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临床研究
DTI在穿支动脉粥样硬化性脑梗死患者短期预后的应用价值
荆彦平 郭振安 孙留严 吴连强 王熹 荆怡玟 陈丽微 吴肖峰 薛惠元

Cite this article as: JING Y P, GUO Z A, SUN L Y, et al. Application value of DTI in short-term prognosis of patients with branch athero-matous disease[J]. Chin J Magn Reson Imaging, 2023, 14(7): 32-36, 72.本文引用格式:荆彦平, 郭振安, 孙留严, 等. DTI在穿支动脉粥样硬化性脑梗死患者短期预后的应用价值[J]. 磁共振成像, 2023, 14(7): 32-36, 72. DOI:10.12015/issn.1674-8034.2023.07.006.


[摘要] 目的 探讨扩散张量成像(diffusion tensor imaging, DTI)技术在评估穿支动脉粥样硬化性脑梗死(branch athero-matous disease, BAD)以及皮质脊髓束(corticospinal tract, CST)完整性和损害程度的价值,协助预判临床预后。材料与方法 回顾性分析河南科技大学附属黄河三门峡医院2020年7月至2022年9月经临床诊断为BAD患者病例31例,根据患者的美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分及徒手肌力评定(Manual Muscle Test, MMT)评分,将患者进行预测分组,分为恢复组、部分恢复组和瘫痪组;同时通过DTI获取关键感兴趣区(region of interest, ROI)白质纤维束部分各向异性分数(fractional anisotropy, FA)及CST与BAD梗死部位的相对位置(相邻、部分穿过、穿过)关系,将患者预测为恢复组(相对位置为相邻)、部分恢复组(相对位置为部分穿过)及瘫痪组(相对位置为穿过);患者在治疗后1周、2周、4周进行NIHSS评分、MMT评分,并将评估结果作为实际值。行Pearson相关分析和偏相关分析探讨FA值、CST损害程度与NIHSS及MMT评分的相关性,并采用多因素线性逐步回归分析验证其线性数量关系。结果 31例患者FA图及表观扩散系数(apparent diffusion coefficient, ADC)图显示良好,结构清晰,梗死灶FA值较镜像侧相应部位正常脑组织降低,ADC值降低,t值分别为2.836、2.107,P值分别为0.015、0.010,差异有统计学意义(P<0.05)。CST重建显示良好,左右两侧显示率均为100%;纤维束重建后10例患者可见CST与梗死灶邻近但未穿过梗死灶,这部分患者预后良好,肌力恢复较快,恢复程度明显;11例患者CST部分穿过梗死灶,这部分患者预后稍差,肌力恢复稍差;10例患者CST全部穿过梗死灶,这部分患者预后差,病程长,肌力减退明显。经相关分析显示,BAD患者NIHSS评分、MMT预测评分及治疗后实际评分与患侧FA值呈正相关(P均<0.05);进一步行多因素线性逐步回归,患侧CST与BAD梗死部位的相对位置(相邻、部分穿过、穿过)关系与评分的恢复组、部分恢复组、瘫痪组存在线性回归关系。结论 DTI技术能对BAD以及CST完整性进行有效评估,其评估结果与临床预测及实际预后存在高度正相关性,可为临床治疗及评估预后提供依据。
[Abstract] Objective To investigate the value of diffusion tensor imaging (DTI) technology in evaluating the integrity and damage degree of perforator atherosclerotic cerebral infarction branch athero-matous disease (BAD) and corticospinal tract (CST), and to help predict clinical prognosis.Materials and Methods A total of 31 cases of patients with BAD from July 2020 to September 2022 were analyzed. According to the National Institutes of Health Stroke Scale (NIHSS) score and Manual Muscle Test (MMT) score, the patients were divided into prediction groups (recovery group, partial recovery group and paralysis group). At the same time, the fractional anisotropy (FA) of the key region of interest (ROI) and the relative position (adjacent, partially through, through) of CST and BAD infarction site were obtained by DTI, patients were predicted as recovery (relative adjacent), partial recovery (relative partial crossing) and paralysis (relative through); NIHSS score and MMT score were performed at 1, 2, and 4 weeks after treatment, and the evaluation results were taken as the actual values. Pearson correlation analysis and partial correlation analysis were performed to explore the correlation between FA value, CST extent of damage and NIHSS and MMT score, and multivariate linear stepwise regression analysis was used to verify the linear quantitative relationship.Results The FA and apparent diffusion coefficient (ADC) images of 31 patients showed good structure and clear structure. The FA value of the infarct and the corresponding normal brain tissue on the mirror side decreased, and the ADC value decreased, t values were 2.836 and 2.107, and P values were 0.015 and 0.010, respectively, and the differences were significant (P<0.05). The reconstruction of the corticospinal tract was good, and the visualization rate of the left and right corticospinal tracts was 100%. After fiber bundle reconstruction, 10 patients showed CST adjacent to the infarct but did not cross the infarct. These patients had a good prognosis, and their muscle strength recovered quickly and the recovery degree was obvious. In 11 patients, CST partially passed through the infarct. The prognosis of these patients was slightly worse, and the recovery of muscle strength was slightly worse. All the 10 patients had CST through the infarct. The prognosis of these patients was poor, the course of disease was long, and the muscle strength decreased significantly. Correlation analysis showed that NIHSS score, MMT predicted score and actual score after treatment were positively correlated with FA value of the affected side (all P<0.05). Multiple linear stepwise regression was performed. The relative position of the affected side CST and the BAD infarct site (adjacent, partially through, and through) had a linear regression relationship with the score of the recovery group, partial recovery group, and paralysis group.Conclusions DTI technology can effectively evaluate the integrity of BAD and CST, and the evaluation results are highly positively correlated with clinical prediction and actual prognosis, which can provide a basis for clinical treatment and prognosis assessment.
[关键词] 穿支动脉粥样硬化性脑梗死;扩散张量成像;磁共振成像;皮质脊髓束;美国国立卫生研究院卒中量表
[Keywords] branch athero-matous disease;diffusion tensor imaging;magnetic resonance imaging;corticospinal tract;National Institutes of Health Stroke Scale

