs) 增强的 HR-VWI 和传统的 Gadovist 被用于动脉粥样硬化 (AS) 兔模型的系统直方图分析中的斑块易损性评估。<break> <break> <break><break>结果：由于 GdMG NC 对泡沫巨噬细胞具有令人信服的靶向能力，注射前基线的对比噪声比 (CNR) 从 6.50 显着提高到 36.91 (p<0.001) ，比 Gadovist 方法增加了 1.39 倍。Spearman 相关性检验证实，基于 GdMG NCs HR-VWI 的直方图分析得出的变异系数 (CV) 确实与病理脆弱性指数 (VIP) 显着正线性相关 (p < 0.05)，调整后的 R2 = 0.775。最后，