In this cross-sectional study, we tested the construct validity of a "total SVD score," which combines individual MRI features of small-vessel disease (SVD) in one measure, by testing associations ...with vascular risk factors and stroke subtype.
We analyzed data from patients with lacunar or nondisabling cortical stroke from 2 prospective stroke studies. Brain MRI was rated for the presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces independently. The presence of each SVD feature was summed in an ordinal "SVD score" (range 0-4). We tested associations with vascular risk factors, stroke subtype, and cerebral atrophy using ordinal regression analysis.
In 461 patients, multivariable analysis found that age (odds ratio OR 1.10, 95% confidence interval CI 1.08-1.12), male sex (OR 1.58, 95% CI 1.10-2.29), hypertension (OR 1.50, 95% CI 1.02-2.20), smoking (OR 2.81, 95% CI 1.59-3.63), and lacunar stroke subtype (OR 2.45, 95% CI 1.70-3.54) were significantly and independently associated with the total SVD score. The score was not associated with cerebral atrophy.
The total SVD score may provide a more complete estimate of the full impact of SVD on the brain, in a simple and pragmatic way. It could have potential for patient or risk stratification or early efficacy assessment in clinical trials of interventions to prevent SVD progression and may (after further testing) have a useful role in clinical practice.
Perivascular spaces include a variety of passageways around arterioles, capillaries and venules in the brain, along which a range of substances can move. Although perivascular spaces were first ...identified over 150 years ago, they have come to prominence recently owing to advances in knowledge of their roles in clearance of interstitial fluid and waste from the brain, particularly during sleep, and in the pathogenesis of small vessel disease, Alzheimer disease and other neurodegenerative and inflammatory disorders. Experimental advances have facilitated in vivo studies of perivascular space function in intact rodent models during wakefulness and sleep, and MRI in humans has enabled perivascular space morphology to be related to cognitive function, vascular risk factors, vascular and neurodegenerative brain lesions, sleep patterns and cerebral haemodynamics. Many questions about perivascular spaces remain, but what is now clear is that normal perivascular space function is important for maintaining brain health. Here, we review perivascular space anatomy, physiology and pathology, particularly as seen with MRI in humans, and consider translation from models to humans to highlight knowns, unknowns, controversies and clinical relevance.
Enlarged perivascular spaces in the brain are common but generally overlooked and of uncertain pathophysiology. They may reflect underlying cerebral small vessel disease. We determined whether ...enlarged perivascular spaces were associated with lacunar stroke subtype and white matter hyperintensities, markers of established small vessel disease.
We prospectively recruited patients with acute ischemic lacunar or cortical stroke. Age-matched nonstroke control subjects were also recruited. We rated basal ganglia and centrum semiovale enlarged perivascular spaces 0 to 4 (0=none, 4=>40) on T2-weighted MRI and white matter hyperintensities. We compared enlarged perivascular spaces between stroke subtypes and control subjects and assessed associations with vascular risk factors and white matter hyperintensities.
We recruited 350 patients; 129 lacunar, 124 cortical stroke, and 97 age-matched control subjects. Adjusting for vascular risk factors and white matter hyperintensities, total enlarged perivascular spaces were associated with lacunar stroke subtype (P=0.04) in the acute stroke group (n=253); basal ganglia enlarged perivascular spaces were associated with lacunar stroke subtype (P=0.003), deep (P=0.02) and periventricular white matter hyperintensities (P=0.01); in all 350 subjects, total enlarged perivascular spaces were associated with deep (P<0.001) and periventricular (P<0.001) white matter hyperintensities.
Although prevalent in patients with vascular risk factors and stroke, enlarged perivascular spaces are specifically associated with lacunar ischemic stroke and white matter hyperintensities. Further studies should determine the mechanism of this association while including adequate controls to account for stroke and vascular risk factors. Enlarged perivascular spaces should not be overlooked in studies of small vessel disease.
Advanced MRI in cerebral small vessel disease van den Brink, Hilde; Doubal, Fergus N; Duering, Marco
International Journal of Stroke,
01/2023, Letnik:
18, Številka:
1
Book Review, Journal Article
Recenzirano
Odprti dostop
Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. This review summarizes recent developments in advanced neuroimaging of cSVD with a focus on clinical and research ...applications. In the first section, we highlight how advanced structural imaging techniques, including diffusion magnetic resonance imaging (MRI), enable improved detection of tissue damage, including characterization of tissue appearing normal on conventional MRI. These techniques enable progression to be monitored and may be useful as surrogate endpoint in clinical trials. Quantitative MRI, including iron and myelin imaging, provides insights into tissue composition on the molecular level. In the second section, we cover how advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, which could be targeted in mechanistic research and early-stage intervention trials. Such techniques include the use of dynamic contrast enhanced MRI to measure blood–brain barrier permeability, and MRI methods to assess cerebrovascular reactivity. In the third section, we discuss how the increased spatial resolution provided by ultrahigh field MRI at 7 T allows imaging of perforating arteries, and flow velocity and pulsatility within them. The advanced MRI techniques we describe are providing novel pathophysiological insights in cSVD and allow improved quantification of disease burden and progression. They have application in clinical trials, both in assessing novel therapeutic mechanisms, and as a sensitive endpoint to assess efficacy of interventions on parenchymal tissue damage. We also discuss challenges of these advanced techniques and suggest future directions for research.
