基于弥散张量成像分析脑小血管病患者白质结构改变及其与步态障碍的相关性研究OA
Study on the correlation between the change of white matter structure and gait disorder in patients with cerebrovascular disease based on diffusion tensor imaging
目的 采用自动纤维定量(AFQ)技术基于弥散张量成像(DTI)分析脑小血管病(CSVD)患者白质纤维束微结构改变及其与步态障碍的关系.方法 前瞻性纳入2024年9月至2025年5月于徐州医科大学第二附属医院神经内科门诊就诊或住院的CSVD患者.收集患者的临床资料,包括人口统计学资料(年龄、性别、受教育年限、体质量指数)、脑血管危险因素(高血压病、糖尿病、卒中史、高脂血症、吸烟史、饮酒史)、实验室检查(总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、脂蛋白 a、空腹血糖、糖化血红蛋白、同型半胱氨酸、尿酸、肌酐)、入组后72 h内蒙特利尔认知评估量表视空间执行功能评分、脑室旁白质高信号评分、深部白质高信号评分、腔隙性脑梗死、脑微出血、扩大的血管周围间隙(>10个)、脑萎缩、偶发扩散加权成像阳性、皮质微梗死、皮质表面铁沉积.入组72 h内采用可穿戴运动及步态量化评估系统对所有患者进行步态分析并获取多组步态参数:基础时空参数[起立-行走测试(TUG)时间、步速、步频、行走时长、坐下时长、起立时长、步长、跨步长、支撑相、摆动相]、行走平衡性参数(步长变异度及躯干前、后、左、右倾角度峰值)、对称性参数(步长不对称性)、转向灵活参数(转向时长、转向过程角速度峰值、转向过程平均角速度)、协调性(相对平均相位差、相位协调指数、左右脚协调性).所有患者入组72 h内均完成简易体能状态量表(SPPB)评估.根据SPPB评分将所有患者分为步态正常组(SPPB评分≥10分)和步态障碍组(SPPB评分<10分);采集3.0T MRI-DTI数据,依据约翰霍普金斯大学白质纤维束图谱及路径点,将全脑流线分为20条白质纤维束,并将每条纤维束等距划分为100个节点,采用AFQ技术提取每条白质纤维束100个节点的各向异性分数(FA)、平均扩散率(MD)、轴向扩散率(AD)、径向扩散率(RD).比较两组患者的临床资料、步态参数及影像学资料,采用偏态相关性分析探究各步态参数与各白质纤维束所有节点FA、MD、AD、RD平均值的相关性;为进一步控制混杂因素的影响,以各步态参数及SPPB评分为因变量,以与步态参数有相关性的纤维束节段FA、MD、AD、RD平均值为自变量并对自变量进行多重共线性检验,排除存在共线性[容差<0.1或方差膨胀因子(VIF)>10]的变量后采用逐步回归法进行多元线性回归分析,探究纤维束不同节段FA、MD、AD、RD平均值与各步态参数的关系.结果 共纳入60例CSVD患者,男31例,女29例,年龄45~80岁,平均(64±11)岁,其中步态正常组31例,步态障碍组29例.(1)与步态障碍组比较,步态正常组患者的受教育年限更长,体质量指数更低(均P<0.05),余临床资料的组间差异均无统计学意义(均P>0.05);与步态正常组相比,步态障碍组患者的TUG时间、行走时长、步长变异度、转向时长均更高,步速、步长、跨步长、转向过程角速度峰值、转向过程平均角速度均更低(均P<0.05).(2)步态障碍组的左侧扣带前部(节点10-20、30-35)的FA均低于步态正常组[经错误发现率(FDR)校正,均P<0.05];左下纵束前部(节点1-43、53-56)MD、左侧扣带前中部(节点12-17、29-60)RD、左下纵束前部(节点10-29)AD均高于步态正常组(经FDR校正,均P<0.05).(3)偏态相关性分析结果显示,左侧扣带前部(节点10-20)FA平均值与转向时长(r=-0.330,P=0.027)成负相关,与转向过程角速度峰值(r=0.301,P=0.045)、转向过程平均角速度(r=0.355,P=0.017)成正相关;左下纵束前部(节点 1-43)MD 平均值与步速(r=-0.306,P=0.039)、步长(r=-0.344,P=0.019)、跨步长(r=-0.347,P=0.018)成负相关;左侧扣带前中部(节点29-60)RD平均值与TUG时间(r=0.326,P=0.029)、行走时长(r=0.383,P=0.009)、转向时长(r=0.512,P=0.001)成正相关,与步速(r=-0.304,P=0.042)、转向过程平均角速度(r=-0.504,P=0.001)、转向过程角速度峰值(r=-0.466,P=0.001)成负相关;左下纵束前部(节点10-29)AD平均值与步速(r=-0.354,P=0.016)、步长(r=-0.337,P=0.022)、跨步长(r=-0.347,P=0.018)、转向过程平均角速度(r=-0.341,P=0.020)成负相关,与行走时长(r=0.323,P=0.029)、坐下时长(r=0.383,P=0.009)成正相关.余步态参数与纤维束节段指标平均值均无相关性(均P>0.05).(4)共线性分析显示,无存在共线性的变量.多元线性回归分析显示,控制混杂因素后,左下纵束前部(节点1-43)MD平均值与步长(β=-0.380,P=0.008)、跨步长(β=-0.431,P=0.002)成负相关;左下纵束前部(节点10-29)AD平均值与转向过程平均角速度成负相关(β=-0.391,P=0.007);左侧扣带前中部(节点 29-60)RD 平均值与 TUG 时间(β=0.667,P=0.002)、行走时长(β=0.387,P=0.007)及SPPB评分(β=0.413,P=0.002)成正相关,与步速(β=-0.706,P=0.013)及转向过程角速度峰值(β=-0.296,P=0.040)成负相关.余纤维束节段FA、MD、AD、RD平均值均与各步态参数及SPPB评分无相关性(均P>0.05).结论 CSVD步态障碍患者的左侧扣带前部、左下纵束前部白质微结构存在多节段损伤,且影响其步态功能.
Objective To analyze the microstructural changes of white matter fiber tracts in patients with cerebral small vessel disease(CSVD)based on diffusion tensor imaging(DTI)using automatic fiber quantification(AFQ)technology and to explore the relationship between these changes and gait disorders.Methods Patients with CSVD who visited the Department of Neurology of the Second Affiliated Hospital of Xuzhou Medical University from September 2024 to May 2025 were prospectively included.Clinical data were collected from all patients enrolled,including demographic data(age,gender,years of education,body mass index),cerebrovascular risk factors(hypertension,diabetes,history of stroke,hyperlipidemia,smoking history,drinking history),laboratory tests(cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,lipoprotein a,fasting blood glucose,glycated hemoglobin,homocysteine,uric acid,creatinine),Montreal cognitive assessment scale visuospatial