分享:
分享到微信朋友圈
X
DCE-MRI定量技术专题
脑梗死后微血管渗透性改变及出血性转化的预测
许鹏君 孙钢 姜庆军 刘凯 李理 杨振

许鹏君,孙钢,姜庆军,等.脑梗死后微血管渗透性改变及出血性转化的预测.磁共振成像, 2015, 6(8): 575-580. DOI:10.3969/j.issn.1674-8034.2015.08.004.


[摘要] 目的 探讨缺血性脑梗死后急性期和亚急性期微血管渗透性改变及脑梗死后出血性转化(hemorrhagic transformation,HT)的预测。材料与方法 收集缺血性脑梗死病人43例,急性期10例,亚急性期33例,进行常规MRI及DCE-MRI扫描。利用药代动力学模型计算容积转运常数Ktrans,比较每一个病人梗死区和对侧正常脑组织的Ktrans值以及出血组和非出血组的Ktrans值有无差异,比较不同时期梗死区强化对预测HT的意义。结果 所有病人梗死区Ktrans值较对侧正常脑组织明显增高(P<0.05)。10例在急性期有脑实质强化的病人都有继发出血,在亚急性期和慢性期15例病人有继发出血,18例没有继发出血,Fisher's精确检验有统计学意义(P<0.05)。与亚急性期HT或没有HT的病人相比,急性期有HT组病人的Ktrans值明显增高(P <0.05 ),但是亚急性期HT和非HT的病人Ktrans值比较没有统计学差异(P>0.05)。结论 急性期脑实质强化对HT的预测有更高的特异性,且渗透性比亚急性期更高。早期脑实质强化及HT与毛细血管内皮的紧密连接和基底膜损伤有关。后期脑实质强化及HT与侧枝循环的建立有关,DCE-MRI可以定量评估血脑屏障的渗透性,对进一步研究HT的分型提供更科学的依据。
[Abstract] Objective: To evaluate the permeability changes in ischemic infarction in patients of acute stage and subacute stage and to predict the post-infarction hemorrhagic transformation.Materials and Methods: The data of 43 patients (10 acute stage and 33 subacute stage) who had routine MRI and DCE-MRI performed were retrospectively analyzed. Volume transitional co-efficiency (Ktrans) was measured with pharmacokinetic model. Statistical analysis of Ktrans was performed in the following different groups: infarcted tissue and contralateral normal tissue; hemorrhagic group and non-hemorrhagic group. The correlation of enhancement of different stages was analyzed by Fisher's test.Results: The Ktrans values of infarcted areas dramatically increased compared to those in the conterlateral’s in all cases (P<0.05). Subsequent hemorrhage was found in all 10 cases of acute stage and 15 cases of subacute stage while not found in the rest 18 cases, which was statistically different with Fisher's test (P<0.05). Ktrans values of cases with HT of acute stage were significantly higher than those with or without HT in subacute stage respectively (P<0.05). However, there was no statistical difference in Ktrans values between HT group and non-HT group in subacute stage.Conclusion: The specificity was better in early parenchymal enhancement in predicting HT and the permeability was higher compared to later periods. Early parenchymal enhancement and subsequent HT is likely associated with injury of early capillary endothelial cells of tight dense connections and basement membranes. Parenchymal enhancement in later period and HT is likely associated with establishment of collateral circulation. DCE-MRI could quantitatively evaluate osmotic quantity. It is of great help for further research on HT category.
[关键词] 出血性转化;微血管;血脑屏障;脑梗死;磁共振成像
[Keywords] Hemorrhagic transformation;Microvessels;Blood-brain barrier;Brain infarction;Magnetic resonance imaging

