Abstract
目的
应用三维伪连续动脉自旋标记技术(3D pseudocontinuous arterial spin labeling,3D pcASL), 探讨抑郁合并高血压患者脑血流灌注特点,并分析其与抑郁程度的相关性。
方法
16例临床诊断为抑郁的患者为抑郁组(男3例、女13例,年龄42~72岁),16例高血压患者为高血压组(男3例、女13例,年龄41~68岁),16例抑郁合并高血压患者为共病组(男3例、女13例,年龄45~74岁),16例健康者为对照组(男3例、女13例,年龄43~68岁)。使用GE 3.0T磁共振扫描3D pcASL序列并自动生成脑血流图,使用统计参数图(statistical parametric mapping,SPM8)软件对脑血流图进行预处理、空间标准化和平滑。使用方差分析比较4组之间脑血流灌注差异,提取脑血流灌注减低区的平均脑血流值与17项汉密尔顿抑郁量表(Hamilton depression scale,HAMD-17)进行相关分析。
结果
与对照组比较,共病组可见多个脑区出现脑血流灌注减低,包括双侧额上回、双侧额中回、双侧额下回、右侧顶上回、右侧顶下回、右侧缘上回、左侧尾状核、左侧岛叶,差异有统计学意义。与对照组比较,抑郁组脑血流灌注在双侧额中回出现下降趋势,但差异无统计学意义;高血压组未出现脑血流灌注异常。与抑郁组比较,共病组在双侧额叶和右侧缘上回脑血流灌注减低;与高血压组比较,共病组在左侧额中回脑血流灌注减低。相关分析显示各灌注减低区平均脑血流值与HAMD-17量表评分未见明显相关。
结论
尽管抑郁患者、高血压患者未见脑部脑血流灌注减低,但共病患者存在多个脑区脑血流灌注减低,提示高血压可能对脑血流低灌注有协同促进作用。
Keywords: 抑郁症, 高血压, 动脉自旋标记, 脑血流
Abstract
Objective
To evaluate cerebral blood flow (CBF) in patients with comorbid hypertension in depression using 3D pseudocontinuous arterial spin labeling (3D pcASL) and to compare the dif-ferences of CBF values in depression, hypertension, and comorbid hypertension between depression and healthy control groups. To investigate the correlation between CBF values and degrees of depression.
Methods
Sixteen patients with depression (depression group, 3 males and 13 females, age range of 42-72 years old), sixteen patients with hypertension (hypertension group, 3 males and 13 females, age range of 41-68 years old), sixteen patients with comorbid hypertension in depression (comorbidity group, 3 males and 13 females, age range of 45-74 years old), and sixteen healthy controls (control group, 3 males and 13 females, age range of 43-68 years old) were recruited. 3D pcASL sequence was performed by GE 3.0T magnetic resonance scanner and CBF map was generated automatically. Statistical parametric mapping (SPM8) was performed to preprocess the CBF map, which was spatially normalized and smoothed. Comparison of the CBF values among the four groups was conducted by ANOVA. Correlation between the average CBF values in areas of decreased CBF and Hamilton depression scale (HAMD-17) was investigated.
Results
The patients with comorbid hypertension in depression demonstrated lower CBF in bilateral superior frontal gyri, middle frontal gyri, inferior frontal gyri, right superior parietal gyrus, right inferior parietal gyrus, right supramarginal gyrus, left caudate nucleus and left insula lobe in comparison with the controls. Compared with control group, CBF values decreased in bilateral frontal lobes, but did not reach statistical significance. There were no significant differences of CBF values between the patients with hypertension and control subjects. Compared with depression, the patients with comorbid hypertension in depression showed lower CBF values in bilateral frontal lobes and right supramarginal gyrus. Compared with hypertension, lower CBF values in left middle frontal gyrus in the patients with comorbid hypertension in depression were shown. Correlation analysis indicated that no correlation between CBF values and scores of HAMD-17 was shown.
