【作者】 李响；

【导师】 李松柏；

【作者基本信息】 中国医科大学 ， 放射科， 2010， 博士

【摘要】 脑血管痉挛(cerebral vasospasm, CVS)是蛛网膜下腔出血(subarachnoid hemorrhage, SAH)最常见的并发症之一,常可引起严重的脑组织缺血和／或迟发性缺血性脑损害,是蛛网膜下腔出血致死和致残的主要原因。CVS依其发生时间,可分为早发性和晚发性两种。前者多见于SAH后0.5h～3d内,持续时间较短,且常于4h内缓解,故也称急性脑血管痉挛；后者又称迟发性脑血管痉挛(delayed cerebral vasospasm, DCV),于出血后4～15d发生,7～10d为高峰期,2～4w可逐渐缓解,部分病人可发展为脑梗塞。目前临床上还没有判断和评估发生延迟性脑梗塞几率的方法。以往DSA是动脉瘤及脑血管痉挛诊断的金标准,但其毕竟属于有创性检查,目前主要在同时拟行介入治疗时应用。近年研究发现MSCTA在动脉瘤及脑血管痉挛的诊断中具有重要的作用,但是DSA、MSCTA都难以对脑血管痉挛后所继发的脑组织缺血情况进行准确客观的评估。灌注是指血流通过毛细血管网将携带的氧和营养物质输送给组织细胞的过程,在一定程度上能反映器官、组织的血流动力学状态和功能情况。通过CT来直观显示活体灌注过程并作定量分析的方法称为CT灌注成像。CT灌注成像(CT perfusion imaging)是指经静脉团注对比剂的同时对选定层面行动态或连续扫描,以获得该层面内每一像素的时间—密度曲线(time-density curve, T-DC),然后根据该曲线利用不同的数学模型计算组织的血流动力学参数,以此来评价组织器官的灌注状态。灌注成像能够反映人类组织和器官的血流灌注量的变化,目前已成为影像医学研究的热点,是研究活体组织器官血流动力学最广泛的方法。因此,CT灌注成像有望能更好的反映蛛网膜下腔出血后脑血管痉挛所引起的一系列继发性病理、生理改变。2005年11月西门子公司推出了世界上首台双源CT (Dual Source Computed Tomography, DSCT)。该系统不仅进一步优化了非去卷积法的常规灌注,而且还提出了全新的全脑灌注模式,提出了PBV、PWM两个全新的灌注参数,有望能够更好的反应蛛网膜下腔出血后所继发的脑组织缺血性改变,国内外在此方面也未见报道,其应用价值有待于进一步的研究。因此,本课题拟就双源CT全脑及常规灌注在蛛网膜下腔出血后脑血管痉挛及其所继发的脑缺血性改变中的价值和作用进行研究。材料与方法1、临床资料收集中国医科大学附属第一医院2008年6月～2009年10月期间收治的动脉瘤性蛛网膜下腔出血病人58例,其中男23例,女35例,年龄37～75岁,平均年龄53.2岁。58例病人中有13例只进行了CT常规灌注扫描,16例只进行了全脑灌注扫描,其余病例均先后于住院期间进行了全脑灌注和常规灌注扫描。对照病人23例,均因头晕等原因而行CTA、全脑及常规灌注检查,年龄22～56岁,平均43.9岁。23例对照病人中只有5例先后进行了常规灌注和全脑灌注,其余病例均只进行了常规灌注或全脑灌注检查。对照组所有病例CT灌注及CTA图像均未见异常2、检查方法(1)常规灌注检查：所有患者均采用西门子公司Somatom Definition双源CT机,使用其特定序列Specials/Neuro PCT进行扫描。即先行全脑平扫,确定灌注扫描的靶层面后,而后用高压注射器经肘静脉以6ml／s的速度快速团注非离子造影剂40ml,注射后同速率跟注30ml生理盐水。注射开始后延迟6s,于基底节及其上方层面行脑灌注扫描,扫描覆盖范围28.8mm,扫描时间40s。(2)全脑灌注检查：所有患者均使用西门子Somatom Definition双源CT,Specials/Neuro PBV序列扫描。先行全脑平扫,层厚1.0mm,间隔0.7mm。然后用高压注射器经肘静脉以4ml／s的速度快速团注非离子型造影剂50ml,注射后同速率跟注50ml生理盐水。以造影剂示踪技术触发全脑灌注扫描,其扫描参数与平扫参数一致。3、图像处理及分析(1)常规灌注：将扫描获得的数据传到西门子工作站进行后处理,重建出常规灌注图像,选取6-8个感兴趣区测量灌注参数。将所有感兴趣区上测得的灌注参数值的平均值作为该病例该灌注参数的脑灌注值。并比较延迟梗塞组、无延迟梗塞组和对照组各灌注参数值之间的差异,对于具有显著性差异且符合正态分布的参数通过95%可信区间拟定各组正常参考值范围,作为脑组织缺血评估的参考标准。然后再由两名放射科医师采用盲法对42例蛛网膜下腔出血病人灌注参数图和CT平扫图像进行诊断。比较灌注成像与CT平扫对限局性脑缺血的检出率。(2)全脑灌注：将扫描获得的数据传到Syngo MMWP工作站进行后处理,重建出全脑PBV、PWM和CTA图像,在全脑灌注PBV、PWM图像上测量感兴趣区的灌注值。然后计算各个脑叶感兴趣区的平均值作为该病例该参数的脑灌注值。比较SAH与对照组之间、死亡病例与存活病例之间各脑叶灌注值的差异,分析优势出血侧与灌注减低区的关系,并进一步比较PBV、PWM在对照组、无延迟脑梗塞组、延迟脑梗塞组之间的差异。对于服从正态分布且具有显著性差异各组的灌注参数通过95%可信区间确定该灌注参数的参考值范围,以此作为评估的参考标准。4.统计分析采用SPSS13.0统计软件包进行统计学处理,以P<0.05作为具有显著性差异的标准。结果1、CT常规灌注成像对动脉瘤性蛛网膜下腔出血所继发的限局性缺血性病变具有较高的检出率,高于CT平扫,具有显著性差异,P<0.05。2、CBF值在延迟梗塞组、无延迟梗塞组和对照组间均具有显著性差异,PEP值对照组与延迟梗塞组、无延迟梗塞组之间具有显著性差异,而后两组间未见显著性差异,CBV值虽然总体有差异,但SNK法并未检出三组间的显著性差异。MIP、AP值延迟梗塞组与对照组间具有显著性差异,TTS. TPP值延迟梗塞组与对照组、无延迟梗塞组间具有显著性差异,而后两组间未见显著性差异。3、PBV值在延迟梗塞组、无延迟梗塞组、对照组之间均有显著性差异,P＜0.05(F=103.665)。PWM值对照组与无延迟脑梗塞组间具有显著性差异,其它各组间未见显著性差异。4、PBV、PWM、CT平扫对限局性缺血性病变的检出率有显著性差异,PBV高于PWM高于CT平扫。5、38例SAH患者各脑叶PBV值均小于对照组各脑叶PBV值,具有显著性差异,P<0.05。6、8例死亡病例各脑叶PBV值低于非死亡病例各脑叶PBV值,但只有顶叶PBV值具有显著性差异,P<0.05(t=2.474)。7、蛛网膜下腔出血优势出血侧与灌注减低的部位有一定的关联,P<0.05。结论1、常规CT灌注成像能够反应蛛网膜下腔出血后脑组织血流动力学变化,并对蛛网膜下腔出血后所继发的限局性缺血性病变的检出较敏感。常规CT灌注参数能够对蛛网膜下腔出血后是否存在脑组织血流灌注减低和能否发生延迟脑梗塞进行评估。CBF<25ml/min/100ml可以作为脑组织灌注减低的评估标准。MIP>47HU或AP>34HU可以作为病人不会发生延迟性脑梗塞的评估标准。2、CT全脑灌注能够反应蛛网膜下腔出血后脑组织血流动力学变化,蛛网膜下腔出血后脑组织血流灌注减低。PBV不但对蛛网膜膜下腔出血所继发的限局性缺血性病变的检出很敏感,而且能够对能否发生延迟脑梗塞和是否发生了血流灌注减低进行评估。并初步认为PBV<10ml/l,可作为延迟脑梗塞发生的高危标准,PBV<14ml/l可作为脑组织灌注减低的标准,具有重要的临床应用价值。更多还原

