Abstract: Objective  To investigate the characteristics of brain microstructural changes in patients of cerebral small vessel disease (CSVD) combined with obstructive sleep apnea (OSA) by tract-based spatial statistics (TBSS) based on diffusion tensor imaging (DTI). 
Methods   The study included patients with CSVD who were hospitalized in the Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University from September 2018 to June 2020. Data on demographic information, clinical characteristics, scores of cognitive function assessment scale and sleep quality scale, CSVD routine imaging, DTI, polysomnography (PSG) parameters were collected. According to the apnea hypopnea index (AHI), they were divided into OSA group (AHI≥5) and non-OSA group (AHI<5). The different regions in cerebral white matter between two groups as well as their fractional anisotropy (FA) and mean diffusivity (MD) values were calculated by TBSS. The correlation between MD and PSG parameters, cognitive function scores, CSVD imaging markers, and CSVD burdens were also analyzed. 
Results  A total of 39 CSVD patients were included, of which 7 were excluded due to the lack of MRI data/parameter inconsistency/poor image quality, therefore 32 were eventually included. OSA group included 21 patients with an average age of (64.14±11.57) years old and 18 males (85.7%) while 11 patients without OSA was (67.64±8.95) years old, including 6 males (54.5%). TBSS showed that MD value of OSA group was increased in the bilateral anterior thalamic radiation, bilateral corticospinal tract, bilateral cingulate gyrus, bilateral hippocampus, forceps major and forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral inferior/superior longitudinal fasciculus and bilateral uncinate fasciculus compared with non-OSA group (P<0.001). Bivariate correlation analysis showed that MD increase in OSA group was positively correlated with white matter hyperintensity (WMH) (r=0.646, P<0.05) and Fazekas grade 2 to 3 (r=0.458, P<0.05), and negatively correlated with Montreal cognitive assessment (MoCA) (r=-0.374, P<0.05). There was no significant correlation with mini-mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS-cog), sleep quality assessment scale, AHI, PSG parameters, other CSVD imaging markers and CSVD burdens (P>0.05). 
Conclusions  CSVD patients with OSA have more extensive white matter fiber damage, and extensive brain microstructure damage is closely related to high white matter signal and cognitive dysfunction.

Key words: Cerebral small vessel disease; Obstructive sleep apnea; Diffusion tensor imaging; White matter hyperintensity; Cognitive function

摘要： 目的 采用弥散张量成像（diffusion tensor imaging，DTI）基于纤维束示踪的空间统计分析（tract-based spatial statistics，TBSS）方法探讨脑小血管病（cerebral small vessel disease，CSVD）合并阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）患者的大脑微结构变化特点。
方法 纳入于2018年9月—2020年6月在中山大学附属第一医院神经内科病房住院的CSVD患者，收集人口学信息、临床资料、认知功能评估量表评分、睡眠质量量表评分、CSVD常规影像学资料以及DTI、多导睡眠监测（polysomnography，PSG）参数等。以呼吸暂停低通气指数（apnea hypopnea index，AHI）5次/小时为界，分为OSA组（AHI≥5次/小时）与不伴OSA组（AHI＜5次/小时），通过TBSS方法计算大脑白质存在差异的区域及其各向异性分数（fractional anisotropy，FA）和平均扩散系数（mean diffusivity，MD），并对MD与睡眠监测参数、认知功能评分、CSVD影像标志物和CSVD负荷进行相关性分析。
结果 本研究共纳入CSVD患者39例，其中7例因缺乏MRI数据/参数不一致/图像质量差而被排除，最终纳入32例患者。OSA组21例，平均年龄为（64.14±11.57）岁，男性18例（85.7%）；不伴OSA组11例，平均年龄为（67.64±8.95）岁，男性6例（54.5%）。TBSS分析显示，与不伴OSA组相比，OSA组在双侧丘脑前放射、双侧皮质脊髓束、双侧扣带回、双侧海马、大钳、小钳、双侧额枕下束、双侧上/下纵束、双侧钩束等部位的MD增加（P＜0.001）。双变量相关性分析发现，OSA组MD增加与脑白质高信号相对体积（r=0.646，P＜0.05）和Fazekas 2～3级（r=0.458，P<0.05）呈正相关，与MoCA评分呈负相关（r=-0.374，P＜0.05），与MMSE评分、阿尔茨海默病评估量表-认知亚量表评分、睡眠质量评估量表、AHI、PSG参数、其他CSVD影像标志物及CSVD负荷之间无相关性（P＞0.05）。
结论 CSVD合并OSA患者存在更为广泛的脑白质纤维损害，且大脑微结构广泛损害和脑白质高信号及认知功能障碍密切相关。

关键词: 脑小血管病; 阻塞性睡眠呼吸暂停; 弥散张量成像; 脑白质高信号; 认知功能