应用压力导丝评估脑血流动力学变化的可行性研究

发布时间：2018-05-07 13:09

本文选题：颅内大动脉 + 狭窄　；参考：《南方医科大学》2016年博士论文

【摘要】：第一章压力导丝技术对颅内大动脉狭窄的严重性评估——可行性研究研究背景及目的：在亚洲特别是东南亚包括中国汉族人群中,颅内大动脉粥样硬化性狭窄是缺血性脑卒中的主要发病原因之一。目前针对颅内大动脉粥样硬化性狭窄的治疗方法主要包括球囊扩张成形术、支架植入术和积极的药物干预等。2011年发布的SAMMPRIS研究比较了单纯积极药物治疗与积极药物治疗联合球囊扩张成形及其支架植入术(PTAS)对于症状性颅内大动脉粥样硬化性狭窄(狭窄率70%-99%)的疗效。该研究的长期随访发现,单纯积极药物治疗对颅内大动脉粥样硬化性狭窄高危患者的早期收益优于Wingspan支架植入。然而,也有其他研究发现对于高风险的颅内大动脉粥样硬化性狭窄患者,Wingspan支架植入优于单纯药物治疗。因此,如何筛选高风险的颅内大动脉粥样硬化性狭窄病变可能相比追求卓越的治疗技术更重要。在筛选高风险的颅内大动脉粥样硬化性狭窄病变时,不能简单将血管病变的狭窄率与临床症状及其预期预后直接关联,传统地单纯依靠狭窄率来判定狭窄的功能性意义的评估方法必然受到挑战。当缺少了血流动力学评估的数据,慢性狭窄的病变的管理常常变得异常困惑,尤其是狭窄率为40%-69%的临界病变。因此,对于脑血管造影提示的形态学狭窄,其功能意义的评估具有极大的临床指导价值。血流储备分数(Fraction flow reserve, FFR)指导的血运重建策略在心血管介入治疗中已经得到广泛应用。目前,在2010版欧洲心肌血运重建指南中,FFR已作为IA级建议推荐指导冠脉狭窄血运重建,它将传统的依据冠脉狭窄的形态学特征判断病变的严重性上升到依据狭窄的功能性意义来判断病变的严重性,从而真正的从病理生理层面来制定治疗策略。但是,这一采用压力导丝进行的有创血流动力学评估技术在颅内大动脉粥样硬化性狭窄评估中的可行性如何,尚不明确。方法：我们从2013年3月至2014年5月,连续入组了12例准备行球囊扩张成形及其支架植入术(PTAS)治疗或狭窄程度在40%-69%的颅内大动脉粥样硬化性狭窄的患者(包括颈内动脉颅内段、大脑中动脉M1段、椎动脉颅内段和基底动脉)。在球囊扩张成形及其支架植入术(PTAS)之前和/或术后,分别使用压力导丝技术测量跨狭窄压力差,并与狭窄程度进行比较。颅内大动脉狭窄率的计算采用WASID标准测量：狭窄率=[(1-(狭窄病变处管腔直径/正常管腔直径))]×100,狭窄病变处的管腔直径指的是病变最严重处的管腔直径,正常管腔直径指的是病变处附近正常管腔的直径。测定了所有待评估颅内大动脉狭窄病变的Pd/Pa值,采用Pd/Pa比值≤0.7作为存在显著血流动力学障碍的界值,提示需要支架植入治疗；当该值大于0.8时,对该病变采用优化药物治疗方案；当该值在0.7和0.8之间时,是否需要支架植入由术者综合患者其他临床特征进行决策。对于支架植入的患者,当支架植入后,再次测量病变处的Pd/Pa值。分别在患者入组时、压力导丝评估后24h、出院时、术后30天、90天和180天进行随访。记录基线临床资料(包括年龄、性别、NIHSS评分等)、器械相关及其手术相关的严重不良事件,并观察远期脑缺血事件的复发情况(TIA或者缺血性卒中)。结果：在所有入组的12例患者中,压力导丝均能够到达待评估血管病变部位,没有发生器械相关及其手术相关的严重不良事件。其中狭窄病变位于前循环的有10例,位于后循环的有2例。本研究中,压力导丝技术能够获得非常准确的血流动力学参数：Pa、Pd、Pd/Pa和△P。其中行PTAS的7例患者,跨狭窄压力差△P从术前的59.0±17.2mmHg下降到术后的13.3±13.6mmHg(P0.01)。将MCA重度狭窄(狭窄率≥70%)和非重度狭窄病变(狭窄率70%)的△P进行比较,可见在重度狭窄组的最低跨狭窄压力阶差AP为31mmHg,而在非重度狭窄组中,最高的跨狭窄压力阶差△P才18mmHg。在随访期间,只有一例患者在研究期间发生TIA复发,考虑可能与该患者拒绝行支架植入术相关。其他患者均未出现缺血事件复发。结论：这种新的脑血流动力学评估方法,使得我们能够直接在术中即时获得Pa、Pd和Pd/Pa值,并且可以快速计算得到跨狭窄压力阶差AP。这种便捷高效地脑血流动力学评估方法,可以帮助脑血管介入医师更好地认识脑动脉狭窄的功能性意义,从而更加准确的选择合适的治疗方案,并且有助于在PTAS后即刻术中观察PTAS的治疗效果,以判断是否需要后续补救治疗。第二章压力导丝技术对毕格犬颅外段颈动脉狭窄严重性评估的理论探索研究背景及目的：脑血管病已上升成为我国城乡居民的首位致死原因。按照累积的病变血管分布划分,颅内、外大动脉狭窄导致的缺血性脑血管疾病所占比例最大。流行病学相关研究表明,颈总动脉、颈内动脉颈段(C1段)狭窄及闭塞导致的缺血性事件大约占到所有脑卒中的25%。颈动脉狭窄病变行颈动脉重建的目的主要还是预防脑卒中的发生。从病理生理层面来看,颈动脉支架置入起到预防脑卒中的作用,可能与血流动力学的改善和/或狭窄局部易损斑块被支架覆盖有关。但是,目前临床操作中,颈动脉支架植入术的主要适应症之一：无症状患者选择狭窄程度70%以上的标准,更多是基于对狭窄后血流动力学的担心。从血流动力学角度分析,对于狭窄程度在70%以上,如果狭窄局部血管壁并没有易损斑块的患者是否一定需要置入支架,尚不明确。本研究拟通过球囊扩张制作颈动脉狭窄直至闭塞的过程,模拟不同程度的颈动脉狭窄,从而获得狭窄／闭塞远端压力Pd值、狭窄近端压力Pa值以及Pd/Pa值等血流动力学参数,观察所获得的参数是否能够用来指导筛选具有功能意义的颈动脉狭窄病变；并且观察颈动脉狭窄／闭塞后,willis动脉环在代偿血流的重新分配中的作用及其可能机制。方法：选择清洁级健康成年毕格犬5只,均为雄性,体重13-18 kg。使用速眠新(剂量0.1ml/kg)联合硫酸阿托品(剂量0.5mg)进行诱导麻醉,麻醉后固定于自制操作台上,经口气管插管,插管后采用自主通气；术中使用丙泊酚静脉泵注射维持麻醉(剂量1mg/kg/h)给予持续吸氧,氧流量控制在2ml/min,根据实验动物的角膜反射消失、及呼吸节律保持在12至16次/min控制麻醉深度。先选择一侧颈总动脉(CCA)进行压力导丝血流动力学评估,将6F指引导管置于CCA下段近开口处,指引导管头端与CCA开口距离小于2cm。将球囊(规格4.0x20 mm)近端mark置于颈总动脉的中段,球囊置入使用压力导丝作支撑；将压力导丝的压力感受器置于球囊远端约3cm处,通过球囊扩张压力的调整,获得不同Pd/Pa值(从1.0逐步将至0.95、0.9、0.8、0.7和闭塞,允许误差范围±0.01),每个节点待稳定后维持3分钟以上,对应的使用TCD观察双侧MCA血流速度、频谱的变化,由两位熟练的超声诊断医师同时经毕格犬的双侧颞窗来完成TCD血流动力学参数的采集,包括收缩期峰值流速Vs、平均流速Vm、舒张期末流速Vd、阻力指数RI、搏动指数PI。然后观察对侧颈内动脉,操作方法与前相同。术中在不同节点观察血流动力学参数变化的同时,采用TCD观察大脑中动脉血流速度、频谱的变化,记录球囊扩张的同侧和对侧MCA的血流动力学参数。