荆彦平 1*   郭振安 1   孙留严 1   吴连强 1   王熹 1   荆怡玟 1   陈丽微 2   吴肖峰 2   薛惠元 2  

1 河南科技大学附属黄河三门峡医院影像中心,三门峡 472000

2 河南科技大学附属黄河三门峡医院神经内科,三门峡 472000

通信作者:荆彦平,E-mail:jingyanping5858@126.com

作者贡献声明:荆彦平设计本研究的方案,起草和撰写稿件,获取、分析或解释本研究的数据,对稿件重要的智力内容进行了修改,获得了中国电建集团医疗健康产业基金项目的资助;郭振安、孙留严、吴连强、王熹、荆怡玟、陈丽微、吴肖峰、薛惠元获取、分析或解释本研究的数据,对稿件重要的智力内容进行了修改;全体作者都同意发表最后的修改稿,同意对本研究的所有方面负责,确保本研究的准确性和诚信。


基金项目: 中国电建集团医疗健康产业基金项目 2022036
收稿日期:2022-10-28
接受日期:2023-06-25
中图分类号:R445.2  R743.3 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2023.07.006
本文引用格式:荆彦平, 郭振安, 孙留严, 等. DTI在穿支动脉粥样硬化性脑梗死患者短期预后的应用价值[J]. 磁共振成像, 2023, 14(7): 32-36, 72. DOI:10.12015/issn.1674-8034.2023.07.006.