Conclusion
Although there were no significant decreases of CBF values in patients with depression and hypertension, regional hypoperfusions were observed in patients with comorbid hypertension in depression. Hypertension might play a sy-nergistic action on cerebral hypoperfusion in patients with comorbid hypertension in depression.
Keywords: Depressive disorder, Hypertension, Arterial spin labeling, Cerebral blood flow
抑郁症是常见的一种精神疾病,表现为情绪低落、思维迟缓等,其发病率逐年上升。关于抑郁症患者脑血流灌注改变各研究尚不一致,3D伪连续动脉自旋标记(pseudocontinuous arterial spin labeling,pcASL)技术是近些年来用于评估脑血流灌注的一种新影像学方法[1],其将动脉中水分子作为内源性标记物测定脑血流灌注。随着年龄增长及高血压发病率上升,不少抑郁症患者合并高血压,目前国内尚未见对抑郁合并高血压患者进行3D pcASL脑血流灌注的研究。
本研究采用3D pcASL技术测量抑郁组、高血压组、抑郁合并高血压组(共病组)和正常对照组脑血流灌注,并与抑郁程度评分进行相关分析,观察共病组患者脑血流灌注特点及高血压对抑郁的影响。
1. 资料与方法
1.1. 一般资料
抑郁组:16例抑郁症患者均符合美国《精神疾病诊断与统计手册》第4版(DSM-Ⅳ)诊断标准,男3例、女13例,年龄42~72岁,平均(58.1±8.1)岁。高血压组:16例高血压患者高血压病史均1年以上,平均病程为(8.7±3.7)年,均服用降压药控制,血压控制在收缩压130~140 mmHg、舒张压 80~100 mmHg(1 mmHg=0.133 kPa),男3例、女13例,年龄41~68岁,平均(58.6±7.1)岁。共病组:16例抑郁合并高血压患者,其抑郁诊断标准同抑郁组,高血压病史1年以上并服降压药控制,平均病程为(7.6±2.9)年,血压控制情况同高血压组,男3例、女13例,年龄45~74岁,平均(61.0±6.4)岁。对照组:16例健康者,男3例、女13例,年龄 43~68岁,平均(56.1±8.6)岁。
所有受试者均无脑部肿瘤、脑部外伤史、脑血管疾病等病史,均为右利手,且全部进行的17项汉密尔顿抑郁量表(Hamilton depression scale,HAMD-17)的测定。本研究经北京大学第三医院医学科学研究伦理委员会审批通过,所有受试者均知情同意。
1.2. 方法
1.2.1 磁共振检查 磁共振(magnetic resonance,MR)扫描采用3.0T(GE Discovery 750)8通道相控阵头线圈。所有受试者先进行常规结构扫描排除颅脑病变。扫描序列:3D T1SPGR,T2W轴位,T2 FLAIR轴位。3D T1 SPGR扫描参数:TR=4.9 ms,TE=2 ms,层厚=1 mm,层间距=0 mm,FOV 24 cm×24 cm,矩阵240×240,共170层覆盖全脑,扫描时间6 min 34 s。随后扫描3D pcASL序列,扫描参数:TR=4 632 ms,TE=10.5 ms,层厚=4 mm,层间距=0 mm,体素大小2 mm×2 mm×4 mm,标记后延迟时间=1.5 s,扫描范围与3D T1 SPGR结构像一致,扫描时间195 s。
1.2.2 数据分析 GE公司MR后处理软件自动生成全脑脑血流图,采用统计参数图(statistical parametric mapping 8,SPM8)软件进行图像预处理(头动校正、配准、分割、标准化、平滑)。将脑血流图配准到加拿大蒙特利尔神经研究所(Montreal Neurologic Institute,MNI)标准脑空间,3D T1SPGR图像分割并与脑血流图配准、标准化。标准化后图像重新采样,体素为2 mm×2 mm×2 mm,各向同性,采用6 mm半高全宽高斯核进行空间平滑。WFU PickAtlas软件提取CBF灌注改变脑区为模板,提取计算每个被试相应脑区平均脑血流值。
1.3. 统计学分析
采用SPM8软件方差分析比较抑郁组、高血压组、共病组和对照组全脑脑血流值,以体素为基础进行组间比较,得到存在脑血流灌注差异的脑区,比较4组间脑血流值差异。选择P=0.001,最小团块尺寸50个象素,得到校正结果,并将结果显示在MNI坐标系中。
使用SPSS 19.0统计分析软件,采用卡方检验(Fisher)比较各组性别差别;采用方差分析比较各组年龄、抑郁评分及脑血流灌注差异脑区平均脑血流值差异,其中抑郁评分及平均脑血流值差异的组间两两比较采用LSD-t检验;脑血流灌注差异脑区平均脑血流值与HAMD-17评分进行Pearson相关分析。
