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综述
术前预测脑高灌注综合征的影像研究进展
兰怡娜 娄昕

兰怡娜,娄昕.术前预测脑高灌注综合征的影像研究进展.磁共振成像, 2018, 9(12): 955-960. DOI:10.12015/issn.1674-8034.2018.12.014.


[摘要] 高灌注综合征(cerebral hyperperfusion syndrome,CHS)是颈动脉支架植入术(carotid artery stenting,CAS)和颈动脉内膜剥脱术(carotid endarterectomy,CEA)后少见但致死率极高的并发症。因此,术前预测CHS对于治疗方案的选择以及预后有着重要的临床意义,影像学技术是目前最常见的预测方法。笔者主要对当前常见影像技术预测CHS的方法及最新进展进行综述。
[Abstract] A rare but potentially fatal postoperative complication after carotid artery stenting (CAS) and carotid endarterectomy (CEA) is cerebral hyperperfusion syndrome (CHS). Predicting CHS plays a pivotal role in prognosis and treatment strategy. And imaging technique is the most commonly applied for predicting CHS. This literature review summarizes the latest study on predicting CHS using different imaging technique.
[关键词] 颈动脉支架植入术;颈动脉内膜剥脱术;高灌注综合征;影像技术;磁共振成像
[Keywords] Carotid artery stenting;Carotid endarterectomy;Cerebral hyperperfusion syndrome;Imaging technique;Magnetic resonance imaging

兰怡娜 解放军总医院放射诊断科,北京 100853

娄昕* 解放军总医院放射诊断科,北京 100853

通讯作者:娄昕,E-mail:louxin@301hospital.com.cn


基金项目: 国家自然科学基金项目 编号:816711 26,81730048 科技部国家重点研发计划 编号:2016YFC01001004
收稿日期:2018-06-13
中图分类号:R445.2; R743 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2018.12.014
兰怡娜,娄昕.术前预测脑高灌注综合征的影像研究进展.磁共振成像, 2018, 9(12): 955-960. DOI:10.12015/issn.1674-8034.2018.12.014.

       动脉粥样硬化导致的颈动脉狭窄是急性脑卒中的常见原因[1]。颈动脉支架植入术(carotid artery stenting,CAS)和颈动脉内膜剥脱术(carotid endarterectomy,CEA)是治疗颈动脉狭窄常见的手术方式,可有效预防患者脑梗死的发生[2,3]。但是术后会发生少见但致死率极高的并发症,即高灌注综合征(cerebral hyperperfusion syndrome,CHS)。Sundt等[4]在1975年首次提出了CEA术后CHS的概念,之后随着CAS技术的兴起,在CAS术后也出现了CHS。经过对CHS的一系列经验总结,大多数学者认为术后满足以下几点就可以诊断为CHS:(1)临床特征主要包括新发的单侧头痛、癫痫、意识不清;(2)影像特征包括急性的脑水肿和脑出血并且没有新发的梗死灶;(3)术后脑血流量(cerebral blood flow,CBF)较术前增加≥100%[5,6,7,8]。对于CHS的发病机制目前国内外学者主要持有两种观点:(1)颈内动脉重度狭窄导致患侧大脑半球处于低灌注状态,从而使脑内小动脉极度扩张;(2)由于脑血管调节能力受损,对术后急剧升高的CBF无法进行有效调节[9]。CHS若不及时治疗,会导致严重的脑水肿、颅内出血,最终导致死亡。虽然我们对CHS有了比较全面的认识,但是如果可以提前预测CHS,对患者治疗方案的选择以及术后管理都有积极的意义。既往通过对CHS患者的分析发现,发生CHS的危险因素有同侧颈内动脉重度狭窄、对侧颈内动脉狭窄、围手术期高血压、侧支循环形成不充分以及脑卒中史等[5]。虽然我们了解了CHS的危险因素,但要准确定量预防CHS还需要一些辅助方法。随着影像技术的进步,对于CHS的研究更加深入,不仅能做到术前定性预测,还可以更加准确地进行定量预测。本文主要通过对MRI、数字减影血管造影(digital subtraction angiography,DSA)、放射性核素成像、经颅多普勒超声(transcranial doppler,TCD)、CT灌注成像(computed temography perfusion,CTP)等影像方法预测CHS的新技术进行综述。