0 前言

       穿支动脉粥样硬化性脑梗死(branch athero-matous disease, BAD)是急性缺血性卒中的常见类型,占所有缺血性卒中病因的10%~15% [1]。尽管临床积极应用抗血小板及溶栓药物治疗BAD,但其相关的急性期症状仍可能出现波动或恶化[2, 3],多表现为发病48~72 h内以进行性运动功能缺失(progressive motor deficiency, PDM)为主的早期神经功能恶化(early neurological deterioration, END)情况。研究发现,与其他卒中亚型相比,BAD出现END比例较高,其中豆纹动脉及脑桥旁正中动脉分布区的BAD更容易出现END[4]。此外,学者研究发现BAD多表现为进展性运动障碍,即卒中发病5 d内持续至少24 h的运动障碍增加,在美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分中,至少增加2分,其发生率在17%~75%[5],最终导致功能不良结局。有研究表明BAD与临床短期预后具有相关性[4, 5],BAD的具体损害程度一直是临床研究的瓶颈问题。本研究将扩散张量成像(diffusion tensor imaging, DTI)技术在BAD中皮质脊髓束(corticospinal tract, CST)完整性和损害程度的评估价值进行探讨,通过CST损害情况早期评估BAD的严重程度,很好地解决了这一瓶颈问题,为临床治疗及评估预后提供依据。

1 材料与方法

1.1 研究对象

       回顾性分析河南科技大学附属黄河三门峡医院2020年7月至2022年9月经临床诊断为BAD患者病例31例,其中男18例,女13例,年龄37~75(59.21±2.13)岁,在发病3~72 h进行MRI及DTI扫描;临床均有左侧或右侧肢体肌力减弱。纳入标准:(1)年龄18~80岁;(2)经扩散加权成像(diffusion weighted imaging, DWI)证实的豆纹动脉和脑桥旁正中动脉新发梗死,若表现为短暂性脑缺血发作(transient ischemic attack, TIA),须同时在DWI上可见新发梗死病灶;(3)无大动脉疾病(责任动脉血管>50%狭窄)和心源性栓塞的证据;(4)符合BAD定义的初次发病,且为单侧,行DTI检查前未接受相关治疗;(5)起病至入组时间<72 h,若起病时间不详,则须末次正常时间至入组时间<72 h;(6)签署扫描注意事项知情同意书。排除标准:(1)DWI提示急性双侧大脑梗死患者;(2)既往遗留明显神经功能缺损患者;(3)其他明确病因所致的卒中,如烟雾病、动脉夹层、血管炎等;(4)合并其他神经系统疾病或精神病;(5)伴有严重心脏、肝脏、肾脏功能衰竭、出凝血功能障碍者。本研究遵守《赫尔辛基宣言》,并获得河南科技大学附属黄河三门峡医院伦理委员会批准(批准文号:2022LL58),免除受试者知情同意。

1.2 扫描方法及后处理

       MRI扫描使用美国GE 3.0 T SIGNA Pioneer超导型扫描仪,32通道头颈联合相控阵线圈,扫描定位像及横轴位T1WI(TR/TE 2484.7 ms/26.7 ms,TI 790.8 ms,FA 111.0°)、液体衰减反转恢复(fluid attenuated inversion recovery, FLAIR)T2WI(TR/TE 8000.0 ms/111.6 ms,TI 2341.0 ms,FA 160.0°)、DWI(TR/TE 5731.0 ms/78.4 ms,FA 90.0°),层厚5 mm,层间隔0.5 mm。采用平面回波成像(echo planar imaging, EPI)序列进行DTI原始数据扫描,矩阵128×128,层厚5 mm,层间隔0 mm,层数464层,在12个方向上施加扩散梯度,扫描时间为4 min 52 s。

       所有入组患者参照同一层面的T2WI FLAIR及DWI图像,选择梗死区最大层面,分别于梗死灶中心区及对侧镜像区设置感兴趣区(region of interest, ROI),分别测定每个ROI的各向异性分数(fractional anisotropy, FA)值、表观扩散系数(apparent diffusion coefficient, ADC)值,应用Readyview软件包完成DTI数据的处理,得到部分FA值及彩色编码FA图,并同时测量对侧相应部位脑组织FA值与ADC值作为对照。最后以侧脑室旁或基底节区设定的ROI以及镜像侧ROI或以双侧内囊后肢为另一个ROI,作出双侧CST图,并保存横断面图像,了解CST与梗死灶的相互关系。

