MRI-visible perivascular spaces in basal ganglia but not centrum semiovale or hippocampus were related to deep medullary veins changes

Our purpose is to assess the role of deep medullary veins (DMVs) in pathogenesis of MRI-visible perivascular spaces (PVS) in patients with cerebral small vessel disease (cSVD). Consecutive patients recruited in the CIRCLE study (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT03542734","term_id":"NCT03542734"}}NCT03542734) were included. Susceptibility Weighted Imaging-Phase images were used to evaluate DMVs based on a brain region-based visual score. T2 weighted images were used to evaluate PVS based on the five-point score, and PVS in basal ganglia (BG-PVS), centrum semiovale (CSO-PVS) and hippocampus (H-PVS) were evaluated separately. 270 patients were included. The severity of BG-PVS, CSO-PVS and H-PVS was positively related to the increment of age (all p < 0.05). The severity of BG-PVS and H-PVS was positively related to DMVs score (both p < 0.05). Patients with more severe BG-PVS had higher Fazekas scores in both periventricle and deep white matter (both p < 0.001) and higher frequency of hypertension (p = 0.008). Patients with more severe H-PVS had higher frequency of diabetes (p < 0.001). Besides, high DMVs score was an independent risk factor for more severe BG-PVS (β = 0.204, p = 0.001). Our results suggested that DMVs disruption might be involved in the pathogenesis of BG-PVS.     

Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease

In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.     

Venous disruption affects white matter integrity through increased interstitial fluid in cerebral small vessel disease

Deep medullary veins (DMVs) participate in the drainage of surrounding white matter. In cerebral small vessel disease (CSVD), disrupted DMVs were often observed together with damaged white matter, but the phenomenon lacked validation and explanation. We hypothesized that venous disruption might cause white matter damage through increased interstitial fluid resulting from hemodynamic alteration, and we designed a comprehensive multi-modality MRI study to testify our hypothesis. Susceptibility-weighted imaging was used to investigate the characteristics of DMVs and derive DMVs scores. Free water elimination diffusion tensor imaging model was used to analyze interstitial fluid fraction (fraction of free water, fFW) and white matter integrity (tissue fractional anisotropy, FAt). Totally, 104 CSVD patients were included. Total DMVs score was associated with FAt of DMVs drainage area. The effect of total DMVs score on FAt was mediated by fFW, after controlling for age, sex, hypertension, regional cerebral blood flow and lacune numbers. The relationships between DMVs score, fFW and FAt were also significant in most DMVs drainage subregions. Therefore, we discovered the DMVs disruption – increased interstitial fluid – white matter damage link in CSVD patients, which was independent of arterial perfusion variations.     

脑小血管病非痴呆患者脑微出血与认知功能相关性研究

目的探讨脑小血管病非痴呆患者脑微出血(CMBs)数量、部位与认知功能损害的相关性。方法收集82例脑小血管病非痴呆伴有CMBs患者的临床资料,行头部MRI及磁敏感加权成像(SWI)检查,记录CMBs部位、数量,并完成MMSE和蒙特利尔认知评估量表(Mo CA)评分。结果 CMBs好发部位是基底节、颞叶及额叶;CMBs数量与Mo CA总分呈负相关(r=-0.293,P=0.014)有关,尤其在注意集中、延迟记忆(r=-0.266,P=0.026;r=-0.237,P=0.048)。额叶CMBs与视结构执行技能呈负相关(r=-0.240,P=0.03)。枕叶CMBs与语言、定向呈负相关(r=-0.218,P=0.049;r=-0.242,P=0.028)。岛叶和基底节区域CMBs与注意集中呈负相关(r=-0.236,P=0.033;r=-0.248,P=0.024)。DPWM区域CMBs与Mo CA总分、注意集中、记忆、语言呈现负相关(r=-0.269,P=0.015;r=-0.219,P=0.048;r=-0.240,P=0.030;r=-0.295,P=0.007)。结论 CMBs作为CSVD的标志物之一,在认知、早期诊断及病程发展中扮演着重要作用。     

