【作者】 张向前；

【导师】 陆兵勋； 李涛平；

【作者基本信息】 南方医科大学 ， 神经病学， 2009， 博士

【摘要】 近年,阻塞性睡眠呼吸暂停低通气综合征（OSAHS）因其与缺血性卒中的相关性受到神经科医生越来越多的关注。已有研究显示OSAHS患者存在认知功能障碍,但关于OSAHS白质病变的报道极少。本研究的出发点是通过弥散张量成像（DTI）方法显示OSAHS可能存在的脑白质微细结构损害及其与认知功能障碍的相关性,并对腔隙性脑梗死（LI）和多发性硬化（MS）脑白质形似正常区微细结构损害进行研究。本研究分为四部分:一、正常成人脑白质微细结构DTI研究;二、阻塞性睡眠呼吸暂停低通气综合征（OSAHS）脑白质微细结构损害与认知功能障碍DTI研究;三、腔隙性脑梗死（LI）脑白质形似正常区微细结构损害DTI研究;四、复发-缓解型多发性硬化（MS）脑白质形似正常区微细结构损害DTI研究。一、正常成人脑白质微细结构DTI研究1.1研究目的通过磁共振弥散张量成像（DTI）方法,研究和探讨正常人脑白质微细结构特点。1.2研究方法运用DTI测定脑部各感兴趣区（ROI）部分各向异性（FA）和表观弥散系数（ADC）,并进行胼胝体纤维成像。统计分析由SPSS 13.0统计软件包完成,其中计量资料用（?）±SD表示,两组间比较采用配对样本t检验,以P＜0.05为差异有统计学意义。1.3研究结果1.3.1双侧大脑半球相同解剖部位的FA值双侧大脑半球相同解剖部位的FA值逐一比较,均无显著差异（P＞0.05）:双侧大脑半球相同解剖部位的ADC值逐一比较,亦无显著差异（P＞0.05）。1.3.2灰质和白质的FA值及ADC值大脑半球的灰质结构（如海马旁回、前部扣带回）以及以灰质团块为主要成分的结构（尾状核头、丘脑）的FA值显著低于白质结构。1.3.3大脑半球各解剖部位的FA值排序FA值由高到低排序依次为:胼胝体压部、胼胝体膝部、胼胝体干、右侧内囊后肢、左侧内囊后肢、左侧内囊膝部、右侧内囊膝部、右侧视放射、左侧半卵圆中心、左侧视放射、右侧半卵圆中心、右侧内囊前肢、左侧内囊前肢、左侧前部扣带、右侧前部扣带、右侧前角周围白质、右侧外囊、左侧前角周围白质、左侧外囊、左侧额叶白质、右侧额叶白质、右侧后角周围白质、左侧后角周围白质、右侧丘脑、左侧丘脑、右侧前部扣带回、右侧海马旁回、左侧尾状核头、左侧海马旁回、左侧前部扣带回、右侧尾状核头。从白质纤维的走行方向看,连合纤维的各向异性程度最高,其次为投射纤维,再次为联络纤维,灰质或以灰质团块为主要成分的结构FA值最低。1.4研究结论（1）尽管正常成人大脑的双侧半球间存在诸如语言等的功能上的不对称,但是大脑双侧半球相应部位的FA值差异无统计学意义,说明正常成人双侧大脑半球白质纤维排列的紧密程度基本一致。（2）正常成人脑内不同组织及解剖部位的弥散各向异性程度不同,脑白质的弥散各向异性远大于脑灰质。（3）正常成人脑白质的不同解剖部位,其各向异性也不相同,脑白质连合纤维的各向异性程度最高,其次为投射纤维,再次为联络纤维。二、阻塞性睡眠呼吸暂停低通气综合征（OSAHS）脑白质微细结构损害与认知功能障碍DTI研究2.1研究目的研究OSAHS可能存在的白质损害、认知障碍及睡眠结构,并分析三者之间的关系。2.2研究方法运用DTI技术,测定脑部各感兴趣区（ROI）FA值和ADC值,并进行胼胝体纤维成像;检测MMSE、修订韦氏记忆量表（WMS-RC）得分;应用多导睡眠图（PSG）进行睡眠监测。统计分析由SPSS13.0统计软件包完成,其中计量资料用（?）±SD表示,两组间比较采用独立样本t检验,相关性分析采用Partial偏相关分析,以P＜0.05为差异具有统计学意义。2.3研究结果2.3.1 OSAHS脑部各解剖结构的FA值OSAHS组多个脑部解剖结构FA值降低,与对照组存在显著差异:右侧额叶白质（t＝2.367,P＝0.029）、胼胝体压部（t＝2.118,P＝0.048）、左侧前部扣带回（t＝6.127,P＝0.000）、右侧前部扣带回（t＝5.673,P＝0.000）、左侧前部扣带（t＝7.067,P＝0.000）、右侧前部扣带（t＝9.934,P＝0.000）、左侧半卵圆中心（t＝4.320,P＝0.000）、左侧前角周围白质（t＝2.778,P＝0.012）、右侧前角周围白质（t＝2.316,P＝0.033）、左侧后角周围白质（t＝6.012,P＝0.000）、右侧后角周围白质（t＝7.256,P＝0.000）、左侧海马旁回（t＝4.055,P＝0.001）、右侧海马旁回（t＝4.134,P＝0.001）、左侧外囊（t＝2.619,P＝0.017）、右侧外囊（t=2.548,P=0.020）。而左侧额叶白质、胼胝体膝部、胼胝体干、双侧内囊前肢、双侧内囊膝部、双侧内囊后肢、双侧视放射、右侧半卵圆中心、双侧尾状核头、双侧丘脑的FA值与对照组无显著差异（P>0.05）。2.3.2 OSAHS脑部各解剖结构的ADC值OSAHS脑部部分解剖结构ADC值升高,与对照组存在显著差异:右侧额叶白质（t=-2.793,P=0.012）、胼胝体干（t=-2.741,P=0.013）、胼胝体压部（t=-4.871,P=0.000）、左侧前部扣带回（t=-15.359,P=0.000）、右侧前部扣带回（t=-14.452,P=0.000）、右侧前部扣带（t=-2.863,P=0.010）、左侧半卵圆中心（t=-2.263,P=0.036）、左侧前角周围白质（t=-2.291,P=0.034）。左侧额叶白质、胼胝体膝部、左侧前部扣带、双侧内囊前肢、双侧内囊膝部、双侧内囊后肢、右侧半卵圆中心、双侧视放射、右侧前角周围白质、双侧后角周围白质、双侧丘脑、双侧尾状核头、双侧海马旁回、双侧外囊的ADC值则与对照组无显著差异（P>0.05）。2.3.3 OSAHS胼胝体纤维束成像运用纤维束成像方法（DTT）进行胼胝体成像,可见胼胝体嘴、膝、体部（干）、压部、额钳和枕钳纤维排列紧密,粗细均匀,走行一致,结构完整,未见变细、断裂现象。与健康对照组相比较,肉眼观察未见胼胝体纤维受损。2.3.4 OSAHS患者睡眠结构分析2.3.4.1 OSAHS患者基本资料及PSG参数对比OSAHS组与正常对照组的基本资料发现:OSAHS组体重指数（BMI）、收缩压（SBP）、舒张压（DBP）显著升高（t=-3.424,P=0.003;t=-2.441,P=0.025;t=-2.952,P =0.009）。分析两组PSG参数发现,其中Ⅰ期占总睡眠时间的比例显著升高,Ⅲ期+Ⅳ期占总睡眠时间的比例显著降低,AHI显著高于正常人,夜间平均动脉血氧饱和度（SaO₂）、最低SaO₂均显著低于正常人,差异具有统计学意义（t=-4.827,P=0.000;t=3.052,P=0.004;t=-5.185,P=0.000;t=4.028,P=0.001;t=6.243,P=0.000）。