神经保护剂干预实验性缺血半暗带演变规律的磁共振动态观察

目的研究大鼠急性脑缺血模型缺血半暗带(IP)的扩散加权成像(DWI)和扩散张量成像(DTI)演变规律。材料与方法制作大鼠大脑中动脉闭塞(MCAO)缺血模型。分为应用神经保护剂组及对照组。在0.5～48h内行T2WI(T2WI)、DWI及DTI检查,测定缺血灶不同部位的表观弥散系数(ADC)、平均弥散系数(DCavg)、部分各向异性(FA)值,计算病侧与对侧正常组织的相对值rADC、rDCavg、rFA值。结果神经保护剂组与对照组的相对(r)ADC值、rDCavg值、rFA值,2h以内组间各ROI间差异均无统计学意义(P>0.05)。3～6h以后,两组间差异有统计学意义(P<0.01)。24h、48h两组间差异无统计学意义(P>0.05)。结论大鼠MCAO模型缺血灶ADC、DCavg、FA值具有特征性演变规律;IP存在的时间窗为9～12h,应用神经保护剂后IP存在时间可延长至24h。     

常压高浓度氧对缺血再灌注大鼠保护作用的DWI研究

目的利用磁共振扩散加权成像(diffusion-weighted imaging,DWI)评价常压高浓度氧(normobaric oxygen,NBO)对急性脑缺血再灌注大鼠的保护作用。方法成年雄性SD大鼠16只,采用线栓法制作右侧大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)缺血模型,随机分为NBO组和对照组,每组8只,NBO组大鼠于MCAO模型后吸入常压氧气3 h。每组均在MCAO后2 h拔出线栓恢复脑组织血流灌注,MCAO后分别于30 min、6 h、24 h行头颅DWI。DWI上测量大鼠的脑梗死体积增长率及脑梗死中心区和边缘区的相对表观扩散系数(relative appar-ent diffusion coefficient,rADC)值。24 h后取脑行HE染色,并与DWI结果进行比较。结果 NBO组与对照组大鼠右侧大脑中动脉供血区均可见异常高信号,ADC图上表现为低信号。NBO组大鼠6 h和24 h脑梗死体积增长率均低于对照组(P<0.05)。6 h和24 h NBO组梗死病灶中心区rADC值与对照组差异无统计学意义(P>0.05);NBO组梗死病灶边缘区rADC值高于对照组(P<0.01)。NBO组和对照组大鼠HE染色脑梗死灶与相应DWI层面差异无统计学意义(P>0.05)。结论 DWI对显示NBO对急性脑缺血再灌注大鼠的保护作用有重要价值。     

大鼠脑缺血再灌注的磁共振扩散加权成像研究

目的：采用磁共振扩散加权成像（DWI）评价大鼠脑缺血早期再灌注的动态变化,观察缺血早期再灌注对脑梗死的保护作用。方法：选取16只SD雄性大鼠,采用线栓法制作右侧大脑中动脉闭塞（MCAO）脑缺血模型,随机分为缺血再灌注组（缺血2h后再灌注）及对照组（永久性缺血）,每组8只。分别于制作MCAO模型后30min、2h、6h、12h及24h行MRI扫描。计算并比较缺血再灌注组与对照组大鼠每次扫描的脑梗死体积、脑梗死体积的增长率、脑梗死最大层面梗死区域的ADC值和rADC值。磁共振检查结束后处死大鼠,断头取脑行HE染色,并与DWI结果进行比较。结果：缺血再灌注组和对照组大鼠MCAO后DWI均显示右侧大脑中动脉供血区异常高信号,ADC图上为低信号。MCAO后2h、6h、12h及24h的DWI图上缺血再灌注组体积增长率均低于对照组,仅12h及24h时差异有统计学意义（P〈0.05）。MCAO后30min缺血再灌注组与对照组梗死区ADC值及rADC值差异均无统计学意义（P〉0.05）,但2h、6h、12h及24h时缺血再灌注组梗死区ADC值及rADC值均明显小于对照组（P〈0.05）。缺血再灌注组与对照组大鼠MCAO后HE染色均显示脑梗死灶体积与相应DWI层面差异无统计学意义（P〉0.05）。结论：DWI是评价超早期脑梗死再灌注的敏感方法,为脑梗死的疗效评价提供客观依据。     