【Abstract】 Cerebral vasospasm(CVS) is a common complication in the early clinical course after subarachnoid hemorrhage(SAH). As one of the devastating neurological disorders, the overall outcome in patients with aneurysmal (SAH) is still poor. CVS can be divided into early and late onset according to its occurrence time. The former is more common in SAH after 0.5h-3d, often mitigate in 4h, which is also called acute cerebral vasospasm. The latter was also known as delayed cerebral vasospasm (DCV), 4-15d after hemorrhage, peak at 7～10d, relieve at 2～4 weeks, some part can develop into cerebral infarction. At present, there is no clinical approach to judge and evaluate the delayed cerebral infarction risk. The golden standard of anatomic demonstration of aneurysm and cerebral vasospasm is digital subtraction angiography (DSA), which provides an accurate depiction of the intracranial vessels. However, it is an invasive procedure with complication, major in the intervention. Multisection CT angiography (MSCTA) has recently emerged as a reliable and accurate method for the rapid diagnosis and monitoring of cerebral vasospasm. But both DSA and MSCTA are difficult to access the cerebral ischemia secondary to cerebral vasospasm accurately and objectively.Perfusion is the process that the oxygen and nutrients are carried through the capillary network to the tissue cells, reflect hemodynamic status and functions of the organs and tissues. CT perfusion imaging refers to dynamic or continuous scanning the selected level after the intravenous bolus injection of contrast medium, to obtain the time-density curve (TDC) of each pixel within the slice, then evaluate the perfusion status of tissues and organs according to the hemodynamic parameters calculated using different mathematical models of the curve. Perfusion imaging can reflect the blood perfusion volume changes of organs and tissues, which has became a hot and widely used method to study the kinetics of tissues and organs. Therefore, CT perfusion imaging is expected to reflect a series of secondary pathology, physiological changes caused by the cerebral vasospasm after SAH.The first DSCT came into use at November,2005. It not only optimized the conventional perfusion, but also put forward a new model of global cerebral perfusion, accompany with two parameters PBV and PWM, expected to reflect cerebral ischemia secondary to SAH. There is not relevant report at home and abroad currently, therefore, further exploration is needed. In the subject, we intended to evaluate the importance of vasospasm after SAH and the secondary cerebral ischemic changes through dual-source CT whole-brain and routine perfusion.Materials and Methods1. PatientsDuring the period from June 2008 to October 2009,58 consecutive patients (23 men and 35 women) aged 