许鹏君 济南军区总医院医学影像科,济南 250031

孙钢* 济南军区总医院医学影像科,济南 250031

姜庆军 济南军区总医院医学影像科,济南 250031

刘凯 济南军区总医院医学影像科,济南 250031

李理 济南军区总医院医学影像科,济南 250031

杨振 济南军区总医院医学影像科,济南 250031

通讯作者:孙钢,E-mail:cjr.sungang@vip.163.com


收稿日期:2015-05-05
接受日期:2015-06-04
中图分类号:R445.2; R743.3 
文献标识码:A
DOI: 10.3969/j.issn.1674-8034.2015.08.004
许鹏君,孙钢,姜庆军,等.脑梗死后微血管渗透性改变及出血性转化的预测.磁共振成像, 2015, 6(8): 575-580. DOI:10.3969/j.issn.1674-8034.2015.08.004.

       随着人口老龄化的进展,脑梗死成为危害我国中老年人健康和生命的重要疾病之一。出血性转化(hemorrhagic transformation,HT)是缺血性脑梗死后常见的并发症,是脑梗死自然转归过程之一,也可以发生在抗凝或栓塞治疗后。临床研究[1]发现,急性脑梗死后自发出血性转化的发生率为10%~43%,应用溶栓药后出血性转化率可以提高2~ 3倍[2]。HT的发生限制了溶栓治疗的应用。近年来许多学者对脑梗死后出血性转化的发生、发展及预测进行了大量研究,研究表明[3] HT转化发生在微血管水平,其主要机制是血脑屏障(blood-brain barrier,BBB)完整性的破坏和渗透性的增加。而脑实质对比增强的出现被认为是血脑屏障的破坏[4]。现在,新的MRI影像技术动态增强磁共振成像,不但可以对病灶的强化特点进行评估,还可以对血脑屏障的渗透性进行定量分析。它利用药代动力学Extended Tofts双室模型,描述了对比剂在血浆和组织间隙之间交换的动力学过程。其最大的优点是可以定量测量微血管的渗透性,以Ktrans值表示。Ktrans是指对比剂从血管(血浆)空间渗漏到血管外细胞外空间(EES)的转运系数,它受血流、内皮细胞通透性、内皮细胞表面积的影响,能够反映新生血管的通透性[5]

       本文的目的是对脑梗死病人进行DCE-MRI定量分析,利用药代动力学Extended Tofts Linear双室模型拟合计算Ktrans值,探讨缺血性梗死后急性期和亚急性期微血管的渗透性改变及对脑梗死后出血性转化的预测。

1 材料与方法

1.1 材料

       共选择43例缺血性脑梗死病人,女性18例,男性25例。年龄42~ 74岁,平均57岁。急性期10例,亚急性期33例。急性期定义为起病72 h以内,亚急性期定义为起病10~ 15 d。所有病例都是幕上大脑半球梗死,所有病人都未进行抗凝剂栓塞药物的应用。所有患者都签署研究及对比剂增强知情同意书。

1.2 影像方法

       扫描用Signa discovery 750 3.0 T MRI(GE Healthcare, USA),采用8通道头颅线圈。MR影像序列包括:T1WI、T2WI、T2FLAIR、DWI、SWAN和T1W DCE-MRI。首先利用常规序列(尤其是DWI)判断病人有无梗死及梗死区范围,然后做动态增强扫描,选择梗死区有强化的病例(无强化的没有入组)。脑实质强化的定义为:在DWI显示为高信号的脑梗死区内Ktrans图及CET1-WI图出现高信号。后期复查时用非增强的T1WI及SWAN检验病灶是否有继发出血。因为SWAN序列是一种以T2*WI加权梯度回波序列作为序列基础,根据不同组织间的磁敏感性差异提供对比增强机制的技术,其最大优势是对出血的高度敏感。HT的定义为在梗死区,SWAN上出现低信号或在T1WI出现高信号。如果第一次扫描是在急性期,复查时间是10~ 15 d,如果第一次扫描是在亚急性期,复查时间是在23~ 30 d。如果在亚急性期第一次扫描的时候就有出血将不进行复查。

