【作者】 王静；

【导师】 吴江；

【作者基本信息】 吉林大学 ， 神经病学， 2011， 博士

【摘要】 脑血管病是危害人类健康的常见病、多发病,其中缺血性脑血管病占80%以上,且具有高发病率、高死亡率、高致残率及高复发率的特点,给患者造成极大的痛苦和严重的社会经济负担,在我国已成为一个严重的公共卫生问题。因此加强对缺血性脑血管病的研究,针对每个病人的具体危险因素,积极进行早期干预,制定具体防治方案成为医学界的一个重要课题之一。近年来,由于加深了对缺血性脑血管病的病理生理过程研究,提出了治疗时间窗、缺血半暗带和再灌注损伤等概念,更新了缺血性脑卒中的防治观念,国内外研究者对脑灌注与缺血性脑血管病之间的关系逐渐重视起来,出现了多种观察分析脑血流灌注的方法,如氙-CT灌注成像、CT灌注成像、磁共振灌注/弥散成像、单光子发射计算机断层显像、正电子发射体层成像等。本研究所探讨的氙-CT（Xe-computed tomography, Xe-CT）脑灌注成像技术是一种传统测定活体组织灌注的影像学方法,利用氙-CT的高分辨率、准确定量、快速、重复性好、无创等特点,检测脑血流灌注情况,可以早期显示脑缺血的部位、损伤范围,确定可逆性损伤区域,并能够评估侧枝循环和脑血管储备能力,为神经保护治疗提供影像学信息,从而制定有效的治疗方案,减少溶栓治疗中对时间窗的依赖,为脑动脉狭窄支架治疗提供脑灌注信息。本研究总结了Xe-CT扫描序列参数及扫描方案,以期为临床防治提供可靠的脑组织血流灌注影像学依据;另一方面,通过对单侧颈内动脉、大脑中动脉狭窄及脑供血动脉狭窄支架置入术前后脑血流灌注变化的研究,为临床综合评估患者病情、制定个体化治疗方案并判断预后提供依据。主要做了以下三部分工作:第一部分正常成年人Xe-CT灌注成像的脑血流动力学研究目的应用Xe-CT对正常成年人脑组织进行灌注成像研究,明确Xe-CT灌注成像技术参数并确立扫描方案,测量我国北方成年人的脑血流动力学指标的正常范围,从而评价脑缺血患者脑血流灌注的情况提供参考值。资料与方法2005年10月至2007年10月期间选择20例正常成年人志愿者在吉大一院进行Xe-CT灌注检查,应用美国多样化诊断产品公司（Diversified Diagnostic Products Inc,DDPI）生产的Xenon-CT CBF系统,配套的CT扫描仪是西门子公司生产的PLUS4 CT扫描机。吸入氙气前先行2次基线扫描,然后经呼吸面罩吸入由浓度为33%的氙气和67%的氧气组成的混合气体,在吸入氙气的过程中连续扫描4次,总共扫描时间约4.5min。将CT采集的数据传入Xenon-CT CBF工作站,应用专用软件进行脑血流的计算。应用CBF分析软件自带的自动皮质六分区法自动划出6个不同的感兴趣区双侧大脑前动脉（anterior cerebral artery, ACA）、大脑中动脉（middle cerebral artery, MCA）和大脑后动脉（posterior cerebral artery, PCA）供血区分别计算出各区的脑血流量（CBF）;根据Demasio[1]1983年对50岁年龄组的血管分区的划分方法,手工划出ACA、MCA和PCA的血管分布区,分别计算出各区的CBF;在双侧丘脑（Thalamus）、基底节区包括尾状核（Caudate nucleus）和壳核（Putamen）分别放置椭圆形感兴趣区ROI。比较手工法和自动皮质六分区法各供血区测得的脑血流量之间的差异。结果手工法和自动皮质六分区法各供血区测得的脑血流量没有明显差异;两侧大脑半球（ACA、MCA、PCA供血区）脑血流量之间没有明显差异。并得到正常成年人脑血流量的大致范围:ACA供血区平均CBF为（54.5±9.1）ml·min^-1·100g^-1、MCA为（55.4±5.3）ml·min^-1·100g^-1、PCA为（52.2±8.7）ml·min^-1·100g^-1、丘脑为（66.2±8.6）ml·min^-1·100g^-1、尾状核为（60.4±9.3）ml·min^-1·100g^-1、壳核为（63.8±8.9）ml·min^-1·100g^-1。第二部分颈内动脉及大脑中动脉狭窄患者脑血流灌注的Xe-CT灌注研究目的通过应用Xe-CT脑灌注成像技术对单侧颈内动脉及大脑中动脉狭窄的患者进行研究,分析其脑灌注特点,探讨动脉狭窄后脑血流动力学改变与脑梗死发生之间的关系,从而为综合评估患者状态、制定个体化治疗方案并判断预后提供依据。资料与方法收集2005年10月至2008年12月期间在吉林大学第一医院诊治的经血管检查证实单侧颈内动脉或大脑中动脉狭窄的缺血性脑血管病患者84例。经CTA及DSA检查测量血管狭窄程度,并根据不同的狭窄程度进行分组:Ⅰ组（轻度狭窄）:狭窄度<50%;Ⅱ组（中度狭窄）:狭窄度为50%⁶9%;Ⅲ组（重度狭窄或闭塞）:狭窄度70%¹00%。此外,利用CTA结合DSA观察Willis环的完整性及侧枝代偿情况。初级侧枝循环指通过颅底Willis环沟通的血管;次级侧枝循环主要是颅外向颅内代偿的侧枝血管如眼动脉或通过软脑膜代偿的侧枝血管。本研究根据不同侧枝代偿方式分两组:a组,初级侧枝循环;b组,出现次级侧枝代偿。所有患者在行CTA或DSA检查后1周内进行Xe-CT灌注成像检查,应用CBF分析软件进行脑血流量的定量分析,观察患侧与对侧脑血流量的差异,脑血管狭窄程度与脑血流量值之间的相关关系及不同侧枝代偿途径的脑血流灌注差异。结果46例颈内动脉狭窄和38例大脑中动脉狭窄患者中,轻度狭窄组脑血流量无明显降低,中、重度狭窄或闭塞组血流量不同程度降低,低灌注区域不同程度增大;颈内动脉狭窄患者及轻度大脑中动脉狭窄患者的脑血流量降低程度与动脉狭窄程度无明显相关性,而中、重度大脑中动脉狭窄患者脑血流灌注与动脉狭窄程度有等级相关性;脑动脉严重狭窄或闭塞时,次级侧枝代偿者CBF较仅有初级侧枝代偿者减低更明显,低灌注区域面积也较大,脑血流灌注减低更明显。第三部分脑动脉狭窄支架置入术前后脑血流变化的Xe-CT灌注研究目的通过Xe-CT灌注成像技术观察脑动脉狭窄患者支架置入术前后的脑血流灌注变化。资料与方法选取吉大一院2005年10月至2008年12月期间收治的缺血性脑血管病患者中经脑血管造影证实的脑供血动脉狭窄者共21例,经氙气CT灌注成像检查,确定有血液动力学改变并符合手术指征者行支架植入术,并于术后1周内复查氙气CT检查。结果21例脑血管狭窄的患者中2例Xe-CT灌注成像检查没有出现低灌注区,行负荷试验,1例显示脑血管储备能力正常,不需支架治疗,另1例负荷试验后发现脑储备能力较差,建议行支架治疗,余19例均有不同程度低灌注区;行支架置入术后,狭窄侧脑血流量较术前明显改善,与健侧比较无明显差别,脑灌注正常区域及轻度缺血区、缺血半暗带区域面积较术前增加,梗死区域无明显变化。结论（1）Xe-CT灌注成像技术能够对脑组织血流量进行准确的定量测量,为临床了解患者脑血流灌注情况提供客观依据;（2）脑动脉狭窄的程度与脑血流灌注减低不完全相关,但是当出现次级侧枝循环开放时,则提示脑血流动力学受损较重,脑血流灌注明显减低。（3）头颈部动脉狭窄时,Xe-CT可以准确的定量评价患者脑血流灌注情况,通过Xe-CT负荷试验,能够评估脑血管储备能力,为临床选择治疗方案提供影像学帮助;（4）Xe-CT灌注成像技术能作为客观的评价支架置入术的疗效和预后的指标。更多还原

