头颈部动脉斑块负荷及性质影响脑组织代谢及循环机制的多模态MRI评估

Atherosclerosis is a contributor that causes changes in cerebral circulation and metabolism and the final prognosis varies accordingly. Current studies on high resolution vessel wall MR imaging of plaque were limited to extracranial common carotid artery, internal carotid artery or intracranial artery alone and lacked overall plaque evaluation along arterial trajectory, thus the relationship between plaque and cerebral metabolism and circulation remains unclear. Therefore, in this study, high-fat-fed and balloon-injured rabbit models are used to explore correlation between imaging features and pathology of unstable plaque in carotid and intracranial arteries together, and impact of plaque on cerebral circulation and metabolism. Multi-modal head and neck combined vessel wall MR imaging and imaging of brain tissue are acquired to assess the overall plaque burden and vulnerability in the common carotid artery, internal carotid artery and intracranial artery, and to explore their impact on collateral circulation grading, cerebral metabolism and circulation in patients with ischemic stroke, therefore search for the imaging features affecting severity and prognosis of stroke. MRI imaging features based on animal trial and ischemic stroke patients are also collected for asymptomatic patients with high risk and normal volunteers. A 2-year follow-up or stroke onset is regarded as observation endpoint to help identify sensitive imaging indicators and to determine patients who need drug intervention. By advancing the treatment to stroke prevention stage, this study can be of great value.

动脉粥样硬化可引起脑组织循环和代谢的变化，并影响最终预后。目前高分辨血管壁MR成像只局限于颅外颈总动脉、颈内动脉或者颅内动脉单一部位斑块的研究，缺乏颈动脉整体路径上斑块的负荷研究，并且斑块与脑组织代谢和循环的关系还需进一步证实。本研究采用兔高脂喂养和球囊损伤模型，分析颈动脉和颅内动脉整体路径上不稳定斑块的MR影像特征与病理学的相关性及其对脑组织循环和代谢的影响。采集缺血性脑卒中病人头颈部动脉及脑组织的多模态MRI数据，探究颈总动脉、颈内动脉及颅内动脉整体斑块的负荷和不稳定性对病人侧支循环分级、脑组织代谢和循环的影响，寻找影响卒中严重程度及预后的影像学指标。根据动物和卒中病人不稳定斑块的影像学特征，对无症状高风险及正常志愿者前瞻性地判断斑块不稳定性，以2年随访或脑卒中发作作为观察指标，找出药物干预的敏感性影像学指标，预警脑卒中的发生。该研究将脑卒中治疗阶段提前到预防阶段，具有非常重大的价值。

1. 研究立项背景：.颅内动脉粥样硬化性疾病导致的缺血性脑卒中在中国占较高比例，易损斑块是导致卒中发生的主要病因，易损斑块的检出和判定主要依赖于病理学。随着影像技术的发展，高分辨率血管壁成像（High-resolution Vessel Wall Imaging, HR-VWI）已应用于临床检出不稳定斑块。但是既往研究多关注于颈部斑块，对颅内斑块的特征研究较少，且缺乏病理验证。此外，动脉粥样硬化病变对颅内代谢及循环的关系还需要进一步研究。..2. 研究目的：.通过动物实验明确颅内外动脉不稳定斑块的病理学表现与影像学特征的关系；定量不稳定斑块，以评估其对血流东动力学、侧支及代谢的影响；对高危人群的斑块进行定量分析，预测卒中发生。..3. 研究内容及研究方法：.（1）建立动脉粥样硬化动物模型，找出反映不稳定斑块病理特征的影像学参数；（2）评价斑块的影像学特征，探究其与上游血流动力学、侧支循环、脑组织代谢状态等的关系，找出影响脑组织不可逆梗死的斑块特征及其他指标；（3）探究高危人群的斑块特征，并随访观察斑块变化，获得预测卒中发生的临床及影像学因素。..4. 重要结果及关键数据：.（1）联合HR-VWI及巨噬细胞特异性靶向对比剂发现靶向增强磁共振成像测量斑块检出数量、血管壁面积、斑块面积的变化趋势更敏感。（2）利用STAGE-MRA测量软脑膜侧支，图像质量、信噪比及测量数量均优于TOF-MRA，大脑中动脉M1-2段不同的斑块特征（如动脉重塑比率及管壁标准指数）是预测软脑膜侧支数量的独立预测因子。利用STAGE-QSM测量不对称皮质静脉体积所得的体积对判断缺血半暗带有较高的诊断效能。（3）卒中高危人群豆纹动脉的数量及长度随着相对于正常志愿者减少，数值减低，高危人群年龄的增长会引起基底节区腔梗灶数量增多。..5. 科学意义：.基于动物实验探索HR-VWI的影像学表现与病理表现的关系，证实其评估不稳定斑块的可行性，利用HR-VWI探究动脉粥样硬化病变对脑组织代谢、下游血流动力学及侧支循环的影响，以期为临床提供可视化的诊断依据，找到潜在治疗靶点，预防卒中发生，减轻患者、社会及国家的负担。