executive function score within 72 h after enrollment,periventricular white matter hyperintensity score,deep white matter hyperintensity score,lacunar infarction,microbleeds,enlarged perivascular spaces(>10),brain atrophy,incidental diffusion-weighted imaging positivity,cortical microinfarction,and cortical surface iron deposition.Within 72 h after enrollment,gait analysis was performed on all patients using a wearable motion and gait quantification assessment system,and multiple gait parameters were obtained:basic spatiotemporal parameters(timed up and go test[TUG]time,gait speed,cadence,walking duration,sitting duration,standing duration,step length,stride length,stance phase,swing phase),walking balance parameters(step length variability,peak trunk[forward,backward,left,right]tilt angle),symmetry parameters(step length asymmetry),turning flexibility parameters(turning duration,peak angular velocity during turning,average angular velocity during turning),and coordination(relative mean phase difference,phase coordination index,left-right foot coordination).All enrolled patients completed the short physical performance battery(SPPB)within 72 h of enrollment.According to the SPPB score,all patients were divided into the normal gait group(SPPB score ≥ 10 points)and the gait disorder group(SPPB score<10 points).3.0T MRI-DTI data were collected,and the whole brain streamlines were divided into 20 white matter tracts based on the Johns Hopkins University white matter tractography atlas and path points.Each tract was equally divided into 100 nodes,and AFQ technology was used to extract the fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(AD),and radial diffusivity(RD)values of each node of the 100 nodes of each white matter tract.The clinical data,gait parameters,and imaging data of the two groups of patients were compared.Partial correlation analysis was used to explore the correlation between each gait parameter and the average values of FA,MD,AD,and RD of all nodes of each white matter tract segment.To further control the influence of confounding factors,multiple linear regression analysis was performed with each gait parameter and SPPB scores as the dependent variable and the average values of FA,MD,AD,and RD of the white matter tract segments correlated with the gait parameters as the independent variables.All independent variables were subjected to multicollinearity tests.Variables with collinearity(with the tolerance less than 0.1,and the variance inflation factor[VIF]greater than 10)were excluded,the rest variables were analyzed with multiple linear regression to explore the relationship between the average values of FA,MD,AD,and RD of different segments of the white matter tracts and each gait parameter.Results A total of 60 patients with CSVD were included,including 31 males and 29 females,aged 45 to 80 years,with an average age of(64±11)years.Among them,31 patients had normal gait and 29 had gait disorders.(1)Compared with the gait disorder group,the normal gait group had a longer education duration and a lower body mass index(all P<0.05),while there were no statistically significant differences in the other indicators between the two groups(all P>0.05).Compared with the normal gait group,the gait disorder group had longer TUG time,walking duration,step length variability,and turning duration,and lower gait speed,step length,stride length,peak angular velocity during turning,and average angular velocity during turning(all P<0.05).