【Abstract】 Cerebrovascular diseases has become common in China, especially in the North area, more than 80% patients are ischemic cerebrovascular disease. Ischemic cerebrovascular disease has become one of the most fatal diseases to the public health, characterized by the high incidence, mortality, multilation, and relapse rate. Therefore,it is of great significance to strengthen the relevant research in order to improve the early diagnosis and individual treatment efficiency for ischemic cerebrovascular diseas. In recent years, followed by the evolvement of research on the pathophysiology of ischemic cerebrovascular disease, ischemic penumbra, therapeutic time window and reperfusion injury are put forward. And domestic and foreign researchers pay attention to the relationship between cerebral perfusion and ischemic cerebrovascular disease. There are many kinds of methods to evaluate cerebral perfusion, Xenon-enhanced computed tomography （Xe-CT） which studied in our project is one of traditional imaging methods evaluating living perfusion. Xe-CT system is applied to provide the quantitative CBF （cerebral blood flow） using stable（nonradioactive） Xenon associated with CT scanner. The position, range of ischemic cerebral tissue can be shown early using Xe-CT, and make sure the irreversible damage area, evaluate collateral circulation and cerebrovascular reserve capacity. Thus imaging basis are provided for neuroprotective treatment. So Xe-CT has an important role in ischemic stroke therapeutic intervention as a quantitative, reproducible, rapid, and safe modality, which can provide valuable physiologic data that can optimize patient triage and aid in management.The research include: 1.The cerebral hemodynamics study using Xenon-CT perfusion imaging in normal adults; （2） The study on Xenon-CT perfusion imaging in patients with cerebrovascular stenosis; （3） To evaluate the hemodynamic characteristics of cerebral artery stenosis and curative effect of stent placement using Xenon-CT.Part 1: The application of Xe-CT on the cerebral hemodynamics of normal adultsObjective To study the cerebral hemodynamics of normal adults using Xe-CT, mke sure the scanning program, and confirm the normal reference values of cerebral perfusion in north China adults. Materials and Methods This study collected a total of 20 cases of healthy volunteers, using Xe-CT CBF system produced by Diversified Diagnostic Products Inc, associated with CT scanner, associated with PLUS4 CT scanner produced by Siemens.Result There are no significant differences between manual and automatic cortex 6 sector method which evaluate CBF （cerebral blood flow）,and there are no significant differences between bilateral cerebral hemisphere blood flow. The mean CBF values of normal adults in north China are measured: ACA, MCA and PCA territory （54.5±9.1）ml·min^-1·100g^-1,（55.4±5.3）ml·min^-1·100g^-1,（52.2±8.7）ml·min^-1·100g^-1,thalamus（66.2±8.6）ml·min^-1·100g^-1、caudate nucleus（60.4±9.3）ml·min^-1·100g^-1、putamen（63.8±8.9）ml·min^-1·100g^-1.Part 2: The study on Xenon-CT perfusion imaging in patients with ICA or MCA stenosisObjective To study the cerebral hemodynamics of patients with ICA or MCA stenosis using Xe-CT, analyze the cerebral perfusion characters, and demonstrate the relationship between cerebral hemodynamics changes in patients with cerebrovascular stenosis and infarct, guiding for the choice of the proper treatment and prognostic evaluation.Materials and Methods This study collected a total of 84 cases of ischemic stroke patients with ICA or MCA stenosis during June 2005 and June 2007 in the department of neurology in the First Hosital of Jilin University. 