ADC及rADC值对缺血性脑梗死缺血半暗带的诊断价值

【摘要】目的：探讨表观扩散系数（ADC）值及相对表观扩散系数（rADC）值在评价缺血性脑梗死缺血半暗带中的应用价值。方法：对42例超急性期脑梗死患者行常规CT、MRI、DSA检查,并于24h后行CT及MRI复查,根据患者出现临床症状到MRI检查时间分为超急性期（发病6h以内）、急性期（6~24h）和亚急性早期(24h~7d)。对比分析不同时期患侧梗死核心区、缺血半暗带与健侧镜像区的ADC及rADC值。结果：超急性期、急性期及亚急性期梗死核心区ADC值及rADC值均低于健侧镜像区,缺血半暗带ADC值及rADC值仅轻度下降,平均降幅为20%。梗死核心区与缺血半暗带ADC值及rADC值随着发病时间延长,上升趋势不同。缺血半暗带ADC值及rADC值均高于梗死核心区,差异有统计学意义（P<0.01）。结论：ADC值及rADC值对判定缺血半暗带具有较高的临床应用价值,有望成为一种简便易行的确定缺血半暗带的检查方法,为指导患者进行临床治疗提供重要的影像学依据。     

水通道蛋白-4在脑缺血半暗带组织中的表达

目的探讨水通道蛋白4(AQP4)在缺血半暗带(IP)中的表达规律。方法将健康Wistar大鼠36只,体重300～400g,雌雄不拘,数字表法随机分为对照组(6只)和栓塞组(30只);栓塞组又分为大脑中动脉栓塞(MCAO)后15min、30min、1h、3h、6h及24h组,每组各5只大鼠;对照组的大脑中动脉不栓塞,其余操作同栓塞组。对各组行脑部T1WI、T2WI和扩散加权成像(DWI)扫描。界定影像半暗带,计算影像半暗带和中心梗死区的相对表观扩散系数(rADC1和rADC2),将缺血脑组织进行红四氮唑(TTC)染色,并与扩散加权成像(DWI)对比。取最大层面的缺血半暗带组织进行病理观察、免疫组织化学及逆转录聚合酶链反应(RTPCR)实验,用图像分析检测AQP4的表达变化。结果对照组的MRI未见异常,相对表观扩散系数及AQP4表达无明显改变。栓塞组于15min即在DWI上出现高信号;栓塞后1h在T2WI出现高信号,rADC1在24h内呈下降趋势,在1h内下降最明显,从15min的(70.4±6.9)%下降到1h的(53.5±10.9)%;而rADC2呈现先降后升的变化规律,从15min的(71.4±6.6)%下降到3h的(45.7±10.5)%,然后回升到24h的(78.7±11.5)%。在24h内,AQP4基因表达逐渐上升,从15min的0.42±0.05上升到24h的1.18±0.12,与rADC1呈显著负相关(r=-0.966,P<0.001)。病理学观察,缺血半暗带组织呈细胞内水肿改变。结论细胞内水肿是脑缺血半暗带组织的病理基础之一,AQP4表达增强是缺血半暗带形成的重要原因,半暗带组织的rADC值下降可以间接反映AQP4表达上升的水平。     

