MRI of focal cerebral ischemia using (17)O-labeled water.

This work presents a novel approach for quantifying low concentrations of H(2)(17)O in vivo and explores its utility for assessing cerebral ischemia. Oxygen-17 enriched water acts as a T(2) shortening contrast agent whose effect can be suppressed by decoupling at the (17)O frequency during TE interval in a spin-echo MR image. Serial T(2)-weighted echo planar images were acquired in phantoms and rat brain with decoupler power alternated every eight images. The resulting periodic signal change (proportional to H(2)(17)O concentration) was detected by cross-correlating the square-wave decoupler power timecourse with the signal intensity in each voxel. Natural abundance (0.037 atom%) images of H(2)(17)O in rat brain were generated. The transverse relaxivity of H(2)(17)O in brain was estimated, R(2) = 2.4+/-0.5 s(-1)(atom%)(-1). After bolus injection of 1 ml of 10 atom% H(2)(17)O, brain H(2)(17)O concentration was estimated at 0.06+/-0.01 atom%. In the rat focal ischemia model, (17)O cross-correlation maps compared well with diffusion and Gd-DTPA perfusion images to indicate infarct location. Magn Reson Med 43:876-883, 2000.     

Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion.     

Venous signal suppression in 3D dynamic Gd-enhanced carotid artery imaging using the eigenimage filter.

A three-dimensional dynamic gadolinium-enhanced carotid artery imaging protocol with 10 sec per phase was evaluated with respect to the acquisition of an arterial-only phase after contrast bolus injection. Subsequently, the eigenimage filter was used to suppress any venous signal based on a difference in arterial and venous temporal enhancement patterns. From 63 consecutive scans of the carotid bifurcation, venous enhancement in the maximal arterial phase was found to be absent in 43%, weak in 19%, and strong in 38% of cases. Our eigenimage filter successfully suppressed the low signal veins in 100% and the high signal veins in 67% of cases. The number of acquired high-quality arterial-only images increased from 43% without to 87% with the use of the filter. In conclusion, even when a dynamic scan cannot resolve the short physiological delay between arterial and venous enhancement, the eigenimage filter can effectively be used to suppress the veins. Magn Reson Med 42:307-313, 1999.     

Multispectral analysis of the temporal evolution of cerebral ischemia in the rat brain

A major difficulty in staging and predicting ischemic brain injury by magnetic resonance (MR) imaging is the time-varying nature of the MR parameters within the ischemic lesion. A new multispectral (MS) approach is described to characterize cerebral ischemia in a time-independent fashion. MS analysis of five MR parameters (mean diffusivity, diffusion anisotropy, T2, proton density, and perfusion) was employed to characterize the progression of ischemic lesion in the rat brain following 60 minutes of transient focal ischemia. k-Means (KM) and fuzzy c-means (FCM) classification methods were employed to define the acute and subacute ischemic lesion. KM produced an estimate of lesion volume that was highly correlated with postmortem infarct volume, independent of the age of the lesion. Overall classification rates for KM exceeded FCM at acute and subacute time points as follows: KM, 90.5%, 94.4%, and 95. 9%; FCM, 82.4%, 90.6%, and 82.6% (for 45 minutes, 180 minutes, and 24-120 hours post MCAO groups). MS analysis also offers a formal method of combining diffusion and perfusion parameters to provide an estimate of the ischemic penumbra (KM classification rate = 70.3%). J. Magn. Reson. Imaging 2000;12:842-858.     

Sodium mapping in focal cerebral ischemia in the rat by quantitative 23Na MRI

Purpose

To validate ²³Na twisted projection magnetic resonance imaging (MRI) as a quantitative technique to assess local brain sodium concentration ([Na⁺]_br) during rat focal ischemia every 5.3 minutes.

Materials and Methods

The MRI protocol included an ultrashort echo‐time (0.4 msec), a correction of radiofrequency (RF) inhomogeneities by B₁ mapping, and the use of 0–154 mM NaCl calibration standards. To compare MRI [Na⁺]_br values with those obtained by emission flame photometry in precision‐punched brain samples of about 0.5 mm³ size, MR images were aligned with a histological three‐dimensional reconstruction of the punched brain and regions of interest (ROIs) were placed precisely over the punch voids.