结果：Pd/Pa值从1.0降至0.95期间,TCD血流参数包括收缩期峰值流速、平均流速和舒张期末流速均没有明显的变化(同侧两组间Vs、Vm和Vd值的比较分别为：40.6±9.7 vs 39.7±9.6,P=0.837；28.4±7.2 vs 27.9±7.3,P=0.879；23.4±7.6 vs 23.2±7.7,P=0.954；对侧两组间Vs、Vm和Vd值的比较分别为：46.1±6.6 vs 45.9±6.3,P=0.946；29.9±4.4 vs 30.2±4.3,P=0.879；24.0±6.0 vs23.9±6.3,P=0.971)。继续将Pd/Pa值从0.95逐步降至0.9、0.8、0.7,直至球囊完全闭塞颈总动脉,分别待每个节点的Pd/Pa值稳定后,维持三分钟以上,记录相应的TCD血流动力学参数,TCD参数改变显著(P0.05)。当Pd/Pa从1.0降至0.95时,TCD没有发现同侧或者对侧MCA显著的血流动力学变化。当Pd/Pa继续下降至0.9及以下时,随着Pd/Pa比值的逐步下降,可以观察到同侧MCA血流动力学参数进行性下降,最终达到最小值；对侧MCA血流动力学参数进行性上升,最终达到最大值。结论：本研究证实了在颈动脉颅外段狭窄的评估中,用于区分功能性颅外段颈动脉狭窄的Pd/Pa值的截点可能在0.95-0.9之间；在Pd/Pa值下降至0.95-0.9之间时,willis动脉环代偿功能开始激活,并且在代偿血流的重新分配中起到重要作用。未来在颈动脉颅外段狭窄的评估中,使用压力导丝技术获得的Pd/Pa值可能是一个重要的血流动力学参数。第三章综述脑血管狭窄的血流动力学评估脑卒中的发生机制主要包括栓塞和血流动力学障碍,以及两者共同作用的混合性机制。脑血管闭塞部位的不同,位于远端还是近端,串联病变还是小血管病变,临床表现形式多种多样,其中无不掺杂着血流动力学障碍的因素。传统的脑血管狭窄评估更倾向于狭窄的形态学判定,对于狭窄的功能性意义,特别是血流动力学认识不足。近年来,在脑血流动力学评估方面的有了很大的发展,但是我们现有临床指南对于脑血管狭窄病变的决策更多地是基于形态学评估,无论是无创的彩色多普勒超声、经颅多普勒超声、CT动脉成像、MR动脉成像,还是有创的脑血管造影DSA检查,往往采用狭窄率来衡量狭窄的严重性。这更多地是对结构上的评定,对于狭窄的功能性意义评估较少,因此对于特定狭窄病变是否会导致远期的不良终点事件的判断显得依据不足。这样,可能导致部分需要介入治疗的狭窄病变被遗漏,或者部分不需要介入治疗的狭窄病变被放置了支架/球囊成形术。功能性评估方面,传统的脑血流储备评估方法如CT灌注成像、MRI灌注成像、PET灌注成像、SPECT灌注成像以及其他无创试验通常可提示多支血管病变患者存在缺血,但却不能判断特定的缺血区域以及准确定位引起该区域缺血的狭窄病变部位,对血管病变的空间分辨率较差,不能够很好地指导介入治疗决策。近来在在冠脉狭窄评估中兴起的FFR理论,具有许多独一无二的特性,使得该指数特别适合用于指导冠脉狭窄的功能性评估,并有助于介入医师在导管室做出合适的治疗决策。其主要优点包括：1、具备参考值明确,正常血管的FFR值等于1.0；2、缺血病变评估的临界值相当明确,小于0.75时建议支架治疗,大于0.80时建议可推迟支架治疗,介于0.75和0.80之间的灰色区间较窄；3、其评估过程,不会受到全身血流动力学参数变化的影响；4、该参数充分考虑到了侧枝循环的贡献率；5、FFR值可以在狭窄严重程度与待灌注组织区域之间建立起特殊联系；6、FFR具有极好的空间分辨率,有助于临床实时动态评估。使用压力导丝行血管内血流动力学评估在冠脉介入已经得到了成熟的应用,对冠脉狭窄的评估具有极高的指导价值,越来越受到临床医师的重视,并且已经推广用于指导严重肾动脉狭窄的血管内介入治疗策略,但是目前在脑血流储备评估中的应用仍然是空白。未来我们是否能够将心血管评估中得到广泛应用的FFR理论推广到脑血管狭窄的评估中。目前,已经有研究者开始了初步探索。本章节将针脑血管狭窄的血流动力学评估展开综述及展望。
[Abstract]:Evaluation of the severity of intracranial large artery stenosis in the first chapter: the feasibility study background and objective: in Asia, especially in Southeast Asia, including Chinese Han population, intracranial large atherosclerotic stenosis is one of the main causes of ischemic stroke. Narrower therapies include balloon dilatation, stent implantation, and active drug intervention in the.2011 years of SAMMPRIS studies comparing simple active drug therapy and active drug therapy combined with balloon dilatation and stent implantation (PTAS) for symptomatic intracranial large atherosclerotic stenosis (70%-99%) Long term follow-up of this study found that the early benefit of simple active drug therapy for patients at high risk of intracranial atherosclerotic stenosis is better than Wingspan stent implantation. However, there are other studies that have found that Wingspan stent implantation is superior to simple drug therapy for high-risk patients with large atherosclerotic stenosis. Therefore, how to screen high risk intracranial large atherosclerotic stenosis may be more important than the pursuit of excellent treatment. In screening high risk intracranial large atherosclerotic stenosis, the stenosis rate of vascular lesions can not be directly related to the clinical symptoms and