脑小血管病磁共振影像研究概况

脑小血管病（cerebral small vessel disease,cSVD）是血管性痴呆最常见的病因,且约占 卒中病因的1/5。目前对cSVD的认识主要是通过磁共振成像（magnetic resonance imaging,MRI）进 行,cSVD在MRI上的表现包括腔隙性梗死（lacunar infarction,LI）与腔隙灶、白质高信号（white matter hyperintensities,WMH）、血管周围间隙扩张（dilated Virchow-Robin space,dVRS）、脑微出血（cerebral microbleeds,CMBs）及脑萎缩。本文综述上述cSVD磁共振影像学表现定义、分级及推荐序列等的研究 概况。     

Progression of MRI markers in cerebral small vessel disease: Sample size considerations for clinical trials

Detecting treatment efficacy using cognitive change in trials of cerebral small vessel disease (SVD) has been challenging, making the use of surrogate markers such as magnetic resonance imaging (MRI) attractive. We determined the sensitivity of MRI to change in SVD and used this information to calculate sample size estimates for a clinical trial. Data from the prospective SCANS (St George’s Cognition and Neuroimaging in Stroke) study of patients with symptomatic lacunar stroke and confluent leukoaraiosis was used (n = 121). Ninety-nine subjects returned at one or more time points. Multimodal MRI and neuropsychologic testing was performed annually over 3 years. We evaluated the change in brain volume, T2 white matter hyperintensity (WMH) volume, lacunes, and white matter damage on diffusion tensor imaging (DTI). Over 3 years, change was detectable in all MRI markers but not in cognitive measures. WMH volume and DTI parameters were most sensitive to change and therefore had the smallest sample size estimates. MRI markers, particularly WMH volume and DTI parameters, are more sensitive to SVD progression over short time periods than cognition. These markers could significantly reduce the size of trials to screen treatments for efficacy in SVD, although further validation from longitudinal and intervention studies is required.     

脑小血管病MRI表现对痴呆的预测作用

随着全球老龄化,痴呆发病率快速上升,而且痴呆具有不可逆性、缺乏有效治疗措施,故 探索预测痴呆发生的有效指标成为关键。脑小血管病（cerebral small vessel disease,CSVD）被认为与 痴呆密切相关,其颅脑磁共振成像（magnetic resonance imaging,MRI）可表现为腔隙（lacunes）、新发皮 层下小梗死（recent small subcortical infarcts）、脑白质高信号（white matter hyperintensities,WMH）、扩 大的血管周围间隙（enlarged perivascular spaces,EPVS）及脑微出血（cerebral microbleeds,CMB）等。本文 通过综述CSVD颅脑MRI表现与痴呆相关性的研究进展,发现多发静息性或位于基底节区的腔隙性梗死 （lacunar infarction,LI）或腔隙、重度WMH、多脑叶分布性脑叶微出血（lobar microbleeds,LMB）,均可作 为预测痴呆发生的有效指标。     

Capillary transit time heterogeneity inhibits cerebral oxygen metabolism in patients with reduced cerebrovascular reserve capacity from steno-occlusive disease

The healthy cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A disruption of this homogeneity may inhibit the extraction of oxygen. A high degree of capillary transit time heterogeneity (CTH) describes that some capillaries have very low blood flows, while others have excessively high blood flows and consequently short transit times. Very short transit times could hinder the oxygen extraction due to insufficient time for diffusion of oxygen into the tissue. CTH could be a consequence of cerebral vessel disease. We examined whether patients with cerebral steno-occlusive vessel disease demonstrate high CTH and if elevation of cerebral blood flow (CBF) by administration of acetazolamide (ACZ) increases the cerebral metabolic rate of oxygen (CMRO₂), or if some patients demonstrate reduced CMRO₂ related to detrimental CTH. Thirty-four patients and thirty-one healthy controls participated. Global CBF and CMRO₂ were acquired using phase-contrast MRI. Regional brain maps of CTH were acquired using dynamic contrast-enhanced MRI. Patients with impaired cerebrovascular reserve capacity demonstrated elevated CTH and a significant reduction of CMRO₂ after administration of ACZ, which could be related to high CTH. Impaired oxygen extraction from CTH could be a contributing part of the declining brain health observed in patients with cerebral vessel disease.     

