Dataset Information

Enlarged perivascular spaces and cerebral small vessel disease.

ABSTRACT:

Background and aims

Enlarged perivascular spaces (also known as Virchow-Robin spaces) on T2-weighted brain magnetic resonance imaging are common, but their etiology, and specificity to small vessel as opposed to general cerebrovascular disease or ageing, is unclear. We tested the association between enlarged perivascular spaces and ischemic stroke subtype, other markers of small vessel disease, and common vascular risk factors.

Methods

We prospectively recruited patients with acute stroke, diagnosed and subtyped by a stroke physician using clinical features and brain magnetic resonance imaging. A neuroradiologist rated basal ganglia and centrum semiovale enlarged perivascular spaces on a five-point scale, white matter lesions, recent and old infarcts, and cerebral atrophy. We assessed associations between basal ganglia-, centrum semiovale- and total (combined basal ganglia and centrum semiovale) enlarged perivascular spaces, stroke subtype, white matter lesions, atrophy, and vascular risk factors.

Results

Among 298 patients (mean age 68 years), after adjusting for vascular risk factors and white matter lesions, basal ganglia-enlarged perivascular spaces were associated with increasing age (P = 0.001), centrum semiovale-enlarged perivascular spaces (P < 0.001), cerebral atrophy (P = 0.03), and lacunar stroke subtype (P = 0.04). Centrum semiovale-enlarged perivascular spaces were associated mainly with basal ganglia-enlarged perivascular spaces. Total enlarged perivascular spaces were associated with increasing age (P = 0.01), deep white matter lesions (P = 0.005), and previous stroke (P = 0.006).

Conclusions

Enlarged perivascular spaces are associated with age, lacunar stroke subtype and white matter lesions and should be considered as another magnetic resonance imaging marker of cerebral small vessel disease. Further evaluation of enlarged perivascular spaces in studies of ageing, stroke, and dementia is needed to determine their pathophysiological importance.

SUBMITTER: Potter GM

PROVIDER: S-EPMC4463944 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Enlarged perivascular spaces (ePVS) are common finding on magnetic resonance imaging (MRI) in elderly. ePVS are thought to be associated with cerebral small vessel disease (SVD) such as white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs). However, the different location of SVD and its relationship to ePVS distribution requires further investigation. Objective: To study the association between location and severity of SVD with ePVS from memory clinic and population-based settings. Methods: This study includes patients from an ongoing memory clinic based case-control study and participants from the population-based: Epidemiology of Dementia in Singapore study (EDIS). All participants underwent a comprehensive standardized evaluation including physical, medical and neuropsychological assessment and a brain MRI. CMBs and lacune location were categorized into strictly lobar, strictly deep and mixed, and ePVS location into centrum semiovale and basal ganglia. WMH volume was automatically segmented and was classified into anterior and posterior distribution. Negative binomial regression models were constructed to analyse associations between SVD and ePVS and the rate ratios (RR) and 95% confidence intervals (CI) were reported. Results: Of 375 patients (median age = 73 years) from memory clinic and 583 participants (median age = 70 years) from EDIS, the median total ePVS count was 17.0 and 7.0, respectively. Increased severity of SVD was not associated with total ePVS counts in both memory clinic and EDIS study. Analysis with the location of SVD and ePVS also showed similar results. However, in EDIS study, presence of ≥2 lacunes [RR = 1.61, 95% CI = 1.3, 2.30, p = 0.009], presence of ≥2 CMBs [RR = 1.40, 95% CI = 1.08, 1.83, p = 0.012], and higher volume of WMH [RR = 1.41, 95% CI = 1.10, 1.81, p = 0.006] were associated with basal ganglia ePVS independent of age, gender and vascular risk factors. Conclusion: In this study, we found that the ePVS were not associated with the location and severity of SVD in the memory-clinic patients. However, only severity of SVD was associated with basal ganglia ePVS in the population-based setting. Our findings will need to be studied further in different cohorts so as to understand the mechanism underlying different SVD types in subclinical and clinical phases as well as for predicting cognitive decline.