2. 结果
2.1. 各组人口学特征及抑郁评分特点
各组间年龄和性别差异无统计学意义(P>0.05)。抑郁组平均HAMD-17评分为(13.5±6.9)分,高血压组为(3.7±2.3)分,共病组为(13.1±4.7)分,对照组为(2.7±2.5)分,抑郁组、共病组抑郁评分高于对照组,差异有统计学意义(P<0.05)。两两比较显示抑郁组和共病组间抑郁评分差异无统计学意义(P>0.05)。
2.2. 各组间脑血流灌注差异
与对照组比较,抑郁组脑血流灌注在双侧额中回出现下降趋势,但差异无统计学意义(P>0.05);高血压组未见明显脑血流灌注减低(P>0.05)。与对照组比较,共病组脑血流灌注在多个脑区出现减低(图1),分别为双侧额上回、双侧额中回、双侧额下回、右侧顶上回、右侧顶下回、右侧缘上回、左侧尾状核、左侧岛叶,与正常对照组差异有统计学意义(F=11.81,P=0.001)。共病组与对照组组间比较结果见表1。
1.
共病组与对照组的脑血流灌注差异图
Differences of cerebral blood flow between comorbidity group and control group
Difference of cerebral blood flow values in frontal and parietal lobes in patients with comorbid hypertension in depression as compared with healthy control subjects were displayed (3D display).
1.
共病组与对照组比较脑血流灌注减低区
Decreased CBF values in patients with comorbid hypertension in depression compared to controls
| Cerebral areas | CBF values/[mL/(100 g·min)] | Peak point MNI | ||||||
| Comorbidity group | Control group | P value | X | Y | Z | F value | ||
| CBF, cerebral blood flow; MNI, Montreal Neurologic Institute. | ||||||||
| Left superior frontal gyrus | 46.7±5.7 | 56.1±11.0 | 0.004 | -30 | 57 | 24 | 19.14 | |
| Right superior frontal gyrus | 40.4±5.6 | 50.2±10.3 | 0.001 | 33 | 6 | 63 | 22.09 | |
| Left middle frontal gyrus | 46.3±7.2 | 55.5±12.0 | 0.006 | -33 | 54 | 24 | 29.89 | |
| Right middle frontal gyrus | 43.9±6.1 | 55.4±11.3 | 0.001 | 36 | 3 | 63 | 21.69 | |
| Left inferior frontal gyrus | 47.7±5.7 | 57.5±9.6 | 0.001 | -48 | 27 | 30 | 23.45 | |
| Right inferior frontal gyrus | 48.8±5.6 | 59.2±10.1 | 0.001 | 54 | 15 | 33 | 21.99 | |
| Right superior parietal gyrus | 32.5±4.4 | 43.7±12.7 | 0.001 | 21 | -72 | 54 | 16.12 | |
| Right inferior parietal gyrus | 42.6±6.6 | 53.9±12.7 | 0.002 | 54 | -30 | 54 | 15.59 | |
| Right supramarginal gyrus | 47.3±5.6 | 56.8±9.8 | 0.002 | 63 | -21 | 45 | 15.64 | |
| Left caudate nucleus | 39.1±4.3 | 46.8±7.4 | 0.002 | -3 | 9 | 3 | 17.47 | |
| Left insular lobe | 49.3±5.9 | 62.3±8.7 | <0.001 | -36 | 12 | 6 | 20.72 | |
与抑郁组比较,共病组出现脑血流灌注减低脑区(图2A),主要为右侧额中回、右侧缘上回、左侧额上回,差异有统计学意义(F=11.81,P=0.001)。与高血压组比较,共病组也存在脑血流灌注减低脑区(图2B),为左侧额中回,差异有统计学意义,但差异脑区体素较小(P=0.001,F=11.81)。
2.