大鼠超急性期脑缺血的磁共振扩散加权成像研究

目的：利用磁共振扩散加权成像（DWI）评价大鼠超急性期脑缺血的诊断价值。方法：12只Wistar雄性大鼠,采用线栓法制作右侧大脑中动脉闭塞（MCAO）脑缺血模型,分别于栓塞后1h和6h行大鼠冠状位磁共振DWI、T2WI和T1WI检查,并测量缺血区DWI异常高信号的体积、表观扩散系数（ADC）值,将所测值进行比较。磁共振检查结束后处死大鼠,断头取脑行TTC染色,并与DWI结果进行比较。结果：大鼠MCAO后1h进行MRI扫描右侧大脑中动脉供血区DWI可见异常稍高信号,ADC为低信号,T2WI和T1WI均未见异常信号;MCAO后6hDWI可见明显高信号,较1hADC值显著减低（P〈0.01）,DWI上梗死灶体积显著扩大（P〈0.01）,T2WI显示缺血区异常高信号,T1WI可见稍低信号。TTC染色者均显示脑梗死灶,与MCAO后6h的DWI显示脑缺血范围一致。结论：DWI对超急性期脑梗死较常规MRI敏感,是超急性期脑缺血重要的检查方法。     

水通道蛋白-4在急性脑缺血组织中的表达与MR扩散加权成像的相关性研究

目的　研究水通道蛋白 4(AQP 4)在急性期缺血脑组织中的表达规律 ,探讨扩散加权成像 (DWI)的分子生物学机制。方法　选Wistar大鼠 36只 ,数字表随机分为对照组 (1 2只 )和手术组 (2 4只 ) ,手术组分为大脑中动脉栓塞 (MCAO)后 1 5min、30min、1h、3h、6h及 2 4h组 (各 4只 ) ;对照组不栓塞 ,其余操作同手术组。分别进行脑部DWI,观察栓塞区异常信号出现的时间 ,测量最大层面高信号的强度比 (rd)和面积比 (rs)、相对表观扩散系数 (rADC)值 ,将脑组织进行红四氮唑 (TTC)染色 ,取与DWI相对应的最大缺血层面切片进行病理观察、免疫组织化学及原位杂交 ,用图像分析技术检测AQP 4蛋白 (△S)、基因 (α)的表达情况 ,并进行统计学分析。结果　对照组的DWI未见异常 ,脑组织无病理改变 ,AQP 4表达无明显变化。手术组在缺血后 1 5min即在DWI上出现高信号 ;在 1h内rADC迅速减小 ,AQP 4表达 (△S、α)、rd DWI与rs DWI都快速增加 ;随着时间推移 ,rADC值进一步下降 ,于 3h达到最低 ,6h开始回升 ,于 2 4h接近正常 ;△S、α、rd DWI与rs DWI在 1～ 6h期间的上升幅度减慢 ,除rd DWI外 ,其余各指标在 6h后又出现一增加高峰。AQP 4表达 (△S、α)与rd DWI和rs DWI都与时间 (T)有明显线性关系 (P =0 0 0 0 1 ) ,AQP 4表达与D     

大鼠急性缺血性脑卒中双指数扩散加权成像研究

目的:探讨大鼠急性缺血性脑卒中MRI及双指数扩散加权成像的动态变化.方法:30只成年雄性Wistar 大鼠随机分为大脑中动脉闭塞(MCAO)永久缺血组11只、缺血再灌注组11只及对照组8只,于术前及术后0.5、3、6、12和24 h分别行单b值、多b值DWI及T2 WI扫描,分析表观扩散参数(ADC)、慢速扩散系数(ADCsl.w)、快速扩散系数(ADCfast)和快速扩散所占容积分数(Afast)的动态变化,以24 h TTC组织染色作为病理对照.结果:永久缺血组ADC、ADCsl.w和Afast先降低,6h到达最低,而后轻度上升;ADCfast缺血后降低,并持续在一个较低水平.缺血再灌注组ADC、ADCslow、ADCfast和Afast于再灌注1.5h回升,但仍低于正常水平,而后逐渐下降,至24 h到达最低水平,且此时与永久缺血组各参数差异均无统计学意义(P＞0.05).ADCfast永久缺血组与再灌注组只在3h时差异有统计学意义(P＜0.05),Afast再灌注组与对照组只在3h时差异无统计学意义(P＞0.05).结论:多b值扩散加权成像可显示缺血不同时间点细胞内、外水分子的扩散受限情况及细胞内、外水分子的转移过程.     