2.3.4.2 OSAHS睡眠结构与脑白质损害的关系将OSAHS组与正常对照组存在显著差异的PSG参数——Ⅰ期占总睡眠时间的比例、Ⅲ期+Ⅳ期总睡眠时间的比例、AHI、平均SaO₂、最低SaO₂,与OSAHS和正常人比较存在显著差异的脑白质的FA值进行偏相关性分析,结果显示:Ⅲ期+Ⅳ期总睡眠时间的比例与右侧前部扣带FA值显著正相关（r＝0.711,P＝0.002）,与右侧后角周围白质FA值显著正相关（r＝0.504,P＝0.015）。AHI与右侧前部扣带FA值显著负相关（r＝-0.637,P＝0.029）。2.3.5 OSAHS认知功能分析2.3.5.1 OSAHS记忆功能及与脑白质损害的关系OSAHS组修订韦氏记忆量表（WMS-RC）记忆商（MQ）及分测验得分:OSAHS组MQ为97.10±10.89,显著低于正常对照组MQ105.20±2.15（t＝2.318,P＝0.026）;图片回忆（t＝2.376,P＝0.023）、再认（t＝2.195,P＝0.034）、视觉再生（t＝2.828,P＝0.007）、背诵数目（t＝3.077,P＝0.004）等4个分测验得分也显著低于正常对照组。将OSAHS组WMS-RC得分中与正常对照组有显著差异的得分——图片回忆、再认、视觉再生、背诵数目、记忆商得分,与OSAHS和正常人比较存在显著差异的脑白质FA值进行偏相关性分析,结果显示:图片回忆得分与右侧后角周围白质FA值呈显著正相关（r＝0.741,P＝0.036）,视觉再生得分与右侧额叶白质FA值正相关（r＝0.562,P＝0.017）,记忆商与右侧额叶白质FA值正相关（r＝0.450,P＝0.030）。2.3.5.2 OSAHS认知功能OSAHS组MMSE平均得分29.47±0.94,显著低于正常对照组得分29.89±0.32（t＝2.484,P＝0.016）;注意计算分测验平均得分4.80±0.41,低于正常对照组得分4.97±0.17,差异显著（t＝2.241,P＝0.029）;时间定向、语言即刻记忆、短时记忆、图形描画平均得分与对照组无统计学差异（t＝1.911,P＝0.061;t＝0.987,P＝0.327;t＝1.415,P＝0.162;t＝0.763,P＝0.448）;地点定向、物体命名、语言复述、阅读理解、语言理解、读写能力得分无变化。2.4研究结论（1）国内首次发OSAHS病人脑白质微细结构广泛受损,联络纤维、连合纤维和投射纤维同时受累。（2）国内首次发现OSAHS病人双侧前部扣带回和海马旁回等与认知功能有关的灰质区域微细结构也同时受累。（3）DTI作为唯一能在活体上无创显示神经纤维完整性和方向性的影像学方法,能够早期发现并定量显示脑白质的微细结构损害。（4）对于显示脑白质的微细结构损害,FA值较ADC值更敏感。（5）OSAHS患者睡眠结构紊乱,浅睡眠显著增多,深睡眠显著减少。（6）OSAHS患者睡眠结构紊乱程度与脑白质受损程度存在相关关系,Ⅲ期+Ⅳ期总睡眠时间的比例越小,与认知功能有关的脑白质受损越严重。（7）OSAHS患者总体认知水平降低,注意与计算力受损。（8）OSAHS患者记忆力降低,短时记忆显著受损。（9）OSAHS患者总体记忆水平及短时记忆受损程度,与右侧额叶白质、右侧后角周围脑白质受损程度呈正相关。三、腔隙性脑梗死（LI）脑白质形似正常区微细结构损害DTI研究3.1研究目的研究LI脑部“形似正常区”可能存在的白质损害及程度。3.2研究方法同实验一。3.3研究结果3.3.1 LI组与正常对照组脑部各解剖结构的FA值比较LI组多个解剖结构FA值降低,与对照组存在显著差异:左侧额叶白质（t＝2.857,P＝0.007）、右侧额叶白质（t＝2.604,P＝0.013）、胼胝体膝部（t＝3.177,P＝0.003）、左侧前部扣带（t＝2.198,P＝0.034）、右侧前部扣带（t＝2.495,P＝0.017）、左侧内囊前肢（t＝5.483,P＝0.000）、右侧内囊前肢（t＝4.619,P＝0.000）、左侧内囊膝部（t＝3.601,P＝0.001）、右侧内囊膝部（t＝2.907,P＝0.006）、左侧内囊后肢（t＝3.243,P＝0.002）、右侧内囊后肢（t＝2.359,P＝0.023）、左侧半卵圆中心（t＝3.167,P＝0.003）、右侧半卵圆中心（t＝2.369,P＝0.023）、左侧视放射（t＝3.167,P＝0.003）、右侧视放射（t＝4.220,P＝0.000）、左侧前角周围白质（t＝3.012,P＝0.004）、右侧前角周围白质（t＝2.112,P＝0.041）、左侧后角周围白质（t＝2.193,P＝0.034）、左侧海马旁回（t＝2.347,P＝0.024）、右侧海马旁回（t＝2.103,P＝0.042）、右侧外囊（t＝3.006,P＝0.005）。胼胝体干、胼胝体压部、双侧前部扣带回、右侧后角周围白质、双侧丘脑、双侧尾状核头、左侧外囊的FA值与对照组无显著差异（P＞0.05）。3.3.2 LI组与正常对照组脑部各解剖结构的ADC值比较与对照组相比较,LI组脑部部分解剖结构ADC值显著升高,差异有统计学意义:胼胝体干（t＝-3.272,P＝0.002）、胼胝体压部（t＝-2.413,P＝0.021）、左侧内囊前肢（t＝-3.059,P＝0.004）、右侧内囊前肢（t＝-3.831,P＝0.000）、右侧内囊膝部（t＝-2.530,P＝0.015）、左侧内囊后肢（t＝-3.047,P＝0.004）、右侧内囊后肢（t＝-2.634,P＝0.012）、左侧半卵圆中心（t＝-2.819,P＝0.007）、左侧后角周围白质（t＝-2.075,P＝0.044）、左侧海马旁回（t＝-2.496,P＝0.017）。双侧额叶白质、胼胝体膝部、双侧前部扣带回、双侧前部扣带、右侧半卵圆中心、双侧视放射、双侧前角周围白质、右侧后角周围白质、双侧丘脑、双侧尾状核头、右侧海马旁回、双侧外囊的ADC值则与对照组无显著差异（P＞0.05）。3.3.3 LI胼胝体纤维束成像胼胝体成像显示:与正常成人胼胝体成像相比,胼胝体额钳及膝部纤维排列稀疏,干、压部纤维变细,有断裂、扭曲现象。3.4研究结论（1）LI常规MRI显示的“形似正常区”DTI可检测到广泛异常,提示白质早期已存在广泛微细结构损害。（2） LI实际存在的白质微细结构损害区域远大于常规MRI所显示的病灶区域。（3） LI双侧海马旁回“形似正常区”显著受损,为LI患者出现的认知功能障碍尤其是记忆功能障碍提供了解剖学基础。（4） LI胼胝体纤维束成像显示胼胝体纤维排列稀疏,纤维变细、断裂、扭曲,说明LI胼胝体纤维受损显著。四、复发-缓解型多发性硬化（MS）脑白质形似正常区微细结构损害DTI研究4.1研究目的研究复发-缓解型MS脑部“形似正常区”可能存在的白质损害及程度。4.2研究方法同实验三。