Results

The Bland–Altman analysis of [Na⁺]_br in normal and ischemic cortex and caudate putamen of seven rats quantitated by ²³Na MRI and flame photometry yielded a mean bias and limits of agreement (at ±1.96 SD) of 2% and 43% of average, respectively. A linear increase in [Na⁺]_br was observed between 1 and 6 hours after middle cerebral artery occlusion.

Conclusion

²³Na MRI provides accurate and reliable results within the whole range of [Na⁺]_br in ischemia with a temporal resolution of 5.3 minutes and precisely targeted submicroliter ROIs in selected brain structures. J. Magn. Reson. Imaging 2009;29:962–966. © 2009 Wiley‐Liss, Inc.     

Separating changes in the intra- and extracellular water apparent diffusion coefficient following focal cerebral ischemia in the rat brain.

Selective intracellular (IC) and extracellular (EC) brain water apparent diffusion coefficient (ADC) values were measured in normal and ischemic rat brain. Selective T(1)-relaxation enhancement of the EC water, using intracerebroventricular (ICV) infusion of an NMR contrast reagent (CR), was used to separate the IC and EC signal contributions. In the CR-infused, normal brain (n = 4), T(1) = 235 +/- 10 ms and T(2) = 46 +/- 2 ms for IC water (85%) and T(1) = 48 +/- 8 ms and T(2) = 6 +/- 2 ms for EC water (15%). Volume-localized ADC(z) (z-gradient axis) values were 0.90 +/- 0.02 (EC+IC), 0.81 +/- 0.05 (IC), 0.51 +/- 0.02 (EC+IC), and 0.53 +/- 0.07 (IC), for normal, CR-infused, ischemic, and ischemic/CR-infused groups, respectively (ADC values are x10(-3) mm(2)/s; n = 5 for each group). Imaging ADC(z) values were 0.81 +/- 0.03 (EC+IC), 0.75 +/- 0.05 (IC), 0.51 +/- 0.04 (EC+IC), and 0.52 +/- 0.05 (IC), respectively, for the same groups. Imaging ADC(av) (average diffusivity) values for the same groups were 0.70 +/- 0.05 (EC+IC), 0.69 +/- 0.06 (IC), 0.45 +/- 0.06 (EC+IC), and 0.44 +/- 0.06 (IC), respectively. These results suggest that the IC water ADC determines the overall water ADC value in normal and ischemic rat brain.     

Inhomogeneous sodium accumulation in the ischemic core in rat focal cerebral ischemia by 23Na MRI

Purpose

To test the hypotheses that (i) the regional heterogeneity of brain sodium concentration ([Na⁺]_br) provides a parameter for ischemic progression not available from apparent diffusion coefficient (ADC) data, and (ii) [Na⁺]_br increases more in ischemic cortex than in the caudate putamen (CP) with its lesser collateral circulation after middle cerebral artery occlusion in the rat.

Materials and Methods

²³Na twisted projection MRI was performed at 3 Tesla. [Na⁺]_br was independently determined by flame photometry. The ischemic core was localized by ADC, by microtubule‐associated protein‐2 immunohistochemistry, and by changes in surface reflectivity.

Results

Within the ischemic core, the ADC ratio relative to the contralateral tissue was homogeneous (0.63 ± 0.07), whereas the rate of [Na⁺]_br increase (slope) was heterogeneous (P < 0.005): 22 ± 4%/h in the sites of maximum slope versus 14 ± 1%/h elsewhere (here 100% is [Na⁺]_br in the contralateral brain). Maximum slopes in the cortex were higher than in CP (P < 0.05). In the ischemic regions, there was no slope/ADC correlation between animals and within the same brain (P > 0.1). Maximum slope was located at the periphery of ischemic core in 8/10 animals.

Conclusion

Unlike ADC, ²³Na MRI detected within‐core ischemic lesion heterogeneity. J. Magn. Reson. Imaging 2009;30:18–24. © 2009 Wiley‐Liss, Inc.     

