脑白质高信号静脉源性机制的多模式磁共振研究

White matter hyperintensities (WMHs), also referred to as leukoaraiosis, is associated with an increased risk of stroke, dementia, and mortality. Clinically, WMHs were always paralleled by ischemic change of arteriole. Despite its importance, the pathogenic mechanisms underlying WMHs is so far unclear. Emerging literatures suggest that cerebral venous collagenosis may cause venous ischemia by increasing vascular resistance and compromising interstitial fluid circulation, with consequent vessel leakage and lead to non-necrotic hyperintensities on MRI. The follow-up study also demonstrated that the chronological development of WMH lesions conformed to the drainage pathway of intracranial vein. We thus hypothesize that cerebral venous hypertension and venous outflow insufficiency may play a role in the pathogenesis of WMHs. However, few postmortem studies have addressed it to date, and there are no quantitative in vivo imaging techniques aimed to characterize their possible relationship. We will design to evaluate the association between distribution and volumes of deep medullary vein and WMH lesions, and investigate whether iron deposition and a damaged blood-brain barrier are the possible mechanisms. These findings may provide a new way to prevent the development of WMHs and evaluate the in vivo pathophysiological mechanism of small vessel disease based on neuroimage.

脑白质高信号（WMHs），既往亦称白质疏松，与卒中、老年痴呆和死亡的风险增加密切相关。临床常将WMHs和"小动脉缺血性改变"相等同，但研究发现WMHs与动脉危险因素并无必然联系，单纯动脉病变尚不足以解释WMHs的发病机制。病理证实，WMHs区颅内静脉管壁胶原异常，管壁增厚；而WMHs者随访研究也发现，WMHs进展的规律和颅内静脉的引流特点相符。故此推测，颅内静脉压力增高致静脉流出功能不全，继发血脑屏障破坏，在WMHs的发病中可能起一定作用，但至今尚无活体影像技术阐明该机制。本项目拟通过新兴的多模式磁共振技术评估WMHs病灶分布和体积与颅内髓静脉引流的相关性，并进一步探讨铁异常沉积、血脑屏障破坏在静脉引流障碍致WMHs白质脱髓鞘中的作用机制，以期阐明WMHs发生和进展的静脉源性机制，为进一步防治WMHs提供新思路及良好的评估平台，并从神经影像水平实现脑小血管病的病理生理机制研究。

脑白质高信号（WMHs），既往亦称白质疏松，与卒中、老年痴呆和死亡的风险增加密切相关。临床常将WMHs和“小动脉缺血性改变”相等同，但研究发现WMHs与动脉危险因素并无必然联系，单纯动脉病变尚不足以解释WMHs的发病机制。病理证实，WMHs区颅内静脉管壁胶原异常，管壁增厚；而WMHs者随访研究也发现，WMHs进展的规律和颅内静脉的引流特点相符。故此推测，颅内静脉压力增高致静脉流出功能不全，继发血脑屏障破坏，在WMHs的发病中可能起一定作用，但至今尚无活体影像技术阐明该机制。本项目通过新兴的多模式磁共振技术评估WMHs病灶分布和体积与颅内髓静脉引流的相关性，并进一步探讨铁异常沉积、血脑屏障破坏在静脉引流障碍WMHs白质脱髓鞘中的作用机制，发现颅内静脉引流障碍与WMHs的严重程度及氧合功能相关，颅内铁沉积可能通过破坏髓鞘和血脑屏障从而导致WMHs，为WMHs发生和进展的静脉源性机制提供了活体影像学证据，为进一步防治WMHs提供新思路及良好的评估平台。