1 MRI新技术

       MRI常规技术可进行术后评估,例如通过扩散加权成像判断术后梗死面积是否缩小,磁敏感加权成像判断术后是否发生了出血性转化,但是在术前预测方面存在局限性[10]。然而随着MRI新技术的发展,不仅可以进行术后手术效果的评估,还可以对术后易发生CHS的患者进行术前预测。MRI预测CHS的新技术主要有动态磁敏感灌注加权成像(dynamic susceptibility contrast perfusion-weighted imaging,DSC-PWI)、液体衰减反转恢复(fluid attenuated inversion recovery,FLAIR)序列、供血区动脉自旋标记(territorial arterial spin labeling,TASL)技术、磁共振血管成像(magnetic resonance angiography,MRA)。

1.1 动态磁敏感灌注加权成像

       DSC是基于静脉快速团注顺磁性对比增强剂(Gd-DTPA)后缩短周围组织T2*信号,得到时间-信号强度曲线,通过观察时间信号曲线的变化可得到脑血容量(cerebral blood volume,CBV)[11,12]。当患者颅内小动脉极度扩张失去正常的血管收缩功能时CBV升高,从而可通过升高的CBV来预测CHS的发生。Fukuda等[13]对70例单侧颈内动脉重度狭窄患者进行分析发现,术后CBF较术前增加≥100%的15例患者中,7例患者可见术前CBV升高,术前CBV正常时CEA术后无CHS发生,通过回归性分析发现术前升高的CBV是CEA术后患者发生CHS的独立预测因素。

1.2 FLAIR序列

       FLAIR序列血管高信号征(FLAIR vascularhyperintensity,FVH)是指在横断面FLAIR T2WI图像上,脑表面匍匐的线状高信号,最常发生在外侧裂,通常代表侧支血流或缓慢的前向血流[14,15]。有研究表明,同时有一级和二级侧支形成的患者比只有一级侧支循环形成的患者血流动力学受损更严重[16,17],所以FVH可代表相应区域脑血管的自动调节能力受损。Wan等[18]纳入16例单侧颈内动脉或大脑中动脉重度狭窄的CAS患者,经研究发现6例患者的7个供血区可见FVH,术后4个供血区CBF增加≥50%;另外10例患者术前未发现FVH,术后CBF增加都未超过50%,有FVH高信号的患者比没有FVH高信号的患者术后发生CHS的风险更高,其中灵敏度可达100%、特异度为80%。

1.3 供血区动脉自旋标记

       TASL也称血管标记动脉自旋标记(vesselencoded arterial spin labeling,VE-ASL),是以ASL原理为基础,对单根颈内动脉或椎动脉进行标记,进而得到靶血管供血区域的灌注体积(perfusion volume,PV)[19]。之前有研究表明术前患侧的颈内动脉PV明显小于对侧,但是术后患侧PV增加,对侧PV降低,从而使两侧大脑半球PV处于相对平衡的状态[20]。术前减少的脑血管反应性(cerebrovascural reactivity,CVR)会导致术后CHS的发生,但是并不是所有患者术后都会发生CHS。因此,Yamamoto等[21]推测术后增加的颈内动脉血流重新分布障碍或许是引起CHS的重要原因。从而对32例CEA和CAS患者通过TASL测量颈内动脉PV发现,术前PV减低时比术前PV正常时术后CBF以及PV上升更明显;并且在术前PV减低时,术后两侧大脑半球PV增加不平衡时更容易发生CHS,然而对于这种增加不平衡容易导致CHS的病理生理学机制目前还不清楚。

1.4 磁共振血管成像

       三维时间飞跃法基于流入增强效应,通过反复激励静止组织与流动组织的饱和效应差异凸显动脉,当观察到血流信号强度降低时可代表脑血流动力学受损[22]。Kuroda等[23]通过三维时间飞跃法MRA (3D time of flight MRA,3D-TOF-MRA)观察81例单侧颈内动脉重度狭窄患者的脑血流变化,发现降低的大脑中动脉信号强度可以预测CHS,灵敏度为100%,特异度为63%,阳性预测值为28%,阴性预测值为100%。原因可能是降低的信号强度代表了受损的血流动力学。此外,Andereggen等[24]通过定量磁共振血管成像(Quantitative MRA),定量评估了25例CEA患者颈内动脉以及大脑中动脉的血流速度,发现颈内动脉以及大脑中动脉的血流速度在CEA之后显著增加,CHS患者的血流速度明显高于没有CHS患者的血流速度,并且颈内动脉和大脑中动脉术前和术后的流速差异越明显患者越容易发生CHS。