4.3研究结果4.3.1 MS组与正常对照组脑部各解剖结构的FA值比较MS组脑部部分解剖结构FA值降低,与正常对照组存在显著差异:左侧额叶白质（t=3.638,P=0.002）、右侧额叶白质（t=3.181,P=0.005）、左侧前部扣带（t=2.471,P=0.023）、右侧前部扣带（t=3.434,P=0.003）、左侧半卵圆中心（t=3.273,P=0.004）、右侧半卵圆中心（t=2.201,P=0.040）、左侧视放射（t=2.281,P=0.034）、右侧视放射（t=3.380,P=0.003）、左侧前角周围白质（t=4.905,P=0.000）、右侧前角周围白质（t=3.674,P=0.002）、左侧后角周围白质（t=2.636,P=0.016）、右侧后角周围白质（t=4.714,P=0.000）、左侧丘脑（t=2.325,P=0.031）、右侧丘脑（t=2.398,P=0.026）、右侧海马旁回（t=2.660,P=0.015）。而胼胝体膝部、胼胝体干、胼胝体压部、双侧前部扣带回、双侧内囊前肢、双侧内囊膝部、双侧内囊后肢、双侧尾状核头部、左侧海马旁回、双侧外囊的FA值与对照组无显著差异（P>0.05）。4.3.2 MS组与正常对照组脑部各解剖结构的ADC值比较MS组脑部部分解剖结构形似正常区ADC值升高,右侧额叶白质（t＝-3.797,P＝0.001）、胼胝体膝部（t＝-2.688,P＝-0.014）、胼胝体干（t＝-4.547,P＝0.000）、胼胝体压部（t＝-3.211,P＝0.004）、左侧半卵圆中心（t＝-4.044,P＝0.001）、右侧半卵圆中心（t＝-4.461,P＝0.000）、左侧后角周围白质（t＝-4.487,P＝0.000）、右侧后角周围白质（t＝-2.652,P＝0.015）、左侧海马旁回（t＝-2.548,P＝0.019）、右侧海马旁回（t＝-2.269,P＝0.034）与对照组存在显著差异。左侧额叶白质、双侧前部扣带回、双侧前部扣带、双侧内囊前肢、双侧内囊膝部、双侧内囊后肢、双侧视反射、双侧前角周围白质、双侧丘脑、双侧尾状核头、双侧外囊的ADC值则与对照组无显著差异（P＞0.05）。4.3.3 MS胼胝体纤维束成像与正常对照组相比,MS胼胝体纤维排列稀疏,走行紊乱,纤维间隙扩大,体部纤维有中断现象。4.4研究结论（1）复发-缓解型MS脑部与认知功能有关的“形似正常白质区”存在常规MRI难以发现的广泛白质微细结构损害,受损区域包括双侧脑室前角周围白质、后角周围白质、额叶白质、半卵圆中心、胼胝体、双侧前部扣带,以双侧脑室前、后角周围白质尤为显著。（2）复发-缓解型MS脑部与记忆有关的“形似正常灰质区”存在常规MRI难以显示的微细结构损害,丘脑、海马旁回细胞的完整性均受到破坏,其中海马旁回损害尤为显著。（3）胼胝体纤维束成像显示MS胼胝体纤维排列稀疏,走行紊乱,纤维间隙扩大,体部纤维有中断现象,表明MS胼胝体纤维受损显著。总结1.正常成人双侧半球白质纤维排列的紧密程度基本一致。2.正常成人脑内不同解剖部位的各向异性程度不同。3.发现OSAHS脑白质微细结构广泛受损,联络纤维、连合纤维和投射纤维同时受累。4.发现OSAHS与认知功能有关的灰质区双侧同时受累。5.FA值较ADC值对于脑白质微细结构损害更敏感。6.OSAHS睡眠结构紊乱与脑白质受损相关,深睡眠越少或OSAHS程度越重,与认知功能有关的白质受损越重。7.OSAHS总体认知水平降低,注意力与计算力受损;OSAHS记忆力降低,短时记忆受损;OSAHS总体记忆水平及短时记忆受损程度,与右侧额叶白质、右侧后角周围白质受损程度正相关。8.LI形似正常白质区有常规MRI未见的广泛微细结构损害。9.LI双侧海马旁回形似正常区显著受损,是LI记忆功能障碍的解剖学基础。10.胼胝体纤维束成像显示LI胼胝体纤维显著受损。11.RRMS与认知相关的形似正常白质区有常规MRI未见的广泛微细结构损害。12.DTI可早期发现RRMS的视觉通路异常。13.RRMS胼胝体纤维轴突膜和髓鞘的破坏程度大于轴突丧失或破裂程度。14.RRMS脑部与记忆有关的形似正常灰质区存在常规MRI未见的损害。15.胼胝体纤维束成像显示RRMS胼胝体纤维广泛受损。创新点1.运用DTI方法研究OSAHS脑白质损害,并发现OSAHS脑白质微细结构广泛受损,与认知功能有关的灰质区域同时受累。2.发现LI形似正常白质区有常规MRI未见的广泛微细结构损害。3.发现DTI可早期识别RRMS的视觉通路异常。更多还原

【Abstract】 In the recent years,the neurologist paid more attention to obstructive sleep apnea-hypopnea syndrome(OSAHS),which proved to be correlative with ischemic stroke.Some studies showed that the patients with OSAHS had cognitive deficit. However,there was few evidences for white matter microstructural lesions in OSAHS. In this study,we try to determine whether OSAHS has white matter microstructural lesions by MR diffusion tensor imaging(DTI),where they are,and whether they correlate with cognitive disfunction.Also,we will detect microstructural lesions in normal-appearing white matter(NAWM) both in patients with lacunar infarction(LI) and in patients with multiple sclerosis(MS).This thesis consists of four parts:the features of brain microstructure in healthy adults,the correlation between white matter microstructural lesions and cognitive disfunction in patients with OSAHS,microstructural lesions in NAWM in patients with LI,and microstructural lesions in NAWM in patients with relapsing-remitting MS.Chapter 1 The features of brain microstructure in healthy adults by DTIOBJECTIVES:To investigate the features of brain microstructure in healthy adults by DTI.METHODS:Fractional anisotropy(FA) and apparent diffusion coefficient(ADC) values was examined in regions of interest(ROI) respectively,and then diffusion tensor tractography(DTT) of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation ((?)