Reduced CMRO2 and cerebrovascular reserve in patients with severe intracranial arterial stenosis: A combined multiparametric qBOLD oxygenation and BOLD fMRI study

Multiparametric quantitative blood oxygenation level dependent (mqBOLD) magnetic resonance Imaging (MRI) approach allows mapping tissular oxygen saturation (StO₂) and cerebral metabolic rate of oxygen (CMRO₂). To identify hemodynamic alteration related to severe intracranial arterial stenosis (SIAS), functional MRI of cerebrovascular reserve (CVR BOLD fMRI) to hypercapnia has been proposed. Diffusion imaging suggests chronic low grade ischemia in patients with impaired CVR. The aim of the present study was to evaluate how oxygen parameters (StO₂ and CMRO₂), assessed with mqBOLD approach, correlate with CVR in patients (n = 12) with SIAS and without arterial occlusion. The perfusion (dynamic susceptibility contrast), oxygenation, and CVR were compared. The MRI protocol conducted at 3T lasted approximately 1 h. Regions of interest measures on maps were delineated on segmented gray matter (GM) of middle cerebral artery territories. We have shown that decreased CVR is spatially associated with decreased CMRO₂ in GM of patients with SIAS. Further, the degree of ipsilateral CVR reduction was well‐correlated with the amplitude of the CMRO₂ deficit. The altered CMRO₂ suggests the presence of a moderate ischemia explained by both a decrease in perfusion and in CVR. CVR and mqBOLD method may be helpful in the selection of patients with SIAS to advocate for medical therapy or percutaneous transluminal angioplasty‐stenting. Hum Brain Mapp 36:695–706, 2015. © 2014 Wiley Periodicals, Inc.     

缺血性卒中患者颅内动脉狭窄的相关危险因素分析

目的 探讨颅内动脉狭窄的狭窄程度、相关危险因素与缺血性脑卒中的关系,为缺血性卒中的防治提供重要依据.方法 90例缺血性卒中患者根据全DSA检查结果分为非狭窄组(狭窄<30%)与颅内动脉狭窄组(狭窄≥30%或闭塞),分析颅内动脉狭窄程度与年龄、性别、高血压、糖尿病、高脂血症、冠心病、家族史、总胆固醇(CHO)、三酰甘油(TG)、高密度脂蛋白胆同醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白 A1(ApoA1)、载脂蛋白B(ApoB)、血清脂蛋白(Lpa)等相关危险因素的关系.结果 (1)本组患者颅内动脉狭窄发生率为67.78%,发生率最高为大脑巾动脉,其次颈内动脉颅内段和椎基底动脉颅内段,发生率最低为大脑后动脉.(2)有高血压、糖尿病的缺血性卒中患者容易发生颅内动脉狭窄,其同归系数、OR值、P值分别为1.659、5.256、0.002,1.657、5.241、0.046.(3)颅内动脉狭窄组HDL-C含量[(0.99±0.30)mmol/L]比非狭窄组[(1.30±0.50)mmol/L]明显降低,差异有统计学意义(t=3.603,P=0.001).(4)年龄、性别、吸烟、既往卒中史、脑血管病家族史、TC、TG、LDL-C、ApoA1、ApoB、Lpa在两组间比较差异无统计学意义(P>0.05).结论 缺血性卒中患者颅内血管狭窄的主要危险因素有高血压、糖尿病,保护因素有HDL-C.     

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis

Objective

To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis.

The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis

‘Vascular steal'' has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n=40) underwent a multimodal 3.0T MRI protocol including structural (T₁-weighted and T₂-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree<50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P<0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.     