the prognosis, and the narrowing of the stenosis is simply dependent on the narrowing of the stenosis. The assessment of the rate to determine the narrow functional significance is inevitably challenged. When the data of the hemodynamic assessment are lacking, the management of chronic stenosis is often abnormally perplexed, especially the critical lesion of the stenosis rate of 40%-69%. Therefore, the assessment of the functional significance of the cerebral angiography hints of the morphological stenosis is extremely important. Large clinical guidance. Blood flow reserve score (Fraction flow reserve, FFR) has been widely used in cardiovascular interventional therapy. Currently, in the 2010 edition of the European myocardial revascularization guide, FFR has been recommended as a IA recommendation to guide coronary narrow and narrow blood revascularization, which is traditionally based on coronary stenosis. The morphological features determine the severity of the lesion to judge the severity of the disease according to the narrow functional significance, so as to make a real treatment strategy from the pathophysiological level. However, the feasibility of the invasive hemodynamic assessment of the pressure wire in the assessment of intracranial large atherosclerotic stenosis Methods: from March 2013 to May 2014, 12 patients with intracranial large atherosclerotic stenosis (intracranial segment, M1 segment of middle cerebral artery, intracranial segment of vertebral artery, and basal arteriosclerosis) were enrolled in 12 consecutive patients who were prepared for balloon dilatation and stent implantation (PTAS) for the treatment of intracranial large atherosclerotic stenosis in 40%-69%. Pressure conductance measurements were used before and after balloon dilatation and / or stent implantation (PTAS) and compared with the degree of stenosis. The stenosis rate of intracranial large arteries was measured by WASID standard: stenosis = [(1- (stenosis of lumen diameter / normal lumen diameter)] * 100, stenosis The diameter of the lumen in the variable cavity refers to the diameter of the lumen in the most serious lesion. The diameter of the normal lumen refers to the diameter of the normal lumen near the lesion. The Pd/Pa value of all the lesions of the intracranial large artery stenosis is measured. The value of the Pd/Pa ratio is less than 0.7 as the boundary value of the significant hemodynamic obstacle, suggesting the need for stent implantation. When the value is greater than 0.8, an optimized drug treatment scheme is used for the lesion. When the value is between 0.7 and 0.8, the stent implantation is required to make decisions on the other clinical features of the patient. For the patient with the stent implantation, the Pd/Pa value of the lesion is measured again after the stent implantation. When the patient enters the group, the pressure wire is evaluated by 24. H, follow up at 30 days, 90 days and 180 days after discharge. Record baseline clinical data (age, sex, NIHSS score, etc.), instrument related