       在预测CHS的MRI新技术中,DSC需要注射外源性对比剂,对比剂的使用会增加检查费用,肾功能损害者也无法进行检查。TASL、MRA、FLAIR无需注射外源性对比剂,但在便捷度方面MRA和FLAIR更具有优势,两者都可以通过直接观察图像来进行术前预测,而TASL则需要专人进行图像后处理之后获得数据结果来进行预测。在准确度方面,FLAIR序列具有较其他检查技术更高的灵敏度和特异度,越来越成为当前学者的研究热点。

2 经颅多普勒超声

       TCD通过探测颅内血管流速变化来预测CHS,术后急剧升高的血流速度会导致CHS的发生,并且和术后的血压升高幅度密切相关[25]。Kablak-Ziembicka等[26]首先通过测量治疗侧和对侧大脑中动脉收缩期峰值流速(peak systolic velocities,PSV)并计算收缩期峰值流速比(PSV ratios,PSVR=PSV术后/PSV术前),发现CAS治疗侧及对侧PSVR> 2.4以及CAS术后对侧大脑中动脉PSV增高是预测脑再灌注损伤的独立危险因素。随后,Iwata等[27]分析了64例CEA患者,通过回归性分析发现大脑中动脉的平均血流速度是术前预测CHS的重要指标,50 cm/s是最佳预测值,灵敏度为77.8%,特异度为87.2%。之后,Lai等[28]又测量了术前和术后30 min大脑中动脉血流速度和血压并计算得到大脑中动脉血流速度比(velocity ratio,VR=V术后/V术前)和血压比(blood pressure ratio,BPR=BP术后/BP术前),从而得到流速血压指数(velocity BP index,VBI=BPR × VR)。通过评估发现CHS患者VBI比非CHS患者升高更明显,并且临界值为2.0时可以很好地预测CHS,灵敏度为83.3%,特异度为98.3%,可见当血流速度和血压结合时对预测CHS会有更高的灵敏度和特异度。TCD无创、简单易行、价廉,结合血压预测CHS时还有很高的灵敏度和特异度,对临床诊疗有一定的应用价值。

3 CT灌注成像

       CTP通过定量测量CBV、CBF、平均通过时间(mean transit time,MTT)以及达峰时间(time to peak,TTP)来预测CHS[29],当MTT明显延长、CBV增加、CBF降低时,表明脑血管自动调节机制遭到了破坏,TTP的延长代表了侧支的形成。但是侧支形成过度又会造成血流动力学的损害,所以TTP的过度延长也是发生CHS的危险因素之一[16,17]。Tseng等[30]连续纳入55例有症状的经过CAS治疗的颈椎颈动脉重度狭窄患者,发现当患者MTT与对侧MTT的差值,即dMTT> 3 s时患者容易发生CHS;此外,CHS患者的rCBV(患侧CBV/对侧CBV)比非CHS患者延长。Chang等[31]通过分析54例经过CAS治疗的重度颈内动脉狭窄患者,发现rCBV指数[(患侧rCBV-对侧rCBV)/对侧rCBV]>0.15、rTTP指数[(患侧rTTP-对侧rTTP)/对侧rTTP]>0.22可以独立预测CHS。Yoshie等[32]研究了113例CAS患者中9例CHS患者,发现静息态MTT和注射乙酰唑胺后的MTT是独立预测CHS的危险因素。并且静息态MTT的临界值为4.85 s,灵敏度为77.8%,特异度为90.4%;注射乙酰唑胺后MTT的临界值为4.87 s,灵敏度为88.9%,特异度为83.7%,所以静息态MTT可以更精确地预测CHS。CTP成像操作方便,扫描时间短,是急诊患者的首选。