To determine the magnitude of potentially causal relationships among vascular risk factors (VRFs), large-artery atheromatous disease (LAD), and cerebral white matter hyperintensities (WMH) in 2 ...prospective cohorts.
We assessed VRFs (history and measured variables), LAD (in carotid, coronary, and leg arteries), and WMH (on structural MRI, visual scores and volume) in: (a) community-dwelling older subjects of the Lothian Birth Cohort 1936, and (b) patients with recent nondisabling stroke. We analyzed correlations, developed structural equation models, and performed mediation analysis to test interrelationships among VRFs, LAD, and WMH.
In subjects of the Lothian Birth Cohort 1936 (n = 881, mean age 72.5 years SD ±0.7 years, 49% with hypertension, 33% with moderate/severe WMH), VRFs explained 70% of the LAD variance but only 1.4% to 2% of WMH variance, of which hypertension explained the most. In stroke patients (n = 257, mean age 74 years SD ±11.6 years, 61% hypertensive, 43% moderate/severe WMH), VRFs explained only 0.1% of WMH variance. There was no direct association between LAD and WMH in either sample. The results were the same for all WMH measures used.
The small effect of VRFs and LAD on WMH suggests that WMH have a large "nonvascular," nonatheromatous etiology. VRF modification, although important, may be limited in preventing WMH and their stroke and dementia consequences. Investigation of, and interventions against, other suspected small-vessel disease mechanisms should be addressed.
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.
Cerebral small vessel disease (SVD) pathophysiology is poorly understood. Cerebrovascular reactivity (CVR) impairment may play a role, but evidence to date is mainly indirect. Magnetic resonance ...imaging (MRI) allows investigation of CVR directly in the tissues affected by SVD. We systematically reviewed the use of MRI to measure CVR in subjects with SVD. Five studies (total n = 155 SVD subjects, 84 controls) provided relevant data. The studies included different types of patients. Each study used blood oxygen level dependent (BOLD) MRI to assess CVR but a different vasoactive stimulus and method of calculating CVR. CVR decreased with increasing white matter hyperintensities in two studies (n = 17, 11%) and in the presence of microbleeds in another. Three studies (n = 138, 89%) found no association of CVR with white matter hyperintensities. No studies provided tissue-specific CVR values. CVR decreased with age in three studies, and with female gender and increasing diastolic blood pressure in one study. Safety and tolerability data were limited. Larger studies using CVR appear to be feasible and are needed, preferably with more standardized methods, to determine if specific clinical or radiological features of SVD are more or less associated with impaired CVR.
Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on ...brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians.
Cerebral small vessel disease (SVD) contributes to 25% of ischemic strokes and 45% of dementias. We aimed to investigate the role of cerebral blood flow (CBF) and intracranial pulsatility in SVD. We ...scanned 60 patients with minor ischemic stroke, representing a range of white matter hyperintensities (WMH). We rated WMH and perivascular spaces (PVS) using semi-quantitative scales and measured WMH volume. We measured flow and pulsatility in the main cerebral vessels and cerebrospinal fluid (CSF) using phase-contrast MRI. We investigated the association between flow, pulsatility and SVD features. In 56/60 patients (40 male, 67.8±8.3 years) with complete data, median WMH volume was 10.7 mL (range 1.4–75.0 mL), representing median 0.77% (0.11–5.17%) of intracranial volume. Greater pulsatility index (PI) in venous sinuses was associated with larger WMH volume (e.g. superior sagittal sinus, β = 1.29, P < 0.01) and more basal ganglia PVS (e.g. odds ratio = 1.38, 95% confidence interval 1.06, 1.79, per 0.1 increase in superior sagittal sinus PI) independently of age, sex and blood pressure. CSF pulsatility and CBF were not associated with SVD features. Our results support a close association of SVD features with increased intracranial pulsatility rather than with low global CBF, and provide potential targets for mechanistic research, treatment and prevention of SVD.
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