37-75 years (median age 53.2 years) were recruited in First hospital of China Medical University, diagnosed with aneurysmal subarachnoid hemorrhage. All together,13 patients underwent routine CT perfusion,16 underwent whole-brain CT perfusion and 29 underwent both. There were 23 patients with dizziness in control group, aged 22-56 years (median age 43.9 years), underwent CT angiography, routine or whole-brain CT perfusion.5 underwent both routine and whole-brain CT perfusion. And all the imaging results were normal.2. Imaging Protocols(1) Routine CT perfusion was performed using DSCT (SOMATOM Definition, Siemens Medical Solutions, Germany). The scanning protocol was Specials/Neuro PCT. The target perfusion slice was performed after the whole-brain plain CT scan.30 ml of contrast agent was injected by intravenously ulnar vein at a flow rate of 4 ml/s followed by 30 ml of saline flush. The scan plane was performed at the level of basal ganglia and the above with 8s delayed, range 28.8mm for 40s.(2) Whole-brain CT perfusion was performed using 64-row DSCT (SOMATOM Definition, Siemens Medical Solutions, Germany). The scanning protocol was Specials/Neuro PBV. After the whole-brain plain CT scan according to section thickness,1.0mm and reconstruction interval,0.7mm,50 ml of nonionic contrast agent was injected by ulnar vein at a flow rate of 4 ml/s followed by 50 ml of saline flush. The whole perfusion was triggered by contrast agent tracer technique. The other parameters were the same as the routine.3. Imaging Process and Analysis(1) Routine CT perfusion:The data was analyzed using Siemens post-processing workstation for rebuild normal perfusion images,6-8 regions of interest (ROI) were set for calculatoion. All the regions of interest measured on the mean perfusion parameters of all the ROIs was considered as brain perfusion value of the case, comparing the perfusion difference among the delayed infarction group, no delayed infarction group and the control group, the reference criterion of cerebral ischemia was regarded as the perfusion parameters for significant differences, in accordance with the normal distribution through the 95% confidence in each group. And then two radiologists diagnosis the 42 cases of patients with SAH through CT perfusion parameter maps and CT plain images. The detection rate of cerebral ischemia of CT perfusion imaging and plain scan was compared, the the perfusion values were compared between low perfusion area and the contralateral corresponding parts.(2) Whole-brain CT perfusion:The data was analyzed using Syngo MMWP post-processing workstation for rebuild whole-brain PBV, PWM and CTA images, to calculate all the ROI s and mean perfusion value on the PBV and PWM images. The perfusion differences of brain lobe was compared between the SAH group and the control group, the dead and survival cases, for the correlation between predominant hemorrhage and low perfusion area. The PBV, PWM differences were compared among the control