4 放射性核素成像

4.1 单光子发射计算机断层扫描

       单光子发射计算机断层扫描(single photon emission computed tomography,SPECT)是借助于单光子核素标记药物来定量测量CBF和CVR的功能性显像[33],术前CVR以及CBF的降低提示脑血管自身调节机制遭到破坏和血流动力学的损害,从而易导致术后CHS的发生。Hosoda等[34]通过SPECT观察到术后第一天CVR减低(CVR<12%)的脑血流量增加比CVR正常(CVR≥12%)的增加更为显著;同时,术后第一天,当CVR减低时颈内动脉流速的增加和CBF的增加有显著的相关性,CVR正常时无相关性,并且当CVR减低时颈内动脉流速增高可导致发生CHS的阈值为330 ml/min。Ogasawara等[35]纳入了51例手术侧颈内动脉重度狭窄的患者,发现术前降低的CVR是术后发生CHS的独立预测因素。Sato等[36]通过测量单侧颈内动脉狭窄的112例患者的中枢苯二氮卓结合受体的潜能(central benzodiazepine receptor binding potential,CBRBP)和CBF发现,术前较高的CBRBP/CBF是CEA术后发生CHS的独立预测因素。Suga等[37]通过观察12例CEA术后发生CHS的患者发现,术前减低的CRV和术中产生的活性氧与术后CHS的发生密切相关。

4.2 正电子发射计算机断层显像

       正电子发射计算机断层显像(positron emission tomography,PET)利用放射性核素示踪技术可以进行CBF、CBV和氧摄取分数(oxygen extraction fraction,OEF)的测定[38]。术前CBV和OEF同时升高可代表脑血管的扩张和自动调节能力遭到破坏,易导致CHS的发生[39]。Kaku等[40]通过观察34例moyamoya病患者术前以及搭桥术后脑灌注和代谢情况,发现在PET术前的相关参数中OEF是有症状CHS患者唯一的独立预测因素,但是有症状CHS患者术前有更高的CBV。

       虽然SPECT、PET预测CHS的临床应用较早,但是因检查费用昂贵、操作复杂并且存在辐射安全问题,在实际临床工作中受到限制。

5 数字减影血管造影

       数字减影血管造影(digital subtraction angiography,DSA)和彩色编码数字减影血管造影(color-coded DSA,CDSA)可通过大脑循环时间(cerebral circulation time,CCT),即脑动静脉循环时间来预测CHS[41]。当术前CCT的延长代表了CBF降低以及脑血管反应性遭到破坏,从而导致大脑循环的严重受损,同时当术后CCT缩短或者和术前相比变化较大时表明了CBF急剧上升,这时对于受损的脑血管自动调节机制来说更容易发生CHS。Narita等[42]通过纳入136例CAS患者首先发现当△CCT(术前的CCT减去术后的CCT)变化较大者容易发生CHS,△CCT> 2.7 s时可预测CHS,灵敏度为100%,特异度为99%。随后Lin等[43]纳入了49例单侧颈动脉重度狭窄的患者,发现术前CCT延长会导致术后CHS的发生,术前延长的CCT最佳预测CHS的时间是7.1 s,灵敏度为67%,特异度为61%。最近,Yamauchi等[44]又通过彩色编码DSA测量33例CAS或血管成形术患者的CCT,发现治疗前CCT延长,以及△CCT (术前的CCT减去术后的CCT)变化较大者都容易发生CHS。术前延长的CCT最佳预测CHS的时间是8 s,灵敏度为100%,特异度为69%;△CCT的最佳预测时间是3.2 s,灵敏度为75%,特异度为100%。通过CCT预测CHS有较高的灵敏度以及特异度,但是DSA属于有创性检查并且辐射剂量较高。

       综上所述,可以通过多种影像学方法预测CHS。MRI新技术中可通过DSC-PWI、FLAIR、TASL、MRA预测术后发生CHS的危险,其中FLAIR序列的FVH无需注射外源性对比剂、便捷、具有较高的灵敏度和特异度,应作为MRI新技术术后预测CHS的首选。此外,TCD无创、简单易行、价廉,结合血压预测CHS时还有很高的灵敏度和特异度,也是预测CHS的有利选择。CTP成像时间短,扫描速度快,虽然有辐射并需注射外源性对比剂,但对于急性脑卒中患者预测CHS更有优势。SPECT、PET因检查费用昂贵、操作复杂并且存在辐射安全问题,在实际临床工作中受到限制。DSA虽可通过术前测量CCT来预测CHS,但是DSA属于有创性检查,并且辐射剂量较高,不作为预测CHS的首选检查。

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