International Journal of Psychiatry and Neurology
Vol.05 No.02(2016), Article ID:17478,6 pages
10.12677/IJPN.2016.52004

The Neuroimaging Assessment Progress of Cognitive Impairment Associated with Cerebral Small Vessel Disease

Weiping Li, Bing Zhang*

Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing Jiangsu

Received: Apr. 15th, 2016; accepted: Apr. 29th, 2016; published: May 3rd, 2016

Copyright © 2016 by authors and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY).

http://creativecommons.org/licenses/by/4.0/

ABSTRACT

Cerebral small vessel disease (CSVD) is the most common vascular cause of cognitive impairment, which refers to a group of ischemic and hemorrhagic changes that mainly affect the small arteries and arterioles. Features seen on neuroimaging include white matter hyperintensities, lacunar infarction, cerebral microbleed and enlarged perivascular space, which can be assessed by both quantitative analysis and semi-quantitative analysis, and this can provide evidence for the explanation of cognitive impairment.

Keywords:White Matter Hyperintensities, Lacunar Infarction, Cerebral Microbleed, Enlarged Perivascular Space, Cognitive Impairment

脑小血管病相关认知功能障碍的影像学 评估研究进展

李卫萍,张冰*

南京大学医学院附属鼓楼医院医学影像科,江苏 南京

收稿日期:2016年4月15日;录用日期:2016年4月29日;发布日期:2016年5月3日

摘 要

脑小血管病主要是指小动脉及微动脉病变引起的缺血或出血性改变,它是引起血管性认知功能障碍主要原因。影像学上主要表现为脑白质高信号,腔隙性脑梗死,脑微出血及血管周围间隙扩大,这四种类型分别可以使用多种评价方法进行定量和半定量评估,对于解释相应的认知功能减退提供了客观依据。

关键词 :脑白质高信号,腔隙性脑梗死,脑微出血,血管周围间隙扩大,认知功能障碍

1. 引言

随着我国人口老龄化速度的加剧及影像学技术的发展,脑小血管病(Cerebral Small Vessel Disease, CSVD)渐被重视,CSVD是引起血管性认知功能障碍(Vascular Cognitive Impairment, VCI)最常见的原因 [1] ,VCI不仅严重影响患者的生活质量,而且给家庭和社会造成了很大的经济负担。VCI的早期诊断和治疗是社会发展的需要,CSVD相关认知功能障碍已成为目前研究的热点 [2] 。本文将从脑小血管病的定义、影像学表现和评估方法及其与认知功能的关系等方面作如下综述。

2. CSVD的定义

CSVD是指颅内小血管病变引起的脑损伤,涉及到的小血管有小动脉、微动脉、毛细血管、小静脉等,临床上以小动脉和微动脉病变多见。CSVD在临床上的表现与其病灶的严重程度和部位相关,由于CSVD极易破坏皮质下神经网络,因此早期轻度认知障碍主要有执行功能、注意力和定向力的受损,表现为信息处理速度减慢、语言流利程度下降、持续的注意力减退、 延迟自由回忆能力下降等 [1] ;随着病情进展认知功能障碍逐步加重,晚期则表现为痴呆。

3. CSVD相关认知功能障碍表现及影像学评估方法

CSVD在影像学上主要表现为以下几种类型:脑白质高信号(White Matter Hyperintensities, WMH)、腔隙性脑梗死(Lacunar Infarction, LI)、脑微出血(Cerebral Mmicrobleed, CMB),血管周围间隙扩大(Enlarged Perivascular Space, EPVS),它们即可同时存在又可单独存在。

3.1. 脑白质高信号

WMH又称脑白质疏松症(leukoaraiosis),是由多种不同病因引起的一组临床综合征,由加拿大学者Hachinski等 [3] 首先提出,指的是脑室周围或皮质下区脑白质内斑点状改变,是一种脑缺血所致的白质脱髓鞘疾病,在CT上表现为脑室旁或半卵圆中心弥漫性低密度灶,在MRI (Magnetic Resonace Imaging)上表现为T1W等低信号,T2W和FLAIR (Fluid Attenuated Inversion Recovery)序列上基本对称的大脑白质高信号片状影,是多种神经系统疾病表现的非特异性神经影像学改变。