(2)The FA values of the anterior cingulate gyrus(nodes 10-20,30-35)in the gait disorder group were lower than those in the normal gait group(false discovery rate[FDR]corrected,P<0.05);the MD values of the anterior part of the left inferior longitudinal fasciculus(nodes 1-43,53-56),the RD values of the anterior-middle part of the left cingulate gyrus(nodes 12-17,29-60),and the AD values of the anterior part of the left inferior longitudinal fasciculus(nodes 10-29)were higher in the gait disorder group than in the normal gait group(FDR corrected,P<0.05).(3)The results of the partial correlation analysis showed that the average FA value of the anterior cingulate gyrus(nodes 10-20)was negatively correlated with turning duration(r=-0.330,P=0.027)and positively correlated with peak angular velocity during turning(r=0.301,P=0.045)and average angular velocity during turning(r=0.355,P=0.017);the average MD value of the anterior part of the left inferior longitudinal fasciculus(nodes 1-43)was negatively correlated with gait speed(r=-0.306,P=0.039),step length(r=-0.344,P=0.019),and stride length(r=-0.347,P=0.018);the average RD value of the anterior-middle part of the left cingulate gyrus(nodes 29-60)was positively correlated with TUG time(r=0.326,P=0.029),walking duration(r=0.383,P=0.009),and turning duration(r=0.512,P=0.001),and negatively correlated with gait speed(r=-0.304,P=0.042),average angular velocity during turning(r=-0.504,P=0.001),and peak angular velocity during turning(r=-0.466,P=0.001);the average AD value of the anterior part of the left inferior longitudinal fasciculus(nodes 10-29)was negatively correlated with gait speed(r=-0.354,P=0.016),step length(r=-0.337,P=0.022),stride length(r=-0.347,P=0.018),and average angular velocity during turning(r=-0.341,P=0.020),and positively correlated with walking duration(r=0.323,P=0.029)and sitting duration(r=0.383,P=0.009).There was no correlation between the remaining gait parameters and the average values of the fiber tract segment indicators(all P>0.05).(4)No variables with collinearity were found by the collinearity test.The multiple linear regression model showed that,after controlling for confounding factors,the average MD value of the anterior part of the left inferior longitudinal fasciculus(node 1-43)was negatively correlated with step length(β=-0.380,P=0.008)and stride length(β=-0.431,P=0.002);the average AD value of the anterior part of the left inferior longitudinal fasciculus(node 10-29)was negatively correlated with average angular velocity during turning(β=-0.391,P=0.007).The average RD value of the left anterior midcingulate(nodes 29-60)was positively correlated with the TUG time(β=0.667,P=0.002),walking duration(β=0.387,P=0.007),and SPPB score(β=0.413,P=0.002),and negatively correlated with gait speed(β=-0.706,P=0.013)and peak turning angular velocity(β=-0.296,P=0.040).No correlation was found between the average values of FA,MD,AD,and RD of the rest segments of the white matter tracts with each gait parameter and SPPB score(all P>0.05).Conclusion CSVD patients with gait disorder exhibited multi-segment white matter microstructural damage in the left anterior cingulum and left anterior inferior longitudinal fasciculus,which affected their gait function.
李姝雅;刘海艳;张翠翠;彭茜钰;高晨舒
221004 徐州医科大学第二附属医院神经内科221004 徐州医科大学第二附属医院神经内科221004 徐州医科大学第二附属医院神经内科221004 徐州医科大学第二附属医院神经内科221004 徐州医科大学第二附属医院神经内科
脑小血管病弥散张量成像步态障碍,神经性白质微结构纤维束
Cerebral small vessel diseaseDiffusion tensor imagingGait disorders,neurologicWhite matter microstructureFiber tracts
《中国脑血管病杂志》 2026 (3)
169-181,13
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