脑小血管病患者 MR 弥散张量成像的改变及与认知功能障碍的关系

目的：探讨脑小血管病患者MR弥散张量成像的改变以及与认知功能障碍间的关系。方法选取我院接受检查的小脑血管疾病患者70例,根据有无认知障碍分为非痴呆认知功能障碍（VCIND）组39例和认知功能正常（NCI）组31例。对患者进行蒙特利尔认知评估（MoCA）及MRI检查,并对弥散张力成像（DTI）进行处理,显示表观弥散系数图（ADC）以及各向异性分数图（FA）,分析MoCA与DTI的相关性。结果 VCIND组MoCA量表评分（17.54±4.31）分,NCI组为（24.01±2.02）分;VCIND组双侧半卵圆中心、双侧额叶、双侧丘脑以及左侧尾状核 FA 值明显低于 NCI组,VCIND 组左侧尾状核ADC值明显高于NCI组,差异有统计学意义（P＜0.05）。双侧半卵圆中心、双侧额叶以及左侧尾状核FA值与MoCA呈正相关（P＜0.05）。结论脑小血管疾病患者认知功能障碍与DTI的FA值呈正相关。     

大脑中动脉狭窄脑深部小梗死发病机制的研究

目的 研究大脑中动脉粥样硬化性狭窄患者脑深部小梗死的发生频率和发病机制。方法86例发病时间〈1周的急件脑梗死患者，行经颅多普勒超声、彩色超声、磁共振血管造影及功能磁共振成像等检查方法被明确诊断为症状性大脑中动脉粥样硬化性狭窄，并排除颈内动脉病变、心源性栓塞以及非动脉粥样硬化性狭窄。利用磁共振扩散加权成像观察梗死灶的形态学表现及特点，分析其发病机制。结果37例（43．02％）症状性大脑中动脉粥样硬化性狭窄患者存在深部小梗死，多呈孤立性单发病灶。其中内囊纹状体梗死及巨大腔隙者18例（20．93％），梗死灶体积多超过两个层面，少数病灶呈多灶分布的特点；直径较小的腔隙性梗死19例（22．09％），梗死灶体积〈15mm，多位于一个层面内。伴有大脑中动脉粥样硬化性狭窄的深部小梗死的患者，病情多不稳定，预后较差。所有脑深部小梗死患者均伴有大脑中动脉主干支狭窄，且梗死灶体积与大脑中动脉粥样硬化性狭窄程度有关，内囊纹状体梗死多见于大脑中动脉重度狭窄者。结论约50％大脑中动脉粥样硬化性狭窄患者存在脑深部小梗死，其发病机制与大脑中动脉粥样硬化斑块或斑块残端血栓蔓延堵塞深穿支动脉入口有关。对此类患者的治疗不同于经典的腔隙性脑梗死。     

Assessing cortical cerebral microinfarcts on iron-sensitive MRI in cerebral small vessel disease

Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC – InTENse study is a serial MRI study including individuals with cerebral small vessel disease (SVD). 54 Participants underwent 10 monthly 3 T MRIs, including diffusion-weighted imaging, quantitative R1 (=1/T1), R2 (=1/T2), and R2* (=1/T2*) mapping, from which MRI parameters within areas corresponding to microinfarcts and control region of interests (ROIs) were retrieved within 16 participants. Finally, we compared pre- and post-lesional values with repeated measures ANOVA and post-hoc paired t-tests using the mean difference between lesion and control ROI values. We observed 21 acute cortical microinfarcts in 7 of the 54 participants (median age 69 years [IQR 66–74], 63% male). R2* maps demonstrated an increase in R2* values at the moment of the last available follow-up MRI (median [IQR], 5 [5–14] weeks after infarction) relative to prelesional values (p = .08), indicative of iron accumulation. Our data suggest that cortical microinfarcts are associated with increased R2* values, indicative of iron accumulation, possibly due to microhemorrhages, neuroinflammation or neurodegeneration, awaiting histopathological verification.     

Hypercholesterolemia is associated with a lower risk of cerebral ischemic small vessel disease detected on brain checkups

Objective

Several studies have reported an association between low cholesterol levels and cerebral small vessel disease (SVD). In this study, we examined whether serum total cholesterol was associated with SVD, including lacunar infarctions and white matter hyperintensity, detected by magnetic resonance imaging (MRI), in participants who had a checkup of the brain.

Methods

We retrospectively investigated 6143 participants aged 40 and over who visited a hospital for a brain checkup in a cross-sectional design. We performed logistic regression analysis to examine the association between total cholesterol and SVD.