An fMRI study of cerebrovascular reactivity and perfusion in obstructive sleep apnea patients before and after CPAP treatment

ObjectiveCerebrovascular reactivity is impaired in patients suffering from obstructive sleep apnea syndrome (OSAS) as demonstrated by transcranial Doppler studies. We use magnetic resonance imaging techniques to investigate the anatomical distribution of cerebrovascular reactivity changes in patients with OSAS, as well as their evolution after therapeutic and sham continuous positive airway pressure (CPAP) treatment.MethodsTwenty-three men with moderate or severe obstructive sleep apnea were compared to a healthy control group (n = 7) using a breath-holding functional magnetic resonance imaging task and the flow-sensitive alternating inversion recovery (FAIR) imaging before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment.ResultsSignificantly higher cerebrovascular reactivity was found in healthy controls as compared to patients in bilateral cortical and subcortical brain regions. Cerebrovascular reactivity increased with therapeutic CPAP in the thalamus and decreased with sham CPAP in medial frontal regions in OSAS patients.Duration of nocturnal hypoxemia and body mass index negatively correlated with cerebrovascular reactivity, particularly in the medial temporal lobe structures, suggesting a possible pathophysiological mechanism for hippocampal injury.There was no difference in perfusion between patients and control group, and no effect of CPAP or sham-CPAP treatment on perfusion in patients.ConclusionsObserved cerebrovascular reactivity changes were neither homogeneous throughout the brain nor followed vascular territories, but rather corresponded to underlying neuronal networks, establishing a relationship between cerebrovascular reactivity and surrounding neuronal activity.     

Measuring vascular reactivity with breath‐holds after stroke: A method to aid interpretation of group‐level BOLD signal changes in longitudinal fMRI studies

Blood oxygenation level‐dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath‐hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task‐related BOLD signal changes. Three methods of analyzing the breath‐hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri‐infarct tissue, both sub‐acutely (～2 weeks) and chronically (～4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri‐infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group‐level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath‐hold‐based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity. Hum Brain Mapp 36:1755–1771, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

大脑中动脉狭窄患者的脑血管反应性与脑梗死相关性研究

目的分析不同临床表现的大脑中动脉狭窄(MCAS)患者的脑血管反应性,探讨其与脑梗死的相关性。方法经经颅多普勒超声(TCD)检测大脑中动脉狭窄患者105例和48例健康对照组,根据症状、体征及脑CT或脑磁共振(MRI)检查将患者分为Ⅰ组(脑梗死组)和Ⅱ组(无脑梗死组),采用TCD屏气试验检测大脑中动脉的屏气指数(HBI),比较Ⅰ组和Ⅱ组与对照组之间的HBI,比较I组和Ⅱ组之间的HBI和血管危险因素。结果Ⅰ组和Ⅱ组的HBI明显低于对照组(P=0.000,P=0.004);Ⅱ组的HBI明显高于Ⅰ组(P=0.000)。Logistic回归分析HBI降低(P=0.000)和高血压(P=0.003)与大脑中动脉狭窄后脑梗死发生密切相关。结论脑血管反应性与脑梗死的发生有关,定期对高血压患者进行TCD及屏气试验监测并进行早期干预,能够预防脑梗死的发生。     

颈内动脉重度狭窄或闭塞患者脑血管反应性和认知功能的相关性研究

目的 探讨不同部位颈内动脉重度狭窄或闭塞患者的脑血管反应性(cerebral vascular reactivity,CVR)和认知功能改变的特点及两者的相关性。方法 选取颈内动脉重度狭窄或闭塞患者58例为病例组,按照狭窄部位分为左侧狭窄组、右侧狭窄组和双侧狭窄组,另选取正常人20例为对照组,采用经颅多普勒超声(transcranial Doppler,TCD)结合屏气试验分别检测各组屏气指数(breath-holding index,BHI),用蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)评估各组的认知功能。结果 病例组的BHI均低于对照组,双侧狭窄组低于左、右侧狭窄组; 右侧狭窄组的MoCA视空间/执行得分低于左侧狭窄组和对照组,左侧狭窄组的延迟记忆得分低于右侧狭窄组和对照组,双侧狭窄组的视空间/执行、延迟记忆和语言功能得分均低于对照组,且MoCA总分低于左、右侧狭窄组; 病例组内的BHI与MoCA总分呈正相关(r=0.411,0.474,0.868,P<0.05)。结论(1)颈内动脉重度狭窄或闭塞患者的BHI明显降低,认知功能也有不同程度损害;(2)颈内动脉重度狭窄或闭塞患者的BHI和MoCA总分有明显关系,将两者结合可更全面地反映认知功能。     