±SD).Paired-samples t test was applied when comparing paired samples.As usual,it was thought to have statistical significance when P<0.05.RESULTS:No significant differences were found in FA values in each ROI from bilateral brain(P>0.05).So was ADC values(P>0.05).Compared with gray matter including parahippocampal gyrus and anterior cingulate gyrus,white matter had higher FA values,such as white matter of left frontal lobe,corpus callosum,anterior cingulum and so on.According to FA values,ROI was sequenced one by one.The highest was splenium of corpus callosum,following genu of corpus callosum,trunk of corpus callosum,right posterior limb of internal capsule,left posterior limb of internal capsule,left genu of internal capsule,right genu of internal capsule,right optic radiation,left centrum semiovale,left optic radiation,right centrum semiovale,right anterior limb of internal capsule,left anterior limb of internal capsule,left anterior cingulum,right anterior cingulum,peripheric white matter of right anterior angle,right external capsule,peripheric white matter of left anterior angle,left external capsule, white matter of left frontal lobe,white matter of right frontal lobe,peripheric white matter of right posterior angle,peripheric white matter of left posterior angle,right thalamus,left thalamus,right anterior cingulate gyrus,right parahippocampal gyrus, left head of caudate nucleus,left parahippocampal gyrus,left anterior cingulate gyrus, and the lowest was right head of caudate nucleus.CONCLUSIONS:Firstly,no significant differences were found in FA values in bilateral brain,which indicated that the density of white matter fibers were also unanimous.Secondly,Anisotropy varied in each brain structure,generally white matter had remarkable higher anisotropy compared with gray matter.Finally,there was different anisotropy in three types nerve fibres:commissural fibers had the highest anisotropy,the following were projection fibers,and internuncial fibers were the lowest.Chapter 2 The relationship between white matter microstructural lesions by DTI and cognitive disfunction in patients with OSAHSOBJECTIVES:To investigate whether OSAHS has white matter microstructural lesions and unstuck sleep architecture,where are white matter microstructural lesions by DTI,and whether white matter microstructural lesions or unstuck sleep architecture correlate with cognitive disfunction.METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.Moreover,MMSE and WMS values were recorded respectively before polysomnogram(PSG) was detected.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation((?)