大鼠脑缺血再灌注DNA单链断裂与凋亡

观察脑缺血再灌注损伤中DNA单链断裂、神经元凋亡的变化,探索它们的关系,发现脑缺血再灌注先引起神经元DNA单链断裂,随后出现神经元凋亡,DNA单链损伤可能是神经元凋亡的机制之一。     

Apparent diffusion coefficient mapping of experimental focal cerebral ischemia using diffusion-weighted echo-planar imaging

Diffusion-weighted, echo-planar imaging (EPI) was used to map regional changes In the apparent diffusion coefficient (ADC) during experimental focal ischemia in the rat brain following permanent middle cerebral arterial occlusion (MCAO). Sixteen 64 × 64 diffusion-weighted EPIs were acquired in 32 s with successively increasing amplitudes of the diffusion-sensitive gradient pulses. A linear least-squares regression algorithm was used to fit 15 of the 16 two-dimensional matrices, on a pixel-by-pixel basis, to solve for the slope from which the ADC value was calculated. The correlation coefficient of the fit, R² was used to filter the final ADC maps, and the ADCs were then scaled appropriately to be displayed in a 256 gray level format. Ranges (bins) of 0.05 × 10⁻³ mm²/s were then grouped and color coded to qualify and quantify the evolution of ischemia in the MCA territory. The percentage of area in the ischemic and contralateral hemispheres in seven ADC bins were calculated at 30, 60, and 120 min after MCAO for 10 animals and demonstrated a significant increase in ADC bins below 0.45 × 10⁻³ mm²/s and a decrease in bins above 0.50 × 10⁻³ mm²/s over the. The postmortem infarct area, as measured by TTC staining, was highly correlated with the portion of the ischemic hemisphere falling below ADC values of 0.55 × 10⁻³ mm²/s at 2 h after stroke onset. These studies suggest that focally ischemic brain tissue can be quantitatively subdivided according to ADC values and that ADC values below 0.55 × 10⁻³ mm²/s 2 h following ischemia highly predict infarction in a rat permanent occlusion stroke model.     

建立犬脑缺血模型的方法研究

 目的 探索一种经济、实用的建立犬局灶脑缺血模型的技术方法.方法 选择内栓子介入栓塞法和颞部微创手术法进行比较研究,采用DSA检测梗阻结果,MRI扫描结果计算梗死体积及术后14 d内每天的神经功能评分.结果 颞部微创手术法较内栓子介入栓塞法,犬存活时间长,试验成本低,可控性好,能更好地模拟临床.结论 在目前技术条件下,颞部微创手术法是一种更经济、实用的建立犬脑缺血模型的技术方法.     

99Tcm-HL91在大鼠缺血脑内分布的放射自显影观察

目的探讨99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)在大鼠局灶性脑缺血脑内的动态分布规律.方法用线栓法建立大鼠局灶性脑缺血模型,SD大鼠42只分为2组①预处理脑缺血组(21只),脑缺血预处理20min,再灌注3 d后再次脑缺血2 h;②脑缺血组(21只),脑缺血2 h.两组按再灌注时间不同(5、30 min及1、2、4、8、12 h)又各分为7个亚组,每组3只.用γ测量和放射自显影方法,观察99Tcm-HL91在大鼠局灶性脑缺血脑内的动态分布规律.结果γ测量结果示,注药后5 min～2 h,两组患侧与健侧脑组织单位质量放射性比值(T/NT)均为1.0左右,差异无显著性(P＞0.05);注药后4 h两组T/NT明显增加,4、8、12 h预处理脑缺血组T/NT分别为1.57±0.13、1.93±0.06、2.25±0.17,与同组2 h比较,差异均有显著性(P均＜0.01),脑缺血组T/NT分别为1.22±0.12、1.59±0.07、1.94±0.09,与同组2 h比较,差异均有显著性(P＜0.05～0.001);注药后4、8、12 h预处理脑缺血组与脑缺血组间两两比较,差异均有显著性(P均＜0.05).放射自显影结果示,注药后5 min～2 h,两组患侧和健侧脑组织银颗粒主要分布于细胞间质和毛细血管中,细胞内分布较少;注药后4 h,两组患侧银颗粒主要分布于脑组织神经细胞内,而细胞间质和毛细血管内分布较少;两组8、12 h亚组分布规律与4 h亚组相同;预处理脑缺血组患侧银颗粒密度明显高于脑缺血组.结论注药后4～12 h,99Tcm-HL91在缺血脑组织内分布明显;预处理缺血脑组织摄取显像剂明显高于非预处理缺血脑组织,临床进行脑显像时应在注药后4 h为宜.     