Large artery intracranial stenosis in young adults with ischaemic stroke

Large artery intracranial stenosis (ICS) is a common finding in stroke patients, but is much less prevalent in Western countries than in Asia and in young adults than in the elderly. We investigated the prevalence and causes of ICS among French young adults with ischaemic stroke. Clinical and radiological data of patients aged 18–54 years treated consecutively for acute ischaemic stroke in the anterior circulation at a tertiary stroke centre were analysed retrospectively. Patients with > 50% ICS were identified. ICS was evaluated using TOF-MRA, vessel wall-MRI, digital subtraction angiography and CT-angiography. A total of 316 patients were included. ICS was diagnosed in 29 patients, resulting in a prevalence of 9.2% (95% CI, 6.2 to 13.3). The leading cause of ICS was atherosclerosis (n = 13), ahead of moyamoya disease (n = 4), dissection (n = 2), vasculitis (n = 2), and reversible cerebral vasoconstriction syndrome (n = 1). The cause of ICAS could not be determined in 7 patients. ICS was found in nearly one in 10 ischaemic strokes among French young adults. Atherosclerosis was the leading cause of ICS. The cause of ICS could not be determined in almost a quarter of the patients.     

血浆一氧化氮水平和脑血管反应性与进展性卒中的关系研究

目的探讨一氧化氮(NO)和脑血管反应性(CVR)与进展性卒中(SIP)的关系。方法对发病24h内住院经头颅CT和/或MRI检查证实为大脑中动脉(MCA)供血区脑梗死患者,以斯堪的那维亚卒中量表(SSS)在住院72h内评分较入院时下降2分以上者判定为SIP患者,共50例;在住院72h内评分较入院时不下降或下降小于2分者判定为非SIP患者,共61例;以无脑梗死的体检者为正常对照组(52例)。采用硝酸还原酶法测定两组NO血浆水平,采用经颅多普勒超声结合屏气试验获取屏气指数(BHI)以评价CVR。结果 SIP组NO水平(40.15±4.73)显著低于非SIP组(56.55±8.35)和对照组(65.5±7.40)(P<0.00l),SIP组BHI(1.01±0.26)低于对照组(1.41±0.34)和非SIP组(1.18±0.30)(P<0.00l),BHI与NO血浆水平呈正相关(r=0.29,P=0.034)。结论 SIP患者的CVR降低与NO水平下降有相关性,CVR的下降是导致SIP的危险因素之一,检测NO水平和BHI有助于预测SIP发生的可能性,为临床治疗决策和预后判断具有重要意义。     

载瘤动脉临时阻断处理颅内动脉瘤的临床研究

目的 探讨载瘤动脉临时阻断处理动脉瘤继发缺血性脑功能损伤的相关因素。方法 63例颅内动脉瘤夹闭过程中行载瘤动脉临时阻断，术后根据相应部位有无脑功能障碍，CT检查阻断血管供应区有无新鲜梗塞灶为标准判断是否造成缺血性脑损伤，并按有无蛛网膜下腔出血、动脉瘤所在部位、Hunt和Hess分级等进行分组对照。结果 63例载瘤动脉临时阻断时间3-59min，术后共有12例出现缺血性脑损伤表现，其中术前有蛛网膜下腔出血(SAH)者11例，Hunt和Hess分级Ⅲ～V者8例，基底动脉5例、大脑中动脉4例。阻断时间16min以内者均无缺血性脑损伤。结论 载瘤动脉临时阻断继发缺血性脑损伤与阻断部位、阻断时间、阻断方式、侧支循环的个体差异、病人术前状况等因素有关。     

Cerebral vasomotor reactivity of bilateral severe carotid stenosis: is stroke unavoidable?

