Peak Width of Skeletonized Mean Diffusivity is Used to Explore the Association of Chronic Renal Failure Correlates and Cerebral Small Vessel Disease

2021 ◽  
Author(s):  
Dan Wang ◽  
Zheng Sun ◽  
YueHua Li
2017 ◽  
Vol 131 (12) ◽  
pp. 1361-1373 ◽  
Author(s):  
Iain D. Croall ◽  
Valerie Lohner ◽  
Barry Moynihan ◽  
Usman Khan ◽  
Ahamad Hassan ◽  
...  

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.


2017 ◽  
Vol 31 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Maria M D’Souza ◽  
SP Gorthi ◽  
Kunal Vadwala ◽  
Richa Trivedi ◽  
C Vijayakumar ◽  
...  

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.


2021 ◽  
Author(s):  
Ana R Fouto ◽  
Rita G. Nunes ◽  
Joana Pinto ◽  
Luísa Alves ◽  
Sofia Calado ◽  
...  

Abstract Purpose Histogram-based metrics extracted from diffusion-tensor imaging (DTI) have been suggested as potential biomarkers for cerebral small vessel disease (SVD), but methods and results have varied across studies. This work aims to assess the impact of mask selection for extracting histogram-based metrics of fractional anisotropy (FA) and mean diffusivity (MD) on their sensitivity as SVD biomarkers.Methods DTI data were collected from 17 SVD patients and 12 healthy controls. For each participant, FA and MD maps were estimated; from these, histograms were computed on two alternative whole-brain white-matter masks: normal-appearing white-matter (NAWM) and mean FA tract skeleton (TBSS). Histogram-based metrics (median, peak height, peak width, peak value) were extracted from the FA and MD maps. These were compared between patients and controls, and correlated with the patients’ cognitive scores (executive function and processing speed).Results White matter mask selection significantly impacted FA and MD histogram metrics and affected their ability to discriminate between groups. Moreover, we observed that the mask can influence the correlations with cognitive measures. Nevertheless, the MD peak height and MD peak width metrics remained significantly correlated with executive function, regardless of the mask.Conclusion Our results corroborate previous reports and further support the value of DTI histogram-based metrics as SVD biomarkers. However, they also highlight the importance of the processing methodology, in particular the choice of white matter mask, as hence the urgent need to mitigate the lack of standardized MRI data-processing pipelines.


Stroke ◽  
2021 ◽  
Author(s):  
Byeong C. Kim ◽  
Young Chul Youn ◽  
Jee Hyang Jeong ◽  
Hyun Jeong Han ◽  
Jong Hun Kim ◽  
...  

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02–0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01932203.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yousef Hannawi ◽  
Eder Caceres ◽  
Mohamed G. Ewees ◽  
Kimerly A. Powell ◽  
Anna Bratasz ◽  
...  

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.


2014 ◽  
Vol 39 (1) ◽  
pp. 39-52 ◽  
Author(s):  
Stephen D.J. Makin ◽  
F.A.B. Cook ◽  
Martin S. Dennis ◽  
Joanna M. Wardlaw

Background: The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure. Methods: We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation. Results: After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the presence of SVD was associated with an increased risk of renal impairment (whether proteinuria or reduced eGFR) OR 2.33 (95% CI 1.80-3.01), when compared to those without SVD. After adjustment for age and hypertension, 15/21 studies still reported a significant association between renal impairment and SVD. Conclusion: We found no specific association between renal impairment and lacunar stroke, but we did find that in individuals who had not had a stroke, having more SVD features on imaging was associated with a worse renal function, which remained significant after controlling for hypertension. However, this finding does not exclude a powerful co-associate effect of age or vascular risk factor exposure. Future research should subtype lacunar stroke sensitively and control for major risk factors.


2020 ◽  
Vol 5 (2) ◽  
pp. 128-137
Author(s):  
Huimin Chen ◽  
Yuesong Pan ◽  
Lixia Zong ◽  
Jing Jing ◽  
Xia Meng ◽  
...  

BackgroundThe effect of cerebral small vessel disease (CSVD) and intracranial arterial stenosis (ICAS) on stroke outcomes remains unclear.MethodsData of 1045 patients with minor stroke or transient ischaemic attack (TIA) were obtained from 45 sites of the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. We assessed the associations of burdens of CSVD and ICAS with new strokes and bleeding events using multivariate Cox regression models and those with modified Rankin Scale (mRS) scores using ordinal logistic regression models.ResultsAmong the 1045 patients, CSVD was present in 830 cases (79.4%) and ICAS in 460 (44.0%). Patients with >1 ICAS segment showed the highest risk of new strokes (HR 2.03, 95% CI 1.15 to 3.56, p=0.01). No association between CSVD and the occurrence of new strokes was found. The presence of severe CSVD (common OR (cOR) 2.01, 95% CI 1.40 to 2.89, p<0.001) and >1 ICAS segment (cOR 2.15, 95% CI 1.57 to 2.93, p<0.001) was associated with higher mRS scores. Severe CSVD (HR 10.70, 95% CI 1.16 to 99.04, p=0.04), but not ICAS, was associated with a higher risk of bleeding events. Six-point modified CSVD score improved the predictive power for bleeding events and disability.InterpretationCSVD is associated with more disability and bleeding events, and ICAS is associated with an increased risk of stroke and disability in patients with minor stroke and TIA at 3 months. CSVD and ICAS may represent different vascular pathologies and play distinct roles in stroke outcomes.Trial registration numberNCT00979589


2021 ◽  
pp. 0271678X2199262
Author(s):  
Shuai Jiang ◽  
Tian Cao ◽  
Yuying Yan ◽  
Tang Yang ◽  
Ye Yuan ◽  
...  

Recent subcortical infarction (RSI) in the lenticulostriate artery (LSA) territory with a non-stenotic middle cerebral artery is a heterogeneous entity. We aimed to investigate the role of LSA combined with neuroimaging markers of cerebral small vessel disease (CSVD) in differentiating the pathogenic subtypes of RSI by whole-brain vessel-wall magnetic resonance imaging (WB-VWI). Fifty-two RSI patients without relevant middle cerebral artery (MCA) stenosis on magnetic resonance angiography were prospectively enrolled. RSI was dichotomized as branch atheromatous disease (BAD; a culprit plaque located adjacent to the LSA origin) (n = 34) and CSVD-related lacunar infarction (CSVD-related LI; without plaque or plaque located distal to the LSA origin) (n = 18). Logistic regression analysis showed lacunes (odds ratio [OR] 9.68, 95% confidence interval [CI] 1.71–54.72; P = 0.010) and smaller number of LSA branches (OR 0.59, 95% CI 0.36–0.96; P = 0.034) were associated with of BAD, whereas severe deep white matter hyperintensities (DWMH) (OR 0.11, 95% CI 0.02–0.71; P = 0.021) was associated with CSVD-related LI. In conclusion, the LSA branches combined with lacunes and severe DWMH may delineate subtypes of SSI. The WB-VWI technique could be a credible tool for delineating the heterogeneous entity of SSI in the LSA territory.


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