Results

SVD was observed in 1456 participants (24%). Adjusting for sex, age, body mass index, hypertension, hypertriglyceridemia, and diabetes, a total cholesterol ≥ 225 mg/dL (the highest quartile) was significantly associated with not having SVD compared with a total cholesterol < 178 mg/dL (the lowest quartile; odds ratio [OR], 0.708; 95% confidence interval [CI], 0.581–0.863). Participants with a total cholesterol of 200–225 mg/dL (the third quartile) tended to have a reduced risk of SVD (OR, 0.832; 95%CI, 0.689–1.005).

Conclusion

Hypercholesterolemia was significantly associated with a lower risk of SVD, detected by MRI, in participants undergoing a brain checkup, after adjusting for potential confounding factors, such as age and hypertension.     

基于纤维束示踪的空间统计分析对脑小血管病合并阻塞性睡眠呼吸暂停患者脑微结构改变的研究

目的 采用弥散张量成像（diffusion tensor imaging,DTI）基于纤维束示踪的空间统计分析（tract-based spatial statistics,TBSS）方法探讨脑小血管病（cerebral small vessel disease,CSVD）合并阻塞性睡眠呼吸暂停（obstructive sleep apnea,OSA）患者的大脑微结构变化特点。方法 纳入于2018年9月—2020年6月在中山大学附属第一医院神经内科病房住院的CSVD患者,收集人口学信息、临床资料、认知功能评估量表评分、睡眠质量量表评分、CSVD常规影像学资料以及DTI、多导睡眠监测（polysomnography,PSG）参数等。以呼吸暂停低通气指数（apnea hypopnea index,AHI）5次/小时为界,分为OSA组（AHI≥5次/小时）与不伴OSA组（AHI＜5次/小时）,通过TBSS方法计算大脑白质存在差异的区域及其各向异性分数（fractional anisotropy,FA）和平均扩散系数（mean diffusivity,MD）,并对MD与睡眠监测参数、认知功能评分、CSVD影像标志物和CSVD负荷进行相关性分析。结果 本研究共纳入CSVD患者39例,其中7例因缺乏MRI数据/参数不一致/图像质量差而被排除,最终纳入32例患者。OSA组21例,平均年龄为（64.14±11.57）岁,男性18例（85.7%）;不伴OSA组11例,平均年龄为（67.64±8.95）岁,男性6例（54.5%）。TBSS分析显示,与不伴OSA组相比,OSA组在双侧丘脑前放射、双侧皮质脊髓束、双侧扣带回、双侧海马、大钳、小钳、双侧额枕下束、双侧上/下纵束、双侧钩束等部位的MD增加（P＜0.001）。双变量相关性分析发现,OSA组MD增加与脑白质高信号相对体积（r=0.646,P＜0.05）和Fazekas 2～3级（r=0.458,P<0.05）呈正相关,与MoCA评分呈负相关（r=-0.374,P＜0.05）,与MMSE评分、阿尔茨海默病评估量表-认知亚量表评分、睡眠质量评估量表、AHI、PSG参数、其他CSVD影像标志物及CSVD负荷之间无相关性（P＞0.05）。结论 CSVD合并OSA患者存在更为广泛的脑白质纤维损害,且大脑微结构广泛损害和脑白质高信号及认知功能障碍密切相关。     

Supratentorial and infratentorial damage in spinocerebellar ataxia 2: A diffusion‐weighted MRI study

Spinocerebellar ataxia type 2 (SCA2) is an autosomal‐dominant degenerative disorder that is neuropathologically characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. Diffusion‐weighted imaging (DWI)–Magnetic Resonance Imaging (MRI) studies of SCA2 have enabled in vivo quantification of neurodegeneration in infratentorial regions, whereas supratentorial regions have been explored less thoroughly. We measured microstructural changes in both infratentorial and supratentorial regions in 13 SCA2 patients (9 men, 4 women; mean age, 50 ± 12 years) and 15 controls (10 men, 5 women; mean age, 49 ± 14 years) using DWI‐MRI and correlated the DWI changes with disease severity and duration. Disease severity was evaluated using the International Cooperative Ataxia Rating Scale and the Inherited Ataxia Clinical Rating Scale. Cerebral diffusion trace ( ) values were generated, and regions of interest (ROIs) and voxel‐based analysis with Statistical Parametric Mapping (SPM) were used for data analysis. In SCA2 patients, ROI analysis and SPM confirmed significant increases in values in the pons, cerebellar white matter (CWM) and middle cerebellar peduncles. Moreover, SPM analysis revealed increased values in the right thalamus, bilateral temporal cortex/white matter, and motor cortex/pyramidal tract regions. Increased diffusivity in the frontal white matter (FWM) and the CWM was significantly correlated with ataxia severity. DWI‐MRI revealed that both infratentorial and supratentorial microstructural changes may characterize SCA2 patients in the course of the disease and might contribute to the severity of the symptoms. © 2013 International Parkinson and Movement Disorder Society     