+SD.Independent-samples t test was applied when comparing OSAHS group with controls.Also,partial correlations was adopted.As usual,it was thought to have statistical significance when P＜0.05.RESULTS:Compared with control group,significant lower FA values were found in multiple regions as below in patients in OSAHS:white matter of right frontal lobe(t＝2.367,P＝0.029),splenium of corpus callosum(t＝2.118,P＝0.048),left anterior cingulate gyrus(t＝6.127,P＝0.000),right anterior cingulate gyrus(t＝5.673,P＝0.000), left anterior cingulum(t＝7.067,P＝0.000),right anterior cingulum(t＝9.934,P＝0.000), left centrum semiovale(t＝4.320,P＝0.000),peripheric white matter of left anterior angle(t＝2.778,P＝0.012),peripheric white matter of right anterior angle(t＝2.316,P＝0.033),peripheric white matter of left posterior angle (t＝6.012,P＝0.000),peripheric white matter of right posterior angle (t＝7.256,P＝0.000),left parahippocampal gyrus(t＝4.055,P＝0.001),right parahippocampal gyrus(t＝4.134,P＝0.001),left external capsule(t＝2.619,P＝0.017), and right external capsule(t＝2.548,P＝0.020).Compared with control group,significant higher ADC values were found in multiple regions as below in patients in OSAHS:white matter of right frontal lobe (t＝-2.793,P＝0.012),trunk of corpus callosum(t＝-2.741,P＝0.013),splenium of corpus callosum(t＝-4.871,P＝0.000),left anterior cingulate gyrus (t＝-15.359,P＝0.000),right anterior cingulate gyrus(t＝-14.452,P＝0.000),right anterior cingulum(t＝-2.863,P＝0.010),left centrum semiovale(t＝-2.263,P＝0.036), and peripheric white matter of left anterior angle(t＝-2.291,P＝0.034).After analyzing correlation between sleep architecture and cognitive disfunction in patients with OSAHS,it was found thatⅢstage plusⅣstage/total sleep time (TST)not only had a significant positive correlation both with right anterior cingulum and with peripheric white matter of right posterior angle,but also had a significant negative correlation with fight anterior cingulum.We also found that the patients in OSAHS had lower memory quotient(MQ), pictures recollection values,recognition values,vision reproduction values,and numbers reciting values than healthy controls(t＝2.318,P＝0.026;t＝2.376, P＝0.023;t＝2.195,P＝0.034;t＝2.828,P＝0.007;t＝3.077,P＝0.004).After analyzing correlation between WMS values and cognitive disfunction in patients with OSAHS,it was found that pictures recollection values,had a significant positive correlation with peripheric white matter of right posterior angle(r＝0.741, P＝0.036),both vision reproduction values and MQ had a significant positive correlation with white matter of fight frontal lobe(r＝0.450,P＝0.030;r＝0.450, P＝0.030).At last,We found that the patients in OSAHS had lower MMSE values and calculation values than healthy controls(t＝2.484,P＝0.016;t＝2.241,P＝0.029)CONCLUSIONS:Firstly,It was found in China for the first time that the patients with OSAHS had extensive white matter microstructural lesions,involving in