脑缺血再灌注神经细胞血小板活化因子受体蛋白特性研究

目的探讨大鼠局灶性脑缺血再灌注后血小板活化因子(PAF)受体特性的变化。方法建立一侧大脑中动脉线栓闭塞再通模型，超速离心制备缺血脑皮质神经细胞突触膜和微粒体。采用放射配基结合实验，检测脑缺血再灌注后PAF受体的平衡解离常数(Kd)和最大结合数量(Bmax)。结果Scatchard作图分析显示，各组样本均存在3个特异性PAF结合位点，其中2个位于微粒体，另1个在突触膜上。单纯缺血90min时，突触膜位点Kd和Bmax明显减小；再灌注1d后，微粒体上2个位点的Kd、Bmax明显下降，至7d均未恢复到假手术组水平。结论缺血再灌注可诱导脑皮质神经细胞PAF受体下调，胞内受体下调晚发于突触膜受体。     

arcaine 对大鼠局灶性脑缺血损伤的神经保护作用

目的 观察N-甲基-D-天冬氨酸(NMDA)受体/通道复合物多胺位点拮抗剂arcaine对脑缺血损伤的神经保护作用.方法 将45只Wistar大鼠随机分为对照组、缺血模型组、术前24h组、术前1h组及术后1h组.后4组大鼠均采用线栓法阻断大脑中动脉制作急性脑梗死模型.缺血模型组在造模成功后1h给予生理盐水(0.4ml/kg),术前24h组、术前1h组和术后1h组分别在术前24、1h和术后1h给予3mg/kg areaine.检测大鼠神经功能行为、脑梗死体积,并观察光镜及电镜下脑组织损伤情况.结果 神经功能评分显示,术前24h组、术前1h组和术后1h组大鼠神经功能行为评分(1.25±0.46、1.33±0.50、1.40±0.58分)与缺血模型组(2.63±0.52分)相比有显著差异(P<0.05),且术后给药对神经运动功能障碍的改善效果较术前给药效果差(P<0.05).术前24h、术前1h组和术后1h组大鼠脑梗死体积百分比(分别为5.72%±2.91%、26.36%±5.30%、36.35%±6.66%)较缺血模型组(51.10%±3.86%)明显减少(P<0.05);术后1h组大鼠脑梗死体积百分比较术前24、1h组增加(P<0.05).除对照组外,各组光镜下病理分级结果 差异无统计学意义.电镜下观察各组大鼠皮层及海马神经元均有不同程度的变性坏死,其中缺血模型组病理损害最为严重.结论 arcaine能够显著减少脑梗死的体积、减轻梗死所致的神经功能损伤,且预防给药效果更佳,但是arcaine对缺血所致神经元超微结构的损伤无明显逆转作用.     

原癌基因c-fos在大鼠急性局灶性脑缺血再灌注损伤和高压氧治疗后表达的变化

目的　探讨原癌基因 c- fos在大鼠急性局灶性脑缺血 /再灌注损伤和高压氧 (HBO)治疗后表达的变化。方法　用血管内细丝栓堵大鼠的大脑中动脉 (MCA ) ,制作成局灶性脑缺血动物模型 ,利用免疫组织化学方法 ,观察了 MCA缺血 1 h,再灌注 4、1 1、2 3、71 h c- fos癌基因表达的变化 ,在以上期间同时应用常压 0 .1 MPa纯氧或 0 .2 5 MPa HBO于开始缺血后 2、9、2 1、45和 6 9h分别治疗 1次 (1 h)。结果　缺血后 5 h,c- fos原癌基因在梗塞区皮层、纹状体、视前区均有明显表达 ,持续 1 2～ 2 4h后开始减弱 ,72 h基本消失。 HBO治疗后 ,各时间点 c- fos癌基因在上述区域的表达均明显减弱。结论　 HBO可明显抑制大鼠急性局灶性脑缺血 /再灌注损伤区 c- fos癌基因的表达     

Prognostic value of rCBF measurements and CT in focal cerebral ischemia

Summary CT is the most effective examination technique for studying the evolution of ischemic attacks, but if performed within the first 3 weeks it does not allow prognosis of possible evolution towards necrosis. CBF measurement and vasoreactivity tests under Althesin do allow this prognosis. Thirty patients whose evolution was checked clinically and by repeated CT examinations (89 in all) underwent CBF measurements (intra-arterial xenon 133) and vasoreactivity tests. In all cases (17 patients) where vasoreactivity had completely disappeared (inverse steal), the infarct evolved towards necrosis.     