共病组与抑郁组、共病组与高血压组的脑血流灌注差异图
Differences of cerebral blood flow between comorbidity group and depression group, comorbidity group and depression group
A, compared with depression, patients with comorbid hypertension in depression showed lower CBF values, mainly in bilateral frontal lobes and right supramarginal gyrus; B, compared with hypertension, lower CBF values in left middle frontal gyrus in patients with comorbid hypertension in depression were shown.
2.3. 脑血流灌注和抑郁程度的相关性
将脑血流灌注减低脑区的平均脑血流值与HAMD-17评分进行相关分析显示,平均脑血流值与HAMD-17评分无明显相关,相关系数分别为:左侧额上回-0.213、右侧额上回-0.201、左侧额中回-0.198、右侧额中回-0.224、左侧额下回-0.213、右侧额下回-0.231、右侧顶上回-0.095、右侧顶下回-0.150、右侧缘上回-0.182、左侧尾状核-0.232、左侧岛叶-0.240(P均>0.05)。
3. 讨论
动脉自旋标记(arterial spin labeling,ASL)技术是一种无创检查方法,以水分子作为内源性对比剂,通过对动脉进行标记来定量测量脑血流灌注。正电子发射断层成像术(positron emission tomography,PET)对脑内葡萄糖代谢的显示与ASL技术对脑血流灌注的显示有很好的一致性,因其操作简便及无创性,ASL已经成为一种测量脑血流灌注的重要方法,特别对抑郁症患者有更好的接受度。本研究采用的3D pcASL技术,信噪比提高、运动伪影减少、图像质量改善[2,3,4],通过将3D与背景抑制结合,成为一个测量脑血流灌注的敏感方法。
抑郁症患者存在形态或功能异常,表现为支持执行功能的额叶异常或支持情感过程的边缘叶、旁边缘及扣带回区域异常,而早期研究多集中在抑郁症患者脑结构改变[5,6]。单光子发射计算机断层成像术(single-photon emission computed tomography,SPECT)和PET测量抑郁症患者脑血流灌注发现,额叶、颞叶、顶叶和边缘皮层下结构脑血流灌注和葡萄糖代谢减低,特别是在额叶和前扣带回。国内外一些研究使用ASL技术对抑郁症患者进行脑血流灌注研究[7,8,9,10,11,12],发现多个脑区存在脑血流灌注变化,特别是额叶-边缘叶-扣带回-纹状体网络存在灌注异常。Lui等[13]报道非难治性抑郁症患者在左侧前额叶出现脑血流灌注下降,而难治性抑郁症患者在双侧额叶及丘脑区域出现脑血流灌注下降。也有研究显示慢性和难治性抑郁症患者双侧前扣带回、左侧前额叶皮层出现脑血流高灌注[14]。脑血流灌注差异脑区并不一致,但主要集中在额叶、前额叶、前扣带回、边缘叶及旁边缘叶,脑血流值在不同的脑区出现升高或下降[15,16]。也有一些研究显示,与对照组比较抑郁症患者脑血流灌注没有明显差异。结果的差异可能是由于抑郁症患者情况不同,如起病时间、性别、首发或者复发、抑郁严重程度、持续时间和抗抑郁药物使用等均可能影响结果。除此之外,ASL的采集和后处理方法也可能影响结果。本研究中,与对照组比较,抑郁症患者脑血流灌注没有出现明显下降,虽然在额叶出现了下降趋势,但是两组之间差异无统计学意义,考虑可能的原因是本组抑郁症患者为非首发抑郁患者,在第一次MR扫描前已经使用了抗抑郁药,可能对结果产生影响,不能完全体现未治疗抑郁症患者脑血流灌注改变,特别是抑郁发作时的脑血流灌注情况。