3 groups were divided by stenosis degree that confirmed by CTA or DSA: groupⅠ（mild）<50%;groupⅡ（moderate）:50%⁶9%;groupⅢ（severe）: >70%. On the other hand, the branch compensation of Willis were observed by CTA or DSA, primary compensation supply by Willis, secondary compensation supply by extracranial vessels such as ophthalmic artery. 2 groups were divided by compensation: group a: primary compensation; group b: secondary compensation. Xe-CT perfusion imaging were examined one weeks after CTA or DSA examination, the CBF differences between ipsilateral cerebrovascular stenosis and contralateral were observed, so as to the relationship between stenosis degree and CBF values and the CBF differences between two kinds of compensations.Result Among 46 patients with ICA stenosis and 38 patients with MCA stenosis, there was no obviously CBF reduction in mild group, in moderate and severe group the CBF reduced; There were no significant relativity between CBF reduction and stenosis degree in ICA stenosis and mild MCA stenosis, and grading relativity were observed in moderate and severe MCA stenosis; In severe cerebrovascular stenosis patients, CBF reduced much more in patients with sencondary compensation than in patients with primary compensation, and low perfusion area were lager.Part 3: To evaluate the hemodynamic characteristics of cerebral artery stenosis and curative effect of stent placement using Xenon-CT.Objective To evaluate the hemodynamic characteristics of cerebral artery stenosis and curative effect of stent placement using Xenon-CT.Methods 21 patients with cerebral artery stenosis confirmed by CTA or DSA were examined and evaluated by Xe-CT, and stent placement performed if the hemodynamic changes occurred, then Xe-CT were examined in one week, measurement and comparison of the changes were taken before and after the therapy.Results There were no low cerebral perfusion area in 2 patients, then burthen test were performed to show that cerebralvascular acetazolamide reactivity was normal in one patient, and in the other patient, cerebralvascular acetazolamide reactivity reduced. The rest of 19 patients had low cerebral perfusion area, stent placement were performed. Preoperative Xe-CT revealed different decrease of CBF in the ipsilateral cortex. Ischemic areas increased significantly after the stenting placement.Conclusions 1.Xe-CT perfusion imaging can provide the quantitative CBF, give impersonal data for clinical diagnosis and treatment. 2. There is no definite relativity between cerebrovascular stenosis degree and reduction of cerebral perfusion, When there is secondary compensation, there is heavy cerebral hemodynamic damge, and cerebral perfusion reduce greatly.3. Xe-CT application can precisely analyze the CBF in a quantitive way in cerebral artery stenosis, and evaluate cerebralvascular acetazolamide reactivity by burthen test, guide the optimal therapeutic treatment, and make an objective evaluation on patients’prognosis. 4. Xe-CT application is beneficial for accurately demonstrating the curative effects of the stent placement.更多还原