大鼠超急性脑缺血再灌注后缺血周围区CT灌注参数动态变化研究

目的:研究多层螺旋CT灌注成像在大鼠大脑中动脉栓塞及再灌注过程中缺血周围区CT灌注参数的动态变化与病理损伤机制之间的关系。方法:将52只SD大鼠随机分为假手术组(A组)、缺血2 h组(B组)和缺血6h组(C组),B组按缺血后再灌注时间分为0h、0.5h、1h、2h、4h、6h、24h组;C组也按缺血后再灌注时间分为0h、0.5h、1h、2h、24h组。每组各4只。各组动物于缺血后再灌注不同时间点行CTPI检查。扫描完成后立即处死大鼠行光、电镜检查。结果:A组脑血流灌注参数相对值及光、电镜结果均未见异常改变。B组随着再灌注时间的延长,rCBF、rCBV值逐渐上升,rMTT、rTTP值逐渐下降,再灌注后与A组比较无统计学意义(P0.05)。光镜显示B组缺血周围区神经元密度减小,部分细胞体积增大呈空泡变,部分神经元胞体及胞核浓缩。C组随着再灌注时间的延长rCBF仍维持在低水平。光镜显示C组R 24h见较多细胞胞浆嗜伊红染。电镜下B组缺血周围区毛细血管基底膜增厚但尚完整。C组缺血周围区胞浆电子密度轻度升高,线粒体嵴有断裂。结论:CT灌注成像在大鼠大脑中动脉栓塞及再灌注过程中的动态变化与病理损伤机制有一定相关性,缺血2h缺血周围区脑组织为可逆性损伤,缺血6h缺血周围区脑组织为不可逆性损伤。     

局灶性脑缺血后失联络区酶组织化学研究

目的 探讨局灶性脑缺血失联络区乙酰胆碱酯酶（AChE）、酸性磷酸酶（ACP）、琥珀酸脱氢酶（SDH）酶活性的变化。方法 通过脑血流放射自显影和大鼠大脑中动脉栓塞（MCAO）模型确定失联络区,用酶组织化学染色法研究AChE、ACP、SDH的活性变化。结果 局灶性脑缺血后失联络区AChE、ACP活性无明显改变,SDH活性下降。结论 局灶性脑缺血失联络区胆碱能神经及溶酶体功能无改变,线粒体代谢活性降低。     

Global and focal cerebral perfusion after aneurysmal subarachnoid hemorrhage in relation with delayed cerebral ischemia

INTRODUCTION: The pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear. We assessed whether DCI relates to focal or global cerebral perfusion on admission and on follow-up imaging. MATERIALS AND METHODS: Twenty-seven SAH patients underwent computed tomography (CT) perfusion (CTP) on admission and at clinical deterioration or 1 week after admission in clinically stable patients. We compared global and focal (least perfused territory) perfusion in patients with DCI (n = 12), clinically stable patients (n = 7), and patients with non-DCI-related deterioration (n = 8). RESULTS: Global cerebral blood flow (CBF) increased on follow-up: 29% (95% confidence interval (CI) 15% to 43%) in patients with DCI, 12% (95%CI -1% to 25%) in stable patients, and 20% (95%CI 4% to 36%) in patients with non-DCI-related deterioration. Focal CBF decreased in patients with DCI, (-23%; 95%CI -58% to 12%) but increased in patients with non-DCI-related deterioration (23%; 95%CI -26% to 55%) and stable patients (7%; 95%CI -30% to 45%).On follow-up, global CBF was lower in patients with DCI (70.0 ml per 100 g/min) than in clinically stable patients (81.6; difference 11.6; 95%CI 0.8 to 22.5 ml per 100 g/min) but comparable to patients with non-DCI-related deterioration (67.6; difference -2.4; 95%CI -11.9 to 7.2 ml per 100 g/min). Focal CBF was lower in patients with DCI (30.7) than in clinically stable patients (53.6; difference 22.9; 95%CI 5.1 to 40.6 ml per 100 g/min) and patients with non-DCI-related deterioration (46.6; difference 15.9; 95%CI -2.6 to 28.4 ml per 100 g/min) CONCLUSION: Our results suggest that DCI is more likely a focal than a global process.