脑梗死rADC值变化与临床分期相关性的初步研究

目的:分析脑梗死各临床分期的相对表现扩散系数(rADC)值变化,探讨rADC值的大小与临床分期的相关性。方法:收集22例脑梗死患者,分别于超急性期(<12h)、急性期(13～72h)、亚急性期(4～14d)、慢性期(15d)行常规序列和磁共振扩散加权成像(DWI)检查。测量各期病灶的ADC值,并计算rADC值,统计不同分期rADC值有无差异。按rADC值大小对临床各期病例进行统计,分析rADC值的大小与临床分期的相关性。结果:脑梗死rADC值在超急性期下降,急性期进一步下降;于亚急性期、慢性期逐渐上升。脑梗死病灶各期的rADC值有明显差异;脑梗死不同分期与rADC值大小有相关性。结论:根据脑梗死rADC值大小可判断其临床发病时间。     

水通道蛋白磁共振分子成像对脑缺血半暗带的评价

目的探讨多b值磁共振扩散加权(MR-DWI)水通道蛋白分子成像(AQP-MRI)对脑缺血半暗带的诊断价值。材料与方法将30只SD大鼠按随机区组设计法分为缺血组(25只,缺血1、3、6、24、48 h各5只)和对照组(5只),缺血组经历1h短暂性大脑中动脉栓塞(MCAO)建立脑缺血模型,两组分别行多模态MRI扫描,采集T2加权液体衰减反转恢复成像(T2-FLAIR)、扩散加权成像(DWI)、动脉自旋标记(ASL)及AQP-MRI(18b值DWI)图像。将AQP-MRI与T2-FLAIR不匹配的区域与传统DWI/T2-FLAIR不匹配和ASL/DWI不匹配作比较,验证AQP-MRI对缺血半暗带的诊断价值,并结合组织病理学进行评价。结果对照组在每个时间点各序列均未见异常信号。缺血组24 h内,AQP-MRI/T2-FLAIR不匹配面积与DWI/T2-FLAIR不匹配面积比较,差异有统计学意义(P<0.001);6 h内,AQP-MRI/T2-FLAIR不匹配面积与ASL/DWI不匹配面积比较,差异有统计学意义(P=0.001)。24 h内半暗带区相对比值与梗死区相对比值及正常脑组织相对比值比较,差异均有统计学意义(P均<0.001),组织病理学结果显示,半暗带区是正常脑组织向坏死转变的过渡。结论与传统的不匹配相比,AQP-MRI/T2-FLAIR不匹配可多层次、更精准地实时动态显示缺血半暗带。AQP-MRI与T2-FLAIR相结合可对缺血半暗带的评价提供有价值的影像学信息。     

急性脑缺血表观扩散系数成像的实验研究

用改良的线栓法大脑中动脉阻塞模型,探讨急性脑缺血及再灌注的表现扩散系数成像特点。方法：２０只ＳＤ大白鼠,分为４组：Ａ组（８只）,非再通组,Ｂ、Ｃ、Ｄ组（各４只）,分别于ＭＣＡＯ３０ｍｉｎ、１ｈ、２ｈ后再通,于不同时间点作ＡＤＣ成像和Ｔ２ＷＩ,并测量感兴趣区的ＡＤＣ、相对ＡＤＣ（ｒＡＤＣ）。结果：ＭＣＡＯ后１５ｍｉｎ好出现缺血区ＡＤＣ下降,而Ｔ２ＷＩ最早在栓塞后２ｈ出现异常。６ｈ内缺血区,ＡＤＣ及ｒ     

超早期脑梗塞及再灌注动物模型的磁共振弥散加权成像研究

目的     

急性脑缺血及再灌注磁共振扩散加权成像的特点

目的 用改良的线栓法制作大脑中动脉阻塞（ＭＣＡＯ）动物模型,探讨急性脑缺血及再灌注的磁共振扩散加权成像（ＤＷＩ）的特点。方法 １８只Ｓｐｒａｇｕｅ－Ｄａｗｌｙ大白鼠,随机分为４组：Ａ组（６只）,非再通组;Ｂ、Ｃ、Ｄ组（各４只）,分别是于ＭＣＡＯ３０分钟、１小时、２小时后再通,于不同时间点作ＤＷＩ和Ｔ２ＷＩ,通过后处理得到表观扩散系数（ＡＤＣ）像并计算感兴趣区的ＡＤＣ、相对ＡＤＣ（ｒＡＤＣ）及ＤＷＩ     

Effects of blood sugar level on rat transient focal brain ischemia consecutively observed by diffusion-weighted EPI and (1)H echo planar spectroscopic imaging.