1.3 临床评分及影像判读

       根据患者入组NIHSS评分,评分表参考中华医学会神经病学分会、中华医学会神经病学分会脑血管病学组制订的中国急性缺血性脑卒中诊治指南(2018)[6],将患者进行预测分组:0~4分为恢复组、5~15分为部分恢复组、≥16分为瘫痪组;根据患者徒手肌力MMT评分,将患者进行预测分组:4~5级为恢复组、2~3级为部分恢复组、0~1级为瘫痪组。由2名高年资(3年)的主治医师对所有入组患者在治疗后1周、2周、4周进行NIHSS评分、徒手肌力评定(Manual Muscle Test, MMT)评分,并将评估结果作为实际值。将后处理的病变侧FA值及ADC值与镜像侧的FA值及ADC值分别保存、记录,同时分析通过DTI获取关键ROI的CST与BAD梗死部位的相对位置,标注二者是相邻、部分穿过或穿过关系,并根据相对位置关系将患者预测为恢复组(相对位置为相邻)、部分恢复组(相对位置为部分穿过)及瘫痪组(相对位置为穿过)。

1.4 数据分析

       根据测量病灶区的FA值与ADC值,并取镜像侧相应部位数值作为对照,应用SPSS软件进行两独立样本t检验,以P<0.05为差异有统计学意义。并将预测值和实际值进行比较,比较采用χ2检验或Fisher确切概率法,以P<0.05为差异有统计学意义。行Pearson相关分析和偏相关分析探讨FA值、CST与NIHSS及MMT评分的相关性,并采用多因素线性逐步回归分析验证其线性数量关系。

2 结果

       31例患者FA图及ADC图显示良好,结构清晰,梗死灶FA值较镜像侧相应部位正常脑组织降低,ADC值降低,t值分别为2.836、2.107,P值分别为0.015、0.010,差异有统计学意义(P<0.05),见表1。CST重建显示良好,左右两侧显示率均为100%;纤维束重建后10例患者可见CST与梗死灶邻近但未穿过梗死灶(图1),这部分患者预后良好,肌力恢复较快,恢复程度明显;11例患者CST部分穿过梗死灶(图2),这部分患者预后稍差,肌力恢复稍差。10例患者CST全部穿过梗死灶(图3),这部分患者预后差、病程长,肌力减退明显。经相关分析显示,BAD患者NIHSS评分、MMT预测评分及治疗后实际评分与患侧FA值呈正相关(P均<0.05);进一步行多因素线性逐步回归,患侧CST与BAD梗死部位的相对位置(相邻、部分穿过、穿过)关系与评分的恢复组、部分恢复组、瘫痪组存在线性回归关系(图4)。