       扫描参数如下:平扫轴位T1WI :TR/TE= 1750/25.1 ms,矩阵= 320 × 256,间隔=1.5 mm,层厚=6 mm,共16层。T2WI:TR/TE =3621/103.8 ms,矩阵=512 × 512,间隔=1.5 mm,层厚= 6 mm,共16层。DWI:TR/TE=5000/70.8 ms,矩阵=160 × 160,间隔=1.5 mm,层厚=6 mm ,b=0和b=1000 s/mm2。SWAN:TR/TE = 78/43.4 ms,矩阵=384 × 320,层厚=2.0/-1.0 mm。动态增强扫描参数:(1)多翻转角T1 Mapping:TR=2.4,TE=1.2,FOV=24 mm × 18 mm,矩阵=160×128,FA分别=3°、6°、9°、12°、15°。层厚=5.0/-2.5 mm。(2)动态增强扫描3D GRE序列翻转角选择12° ,总时间为120 s,共30期,每期4 s。平扫两期后采用高压注射器注射钆双胺对比剂Gd-DTPA-BMA(欧乃影,GE Healthcare),注射速率2 ml/s,注射剂量15 ml。注射对比剂前利用高压注射器进21 ml生理盐水,注射完对比剂后再进行20 ml生理盐水以保证造影剂完全进入血管内,注射速率2 ml/s。

1.3 数据分析

       利用DCEMRI定量分析软件(Omni Kinetics, GE Healthcare)将多翻转角及动态增强扫描图像导入,多翻转角图像用于T1 Mapping计算将多期的动态增强图像从时间亮度信号转换成时间对比剂浓度信号。在动态增强扫描图像中选择上矢状窦血管横截面勾画圆形感兴趣区(region of interes,ROI)作为血管输入函数(vascular input function,VIF),感兴趣区均画在血管横截面中心位置并避免超出血管范围。通过药代动力学双室模型Extended Tofts Linear计算所有层面Ktrans图像。对照DWI图,在Ktrans图上选择梗死灶内有强化(明显异常高信号)的区域划取ROI并测量平均Ktrans值。采用单盲法由两位资深影像学专家对同一病灶进行3次勾画ROI,ROI为椭圆形,大小约为15~ 20像素,避开血管、坏死等位置。急性期先记录每一个ROI的平均值,再计算3次的平均值。在对侧同一位置的正常大脑组织放置大小相同的ROI作为参照,上述同样的方式进行测量。由两个神经放射学专家对HT进行判定并达成一致。

1.4 统计分析

       使用SPSS 19.0软件包对相关资料进行统计分析。计量资料采用单因素方差分析,计数资料采用卡方检验。

       按照有或无HT和不同时期,将病人分为3组:①组:急性期梗死区有脑实质强化,后期复查有继发出血。②组:亚急性期梗死区有脑实质强化,后期有继发出血。③组:在亚急性期梗死区有脑实质强化,后期无继发出血。不同组的Ktrans值的比较采用单因素方差分析(one-factor analysis of variance,one-way ANOVA),两两比较采用最小显著差异t检验(least significant difference t test,LSD-t),P<0.05被认为有统计学意义。计数资料采用卡方检验。

2 结果(图1,图2,图3,图4)

       研究显示,所有病人梗死区Ktrans值较对侧正常脑组织明显增高(P<0.05 )。与亚急性期有HT或没有HT的病人相比,急性期有HT组病人的Ktrans值明显增高(P<0.05),但是亚急性期HT和非HT的病人Ktrans值比较没有统计学差异(P>0.05)。见表1。在急性期,所有梗死区有强化的病人都有继发出血;在亚急性期,15例(58%)病人有HT,18例(42%)病人没有HT。Fisher's精确检验显示P<0.05,有统计学意义。结果显示,急性期梗死区有强化的病人比亚急性期病人更容易表现出继发出血,急性期梗死区强化更提示后期的继发出血,见表2

