CADASIL患者偏头痛发生的多模态脑影像纵向追踪研究

伴有皮质下梗死和白质脑病的常染色体显性遗传性脑动脉病（CADASIL）是因Notch3基因突变导致的遗传性脑小血管病，严重危害人类健康。偏头痛作为其早发症状与腔梗和白质病变的发生密切相关，但其发生机制尚不明确。我们前期初步发现，CADASIL患者偏头痛发生前脑代谢、功能和结构发生了改变。据此我们提出，Notch3突变患者偏头痛发生前和发生后的脑功能和脑结构均可能发生变化。本课题拟采用PET、MRI多模态脑影像融合技术，聚焦CADASIL偏头痛前期患者，探索Notch3突变后偏头痛发生的早期神经变异：通过横向观察及纵向追踪CADASIL患者偏头痛发生前后的关键变异脑区，确定偏头痛发生前后脑功能和脑结构的变异；基于关键脑区和全脑水平观测偏头痛发作期与发作间期的脑功能变化；分析关键脑区影像指标的性别差异及性别对偏头痛发生的调控作用。本研究将为CADASIL的早期预警及其防治提供可借鉴的科学依据。

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease caused by Notch3 gene mutations, which seriously endangers human health. Migraine as its early symptom is closely associated with the incidence of lacunae and white matter lesions. However, little is known about the mechanism underlying migraine onset in CADASIL. Our preliminary study revealed abnormalities in brain metabolism, function and structure before migraine in CADASIL patients. Therefore, we hypothesize that there are brain functional and structural changes in the patients with Notch3 mutations before and after migraine. In this study, we will focus on CADASIL patients during the early stage of migraine by using PET and MRI multimodal brain imaging fusion techniques, and to explore the early neurogenesis of migraine with Notch3 mutations. The key variant brain regions before and after migraine will be investigated by transverse observation and longitudinal tracking, and the brain functional and structural abnormalities before and after migraine will be identified, as well as the brain functional changes during the stage and the interval stage of migraine attack in marker brain regions. Furthermore, the differences based on gender in imaging measures of marker brain regions will be analyzed and the regulation effects of gender on migraine onset will be evaluated. In conclusion, this study will provide the referable scientific evidence for early prediction and prevention in CADASIL patients.