We evaluated the cerebral hemodynamic features of severe bilateral carotid stenosis by assessing and comparing cerebral vasomotor reactivity (VMR) in the middle cerebral (MCA) and vertebral arteries (VA) by transcranial Doppler and the Diamox (1 g acetazolamide i.v.) test. VMR was evaluated by recording the percentage differences in peak systolic blood flow velocity in each MCA and VA at baseline and by the Diamox test. Twenty-eight symptomatic (SCAS) and 31 asymptomatic (ACAS) patients with bilateral severe (>70%) internal carotid artery stenosis were studied. The mean MCA VMR% was 29 +/- 26.9% in SCAS and 43.2 +/- 26.8% in ACAS patients (P < 0.01). Their respective mean VA VMR% was 30.2 +/- 36.5% and 39.6 +/- 24.4% (P = NS). VMR% of the symptomatic MCA side in SCAS patients was significantly lower than the opposite side (20.5 +/- 31.1% and 39.2 +/- 37.9% respectively; P < 0.03). In contrast, the VA VMR% of both sides in SCAS patients remained similar (28.1 +/- 39.3% and 34.6 +/- 47.9% respectively; P = NS). VMR% of the MCA and VA in ACAS patients was also similar for both sides of bilateral carotid stenosis. The cerebral hemodynamic features differ between SCAS and ACAS patients with bilateral carotid occlusive disease in the anterior part of the circle of Willis. An independent cerebral vascular reserve capacity of the posterior circulation is proposed.     

Evaluation of cerebrovascular reserve using xenon-enhanced CT scanning in patients with symptomatic middle cerebral artery stenosis

Cerebrovascular reserve (CVR) is an important prognostic factor in patients with major cerebral arterial steno-occlusive disease. However, few studies have examined CVR in symptomatic intracranial stenosis without ipsilateral extracranial internal carotid artery stenosis. This study sought to evaluate CVR in patients with symptomatic middle cerebral artery (MCA) stenosis using xenon-enhanced computed tomography (Xe/CT) with acetazolamide (ACZ) challenge. Twelve patients with symptomatic MCA stenosis were recruited. All patients were examined by Xe/CT to quantitatively measure resting cerebral blood flow (CBF) and received ACZ challenge to evaluate CVR. For resting CBF, no significant differences were found between the sides in four regions of interest. After the ACZ challenge test, the CVR was significantly different between hemispheres (ipsilateral versus contralateral CVR: 12.9 ± 24.3% versus 28.0 ± 16.8%, respectively; p = 0.005) and in the MCA territory (ipsilateral versus contralateral CVR: 8.7 ± 24.7% versus 29.3 ± 24%, respectively; p = 0.003). However, no significant differences in CVR were detected between cortical comparisons and white matter comparisons from the two sides. Thus, ACZ-challenge Xe/CT is useful for the measurement of CBF and CVR in these patients. Impaired CVR is an important characteristic of patients with symptomatic MCA stenosis.     

支架技术在急性缺血性卒中合并颅内外动脉狭窄中的应用

目的探讨支架技术在急性缺血性卒中合并颅内外动脉狭窄中应用的可行性、安全性及有效性。方法回顾性纳入2014年4月至2016年10月在山东大学附属济南市中心医院神经外科就诊的29例急性缺血性卒中合并颅内外动脉狭窄的患者。经数字减影血管造影（DSA）证实责任动脉闭塞,患者取栓后仍有重度狭窄,遂行球囊扩张、支架置入血管成形术。记录患者治疗前、后7d美国国立卫生研究院卒中量表（NIHSS）评分、30d卒中或短暂性脑缺血性发作的复发率及90d改良Rankin量表评分（mRS）。临床随访分别在术后30d和90d进行。结果29例患者的技术成功率为100％,支架治疗后平均残留狭窄率为（10．4±8．1）％。所有患者均得到随访,30d内再次卒中1例。NIHSS评分：治疗前为（19．5±3．5）分,治疗后7d为（5．8±2．1）分,治疗前后的差异有统计学意义（P〈0．05）。90d患者的病死率为0％,其中28例（97％）90dmRS评分≤2分,预后良好。结论急性缺血性卒中合并颅内动脉狭窄患者应用支架技术的并发症发生率较低且安全、有效;但残余狭窄以及合并基础性疾病、医嘱依从性差被认为是卒中再发的危险因素。     

