Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Cognitive impairment in cerebral small vessel disease induced by hypertension

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

Relationship between total cerebral small vessel disease burden and hemorrhagic transformation of acute ischemic stroke patients after intravenous thrombolysis

Objective To investigate the relationship betweentotal cerebral small vessel disease (CSVD) burden andintracranial hemorrhage transformation (HT) after intravenousthrombolysis in patients with acute ischemicstroke (AIS). Methods One hundred and fifty-four patientswho suffered from ischemic stroke within 4. 5 hoursof onset and received recombinant tissue plasminogen activatorthrombolytic therapy in the emergency green channelof the First Affiliated Hospital of Soochow Universityfrom August 2016 to January 2018 were enrolled. HT examinedby computed tomography scan within 24 hours afterthrombolysis was included. The magnetic resonanceimaging examination was performed within 48 hours. Thepatients were divided into two groups: HT group andcontrol group according to the presence or absence ofHT.

Effects of Progressive Muscle Relaxation Training on Anxiety, Depression, and Quality of Life in Patients with Cerebral Small Vessel Disease

Objective:To explore the effects of progressive muscle relaxation training on anxiety,depression,and quality of life in patients with cerebral small vessel disease(CSVD).Methods:Sixty-one patients with CSVD in the Department of Neurology of a tertiary hospital were divided into an observation group(28 patients)and a control group(33 patients)by lottery method.The control group received conventional nursing care,while the observation group received progressive muscle relaxation training interventions in addition to the conventional care.The Hamilton Anxiety Scale(HAMA),the Hamilton Depression Scale(HAMD),and the Stroke-Specific Quality of Life Scale(SS-QOL)were used to compare the effects before the intervention,7 days after the intervention,and 30 days after the intervention.Results:Over time,at different time points after the intervention,the anxiety and depression scores of patients with CSVD in the observation group were significantly lower than those in the control group(P<0.05).The quality of life scores were significantly higher in the observation group compared to the control group(P<0.05),and these differences were statistically significant.Conclusion:Progressive muscle relaxation training can improve anxiety and depression in patients with cerebral small vessel disease and can effectively enhance their quality of life.

Exosomal miR-320e through wnt2targeted inhibition of the Wnt/β-catenin pathway allevisate cerebral small vessel disease and cognitive impairment

BACKGROUND Exosomal miRNAs play crucial roles in many central nervous system diseases.Cerebral small vessel disease(CVSD)is a small vessel disease that is affected by various factors.This study aimed to investigate the role of exosomal miR-320e in the Wnt/β-catenin pathway stimulated by oxidative stress and assess its clinical correlation with psychiatric symptoms in patients with CVSD.AIM To explore whether exosomal miR-320e could suppress the Wnt/β-catenin pathway and play a protective role in CVSD progression,as well as examine its potential correlation with cognitive impairment and depression in patients with CVSD.METHODS Differentially expressed exosomal miRNAs were filtered by sequencing plasma exosomes from patients with CVSD and healthy controls.Bioinformatics and dual luciferase analyses were used to confirm the binding of miR-320e to Wnt2,and the mRNA and protein levels of downstream components in the Wnt/β-catenin pathway were evaluated when overexpressed or with knockdown of miR-320e under H2O2-induced oxidative stress.In addition,Wnt2-targeting siRNA was used to confirm the role of miR-320e in the Wnt2-mediated inhibition of the Wnt/β-catenin pathway.A retrospective analysis was conducted among patients with CVSD to confirm the correlation between miR-320e expression and the severity of cognitive impairment and depression,which were quantified using the Montreal Cognitive Assessment(MoCA)/Executive Function Assessment(EFA),and the Hamilton Depression Scale(HAMD)/Beck Depression Inventory(BDI),respectively.RESULTS High-throughput sequencing revealed that exosomal miR-320e was downregulated in patients with CVSD.Bioinformatics analysis and dual-luciferase reporter gene experiments showed that exosomal miR-320e inhibited the Wnt/β-catenin pathway in response to oxidative stress by targeting the 3'noncoding region of Wnt2.Uptake of exosomes carrying miR-320e into endothelial cells could also target Wnt2 and inhibit the Wnt2/β-catenin pathway.Elevated miR-320e expression may protect patients with CVSD from relatively severe cognitive impairment and depression,as it was found to have a positive correlation with the MoCA/EFA and HAMD/BDI scores.CONCLUSION Our results suggest that exosomal miR-320e suppresses the Wnt/β-catenin pathway and may play a protective role in CVSD progression.

