scholarly journals Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Yousef Hannawi ◽  
Eder Caceres ◽  
Mohamed G. Ewees ◽  
Kimerly A. Powell ◽  
Anna Bratasz ◽  
...  
Keyword(s):  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Cerebral Small Vessel Disease ◽  
Study Time ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Spontaneously Hypertensive ◽  
Vessel Disease

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.

scholarly journals Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

2017 ◽  
Vol 131 (12) ◽  
pp. 1361-1373 ◽  
Author(s):  
Iain D. Croall ◽  
Valerie Lohner ◽  
Barry Moynihan ◽  
Usman Khan ◽  
Ahamad Hassan ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Mean Diffusivity ◽  
Peak Height ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Single Centre ◽  
Vessel Disease ◽  
Multicentre Studies

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

scholarly journals Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function

2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Surrogate Marker ◽  
Mean Diffusivity ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Damage ◽  
Vessel Disease

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

Abstract P52: Temporal Progression of Cerebral Small Vessel Disease Lesions on Brain Magnetic Resonance Imaging in Spontaneously Hypertensive Stroke Prone Rats

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yousef Hannawi ◽  
Kimerly A Powell ◽  
Anna Bratasz ◽  
Mohamed G Ewees ◽  
Jay L Zweier
Keyword(s):  
Small Vessel Disease ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Volumetric Analysis ◽  
Cerebral Small Vessel Disease ◽  
Male Rats ◽  
Small Vessel ◽  
Spontaneously Hypertensive ◽  
Vessel Disease ◽  
Hemosiderin Deposition

Introduction: Spontaneously Hypertensive Rats- Stroke Prone (SHRSP) are a relevant model for human cerebral small vessel disease (cSVD). However, data are still lacking regarding the neuroimaging correlates of cSVD lesions in SHRSP and their temporal evolution in relationship to histological findings. Methods: 40 SHRSP and 40 Wistar Kyoto control (WKY) male rats were divided into 4 groups (10 WKY and 10 SHRSP) per group. Systolic blood pressure (SBP) was measured using tail-cuff device, weekly. Select animals of each group had brain MRI at 9.4T machine at 7, 16, 24, and 32 weeks of age. Volumetric analysis was completed using manual segmentation of the total brain, ventricles and bilateral hippocampi. Following MRI, brain histology was completed at the same time points. Results: At 6 weeks, SBP was similar (WKY 123.8±0.1 vs SHRSP 130.7±3.2, P=0.09). SHRSP developed hypertension between 9-11 weeks of age and maintained it throughout the experiment (SBP at 31 weeks: WKY 138.1±6 vs SHRSP 169.1±6.7, p=0.0006). At 7 weeks, brain MRI was normal in SHRSP and WKY. Histology was largely unremarkable except for few areas of red blood cell extravasation in couple of SHRSP. At 16 weeks, MRI was normal in WKY and it showed small subcortical hyperintensity on T2 sequences in one SHRSP while histology showed microbleeds (MBs) in 85% of SHRSP. At 24 weeks, brain MRI consistently identified subcortical hyperintensities in SHRSP and H&E showed MBs in all SHRSP in addition to hemosiderin deposition and arteriosclerosis. LFB staining showed areas of demyelination in the corpus callosum. At 32 weeks, SHRSP had hydrocephalus and H&E showed widespread hemosiderin deposition. Volumetric analysis showed larger ventricles in SHRSP (SHRSP 42.3±18.1 ml vs WKY 28.4±7.2 ml, p=0.013) and ventricle size significantly increased with age in SHRSP. Hippocampal and brain volumes were similar in both groups (hippocampal volume: WKY 84.5±8.1 ml vs SHRSP 81.6±2.6 ml, p=0.39; brain volume WKY 2103.4±100.4 ml vs SHRSP 2169.6 ±164.2 ml, p=0.2). Conclusions: SHRSP develop cSVD histological changes early in life and brain MRI showed consistent abnormalities at a later time point. These results have implications in defining cSVD phenotypes in SHRSP in future mechanistic studies.

scholarly journals Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

Abstract P332: Cerebral Small Vessel Disease Score in CADASIL: Relationships to Cognitive Dysfunctions

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Dorothee Schoemaker ◽  
Yesica Zuluaga ◽  
Lina Velilla ◽  
Carolina Ospina ◽  
Francisco Lopera ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Structural Mri ◽  
Vascular Cognitive Impairment ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Perivascular Spaces ◽  
Cerebrovascular Injury ◽  
Vessel Disease ◽  
History Of

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease (cSVD) linked to NOTCH3 mutations and leading to the early onset of stroke and vascular cognitive impairment. Neuroimaging features of CADASIL include extensive white matter hyperintensity, lacunes, cerebral microbleeds and enlarged perivascular spaces. Researchers from the Rotterdam study recently proposed a MRI-based cSVD Score reflecting the overall burden of cerebrovascular injury (Yilmaz et al., 2018). Here, we explored the relevance of this cSVD Score in distinguishing CADASIL subjects from non-carriers and its relationships to cognition. We evaluated 26 NOTCH3 mutation carriers and 25 non-carriers from large Colombian families. Of the CADASIL subjects, 4 had previous strokes (symptomatic) and 22 had no history of strokes (asymptomatic). All subjects underwent a 3T MRI and a neuropsychological evaluation. Structural MRI markers of cSVD, as well as the cSVD Score, were quantified in each subject following established protocols. Demographic, cognitive and neuroimaging features across groups are presented in Table 1. The cSVD Score significantly differed between groups, after adjusting for age (Figure 1-A). In CADASIL subjects, the cSVD Score was negatively related to performance in Memory, Processing Speed, Executive Function, after accounting for age and education (Figure 1-B). These results suggest that the cSVD Score could be a useful marker of disease severity in CADASIL. Longitudinal studies are now needed to determine if this score allows predicting clinical outcomes in CADASIL, such as stroke or dementia.