WMH可引起认知功能障碍 [4] ,主要表现为执行功能障碍、语言、视空间以及主观记忆力损害和精神运动速度减慢,而且对时间定向力、短时记忆力、注意力、计算力等限时任务的损害更严重。皮质下脑白质变性可破坏U型纤维 [5] ,脑室周围的脑白质变性可破坏额叶–皮质下环路 [6] ,前额叶脑白质变性与执行功能的损害密切相关 [7] 。多数研究认为任何部位脑白质变性均可干扰脑内信号传递过程,WMH与脑网络的破坏和认知功能有关,额颞叶WMH与皮层厚度变薄有关,从而使神经信号处理速度减慢,影响认知功能(Tuladhar AM [8] )但也有研究说明WMH与认知功能并未发现有联系 [9] ,如Burns JM的研究认为,随着侧脑室及深部脑白质病变容积的增加,非痴呆人群的认知水平并无相应减低,这种争议可能由于研究样本数量及WMH病灶的部位和程度有关。

目前WMH的影像学评价方法很多,主要有半定量和定量评估。半定量方法主要有:(1) Fazekas分级 [10] ,它是目前最常用的分级方法,是根据脑白质损害在MRI上的严重程度进行分类,主要采用FLAIR(Fluid Attenuated Inversion Recovery)序列。(2) Age-Related White Matter Changes (ARWMC)评估模型 [11] :该量表评价各个脑区的脑白质病变,较Fazekas分级更具体,共评价五个脑区:额叶,顶枕叶,颞叶,幕下及基底节区,对左右侧分别进行评价。得分标准为:无病变(0分),局灶性病变(1分),病灶开始融合(2分),病灶在整个区域弥散分布(3分)。

定量方法主要有:(1) FreeSurfer分析 [12] :脑区分割结果显示FALIR上高信号的容积越大,认知评估量表及测试的评分越低,包括:TMT(Trail Making Test),COWAT(Controlled Oral Word Association Test),Stroop Word等,间接反映WMH与这些认知功能的下降有关(2)DTI(Diffusion Tensor Imaging)分析:有人用纤维束空间统计学(Tract Based Spatial Statistics, TBSS)分析发现双侧扣带束后部各向异性分数(Fractional Anisotropy, FA)值的减低与认知水平下降明显相关 [13] ,扣带束是扣带回与其它脑灰质结构(如海马、海马旁回等)之间的联系纤维,是情景记忆功能的结构基础。

3.2. 腔隙性脑梗死

腔隙性梗死发病率约占脑梗死的1/4,它是由于单一的穿支动脉闭塞所致,一般是指直径小于20 mm的缺血性梗死,主要分布在基底节、丘脑、内囊、豆状核和尾状核等脑穿支动脉供血区域 [14] ,其病理特征为微动脉粥样硬化及小穿支动脉脂质玻璃样变和纤维素样坏死。腔隙性梗死在MRI上表现为T1WI呈低信号而T2WI上呈高信号,病灶呈边缘清晰的圆形、裂隙状或椭圆形。

Grau-Olivares等 [15] 认为,大多数表现为轻偏瘫等不典型腔隙性脑梗死的患者存在认知功能受损,主要表现为执行功能的损害及主动性思维受损。腔隙性脑梗死引起的认知功能的损害与梗死的部位及数目相关 [16] 。如丘脑腔隙性梗死可导致执行功能障碍、记忆缺陷、信息处理速度减慢,壳核和苍白球损害则与记忆和运动速度有关 [17] ;额叶腔隙性梗死可导致注意力及执行协调能力下降,额叶占人类大脑的1/3,是高级认知功能整合的重要脑区;颞叶腔隙性梗死,尤其是海马损害,可导致语言及记忆功能下降,因为内侧颞叶是重要的记忆环路(海马–穹隆–乳头体–丘脑前核–扣带回),当它发生病变时,可出现明显记忆障碍,特别是近事记忆减退;单个皮层或皮质下梗死可以导致对应的认知域如记忆受损,而两个或两个以上部位同时出现梗死,就会出现执行功能下降及信息处理速度减慢,随着梗死部位增加则认知功能更进一步出现下降。

目前腔隙性脑梗死的影像学评价方法是分级法 [18] :在3D-T1W图像上直径 > 或 = 3 mm的局灶性低信号影,而且要排除血管周围间隙,后者在前联合、基底节区、两侧顶叶白质发生率较高。腔隙性脑梗死分级包括,0级:无腔隙性脑梗死病灶;1级:1~3个病灶;2级:>或=4个病灶。

3.3. 血管周围间隙扩大

血管周围间隙是指进入脑实质的小血管壁周围的间隙,正常情况其直径小于2 mm,常位于前联合或脑实质顶部,当其直径大于2 mm时,就称为血管周围间隙扩大(Enlarged Perivascular Space, EPVS),在MRI上表现为圆形或线状,与血管走行一致,边界清楚,直径小于5 mm,通常双侧对称的病灶,T1WI呈低信号,T2WI上呈高信号,FLAIR上低信号,无占位效应。