图1  急性期脑梗死区强化图。女,51岁,突发右侧肢体活动不灵2 d。A:急性期DWI左侧额叶及顶叶片状高信号;B:急性期T1WI左侧额叶及顶叶略低信号,未见高信号出血征象;C:急性期T1WI增强,左侧额叶可见条片状强化影;D:急性期Ktrans图示左侧额叶渗透性增高,Ktrans平均值=0.404,对侧Ktrans平均值=0.017
图2  亚急性期脑梗死区强化图,继发出血。同图1患者,起病14 d。A:亚急性期T1WI左侧额叶及顶叶梗死区可见斑点状高信号;B:亚急性期SWAN左侧额叶及顶叶片状低信号,提示其内有出血;C:亚急性期T1WI增强左侧额叶及顶叶可见条片状强化影;D:亚急性期Ktrans图示左侧额叶及顶叶渗透性增高,额叶病灶Ktrans平均值=0.036,对侧Ktrans平均值=0.007
Fig. 1  The map of enhancement in the infarction area in acute phase. Female patient, 51 years, sudden disability of right limb for 2 days. A: High signals were seen in the left frontal and parietal lobe in acute stage on DWI images; B: Relatively lower signals were found in the left frontal and parietal lobe in acute stage on T1WI images and there was no sign of hemorrhage;C: Flakes enhancement was visible in the left frontal lobe in acute stage on T1WI enhancement images; D: Ktrans diagram demonstrated that permeability of left frontal lobe increased and the average value of Ktrans was 0.404 and 0.017 for lesion area and contralateral area respectively.
Fig. 2  The map of enhancement in the infarction area in subacute phase, secondary hemorrhage. The same patient, 14 days after onset of symptom. A: Spotty high signals were detected in left frontal and parietal lobe in subacute stage on T1WI images; B: Low signals were present in left frontal and parietal lobe in subacute stage on SWAN images which could predict hemorrhage; C: Flakes enhancement was visible in left frontal and parietal lobe in subacute stage on T1WI enhancement images; D: Ktrans diagram demonstrated that permeability of left frontal lobe and parietal increased and the average value of Ktrans located in left frontal lobe was 0.036 and 0.007 for lesion area and contralateral area respectively.
图3  亚急性期脑梗死区强化图,无继发出血。女,56岁,起病12 d。A:亚急性期DWI示右侧颞叶片状略高信号;B:亚急性期T1WI增强示右侧颞叶斑片状强化影;C:亚急性期Ktrans图示右侧颞叶渗透性增高,Ktrans平均值=0.135,对侧Ktrans平均值=0.018;D:后期复查SWAN未见低信号出血征象
图4  亚急性期脑梗死区强化图,继发出血。男,起病13 d。A:亚急性期T1WI增强示左侧额顶叶可见片状强化影;B:亚急性期Ktrans图示左侧额顶叶渗透性增高,Ktrans平均值=0.195,对侧Ktrans平均值=0.005;C:亚急性期DWI示左侧额顶叶略高信号;D:后期SWAN复查显示左侧顶叶片状低信号,提示出血
Fig. 3  The map of enhancement in the infarction area in acute phase, no secondary hemorrhage. Female patient, 56 years, 12 days after onset of symptom. A: Relatively high signals were seen in the right temporal lobe in subacute stage on DWI images; B: Patchy enhancement was shown in the right temporal lobe in subacute stage on T1WI images; C: Ktrans diagram demonstrated that permeability of right temporal lobe increased and the value of Ktrans was 0.135 and 0.018 for lesion area and contralateral area respectively; D: Follow up showed that no hemorrhage was found on SWAN images.
Fig. 4  The map of enhancement in the infarction area in subacute phase, secondary hemorrhage.Male patient, 13 days after onset of the symptom. A: Patchy enhancement was present in the left frontal and parietal lobe in subacute state on T1WI images; B: Ktrans diagram demonstrated that permeability of left frontal and parietal lobe increased and the value of Ktrans was 0.195 and 0.005 for lesion area and contralateral area respectively; C: Relatively high signals were seen in the left frontal and parietal lobe in subacute stage on DWI images; D: Follow up showed that there were patchy low signals in the left parietal lobe in the subsequent SWAN images which predicted hemorrhage.
表1  梗死区和对侧正常脑组织Ktrans值比较以及梗死区急性期HT、亚急性期HT和亚急性期非HT Ktrans值比较
Tab. 1  The Ktrans value comparison in infarct and contralateral normal brain tissue and in infarction regions acute HT, subacute HT, subacute non-HT.
表2  急性期和亚急性期梗死区脑实质强化病人HT的发生率
Tab. 2  The incidence of HT the patient of infarction area parenchymal reinforcement in acute and subacute phase