and surgical related serious adverse events, and observe the recurrence of ischemic events (TIA or ischemic stroke). Results: in all 12 patients, the stress conductance could be found. There were no apparatus related and severe adverse events related to the site of vascular lesions to be assessed. There were 10 cases of narrow lesions located in the anterior circulation and 2 in the posterior circulation. In this study, pressure wire technique was able to obtain very accurate hemodynamic parameters: Pa, Pd, Pd/Pa, and delta P. in 7 patients with PTAS, The span of trans stenosis Delta P decreased from 59 + 17.2mmHg before operation to 13.3 + 13.6mmHg (P0.01) after operation. Compared the severe stenosis (stricture rate 70%) to non severe stenosis (70%), the lowest cross stenosis pressure order AP was 31mmHg in the severe stenosis group, and the highest cross stenosis pressure in the non severe stenosis group. The order difference Delta P was only 18mmHg. during the follow-up period, only one patient had a recurrence of TIA during the study. It was considered possible to be associated with the patient's refusal of stent implantation. Other patients had no recurrence of the ischemic event. Conclusion: this new method of cerebral hemodynamic assessment enables us to directly obtain Pa, Pd, and Pd/Pa values during the operation. And the rapid and efficient method of estimating the cross narrow pressure order difference AP. can help the cerebrovascular interventional physicians to better understand the functional significance of cerebral artery stenosis, so as to choose the appropriate treatment more accurately, and help to observe the therapeutic effect of PTAS in the immediate postoperative period of PTAS. To determine the need for subsequent remedial treatment. The second chapter of the theoretical exploration of the evaluation of the severity of cranial carotid artery stenosis by pressure guided wire technique: cerebrovascular disease has been the leading cause of death in urban and rural areas in China. According to the cumulative distribution of the lesion vessels, intracranial and external major artery stenosis Ischemic cerebrovascular disease accounts for the largest proportion. Epidemiological studies have shown that the common carotid artery, the cervical segment of the carotid artery (C1 segment) and occlusion caused by ischemic events account for approximately the 25%. carotid artery stenosis in all stroke. The purpose of the carotid artery reconstruction is mainly to prevent the occurrence of stroke. The effect of carotid artery stenting on stroke prevention may be associated with improvement of hemodynamics and / or narrowing of localized vulnerable plaque by stent coverage. However, one of the main indications of carotid artery stenting in clinical operation is that asymptomatic patients choose more than 70% of the stenosis degree based on stricture. The concern of hemodynamics. From a hemodynamic point of view, it is not clear whether the stenosis degree is above 70%, if the stenosis of the