抑郁症和高血压的关系较为复杂,两者互相影响,互为危险因素。高血压引起心血管负荷增加,从而影响小血管、血脑屏障功能和血管完整性,导致脑血流量下降。高血压患者脑血流灌注特点可能是由局部小动脉病变引起的脑血流灌注不足,Alosco等[17]发现高血压患者的颞叶和枕叶出现脑血流灌注减低。本研究中,与对照组比较,高血压患者脑血流灌注没有明显下降,考虑原因可能为:本研究中所有高血压患者的病程已超过1年以上,平均达7~8年,但均接受药物治疗且血压控制稳定(正常或轻度升高),从而未见到脑血流灌注明显下降。高血压病程时间、药物使用情况、血压控制情况均可能影响脑血流灌注,尽管抑郁组和高血压组脑血流灌注没有明显下降,但抑郁组额叶区域出现了脑血流灌注下降趋势,而共病组在多个脑区出现了脑血流灌注明显下降,主要为双侧额叶、右侧顶叶、右侧缘上回、左侧尾状核和左侧岛叶,我们推测高血压和抑郁共同促进了脑血流灌注的下降,特别是在额叶区域。
与抑郁组比较,共病组在双侧额叶和右侧缘上回出现了脑血流灌注下降,虽然共病组和抑郁组患者均已经接受药物治疗,但抑郁程度两者差异无统计学意义,因此,考虑在相同抑郁背景下,高血压可能是导致上述脑区脑血流灌注下降的重要因素,特别是在额叶。当与高血压组比较时,共病组出现类似的结果,提示尽管高血压组没有明显脑血流灌注下降,但可能已经存在一定程度的微结构损害,如小血管损害,而抑郁状态加重了脑血流灌注下降。共病组多个脑区存在脑血流灌注的下降,累及范围广泛,提示高血压可能对抑郁症有协同促进作用,当两者共病时,在治疗抑郁的同时,也需要积极控制血压情况。
HAMD-17是常用的评估抑郁程度的评分方法。本研究中抑郁组与共病组患者的HAMD-17评分均高于对照组,脑血流灌注差异脑区平均脑血流值与抑郁程度相关分析显示两者之间无明显相关,考虑本研究中抑郁患者及共病患者在MR扫描前已使用抗抑郁药物,药物治疗后可能会降低HAMD-17评分,因此不能完全反映真实情况。
本研究尚有不足之处:(1)入组数量少,需要进一步扩大样本量;(2)抑郁组患者未进行分级,未分析不同级别抑郁患者脑血流灌注差异;(3)成像分析是基于组间分析,不是针对每一个患者进行分析;(4)抑郁组和共病组均已经过治疗,抑郁的发病时间、治疗方案及疗效均可能影响脑血流灌注,从而产生结果差异。
总之,通过3D pcASL方法对抑郁症、高血压、共病患者及对照组脑血流灌注进行定量测定,发现与对照组比较,抑郁组和高血压组未见脑血流灌注异常,而共病组患者多个脑区出现脑血流灌注下降,提示高血压可能对抑郁症有协同促进作用。3D pcASL作为一种无创的MR灌注成像新技术,对于早期检测脑血流灌注异常有非常重要的作用。
(本文编辑:赵 波)
Funding Statement
“十一五”国家科技支撑计划项目（2009BA77B00）
the National Science and Technology Pillar Program during the 11th Five-Year Plan(2009BA77B00)
References
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