3 讨论

       HT是缺血性脑梗死常见的并发症,是脑梗死自然转归过程之一,也可以发生在抗凝或栓塞治疗后。随着CT和MRI或抗凝和栓塞药的广泛应用,出血性转化的检测率逐渐提高。近年来许多学者对HT的发生和预测进行了大量的研究,但是因为它复杂的发生机制和演变过程仍有许多争议。HT的主要机制是血脑屏障完整性的破坏和渗透性的增加,而脑实质对比增强的出现被认为是血脑屏障的破坏,但是这个现象通常发生在亚急性期到慢性期,在急性期很少看到。现在,利用动态增强MRI及药代动力学模型,可以对血脑屏障的渗透性提供定量信息。

       在HT的发生率方面,研究结果显示所有在急性期梗死区有强化的病人后期复查都有HT,与亚急性期相比有统计学意义。表明急性期梗死区的强化比亚急性期能更好的预示脑梗死的HT。众所周知,梗死区脑实质强化通常发生在亚急性期(大于7 d),因为这时建立了丰富的侧枝循环及再灌注,而脑实质强化很少发生在急性期。Liu等[6]研究发现脑实质强化发生在亚急性晚期,达到高峰是在慢性早期,而在急性期和亚急性早期是没有强化。是否脑实质的强化暗示着脑梗死的继发出血,文献报道不一致。有研究表明梗死区脑实质强化与后期继发出血密切相关[7,8,9]。另有文献报道[8,10,11,12,13],T1WI早期脑实质的强化对预测HT有高度的特异性(85%),但敏感性只有35%。这与笔者的研究结果相一致,在急性期脑梗死的强化是少见的,但对预测脑梗死后继发出血有很高的特异性(100%)。不过笔者的研究样本量过小,还有待于进一步扩大样本量进行研究。笔者认为,早期的对比增强是有必要的,它可以对梗死后HT进行预测,指导临床医生规范合理用药。

       另一结果显示,所有病人梗死区强化的Ktrans值都明显高于对侧正常脑组织,而且急性期梗死区Ktrans值明显高于亚急性期,不管是有HT组还是无HT组。但是亚急性期HT组和无HT组比较Ktrans值没有统计学差异,这个结果没有报道过。笔者最初认为在亚急性期HT组的渗透性会更高,因为这个时期同时看到强化和出血,然而事实并非如此。

       T1WI脑实质强化的出现表明钆对比剂通过破坏的血脑屏障到达血管外间隙。HT发生的主要机制是血脑屏障完整性的破坏和渗透性的增加。血脑屏障是由毛细血管内皮细胞的紧密连接、基底膜和星形胶质细胞足突构成。脑梗死缺血后再灌注,许多介质参与了血脑屏障结构和功能的改变,使毛细血管内皮之间紧密连接和基底膜成份降解,血脑屏障完整性受到破坏,血管通透性增加,引起出血、水肿、甚至实质细胞的死亡。