Project description:ImportanceWith advancing age, an increased visibility of perivascular spaces (PVSs) on magnetic resonance imaging (MRI) is hypothesized to represent impaired drainage of interstitial fluid from the brain and may reflect underlying cerebral small vessel disease (SVD). However, whether large perivascular spaces (L-PVSs) (>3 mm in diameter) visible on MRI are associated with SVD and cognitive deterioration in older individuals is unknown.ObjectiveTo examine whether L-PVSs are associated with the progression of the established MRI markers of SVD, cognitive decline, and increased risk of dementia.Design, setting, and participantsThe prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study assessed L-PVSs at baseline (September 1, 2002, through February 28, 2006) on MRI studies of the brain in 2612 participants. Participants returned for additional MRI from April 1, 2007, through September 30, 2011, and underwent neuropsychological testing at the 2 time points a mean (SD) of 5.2 (0.2) years apart. Data analysis was conducted from August 1, 2016, to May 4, 2017.ExposuresThe presence, number, and location of L-PVSs.Main outcomes and measuresIncident subcortical infarcts, cerebral microbleeds, and progression of white matter hyperintensities detected on MRI; cognitive decline defined as composite score changes between baseline and follow-up in the domains of memory, information processing speed, and executive function; and adjudicated incident dementia cases diagnosed according to international guidelines.ResultsOf the 2612 study patients (mean [SD] age, 74.6 [4.8] years; 1542 [59.0%] female), 424 had L-PVSs and 2188 did not. The prevalence of L-PVSs was 16.2% (median number of L-PVSs, 1; range, 1-17). After adjusting for age, sex, and interval between baseline and follow-up scanning, the presence of L-PVSs was significantly associated with an increased risk of incident subcortical infarcts (adjusted risk ratio, 2.54; 95% CI, 1.76-3.68) and microbleeds (adjusted risk ratio, 1.43; 95% CI, 1.18-1.72) and a greater 5-year progression of white matter hyperintensity volume. The presence of L-PVSs was also associated with a steeper decline in information processing speed and more than quadrupled the risk of vascular dementia. All associations persisted when further adjusted for genetic and cerebrovascular risk factors. The associations with cognitive outcomes were independent of educational level, depression, and other SVD MRI markers.Conclusions and relevanceLarge PVSs are an MRI marker of SVD and associated with the pathogenesis of vascular-related cognitive impairment in older individuals. Large PVSs should be included in assessments of vascular cognitive impairment in the older population and as potential targets for interventions.

Project description:Purpose To describe a fully automated segmentation method that yields object-based morphologic estimates of enlarged perivascular spaces (ePVSs) in clinical-field-strength (3.0-T) magnetic resonance (MR) imaging data. Materials and Methods In this HIPAA-compliant study, MR imaging data were obtained with a 3.0-T MR imager in research participants without dementia (mean age, 85.3 years; range, 70.4-101.2 years) who had given written informed consent. This method is built on (a) relative normalized white matter, ventricular and cortical signal intensities within T1-weighted, fluid-attenuated inversion recovery, T2-weighted, and proton density data and (b) morphologic (width, volume, linearity) characterization of each resultant cluster. Visual rating was performed by three raters, including one neuroradiologist, after established single-section guidelines. Correlations between visual counts and automated counts, as well session-to-session correlation of counts within each participant, were assessed with the Pearson correlation coefficient r. Results There was a significant correlation between counts by visual raters and automated detection of ePVSs in the same section (r = 0.65, P < .001; r = 0.69, P < .001; and r = 0.54, P < .01 for raters 1, 2, and 3, respectively). With regard to visual ratings and whole-brain count consistency, average visual rating scores were highly correlated with automated detection of total burden volume (r = 0.58, P < .01) and total ePVS number (r = 0.76, P < .01). Morphology of clusters across 28 data sets was consistent with published radiographic estimates of ePVS; mean width of clusters segmented was 3.12 mm (range, 1.7-13.5 mm). Conclusion This MR imaging-based method for multimodal autoidentification of perivascular spaces yields individual whole-brain morphologic characterization of ePVS in clinical MR imaging data and is an important tool in the detailed assessment of these features. © RSNA, 2017 Online supplemental material is available for this article.