单侧大脑中动脉中重度狭窄患者脑灌注与脑血管储备力的相关性研究

目的探讨单侧大脑中动脉(MCA)中重度狭窄患者脑灌注与脑血管储备力(CVR)的相关性。方法 31例单侧MCA中重度狭窄患者二氧化碳(CO2)吸入试验前后行CT灌注成像(CTP)检查,在基底节区、放射冠区及半卵圆中心层面选择感兴趣区,测量感兴趣区脑血流量、脑血容量、平均通过时间及达峰时间,以对侧为正常对照,分析患侧MCA供血区的脑灌注。计算双侧MCA区CVR,对脑灌注变化与患侧CVR进行相关性分析。结果 31例患者中有8例(25.81%)灌注正常,23例(74.19%)患侧存在低灌注。CVR正常者15例(48.39%),下降者16例(51.61%)。脑灌注变化与CVR存在等级相关(r=0.462,P=0.009)。结论单侧MCA中重度狭窄患者中存在脑灌注及CVR均正常者,脑灌注变化与其CVR具有正相关。     

TCD对颈内动脉中度及重度狭窄患者脑血流动力学的评估价值

目的应用经颅多普勒超声(transcranial doppler,TCD)评价颈内动脉中度及重度狭窄患者的脑血流动力学变化。方法经数字减影血管造影(digital subtraction angiography,DSA)确诊单侧颈内动脉中度及重度狭窄的患者69例,采用TCD检测其大脑中动脉血流参数,评价其侧支循环开放情况和脑血流储备能力(CRV)。结果 TCD显示侧支循环开放者患侧收缩期峰时血流速度(Vs)、搏动指数(PI)及CVR明显高于无侧支循环开放患者(P0.05),颈内动脉中度狭窄组患侧收缩期峰时血流速度(Vs)、PI值及CVR明显高于重度组(P0.05)。结论颈内动脉狭窄时侧支开放可以改善远端血流动力学指标,但改善程度有限。TCD可检测颈内动脉狭窄患者颅内血流动力学变化,评价颅内侧支循环的建立情况,为临床治疗和评估提供可靠依据。     

认知障碍患者颅内动脉狭窄与脑白质胆碱能通路病变的关系

目的探讨认知功能障碍患者中颅内动脉狭窄与脑白质胆碱能通路病变的相关性。方法连续收集符合入组标准的病例118例。对入组患者行蒙特利尔认知量表(Mo CA)评估认知功能、头颅CT血管成像采集颅内血管信息、头颅磁共振采集脑白质病变情况,按认知功能水平,分为认知功能障碍组(研究组,85例)和认知功能正常组(对照组,33例)。结果相较于对照组,研究组颅内血管狭窄比例较高,差异有统计学意义(P=0.042)。研究组Mo CA总分及其分项均低于对照组,差异有统计学意义(P0.01);研究组CHIPS得分高于对照组,差异有统计学意义(P=0.047)。CHIPS得分与Mo CA评分及其部分分项呈负相关(均P0.05)。颅内动脉狭窄与Mo CA评分及其分项(除抽象功能)呈负相关(均P0.05);CHIPS得分与颅内动脉狭窄呈正相关(P=0.001)。结论颅内动脉狭窄在脑白质胆碱能通路病变致使多领域认知功能障碍过程中起到一定作用。     

Functional connectivity associated with social networks in older adults: A resting-state fMRI study

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social networks using the Social Network Index (SNI) and resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data from 28 non-demented older adults were analyzed with independent components analyses. As expected, four established resting-state networks—previously linked to motor, vision, speech, and other language functions—correlated with the quality (SNI-1: total number of high-contact roles of a respondent) and quantity (SNI-2: total number of individuals in a respondent’s social network) of social networks: a sensorimotor, a visual, a vestibular/insular, and a left frontoparietal network. Moreover, SNI-1 was associated with greater functional connectivity in the lateral prefrontal regions of the left frontoparietal network, while SNI-2 was associated with greater functional connectivity in the medial prefrontal regions of this network. Thus, lateral prefrontal regions may be particularly linked to the quality of social networks while medial prefrontal regions may be particularly linked to the quantity of social networks.