internuncial fibers,commissural fibers and projection fibers.Secondly,gray matter such as bilateral cingulate gyrus and parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.Thirdly,DTI can reveal white matter microstructural lesions in the early stage.Fourthly,FA values was more sensitive than ADC values for white matter microstructural lesions.Fifthly,the patients with OSAHS had unstuck sleep architecture,severity of which correlated with the degree of white matter microstructural lesions.Sixthly,The patients with OSAHS had worse memory function and short-term memory which correlated with white matter microstructural lesions.Finally,both cognitive function and calculation ability was damaged in patients with OSAHS.Chapter 3 Mierostructural lesions in normal-appearing white matter in patients with LI by DTIOBJECTIVES:To investigate microstructural lesions in normal-appearing white matter both in patients with lacunar infarction(LI).METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean+standard deviation((?)±SD) Independent-samples t test was applied when comparing LI group with controls.As usual,it was thought to have statistical significance when P＜0.05. RESULTS:Compared with control group,significant lower FA values were found in multiple regions from normal-appearing white matter or gray matter in patients with LI:white matter of left frontal lobe(t＝2.857,P＝0.007),white matter of right frontal lobe(t＝2.604,P＝0.013),splenium of corpus callosum(t＝3.177,P＝0.003 ),left anterior cingulum(t＝2.198,P＝0.034 ),right anterior cingulum(t＝2.495, P＝0.017),left anterior limb of internal capsule(t＝5.483,P＝0.000),right anterior limb of internal capsule(t＝4.619,P＝0.000),left genu of internal capsule(t＝3.601,P＝0.001), right genu of internal capsule(t＝2.907,P＝0.006 ),left posterior limb of internal capsule(t＝3.243,P＝0.002),right posterior limb of internal capsule(t＝2.359,P＝0.023), left centrum semiovale(t＝3.167,P＝0.003),right centrum semiovale(t＝2.369,P＝0.023),left optic radiation(t＝3.167,P＝0.003),right optic radiation(t＝4.220,P＝0.000),peripheric white matter of left anterior angle(t＝3.012,P＝0.004),peripheric white matter of right anterior angle(t＝2.112,P＝0.041),peripheric white matter of left posterior angle(t＝2.193,P＝0.034 ),left parahippocampal gyrus(t＝2.347,P＝0.024), right parahippocampal gyrus(t＝2.103,P＝0.042),right external capsule(t＝3.006,P＝0.005).Compared with control group,significant higher ADC values were found in multiple regions from NAWM or normal-appearing gray matter(NAGM) in patients with LI:trunk of corpus callosum(t＝-3.272,P＝0.002),splenium of corpus callosum (t＝-2.413,P＝0.021),left anterior limb of internal capsule(t＝-3.059,P＝0.004), right anterior limb of internal capsule(t＝-3.831,P＝0.000),right genu of of internal capsule(t＝-2.530,P＝0.015),left posterior limb of internal capsule(t＝-3.047,P＝0.004),right posterior limb of internal capsule(t＝-2.634,P＝0.012),left centrum