The effects of blood sugar level on transient focal brain ischemia were examined by consecutive diffusion-weighted EPI and (1)H echo planar spectroscopic imaging. A remote-controlled rat intraluminal suture middle cerebral artery occlusion (MCAO) model was prepared. Animals were divided into three experimental groups: control, 1 g/kg, and 2 g/kg glucose groups (n = 6 for each). Saline or glucose was infused intraperitoneally 30 min prior to MCAO. The glucose-loaded groups showed increased lactate accumulation and marked decreases in average diffusion coefficient in the ischemic region during 40-min MCAO. These changes were correlated with blood sugar levels at the onset of MCAO. After reperfusion, all rats in the control and 1 g/kg groups recovered from the ischemic changes, but three rats with marked hyperglycemia in the 2 g/kg group showed irreversible changes. The adverse effects of hyperglycemia on transient focal brain ischemia were clearly demonstrated by sequential 2D images. Magn Reson Med 42:895-902, 1999.     

Rodent stroke induced by photochemical occlusion of proximal middle cerebral artery: evolution monitored with MR imaging and histopathology

PURPOSE: To longitudinally investigate stroke in rats after photothrombotic occlusion of proximal middle cerebral artery (MCA) with magnetic resonance imaging (MRI) in correlation with histopathology. MATERIALS AND METHODS: Forty-two rats were subjected to photochemical MCA occlusion and MRI at 1.5T, and sacrificed in seven groups (n=6 each) at the following time points: 1, 3, 6 and 12h, and at day 1, 3 and 9. T2-weighted (T2WI) and diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) map was performed in all rats. Contrast-enhanced T1-weighted imaging (CE-T1WI) was compared to intravital staining with Evans blue in one group for assessing blood-brain barrier (BBB) integrity. The brain was stained histochemically with triphenyl tetrazolium chloride (TTC) and processed for pathological assessment. The evolutional changes of relative lesion volume, signal intensity (SI), and the BBB integrity on MRI with corresponding histopathology were evaluated. RESULTS: The ischemic lesion volume reached a maximum around 12h to day 1 as visualized successively by DWI, ADC map and T2WI, implicating the evolving pathology from cytotoxic edema through vasogenic edema to tissue death. The ADC of brain infarction underwent a significant reversion after 12h, reflecting the colliquative necrosis. On CE-T1WI, BBB leakage peaked at 6h and at day 3 with a transitional partial recovery around 24h. The infarct volume on T2WI, DWI and ADC map matched well with that on TTC staining at 12h and at day 1 (p>0.05). CONCLUSION: The evolution of the present photothrombotic stroke model in rats could be characterized by MRI. The obtained information may help longitudinal studies of cerebral ischemia and anti-stroke agents using the same model.     

The effects of mannitol and furosemide on brain water changes in normal and MCA-occluded rats: a magnetic resonance study

Mannitol and furosemide treatment of ischaemic brain oedema caused by middle cerebral artery occlusion (MCAO) was studied by MRI in 87 rats. MRI was performed in all rats before and 30–360 min after drug infusion. The examinations were performed in the presence of an intact blood-brain barrier (BBB) 6 h after MCAO, and 3 days after MCAO at the time of maximal disruption of the BBB. Spin echo (SE) sequences were used for imaging and for determination of the relaxation times T1 and T2. Subtraction images were constructed. Furosemide dehydrated healthy and ischaemic brain. Mannitol had no dehydrating effect on healthy brain tissue. However, when the BBB was disrupted in severe oedema mannitol produced a decrease in water content, a shortening of T1 and T2, and a decrease in intracranial pressure (ICP), while in less severe oedema mannitol could increase brain water content, thus aggravating ICP. The subtraction technique allowed visualisation of the transient change in bulk in water animals with disruption of the BBB after mannitol treatment. Correspondence to: K.-Å. Thuomas     