Machine Learning for Selecting Important Clinical Markers of Imaging Subgroups of Cerebral Small Vessel DiseaseBased on a Common Data Model

Differences in the imaging subgroups of cerebral small vessel disease(CSVD)need to be further explored.First,we use propensity score matching to obtain balanced datasets.Then random forest(RF)is adopted to classify the subgroups compared with support vector machine(SVM)and extreme gradient boosting(XGBoost),and to select the features.The top 10 important features are included in the stepwise logistic regression,and the odds ratio(OR)and 95%confidence interval(CI)are obtained.There are 41290 adult inpatient records diagnosed with CSVD.Accuracy and area under curve(AUC)of RF are close to 0.7,which performs best in classification compared to SVM and XGBoost.OR and 95%CI of hematocrit for white matter lesions(WMLs),lacunes,microbleeds,atrophy,and enlarged perivascular space(EPVS)are 0.9875(0.9857−0.9893),0.9728(0.9705−0.9752),0.9782(0.9740−0.9824),1.0093(1.0081−1.0106),and 0.9716(0.9597−0.9832).OR and 95%CI of red cell distribution width for WMLs,lacunes,atrophy,and EPVS are 0.9600(0.9538−0.9662),0.9630(0.9559−0.9702),1.0751(1.0686−1.0817),and 0.9304(0.8864−0.9755).OR and 95%CI of platelet distribution width for WMLs,lacunes,and microbleeds are 1.1796(1.1636−1.1958),1.1663(1.1476−1.1853),and 1.0416(1.0152−1.0687).This study proposes a new analytical framework to select important clinical markers for CSVD with machine learning based on a common data model,which has low cost,fast speed,large sample size,and continuous data sources.

Association between intercellular adhesion molecule-1 to depression and blood-brain barrier penetration in cerebellar vascular disease

BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD remains elusive.AIM To explore the association between intercellular adhesion molecule-1(ICAM-1)and blood-brain barrier(BBB)penetration in CSVD.METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community(Anhui,China)between December 2021 and March 2022.The study population comprised 142 patients,including 80 in the CSVD group and 62 in the control group.Depression was present in 53 out of 80 patients with CSVD.Multisequence magnetic resonance imaging(MRI)and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume,cortical thickness,and cortical area of each brain region.Moreover,neuropsychological tests including the Hamilton depression scale,mini-mental state examination,and Montreal cognitive assessment basic scores were performed.RESULTS The multivariable analysis showed that age[P=0.011;odds ratio(OR)=0.930,95%confidence interval(CI):0.880-0.983]and ICAM-1 levels(P=0.023;OR=1.007,95%CI:1.001-1.013)were associated with CSVD.Two regions of interest(ROIs;ROI3 and ROI4)in the white matter showed significant(both P<0.001;95%CI:0.419-0.837 and 0.366-0.878)differences between the two groups,whereas only ROI1 in the gray matter showed signi-ficant difference(P=0.046;95%CI:0.007-0.680)between the two groups.ICAM-1 was significantly correlated(all P<0.05)with cortical thickness in multiple brain regions in the CSVD group.CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD.ICAM-1 may be associated with cortical thickness in the brain,predominantly in the white matter,and a significant increase in BBB permeability,proposing the involvement of ICAM-1 in BBB destruction.

Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment

Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Magnetic resonance imaging manifestations of cerebral small vessel disease:automated quantification and clinical application

The common cerebral small vessel disease(CSVD)neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts,lacunes,white matter hyperintensities,perivascular spaces,microbleeds,and brain atrophy.The CSVD neuroimaging features have shared and distinct clinical consequences,and the automatic quantification methods for these features are increasingly used in research and clinical settings.This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials.The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

Pandemic of the aging society—sporadic cerebral small vessel disease

Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population.The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD.In this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

Diffusion tensor imaging pipeline measures of cerebral white matter integrity: An overview of recent advances and prospects

Cerebral small vessel disease(CSVD)is a leading cause of age-related microvascular cognitive decline,resulting in significant morbidity and decreased quality of life.Despite a progress on its key pathophysiological bases and general acceptance of key terms from neuroimaging findings as observed on the magnetic resonance imaging(MRI),key questions on CSVD remain elusive.Enhanced relationships and reliable lesion studies,such as white matter tractography using diffusion-based MRI(dMRI)are necessary in order to improve the assessment of white matter architecture and connectivity in CSVD.Diffusion tensor imaging(DTI)and tractography is an application of dMRI that provides data that can be used to non-invasively appraise the brain white matter connections via fiber tracking and enable visualization of individual patient-specific white matter fiber tracts to reflect the extent of CSVD-associated white matter damage.However,due to a lack of standardization on various sets of software or image pipeline processing utilized in this technique that driven mostly from research setting,interpreting the findings remain contentious,especially to inform an improved diagnosis and/or prognosis of CSVD for routine clinical use.In this minireview,we highlight the advances in DTI pipeline processing and the prospect of this DTI metrics as potential imaging biomarker for CSVD,even for subclinical CSVD in at-risk individuals.

HTRA1-related autosomal dominant cerebral small vessel disease

Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL).Recently,increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease(CSVD)with an autosomal dominant pattern of inheritance.This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.Methods:We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1,2020.CARASIL probands with genetic diagnosis reported to date were also reviewed.The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.Results:Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included.Compared with typical CARASIL,HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors(P<0.001),a later onset age(P<0.001),and a relatively slower clinical progression.Alopecia and spondylosis can be observed,but less than those in the typical CARASIL.Thirty-five heterozygous mutations in HTRA1 were reported,most of which were missense mutations.Amino acids located close to amino acids 250-300 were most frequently affected,followed by these located near 150∼200.While amino acids 250∼300 were also the most frequently affected region in CARASIL patients,fewer mutations precede the 200th amino acids were detected,especially in the Kazal-type serine protease domain.Conclusions:HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL.The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.

Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.

Roles of NG2 Glia in Cerebral Small Vessel Disease

Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

脑小血管病的病因和发病机制的最新进展

脑小血管病(CSVD)是一种大脑微血管疾病,是脑卒中的常见原因,也是导致老年人认知障碍的主要原因,但其发病机制尚不清楚,本文对目前主要的脑小血管病的病因及发病机制进行综述,为临床对该病的诊治提供参考。

脑小血管病的诊治现状及未来探索之路

脑小血管病(cerebral small vessel disease,CSVD)是一组临床、影像、病理综合征,主要累及颅内小血管,起病隐匿。CSVD与卒中、认知下降、情感障碍、步态异常及尿便失禁密切相关,给家庭和社会带来沉重的疾病负担和经济负担。但CSVD的致病机制仍不明确,临床诊断标准不统一,临床诊疗和试验研究面临重大挑战。本文旨在汇总当前CSVD的可能病因、发病机制和临床诊疗研究的进展及局限性,展望CSVD未来可能的临床研究方向。