semiovale(t＝-2.819,P＝0.007),peripheric white matter of left posterior angle (t＝-2.075,P＝0.044),left parahippocampal gyrus(t＝-2.496,P＝0.017).DTT for corpus callosum indicated that the fibers in frontal forceps and genu were found sparse,thin and discontinuous.CONCLUSIONS:Firstly,it was found that the patients with LI had extensive microstructural lesions in NAWM.Secondly,NAGM such as bilateral parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.Finally,DTT for corpus callosum indicated that the fibers in frontal forceps and genu were found sparse,thin and discontinuous.Chapter 4 Microstruetural lesions in normal-appearing white matter in patients with relapsing-remitting MS by DTIOBJECTIVES:To investigate microstructural lesions in NAWM in patients with relapsing-remitting MS.METHODS:FA and ADC values was examined in ROI respectively,and then DTT of corpus callosum was operated.The datas were dealed with SPSS 13.0,and numeric variables were represented by mean±standard deviation((?)±SD) Independent-samples t test was applied when comparing LI group with controls.As usual,it was thought to have statistical significance when P＜0.05.RESULTS:Compared with control group,the patients with relapsing-remitting MS had significant lower FA values in multiple regions from NAWM or NAGM as below:white matter of left frontal lobe(t＝3.638,P＝0.002),white matter of right frontal lobe(t＝3.181,P＝0.005),left centrum semiovale(t＝3.273,P＝0.004),right centrum semiovale(t＝2.201,P＝0.040),left optic radiation(t＝2.281,P＝0.034),right optic radiation(t＝3.380,P＝0.003 ),peripheric white matter of left anterior angle (t＝4.905,P＝0.000),peripheric white matter of right anterior angle(t＝3.674,P＝0.002),peripheric white matter of left posterior angle(t＝2.636,P＝0.016),peripheric white matter of right posterior angle(t＝4.714,P＝0.000),left thalamus (t＝2.325,P＝0.031),right thalamus(t＝2.398,P＝0.026),right parahippocampal gyrus (t＝2.660,P＝0.015). Compared with control group,the patients with relapsing-remitting MS had significant higher ADC values in multiple regions from normal-appearing white matter or gray matter as below:white matter of right frontal lobe(t＝-3.797,P＝0.001),genu of corpus callosum(t＝-2.688,P＝0.014),trunk of corpus callosum(t＝-4.547, P＝0.000 ),splenium of corpus callosum(t＝-3.211,P＝0.004 ),left centrum semiovale (t＝-4.044,P＝0.001 ),right centrum semiovale(t＝-4.461,P＝0.000),peripheric white matter of left posterior angle(t＝-4.487,P＝0.000),peripheric white matter of right posterior angle(t＝-2.652,P＝0.015 ),left parahippocampal gyrus(t＝-2.548,P＝0.019), right parahippocampal gyrus(t＝-2.269,P＝0.034).DTT for corpus callosum indicated that corpus callosum fiber had sparse align,enlarged crevice,and discontinuance in the trunk.CONCLUSIONS:Firstly,it was found that the patients with relapsing-remitting MS had extensive microstructural lesions in NAWM from some regions which correlated with cognitive function,involving