症状性小动脉硬化脑小血管病患者脑微出血的危险因素分析

目的 应用头颅MRI的SWI序列检测症状性小动脉硬化脑小血管病(cerebral small vessel disease,CSVD)患者脑微出血(cerebral microbleeds,CMBs)灶,分析不同部位CMBs的临床特征差异及CMBs的危险因素。方法 回顾性纳入2017年3月—2018年10月就诊于新疆昌吉州中医院神经内科的小动脉硬化的CSVD患者。根据有无微出血分为CMBs组与无CMBs组。应用二元logistic回归分析CMBs的独立危险因素;判断CMBs数量分级与独立危险因素的相关性。根据CMBs的位置分为脑叶区亚组、深部区亚组、幕下区亚组。比较脑叶区CMBs与非脑叶区CMBs、深部CMBs与非深部CMBs、幕下区CMBs与非幕下区CMBs亚组之间的临床特征差异。结果 共纳入144例CSVD患者,CMBs组42例(29.2%),无CMBs组102例(70.8%),其中脑叶区18例,深部白质区23例,幕下区9例。二元logistic回归分析显示,低载脂蛋白b水平(OR 0.308,95%CI 0.099～0.957,P=0.042)及高空腹血糖值(OR 1.128,9...     

Patterns of cortical degeneration in an elderly cohort with cerebral small vessel disease

Emerging noninvasive neuroimaging techniques allow for the morphometric analysis of patterns of gray and white matter degeneration in vivo, which may help explain and predict the occurrence of cognitive impairment and Alzheimer's disease. A single center prospective follow‐up study (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study (RUN DMC)) was performed involving 503 nondemented elderly individuals (50–85 years) with a history of symptomatic cerebral small vessel disease (SVD). Age was associated with a global reduction in cortical thickness, and this relationship was strongest for ventrolateral prefrontal cortex, auditory cortex, Wernicke's area, superior temporal lobe, and primary visual cortex. Right and left hemispheres differed in the thickness of language‐related areas. White matter (WM) lesions were generally negatively correlated with cortical thickness, primarily in individuals over the age of 60, with the notable exception of Brodmann areas 4 and 5, which were positively correlated in age groups 50–60 and 60–70, respectively. The observed pattern of age‐related decline may explain problems in memory and executive functions, which are already well documented in individuals with SVD. The additional gray matter loss affecting visual and auditory cortex, and specifically the head region of primary motor cortex, may indicate morphological correlates of impaired sensory and motor functions. The paradoxical positive relationship between WM lesion volume and cortical thickness in some areas may reflect early compensatory hypertrophy. This study raises a further interest in the mechanisms underlying cerebral gray and white matter degeneration in association with SVD, which will require further investigation with diffusion weighted and longitudinal MR studies. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

脑小血管病认知障碍与影像特征分析

目的观察分析脑小血管病(CSVD)认知障碍与磁共振影像特征,为早期发现及治疗依据。方法选取脑小血管病患者86例,另选取80例健康志愿者为对照组。应用MMSE、临床记忆量表、WAIS-RC对86例脑小血管病患者进行认知评估,并分析其磁共振影像特征。结果脑小血管病患者MMSE评分、记忆商数MQ、语言智商VIQ、作业智商PIQ、总智商FIQ与对照组比较下降明显(P0.05);LI组无意义图形再认、人像特点回忆、算术、数字广度、木块图、数字符号的等值量表分下降更显著(P0.01);WML组数字广度、算术、图画填充、木块图、数字符号、图形拼凑、图片排列测试的等值量表分下降更显著(P0.01);CMB组在图像自由回忆、无意义图形再认、数字广度、图画填充、木块图、图片排列测试的等值量表分下降更显著(P0.01);LI、CMB、WML共存组各项测试分值均显著下降(P0.01)。结论脑小血管病存在认知障碍,且磁共振特征可以提示其认知障碍特点,早期发现其磁共振异常表现可以早期进行CSVD防治,延缓及改善CSVD认知障碍。