       袁毅等人[14]研究发现,大鼠大脑中动脉闭塞后再灌注的时间与血脑屏障的通透性改变有密切关系。缺血再灌注后3 h,血脑屏障的通透性开始增加;再灌注6~ 12 h,血脑屏障通透性逐渐增加;再灌注1 d,血脑屏障的通透性升至高峰,2 d以后性逐渐减小。这个结果与Yang等[15]研究的急性和慢性脑血管血脑屏障破坏的结果相一致。章桃等[16]在对大鼠大脑中动脉闭塞后不同时间点再灌注增强扫描的研究中发现,缺血30 min后再灌注未见增强效应,缺血1.5 h后后再灌注脑室系统有显著强化,而缺血2 h后再灌注部分脑实质已经强化,这表明BBB已经受到了破坏,对比剂从受损的脉络丛渗透到了侧脑室BBB并渗透到脑实质内。

       当大面积脑梗死后,脑水肿使梗死灶内及周围组织毛细血管受压而发生缺血坏死,完整性破坏。随着水肿消退,侧支循环逐步开放,已发生坏死的毛细血管破裂引起梗死灶内及周围点片状出血。这一般发生在梗死后的第2周。另外,新生血管形成也是一种脑血流代偿方式。Marti等[17]研究发现,大脑中动脉闭塞48~ 72 h后,脑缺血周围区出现大量新生血管,这种新生血管增生活跃,容易与软脑膜血管的侧支循环发生沟通,尚未成熟的皮质血管会出现血液渗出。所以,在梗死早期,有许多因素引起血脑屏障通透性增加,笔者的结果显示在急性期Ktrans明显高于亚急性期是可以解释的。

       笔者的研究显示,CE-MRI可以评估血脑屏障的破坏,急性脑梗死后出现T1WI脑实质的强化是发生HT的重要预测指标。DCE-MRI可以定量评估渗透量,对进一步研究HT的分型有极大帮助。

       欧洲-澳大利亚急性卒中研究[18](European-Australasian acute stroke study,ECASSll)将脑梗死后出血性转换分为出血性梗死(hernorrhagic infarction, HI)和梗死后脑实质出血(parenchymal hematoma,PH),将HI分为出血性脑梗死-1型(梗死灶边缘小的淤点出血)和出血性脑梗死-2型(梗死区中较大的斑片状出血,无空间占位效应);将PH分为脑实质出血-1型(血肿占梗死区的30%,有轻度占位效应)和脑实质出血-2型(血肿面积大于梗死面积的30%,占位效应明显)。笔者认为上这种分型没有质的区别,只有度的区别,用DCE-MRI可以更精确的定量各种HT类型,为HT的分类提供更科学的依据。由于本组病例较少,笔者没有进一步对HT进行分型,下一步将收集更多的病例可以对各种类型的HT进行定量分析。

       早期脑实质强化在急性期是不常见的,但是对HT的预测有高度的特异性,而且渗透性比亚急性期的更高。早期脑实质强化和HT与毛细血管内皮细胞的紧密连接和基底膜损伤有关,后期脑实质强化和HT与侧支循环的建立有关。DCE-MRI可以定量评估血管的渗透性,对进一步研究HT的分类提供更科学的依据。