图1  女,55岁,右侧脑室旁急性或亚急性脑梗死。1A:DWI显示右侧脑室旁斑片状扩散受限信号;1B:DTI显示右侧脑室旁FA值(0.26 mm2/s)较对侧(0.37 mm2/s)减低;1C:DTI显示横断纤维束重建后CST与梗死灶邻近;1D:DTI显示冠状纤维束重建后CST未穿过梗死灶。
图2  男,67岁,右侧脑室旁多发急性或亚急性脑梗死。2A:DWI显示右侧脑室旁多发斑片状扩散受限信号;2B:DTI显示右侧脑室旁ROI FA值(0.22 mm2/s)较对侧(0.38 mm2/s)减低;2C:DTI显示纤维束重建后CST部分穿过梗死灶;2D:DTI显示冠状纤维束重建后CST部分穿过梗死灶,远端纤维束受损、稀疏。
图3  女,53岁,左侧脑室旁多发急性或亚急性脑梗死灶。3A:DWI显示左侧脑室旁多发斑片状扩散受限信号;3B:DTI显示左侧脑室旁ROI FA值(0.17 mm2/s)较对侧(0.36 mm2/s)减低;3C:DTI显示纤维束重建后CST全部穿过梗死灶;3D:DTI显示纤维束重建后CST全部穿过梗死灶,远端纤维束受损、完全缺失。DWI:扩散加权成像;DTI:扩散张量成像;FA:各向异性分数;CST:皮质脊髓束;ROI:感兴趣区。
Fig. 1  Female, 55-year-old, right paraventricular acute or subacute cerebral infarction. 1A: DWI shows patchy diffuse restricted signals in the right paraventricular region; 1B: DTI shows that the FA value of the right paraventricular is lower than that of the contralateral side; 1C: DTI shows that the CST is adjacent to the infarct after reconstruction of the transection fiber bundle; 1D: DTI shows that CST don't cross the infarct after coronal fiber bundle reconstruction.
Fig. 2  Male, 67-year-old, multiple acute or subacute cerebral infarction foci near the right ventricle. 2A: DWI shows multiple patchy diffusion-restricted signals in the right paraventricular region; 2B: DTI shows that the FA value of the right paraventricular ROI is lower than that of the contralateral side; 2C: DTI shows that the CST partially pass through the infarct after fiber bundle reconstruction; 2D: DTI shows that the CST partially pass through the infarct after coronal fiber bundle reconstruction, and the distal fiber bundle is damaged and sparse.
Fig. 3  Female, 53-year-old, multiple acute or subacute cerebral infarction foci near the left ventricle. 3A: DWI shows multiple patchy diffuse restricted signals in the left paraventricular region; 3B: DTI shows that the FA value of the left paraventricular ROI is lower than that of the contralateral side; 3C: DTI shows that all CST pass through the infarct after fiber bundle reconstruction; 3D: DTI shows that all CST pass through the infarct after fiber bundle reconstruction, and the distal fiber bundle is damaged or completely absent. DWI: diffusion-weighted imaging; DTI: diffusion tensor imaging; FA: fractional anisotropy; CST: corticospinal tract; ROI: area of interest.
图4  进一步行多因素线性逐步回归,患侧CST与BAD梗死部位的相对位置(相邻、部分穿过、穿过)关系(预测值)与恢复组、部分恢复组、瘫痪组的评分(真实值)存在线性回归关系。BAD:穿支动脉粥样硬化性脑梗死;CST:皮质脊髓束。
Fig. 4  Multi-factor linear stepwise regression is further performed, and the correlation (predicted value) between the relative location (adjacent, partially through and through) of the affected CST and the BAD infarction site is linear regression (true value) between the score of recovery group, partial recovery group and paralysis group. CST: corticospinal tract; BAD: branch athero-matous diseas.
表1  梗死灶及梗死灶对侧FA值和ADC值
Tab. 1  FA value and ADC value of the infarct and the contralateral infarct

3 讨论

       受限于传统神经影像技术难以显示穿支动脉[7],目前BAD采用的诊断标准是基于穿支动脉供血区域影像学检查显示的病灶特征的诊断标准[8],临床上对于BAD的影像诊断普遍采用DWI技术,但其很难准确地显示白质纤维束受损范围和神经纤维束的空间关系。本研究采用DTI技术探讨BAD患者的CST损害程度,量化测量病变区白质纤维束的FA值,将CST与BAD病灶的相对位置分为相邻、部分穿过、穿过,并根据NIHSS评分及MMT评分将患者预测为恢复组、部分恢复组、瘫痪组,并在治疗后1周、2周、4周重新根据量表评分作为实际值,通过统计学分析FA值、CST损害程度与量表评分之间的相关性,并证明其存在线性数量关系,得出恢复组(相对位置为相邻)、部分恢复组(相对位置为部分穿过)及瘫痪组(相对位置为穿过)预测值与实际值存在相关性,用以评估患者病情及预后存在科学依据。DTI技术能有效评估BAD对CST的损害情况,协助预判临床预后,指导临床精准治疗,这种无创性的MRI新技术值得进一步深入研究。