scholarly journals Total Cerebral Small Vessel Disease Burden on MRI Correlates With Cognitive Impairment in Outpatients With Amnestic Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Yangyi Fan ◽  
Yicheng Xu ◽  
Ming Shen ◽  
Huailian Guo ◽  
Zhaoxu Zhang
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Linear Regression Model ◽  
Small Vessel Disease ◽  
Multiple Linear Regression Model ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Moca Score

Objectives: The main markers of cerebral small vessel disease (cSVD) on MRI may be entered into a scoring system, with the total score representing the overall burden of cSVD. An association between total cSVD score and cognitive dysfunction has been reported in several cohorts. The present study aimed to investigate this association in outpatients with amnestic disorders.Materials and Methods: Outpatients with amnestic complaints in a memory clinic (n = 289) were recruited retrospectively. All the patients had undergone clinical and cognitive evaluation at first presentation. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scale. The total cSVD score was based on the following markers on MRI: lacune; white matter hyperintensities, microbleed, and enlarged perivascular spaces. The association between total cSVD score and MoCA score was tested via Spearman's analysis and a linear regression model.Results: Among the 289 patients, rates for 0–4 cSVD markers respectively ranged from 30.4 to 2.8%. A multiple linear regression model revealed an inverse correlation between the total cSVD score and MoCA score. The association remained significant after adjusting for gender, age, education, levels of medial temporal lobe atrophy, and classical vascular risk factors [β = −0.729, 95% CI (−1.244, −0.213); P = 0.006]. When individual markers were individually analyzed after adjusting for the same factors, only microbleed associated with MoCA score [β = −3.007, 95% CI (−4.533, −1.480), P < 0.001].Conclusions: A significant association was demonstrated between total cSVD score and cognitive performance in the outpatients with amnestic disorders.

scholarly journals Enlarged Perivascular Spaces on MRI Are a Feature of Cerebral Small Vessel Disease

Stroke ◽  
2010 ◽  
Vol 41 (3) ◽  
pp. 450-454 ◽  
Author(s):  
Fergus N. Doubal ◽  
Alasdair M.J. MacLullich ◽  
Karen J. Ferguson ◽  
Martin S. Dennis ◽  
Joanna M. Wardlaw
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease

scholarly journals Arterial Stiffness Is Associated With Basal Ganglia Enlarged Perivascular Spaces and Cerebral Small Vessel Disease Load

Stroke ◽  
2018 ◽  
Vol 49 (5) ◽  
pp. 1279-1281 ◽  
Author(s):  
Iolanda Riba-Llena ◽  
Joan Jiménez-Balado ◽  
Xavier Castañé ◽  
Anna Girona ◽  
Antonio López-Rueda ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Arterial Stiffness ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease

Abstract WMP59: White Matter Hyperintensities Play a Pivotal Role in Progression of Cerebral Small Vessel Disease: A 7-Year Chinese Urban Community Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yiwei Xia ◽  
Yi Shen ◽  
Yi Wang ◽  
Lumeng Yang ◽  
Yiqing Wang ◽  
...  
Keyword(s):  
Executive Function ◽  
Small Vessel Disease ◽  
Urban Community ◽  
Cerebral Small Vessel Disease ◽  
Pivotal Role ◽  
Small Vessel ◽  
Community Study ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Increased Risk

Objective: To explore the role of WMH in progression of CSVD in an urban community in China over a period of 7 years, and to investigate associations between WMH volume (baseline & progression) and cognitive impairment. Methods: CSVD markers and neuropsychological tests at baseline and follow-up of 191 participants of the Shanghai Aging Study (SAS) were assessed. WMH volume were assessed by automatic segmentation based on U-net model. Lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (ePVS) were rated manually. SVD score was rated as the total burden of CSVD markers. We performed multivariate linear regression and binominal logistic regression. We plotted progression of markers by baseline WMH volume in tertile. Results: Participants with higher baseline WMH volume developed more progression of WMH volume, increased risk of incident lacunes, incident CMBs, and ePVS progression. Mean change of WMH volume over 7 years was 4.27mL (0.62mL/y) for all participants, 3.21mL for participants with 1st tertile WMH volume at baseline, 4.19mL for those with 2nd tertile WMH, and 5.43mL for those with 3rd tertile WMH. Incident lacunes and incident CMBs were predominantly seen in participants with 2nd and 3rd tertile WMH. WMH (baseline & progression) were associated with decline of executive function. Conclusions: WMH play a pivotal role in progression of cerebral small vessel disease and are associated with decline of executive function in a Chinese urban community study over a period of 7 years.

Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook

2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Vessel Disease ◽  
Generation Sequencing ◽  
Cerebral Small Vessel Diseases

: Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described and new sequencing techniques such as Next generation sequencing are available. Brain imaging is a key exam in these diseases. First, since it is often the first exam performed, an MRI is key in selecting patients for genetic testing and for interpreting Next generation sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. With this review, we aim to provide Neurologists and Stroke physicians with an up-to date overview of the current neuroimaging knowledge on monogenic small vessel diseases.

Sign in / Sign up

Export Citation Format

Share Document