[1]
Berger C, Fiorelli M, Steiner T, et al. Hemorrhagic transformation of ischemic brain tissue:asymptomatic or symptomtic?. Stroke, 2001, 32(2):1330.
[2]
Gilligan AK, Markus R, Read S, et al. Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke. Stroke, 2002, 33(9): 2236-2242.
[3]
Hamann GF, Okada Y, del Zoppo GJ. Hemorrhagic transformation and microvascular integrity during focal cerebral ischemia reperfusion. J Cereb Blood Flow Metab, 1996, 16(6): 1373-1378.
[4]
Merten CL, Knitelius HO, Assheuer J, et al. MRI of acute cerebral infarcts, increased contrast enhancement with continuous infusion of gadolinium. Neuroradiology, 1999, 41(4): 242-248.
[5]
Bai XD, Sun XL, Wang Dan, et al. Differentiation between recurrent gliomas and radiationinduced brain injuries using DCE-MRI. Chin J Magn Reson Imaging, 2014, 5(1):1-6.
白雪冬,孙夕林,王丹,等.动态对比增强MRI在鉴别胶质瘤复发及放射性脑损伤中的应用.磁共振成像, 2014, 5(1):1-6.
[6]
Liu HS, Chung HW, Chou MC, et al. Effects of microvascular permeability changes on contrast-enhanced T1 and pharmacokinetic MR imagings after ischemia. Stroke, 2013, 44(7):1872-1877.
[7]
Vo KD, Santiago F, Lin W, et al. MR imaging enhancement patterns as predictors of hemorrhagic transformation in acute ischemic stroke. AJNR Am J Neuroradiol, 2003, 24(4):674-679.
[8]
Kim EY, Na DG, Kim SS, et al. Prediction of hemorrhagic transformation in acute ischemic stroke: role of diffusion-weighted imaging and early parenchymal enhancement. AJNR Am J Neuroradiol, 2005, 26(5): 1050-1055.
[9]
Kastrup A, Groschel K, Ringer TM, et al. Early disruption of the blood-brain barrier after thrombolytic therapy predicts hemorrhage in patients with acute stroke. Stroke, 2008, 39(8): 2385-2387.
[10]
Merten CL, Knitelius HO, Assheuer J, et al. MRI of acute cerebral infarcts, increased contrast enhancement with continuous infusion of gadolinium. Neuroradiology, 1999, 41(4): 242-248.
[11]
Virapongse C, Mancuso A, Quisling R. Human brain infarcts: Gd-DTPA-enhanced MR imaging. Radiology, 1986, 161(3): 785-794.
[12]
Mikulis DJ, Guo G, Wu R, et al. Gadolinium enhancement predicts hemorrhagic transformation in acute ischemic stroke [abstract: 43]. in: 44th annual meeting of the American Society for Neuroradiology. San Diego (CA), DOI: .
[13]
Latour LL, Kang DW, Ezzeddine MA, et al. Early blood-brain barrier disruption in human focal brain ischemia. Ann Neurol, 2004, 56(4): 468-477.
[14]
Yuan Y, Lei LF, Tu QY, et al. The relation of the permeability of blood brain barrier and expression of matrix metal loproteinase 9 in the rats model with cerebral ischemic and reperfusion. Chin J Arterioscler, 2008, 16(7): 510-512.
袁毅,雷立芳,涂秋云,等.大鼠脑缺血再灌注中血脑屏障通透性的改变与基质金属蛋白酶9表达的关系.中国动脉硬化杂志, 2008, 16(7): 510-512.
[15]
Yang Y, Rosenberg GA. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke, 2011, 42(11): 3323-3328.
[16]
Zhang T, Nie TT, Jia YL, et al. Spatiotemporal evolution of blood brain barrier damage associated with changes of brain metabolites following ischemia onset. Chin J Magn Reson Imaging, 2014, 5(6): 473-478.
章桃,聂婷婷,贾岩龙,等.超急性脑卒中血脑屏障和相关脑代谢物变化的研究.磁共振成像, 2014, 5(6): 473-478.
[17]
Marti HJ, Bernaudin M, Bellail A, et al. Hypoxia-induced vaseular endothelial growth factor expression precedes neovaseularization after cerebral isehemia. AmJ Pathol, 2000, 156(3): 965-976.
[18]
Hacke W, Kaste M, Fieschi C, et al. ECASS Study Group: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA, 1995, 274(3): 1017-1025.

上一篇 血流动力学双室模型Extended Tofts Linear在脑胶质瘤DCE-MRI渗透性定量分析的复测性及有效性研究
下一篇 动态增强磁共振定量成像对布氏杆菌性脊椎炎的鉴别诊断价值
  
诚聘英才 | 广告合作 | 免责声明 | 版权声明
联系电话:010-67113815
京ICP备19028836号-2