老年无症状颅内动脉延长扩张症与脑小血管病综合评分的相关性

目的探讨老年无症状颅内动脉延长扩张症(IADE)与脑小血管病(CSVD)综合评分的相关性。方法回顾性分析2019年1月至2021年12月北京医院神经内科门诊查体或就诊且完成3 T头部磁共振成像(MRI)平扫、头部磁共振血管造影(MRA)和头部磁敏感加权成像(SWI)的CSVD患者。通过影像学诊断IADE并进行CSVD综合评分。根据有无IADE,将所有患者分为IADE组与非IADE组;依据CSVD综合评分,将患者分为CSVD无-轻度组与中-重度组,分别比较各组患者的基线资料和影像学资料,采用多因素Logistic回归分析IADE与CSVD总负荷之间的关系。结果共纳入230例CSVD患者,其中IADE组86例、非IADE组144例,CSVD综合评分无-轻度组157例、中-重度组73例。与非IADE组相比,IADE组患者的脑梗死史〔16例(18.6%)比13例(9.0%)〕、口服抗血小板聚集药物〔45例(52.3%)比51(35.4%)〕及CSVD综合评分为中-重度的患者〔36例(41.9%)比37例(25.7%)〕比例更高(均P<0.05)。230例患者中,CSVD综合评分中-重度组IADE患者比例高于无-轻度组〔36例(49.3%)比50例(31.8%),χ2=6.495,P值=0.011〕。多因素Logistic回归分析显示年龄〔OR(95%CI)=1.777(1.124~2.808),P=0.014〕、脑梗死史〔OR(95%CI)=15.481(4.565~52.496),P<0.001〕、颅内外动脉狭窄/闭塞〔OR(95%CI)=0.961(1.003~6.804),P=0.049〕和IADE〔OR(95%CI)=0.037(0.879~2.563),P=0.037〕是中-重度CSVD综合评分的独立危险因素,血红蛋白(≥135.5 g/L)〔OR(95%CI)=0.283(0.114~0.701),P<0.01〕是中-重度CSVD综合评分的保护因素。结论CSVD伴IADE患者在颅内影像表现上全脑受损更明显,且IADE、脑梗死史及颅内动脉狭窄/闭塞是CSVD严重程度的独立危险因素。

CSVD总负荷与大脑中动脉供血区单发皮质下小梗死早期神经功能恶化的相关性研究

目的探讨脑小血管病(CSVD)的磁共振成像(MRI)总负荷与大脑中动脉供血区单发皮质下小梗死(SSSI)患者发生早期神经功能恶化(END)之间的关系。方法收集2020年1月-2021年12月在河北医科大学第三医院神经内科经脑MRI证实为大脑中动脉供血区SSSI患者133例。独立评估了脑MRI中的假定血管源性腔隙、脑微出血、脑白质高信号(WMH)和血管周围间隙扩大的存在,整合各CSVD影像特征,进而确定CSVD总负荷。END定义为入院后72h内美国国立卫生研究院卒中量表(NIHSS)评分增加≥2分或是肌力单项评分增加≥1分。根据患者入院后神经功能缺损程度的进展情况,将患者分为END组和非END组。比较两组的基线资料、单一CSVD影像学标志物和CSVD总负荷。采用Logistic回归分析SSSI患者中CSVD总负荷与发生END的关系。根据梗死部位对SSSI患者进行亚组分析,采用Logistic回归分析CSVD总负荷在不同梗死部位的SSSI患者中与发生END的关系。结果133例SSSI患者,其中30例(22.6%)被诊断为END。END组出现假定血管源性腔隙、脑微出血的比例、脑室周围WMH及CSVD总负荷评分显著高于非END组(P<0.05)。Logistic回归分析显示,CSVD总负荷是SSSI患者卒中后发生END的独立危险因素(P<0.05)。亚组分析结果显示远端SSSI患者的CSVD总负荷与END之间存在显著相关性(P<0.05)。结论CSVD总负荷是大脑中动脉供血区SSSI患者卒中后发生END的独立危险因素,在远端梗死上相关性更显著。

基于fMRI图论网络探索脑小血管病性轻度认知障碍的虚、实证候拓扑属性对照研究

目的基于图论网络探索性分析皮质下脑小血管病性轻度认知障碍虚证、实证的全脑及局部脑网络拓扑属性组间差异。方法前瞻性招募诊断为皮层下小血管病所致轻度血管性认知障碍患者和健康对照,基于GRETNA平台,计算虚证、实证和健康对照比较的组间全局小世界拓扑属性和局部节点强度、节点效率的组间差异。结果三组均具有小世界属性,但仅实证组患者在稀疏度为0.05-0.26内小世界属性δ显著低于对照组(P<0.05);同时,涉及额、顶及小脑等多个脑区的节点效率和节点强度指标均显著区分实证组、虚证组,但虚证患者在节点效率上无阳性脑区(P>0.05),在节点强度上仅表现为少数脑区的节点效率增高(P<0.05)。结论实组在全局拓扑属性及局部拓扑属性上均显著有别于虚证组,说明虚实证候具有显著差异的影像表型,为进一步探讨中医证候在疾病生物学分型的作用提供研究基础。