Late stimulation of the sphenopalatine‐ganglion in ischemic rats: Improvement in N‐acetyl‐aspartate levels and diffusion weighted imaging characteristics as seen by MR

Purpose:

To assess, by MR spectroscopy (MRS) and diffusion weighted imaging (DWI), the ability of electrical stimulation of the sphenopalatine ganglion (SPG) to augment stroke recovery in transient middle cerebral artery occluded (t‐MCAO) rats, when treatment is started 18 ± 2 h post‐occlusion.

Materials and Methods:

¹H‐MRS imaging (¹H‐MRSI) and DWI were used to evaluate ischemic brain tissue after SPG stimulation in rats subjected to 2 h of t‐MCAO. Rats were examined by ¹H‐MRSI, DWI, and behavioral tests at 16 ± 2 h, 8 days, and 28 days post‐MCAO.

Results:

N‐Acetyl‐aspartate (NAA) levels of the stimulated and control rats were the same 16 ± 2 h post‐MCAO (0.52 ± 0.03, 0.54 ± 0.03). At 28 days post‐occlusion, NAA levels were significantly higher in the treated group (0.60 ± 0.04) compared with those of the untreated animals (0.50 ± 0.04; P < 0.05). This effect was more pronounced for regions with low NAA values (0.16 ± 0.03) that changed to 0.32 ± 0.03 (P = 0.04) for the treated group and to 0.10 ± 0.03 (P = 0.20) for the controls. DWI data showed better ischemic tissue condition for the treated rats, but the measured parameters showed only a trend of improvement. The MR results were corroborated by behavioral examinations.

Conclusion:

Our findings suggest that SPG stimulation may ameliorate MR tissue characteristics following t‐MCAO even if treatment is started 18 h post‐occlusion. J. Magn. Reson. Imaging 2010;31:1355–1363. © 2010 Wiley‐Liss, Inc.     

超急性脑梗死再灌注扩散加权-灌注磁共振成像及病理变化

目的应用扩散-灌注(DWI-PI)磁共振成像技术对改良线栓法建立的超急性脑梗死再灌注模型进行实验研究,并与病理结果对照.明确该技术对超急性脑梗死再灌注的评价作用.材料与方法 50只SD大鼠,随机分成5组,A组(10只)行假手术作对照,其余按栓塞时间30 min、1、3、6 h均分成B、C、D、E 4组;行DWI、PI和常规质子密度加权成像(PDWI)、T2WI、T1WI扫描;DWI和PI原始图像重建获得表观扩散系数(ADC)、脑血容量(CBV)、脑血流量(CBF)、平均通过时间(MTT)参数形态图.观察各栓塞时间点和再灌注2、24 h后各项参数变化,并将其结果与四氮唑红(TTC)染色和病理观察对比.结果 A组DWI、PI成像无异常信号,病理观察和TTC染色无变化.B组再灌注2 h DWI高信号消失,ADC值恢复正常化(88.27±1.92)%,24 h继发性ADC值降低和DWI高信号;C组再灌注2 h后ADC值轻度升高,24 h明显降低;D、E组再灌注2、24 h ADC值轻度降低或基本不变;各组再灌注后24 h DWI显示病灶范围无明显扩大.A、B组再灌注后PI各参数指标(CBV、CBF、MTT)恢复和维持正常,而D、E组的信号强度-时间曲线图有3种表现,分别为高灌注、低灌注和正常灌注.超急性脑梗死再灌注后DWI显示的缺血范围与TTC异常染色(白色)范围无显著性差异(方差分析,P＞0.05).结论在超急性脑梗死中大脑中动脉栓塞30 min再灌注后初次DWI异常信号消散是暂时的,以后会发生继发性DWI异常信号,再灌注后初次DWI异常信号消散区24 h后观察到神经元坏死;再灌注可限制病灶进一步扩大,保护缺血半影区.