自主动脉弓至颅内颈动脉全景非增强血管造影与管壁粥样硬化易损斑块同时成像的磁共振序列研发与应用研究

Stroke has become the first cause of death in China. The disruption of atherosclerotic vulnerable plaque with subsequent thromboembli at upstream vascular beds of brain, such as intracranial and extracranial carotid arteries, and aortic arch is believed to be major etiology for ischemic stroke. Currently, measuring luminal stenosis by various angiographic approaches is still the major strategy for assessment of the severity of atherosclerotic disease. However, a number of recent studies have shown that more than 20% of symptomatic carotid arteries with lower grade stenosis developed vulnerable plaques. As such, to direct image the vulnerable plaques at arterial vessel wall is strongly suggested. There are no appropriate imaging techniques developed for plaque imaging of intracranial carotid artery and aortic arch, except for extracranial carotid arteries. This study sought to develop a new MR imaging sequence to simultaneously obtain the non-contrast angiography and intraplaque hemorrhage imaging for the upstream arterial territories (from aortic arch to intracranial carotid artery). This imaging sequence is based on a most recent imaging technique "Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) imaging" which is developed by our group. In this study, by using the new developed imaging technique and a new designed and optimized 36-channel neurovascular coil by our group, we plan to investigate the prevalence of vulnerable plaques at the upstream vascular beds of brain. The relationship of vulnerable plaques at these vascular beds with cerebral ischemic lesions will be also evaluated. By doing this study, a 'one-stop shop' imaging protocol to detect the culprit lesions of patients with ischemic stroke will be established. To acquire the information of plaque vulnerability at these vascular beds by utilizing the new developed imaging technique will be helpful to guide the therapy and prevent the recurrence of future cerebrovascular events.

脑卒中是国人第一位致死性疾病。颅内、外颈动脉、主动脉弓的管壁粥样硬化(AS)易损斑块破裂引发的血栓栓塞是缺血性卒中的主要致病因素。目前临床上仍以测定管腔狭窄程度来评价AS病变的严重性。然而近来研究显示，约有20%以上轻度狭窄的颈动脉存在AS易损斑块。因此，有必要对动脉管壁进行直接成像来评价AS斑块的稳定性。然而，除颅外颈动脉外，目前还没有可靠的成像技术识别颅内颈动脉和主动脉弓管壁易损斑块。本研究将以最新MR成像技术(SNAP)为基础，拟开发一种只需一次采集即可同时进行非增强MRA和管壁易损斑块(斑块内出血)成像的快速、高分辨率MR成像序列，应用本研究组设计的新型36通道神经血管线圈，对缺血性卒中患者脑组织上游血管(自主动脉弓至颅内颈动脉）全景进行成像，探索易损斑块的分布规律及其与脑缺血灶的相关性。本研究将为缺血性卒中责任病变的诊断提供一站式MR成像方法，从而有效指导临床治疗，降低复发风险。

本课题的主要研究内容包括：（1）优化3D磁共振管壁成像序列，包括MERGE、T2-VISTA和SNAP，实现颅内、外动脉和主动脉弓管壁的快速、大范围、一站式成像；（2）优化并改进本研究组自主研发的36 通道神经血管线圈，以提高其在快速、大范围、高分辨率动脉管壁成像时的信噪比；3）应用上述新开发的磁共振序列和线圈，对缺血性卒中患者和社区无症状老年人的颅内动脉、颅外颈动脉和主动脉弓管壁进行成像研究，探索易损斑块的分布规律及其与卒中风险的相关性。..本项目执行期间，课题组严格按照课题任务书中的研究计划开展研究，最终顺利完成课题各项任务，研究结果主要体现在如下方面：（1）成功优化了3D MERGE、T2-VISTA和SNAP磁共振成像序列和神经血管线圈，最终实现了颅内、外动脉管壁大范围一站式成像和主动脉弓管壁成像，并获得了各向同性高空间分辨率（0.8mm）和良好的图像信噪比和可重复性；（2）应用优化的磁共振成像技术开展的临床研究发现：（a）缺血性卒中患者的颅内外并存斑块的发生率高达77.6%；（b）颅内外并存斑块的数目是卒中复发风险的独立预测指标（OR=3.31; 95% CI, 1.09-10.08; p=0.035）；（c）缺血性卒中患者中，颅外颈动脉易损斑块的发生率最高（27.3%），其次是颅内动脉（20%），再次为主动脉弓（3.6%）。..本课题的总体研究成果已明显超出了预期目标，预算执行合理。根据研究结果，课题组共发表了SCI收录的学术论文12篇，总影响因子达47.325，其中影响因子>5的学术论文3篇，在中文核心期刊发表论文6篇。本课题研发的磁共振成像技术现已被推广应用于5项多中心人群队列和药物试验研究中，优化设计的线圈已申请发明专利一项，并已成功转化为产品即将上市。本课题共培养研究生6名，联合培养研究生10名，其中课题组成员周赜辰获得了清华大学优秀博士论文，吴婷婷获得了北京市优秀毕业生。本研究成果为缺血性卒中责任斑块的临床精准诊断和预后评估提供了快速有效的成像工具，并具有广阔的临床推广和产品转化前景。