in bilateral white matter of frontal lobe, centrum semiovale,corpus callosum,anterior cingulum,and especially peripheric white matter of anterior angle and posterior angle.Secondly,NAGM such as bilateral parahippocampal gyrus in the patients with relapsing-remitting MS,which were thought to relate with cognitive function,was also damaged.Finally,DTT for corpus callosum indicated that corpus callosum fiber had sparse align,enlarged crevice,and discontinuance in the trunk.GENERAL CONCLUSIONS:1.It was indicated that the density of white matter fibers were unanimous in bilateral brain.2.Anisotropy varied in each brain structure,generally white matter had remarkable higher anisotropy compared with gray matter.3.There was different anisotropy in three types nerve fibres:commissural fibers had the highest anisotropy,the following were projection fibers,and internuncial fibers were the lowest.4.It was found in China for the first time that the patients with OSAHS had extensive white matter microstructural lesions,involving in internuncial fibers, commissural fibers and projection fibers.5.Gray matter such as bilateral cingulate gyrus and parahippocampal gyrus, which were thought to relate with cognitive function,was also damaged.6.DTI can reveal white matter microstructural lesions in the early stage.Fourthly, FA values was more sensitive than ADC values for white matter microstructural lesions.7.The patients with OSAHS had unstuck sleep architecture,severity of which correlated with the degree of white matter microstructural lesions.8.The patients with OSAHS had worse memory function and short-term memory which correlated with white matter microstructural lesions.9.Both cognitive function and calculation ability was damaged in patients with OSAHS.10.It was found that the patients with LI had extensive microstructural lesions in NAWM.11.NAGM such as bilateral parahippocampal gyrus,which were thought to relate with cognitive function,was also damaged.12.DTT was able to indicate directly that corpus callosum in LI had been damaged.13.It was found that the patients with relapsing-remitting MS had extensive microstructural lesions in NAWM from some regions which correlated with cognitive function,especially in peripheric white matter of anterior angle and posterior angle.14.NAGM such as bilateral parahippocampal gyrus in the patients with relapsing-remitting MS,which were thought to relate with cognitive function,was also damaged.15.DTT indicated that corpus callosum had remarkable damage in RRMS.INNOVATIVE FEATURES1.It was found by DTI that the patients with OSAHS had extensive white matter microstructural lesions,and some gray matter relating with cognitive function was also damaged.2.It was found that the patients with LI had extensive microstructural lesions in NAWM which was difficult to detect by conventional MRI.3.DTI is helpful to detect damage to the visual pathways in the early stage.更多还原