local vessel wall and no vulnerable plaque needs to be placed, it is not clear. This study is to make the carotid stenosis and closure by balloon dilatation, and to simulate different degrees of carotid stenosis. The hemodynamic parameters, such as narrowed / obliterated distal pressure Pd, narrowed proximal pressure Pa and Pd/Pa value, were observed to determine whether the obtained parameters could be used to guide the screening of functional carotid stenosis and to observe the redistribution of the compensatory blood flow of the Willis artery ring after carotid stenosis / occlusion. Methods: 5 healthy adult beagle dogs were selected, all of which were male and 13-18 kg., with a new (dose of 0.1ml/kg) combined with atropine sulfate (dose 0.5mg) for induction of anesthesia. After anesthesia, it was fixed on the self-made operation table, intubated through the mouth trachea, after intubation, and propofol was used in the operation. Pulse injection maintenance anesthesia (dose 1mg/kg/h) was given to continuous oxygen inhalation, oxygen flow was controlled at 2ml/min, the corneal reflex of the experimental animals disappeared, and the respiratory rhythm was maintained at 12 to 16 times of /min control depth. First, one side of the common carotid artery (CCA) was selected to conduct the pressure guide blood flow mechanics assessment, and the 6F guiding tube was placed in the near opening of the lower CCA segment. The head end of the catheter and the CCA opening distance are less than 2cm. to place the proximal mark of the balloon (specification 4.0x20 mm) into the middle part of the common carotid artery, and the balloon is placed with a pressure guide wire. The pressure guide is placed at the distal end of the balloon about 3cm, and the different Pd/Pa values are gradually obtained from 1 to 0.95,0.9,0.8 by the adjustment of the balloon dilatation pressure. 0.7 and occlusion, allowable error range of 0.01), each node remained stable for more than 3 minutes. The corresponding TCD was used to observe the blood flow velocity of bilateral MCA and the change of frequency spectrum. The hemodynamic parameters of TCD were collected by two skilled ultrasound diagnostics at the same time by the bilateral temporal window of the Beagle, including the peak systolic flow velocity Vs, the average velocity of flow. Vm, the end diastolic flow velocity Vd, the resistance index RI, the pulsation index PI. and then observe the contralateral internal carotid artery. The operation method is the same as before. During the observation of the changes in the hemodynamic parameters at different nodes, the blood flow velocity of the middle cerebral artery, the change of the spectrum, the hemodynamic parameters of the balloon dilatation and the contralateral MCA are recorded by TCD. Results: when the Pd/Pa value decreased from 1 to 0.95, the TCD parameters included the peak systolic flow velocity, the average velocity and the end velocity of diastolic phase (Vs, Vm and Vd, respectively: 40.6 + 9.7 vs 39.7 + 9.6, P=0.837; 28.4 + 7.2 vs 27.9 + 0.95, P=0.879; 23.4 + 7.6 vs 23.2 + + +, P=0.954; contralateral The comparison of the values of Vs, Vm and Vd between groups were 46.1 + 6.6 vs 45.9 + 6.3, P=0.946, 29.9 + 4.4 vs 30.2 + 4.3, P=0.879, 24 + 6 vs23.9 + 6.3, P=0.971). The Pd/Pa values were gradually reduced from 0.95 to 0.9,0.8,0.7 until the balloon completely blocked the common carotid artery. After the Pd/Pa values of each node were stable, the records were maintained for more than three minutes and the corresponding records were recorded accordingly. TCD hemodynamic parameters and TCD parameters changed significantly (P0.05). When Pd/Pa was reduced from 1 to 0.95, TCD did not find significant hemodynamic changes on the ipsilateral or contralateral MCA. When the Pd/Pa continued to fall to 0.9 and below, with the gradual decrease of the Pd/Pa ratio, the same side MCA hemodynamic parameters could be observed to be reduced and finally reached the level. Minimum value of the contralateral MCA hemodynamic parameters up and up to the maximum. Conclusion: This study confirms that in the assessment of the stenosis of the extracranial carotid artery, the Pd/Pa value used to distinguish functional extracranial carotid stenosis may be between 0.95-0.9; when the Pd/Pa value falls to 0.95-0.9, the Willis artery rings are compensated. Function begins to activate and plays an important role in redistribution of compensatory blood flow. In the future assessment of the stenosis of the carotid artery, the Pd/Pa value obtained by using the pressure wire technique may be an important hemodynamic parameter. In the third chapter, the main package of cerebral vascular stenosis is reviewed to evaluate the mechanism of cerebral apoplexy. The combination of embolism and hemodynamic disorders, as well as the common mechanism of the two interactions. The different parts of the cerebral vascular occlusion, located at the distal or proximal end, in tandem or in small vascular lesions, are varied in clinical manifestations, including the factors of hemodynamic disorders. The traditional assessment of cerebral vascular stenosis is more prone to stenosis. In recent years, there has been a great development in the assessment of cerebral hemodynamics, but our existing clinical guidelines are more based on morphologic assessment for the decision-making of cerebral vascular stenosis, whether non-invasive color Doppler ultrasound, Cranial Doppler ultrasound, CT arteriography, MR arteriography, or invasive cerebral angiography DSA examination, often using the narrowing rate to measure the severity of stenosis. This is more of a structural assessment, less assessment of the narrow functional significance, and therefore whether a specific narrow lesion can lead to a long-term adverse terminal event. It appears to be inadequate. This may lead to partial loss of stenosis that requires interventional therapy, or partial stenosis requiring no interventional therapy.

【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R743.3

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