3.1 DTI在BAD的应用价值

       DTI技术是在DWI基础上发展、深化而成的另一种无创性白质纤维束成像与后处理技术,可以可视化白质纤维束和定量白质纤维束的完整性,显示纤维束的走行和形态,也可明确梗死区内纤维束及周围解剖关系和受损程度,对脑梗死后神经纤维束损伤的检测显示出明显优势。以往文献大多研究胼胝体纤维束与梗死的相互关系[9],对DTI技术在BAD中CST完整性和损害程度的研究很少,没有指出CST损害与临床预后的相关性,在本研究中,将CST与BAD梗死部位的相对位置作为研究重点,并结合FA值和ADC值分析病变的病理变化及与临床预后的相关性。FA值是DTI常用参数,代表水分子扩散的各向异性,FA值的大小与扩散方向的异性程度呈正相关,是评价脑梗死患者白质纤维束完整性和致密性的重要指标[10, 11]。FA值越低,提示病变区脑组织损害越严重,与文献报道[12, 13]一致。BAD主要累及支配肢体运动功能的CST,CST走行路径上的病变会导致CST出现结构损伤,引起痉挛性偏瘫等严重的PDM症状[14, 15];BAD相关功能障碍的发病机制复杂,除梗死灶直接造成的局部脑结构损伤外,神经纤维束完整性的破坏也影响结构连接以及关键脑区之间联系,是导致功能障碍的主要原因[16, 17]。因此进一步量化、评估BAD相关卒中神经功能缺损程度、明确梗死灶与CST位置关系对预测预后很重要。

3.2 CST与梗死灶相对位置关系

       有学者认为脑梗死病灶区扩散FA降低[18, 19],然而准确定位梗死灶与纤维束的空间关系的研究较少。本研究通过分析31例BAD累及CST的急性期脑梗死患者的DTI图像,利用DTI原始数据进行三维纤维束追踪成像,分析纤维束的方向性及完整性,并显示梗死灶与CST的空间关系,探讨DTI对于脑梗死临床表现的解释以及预测预后,辅助制订临床治疗方案。本研究提示脑梗死区FA值较镜像侧明显降低,ADC值较镜像侧降低,CST穿过梗死灶的患者较相邻及部分穿过者运动功能恢复较差,CST未穿过梗死灶的患者运动功能恢复较好。

3.3 CST受损与临床预后的关系

       NIHSS评分、MMT评分具有较高的敏感性和特异性,可较好反映出患者功能障碍程度[20, 21]。本研究采用 DTI技术评估BAD梗死后功能障碍患者CST完整性及损伤严重程度,通过分析关键脑区FA值、ADC值变化,以及CST受损程度与NIHSS和MMT评分的相关性和线性数量关系,并通过偏相关分析显示,NIHSS和MMT评分与患侧FA值及CST受损程度呈正相关;进一步将评分结果作为因变量,将上述关键脑区FA值及CST受损程度作为自变量,获得多因素线性逐步回归方程,表明FA值及CST受损程度与评分结果存在线性回归关系;同时研究显示,CST穿过梗死灶的患者与CST未穿过梗死灶的患者相比,神经功能缺损较明显,两者有显著性差异,因此我们认为CST未穿过梗死灶的患者预期有更好的运动功能恢复。个别患者虽然CST未经过梗死灶,但也可产生运动功能损伤,可能是由于急性脑梗死时梗死灶周围存在血管源性水肿[22, 23],当然,这种水肿及运动功能损伤很容易恢复。个别CST经过梗死灶的患者相应的运动功能损伤也能有部分恢复,是由梗死灶周边的侧支循环供血代偿所致[24, 25]。在少部分患者中可以观察到CST因细胞毒性水肿而扩散受限,可能最终坏死,这能解释有些患者不能完全恢复或延迟恢复的临床表现[26, 27]。因此认为,通过DTI定量分析CST受损程度可以预测功能障碍的严重程度。

3.4 本研究的局限性

       本研究尚存在一些局限性。第一,样本量相对较少;第二,方法相对较单一,参数较少;第三,NIHSS评分、MMT评分个别受时间及不同医师差异影响,评分结果可能稍有差异;第四,未能将治疗后的CST恢复情况与治疗前做比较。以上的局限性将在今后的研究中进一步完善,使得研究结论更具代表性。

4 总结

       综上所述,本研究提供了其他检查方法无法提供的独特信息,应用DTI技术量化BAD患者的CST受损程度及与病灶的相互空间关系能为BAD患者短期预后评估提供参考性依据,值得推荐。

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