group, no delayed infarction group and the delayed infarction group. The reference criterion was regarded as the perfusion parameters for significant differences, in accordance with the normal distribution through the 95% confidence in each group.4. Statistical AnalysisThe statistic software SPSS 13.0 (SPSS, Chicago, IL, USA) was used. A result was considered significant if the P value was less than 0.05.Results1. The limited ischemic lesions secondary to aneurysmal SAH on routine CT perfusion imaging are detected with a higher rate than that on CT plain scan. There is significant difference, P<0.05.2. For CBF, significant difference was accepted among the delayed infarction group, no delayed infarction group and the control group. For PEP, there was significant difference between the control group and the delayed infarction group, no delayed infarction group, meanwhile, no significant difference between the delayed infarction group and no delayed infarction group. For MIP and AP, there were significant difference between the delayed infarction group and the control group. For TTS and TPP, there were significant difference between the delayed infarction group and the control group, no delayed infarction group, not significant between the latter two groups.3. For PBV, there was a significant difference among the delayed infarction group, no delayed infarction group and the control group, P<0.05(F=103.665). For PWM, there was a significant difference between no delayed infarction group and the control group, no significance between the other groups.4. There was significant difference on the detection of local ischemia among PBV, PWM and CT plain scan, PBV>PWM>CT plain scan.5. PBV of patient lobes is lower than that in control group, with a significant difference, P<0.05.6. PBV in dead cases is lower than that in survival cases, but there is significant difference only in the parietal lobe, P<0.05(t=2.474).7. There may be association between predominant side of subarachnoid hemorrhage and low perfusion area, P<0.05.Conclusion1. Routine CT perfusion imaging can reflect the cerebral hemodynamic changes after subarachnoid hemorrhage, and sensitive to the detection of ischemic lesions secondary to SAH. It also can evaluate whether there is cerebral perfusion reduction, the possibility of delayed cerebral infarction or not. CBF<25ml/min/100ml can be regarded as evaluation criteria of low cerebral perfusion. MIP>47HU or AP>34HU can be used as the evaluation criteria of impossible delayed cerebral infarction.2. Whole-brain perfusion CT can reflect the cerebral hemodynamic changes after SAH, cerebral perfusion reduced after SAH. PBV is not only sensitive in the detection of ischemic lesions secondary to SAH, but also possiblely assess the delay cerebral infarction and low perfusion. PBV< 10ml/1 can be used as delayed cerebral infarction criteria in high-risk, PBV< 14 ml/1 can be used as a standard reduction of low cerebral perfusion, has important clinical value.更多还原