目前血管周围间隙扩大的影像学评价方法包括(1)评分法 [19] ,即在T2WI上0分 = 没有EPVS,1分 ≤ 10 EPVS,2分 = 10~20 EPVS,3分 = 21~40 EPVS,4分 ≥ 40 EPVS.(2)分级法,即在T2WI上0级:无SPVS,1级:直径 < 2 mm,2级:直径2~3 mm,3级:直径 > 3 mm。随着基底节、半卵圆中心及海马区域EPVS数目的增加,认知功能下降越显著 [19] ,包括视空间判断能力和词汇记忆能力等方面。

3.4. 脑微出血

CBM是指脑内微小血管的病变,导致脑实质以微小出血为主要特征的亚临床损害,在MRI梯度回波T2WI及SWI(Susceptibility Weighted Imaging)中表现为直径为2~10 mm的卵圆形低信号,周围脑组织无水肿,边界清楚,多出现在皮质-皮质下白质、基底节区及丘脑、脑干、小脑等小血管分布丰富的区域。

CBM的主要病理改变是微小动脉脂质透明样变性和淀粉样蛋白血管壁沉积,而引起这两种病理改变的病因分别是高血压脑血管病(HV)和脑淀粉样变血管病(CAA) [20] 。HV和CAA对脑内血管影响的区域不同:在CAA中,CMB主要分布于脑叶,而在HV中则主要分布于大脑深部和幕下。CMB是导致SVD患者认知功能损害的危险因素,它独立于其他脑小血管病 [21] ;CMB的数量和部位可能与认知功能的损害程度有关 [22] ,在正常老年人群中,CMB的数量越多,认知功能、记忆力、信息处理速度及执行功能越差,而且MMSE评分越低;CMB的部位对认知功能的影响也同样重要,基底节区CMB患者多数表现为执行功能障碍,丘脑CMB患者则表现为定向力较差 [23] [24] ,而且当CMB位于额颞叶、半球深部和幕下时与信息处理速度和执行功能的降低的关系更为显著 [25] [26] 。

目前脑微出血的影像学评价方法有主要有半定量和定量评估,半定量评估法主要是:The Microbleed Anatomical Rating Scale (MARS) [27] :该评估模型将病灶分为两类:确定性及可能性病灶,然后分别计数幕下、各脑区及脑深部的病灶数目。目前认为CBM通过多种因素直接或间接作用于认知相关区域,造成重要皮质和皮质下结构的破坏或对周围的组织结构功能造成影响 [28] ,从而导致与认知功能的减低 [29] 。

定量评估中:脑微出血导致磁敏感成像上信号改变主要是由于含铁血黄素的沉积,同时也可以反映其他金属离子沉积的数量。方法有(1) SWI相位图分析方法:在SWI相位图上顺磁性的出血灶主要表现为均匀高信号或高信号内伴有点状低信号,而反磁性的钙化灶则表现为低信号,而在SWI重建图中二者均表现为低信号,较难鉴别,因此SWI相位图方法较SWI重建图更为准确。同时该方法可以将SWI序列采集的相位图选取感兴趣区进行相位值的测量,相位值可以反映该区域金属离子沉积的含量,大部分研究认为 [30] 尔兹海默症患者双侧海马、内嗅皮层及额叶皮质的相位值低于正常对照组;有研究认为 [31] MCI患者皮质及小脑内均可见铁含量升高,认为脑内铁稳态的失衡是痴呆发生的前兆。(2) 定量磁敏感图成像(Quantitative Susceptibility Mapping,QSM) :QSM在钙、铁含量及微出血的定量监测中有重要意义,该方法利用微出血灶对局部磁场的影响形成对比增强效应 [32] ,通过定量的优点来反映出血灶,同时也可以避免由于MRI序列不同参数而影响微出血的评价。微出血灶定义为在QSM图上2~10 mm的高信号影,需排除静脉血管。QSM可以计算感兴趣区的磁敏感性 [33] ,较SWI 相位图更为精确。

4. 结论与展望

CVSD是导致血管性认知功能损害的主要原因,对患者的生活质量有很大的影响,脑白质高信号、腔隙性脑梗死、脑微出血及血管周围间隙扩大与认知功能有一定的关系,脑小血管病的认知功能障碍可随疾病进展而缓慢进展。本研究综述多种全面化及具体化影像学评估方法,结合综合性的神经心理学测验量表,对患者进行系统客观的评价,有利于早期诊断和随访观察,为二级预防提供治疗决策。

文章引用

李卫萍,张 冰. 脑小血管病相关认知功能障碍的影像学评估研究进展
The Neuroimaging Assessment Progress of Cognitive Impairment Associated with Cerebral Small Vessel Disease[J]. 国际神经精神科学杂志, 2016, 05(02): 21-26. http://dx.doi.org/10.12677/IJPN.2016.52004

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  34. NOTES

    *通讯作者。

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