Abstract 01: Retinal Microvascular Signs and White Matter MRI Findings: The Atherosclerosis Risk in Communities Neurocognitive Study

Introduction: Cerebrovascular small vessel disease, seen on brain imaging as lacunes and white matter hyperintensities (WMH), is a substrate for dementia in older adults. Diffusion tensor imaging (DTI) is thought to provide early signs of loss of white matter (WM) integrity due to microvascular disease and predicts WM hyperintensity volume. Retinal fundus photography provides surrogate measures of cerebral microvasculature. No studies have quantified the long-term association between retinal signs and DTI measures. Hypothesis: Microvascular retinal signs measured in midlife are associated with small vessel disease measured on brain magnetic resonance imaging (MRI) 18 years later, including reduced WM microstructural integrity (lower fractional anisotrophy [FA] and greater mean diffusivity [MD] by DTI), greater WM hyperintensity volume and greater lacune prevalence. Methods: In a biracial prospective cohort study, retinal signs were measured using fundus photography (1993-1995) with 3-T magnetic resonance imaging conducted in 2011-13. Multivariable-adjusted linear regression was used to quantify the relationships of retinal signs with WM measures. Prevalence of lacunar infarcts by retinal sign status was estimated using log binomial regression. Analyses were adjusted for age [linear and quadratic terms], education, sex, race, intracranial volume, body mass index, smoking, diabetes, hypertension, and ≥1 APOE ε4 alleles. Results: In 1829 men and women (60% [N=1100] female, 27% [N=489] black race, aged 50-72 years when retinal signs were measured), a binary measure comprised of two retinal signs suggestive of arteriolar damage due to hypertension (focal arteriolar narrowing and/or arteriovenous nicking) was associated with worse (lower) FA (standardized β=-0.19, 95% confidence interval [CI]=-0.35, -0.02), worse (higher) MD (β=0.15, 95% CI=0.00, 0.30), greater WM hyperintensity volume (β=0.15, 95% CI=0.01, 0.30), and greater prevalence of lacunes (prevalence ratio=1.33, 95% CI: 0.99, 1.80). Generalized arteriolar narrowing, measured as the central retinal arteriolar equivalent (CRAE, narrowest quartile vs. widest three quartiles) was associated with worse FA (β=-0.13, 95% CI=-0.24, -0.01) and worse MD (β=0.12, 95% CI=0.01, 0.23). Results did not differ by sex, race, hypertension status or APOE ε4 genotype. No associations were found for retinopathy, but only 56 participants had retinopathy. Conclusions: Consistent with prior work, and as expected based on a common underlying pathology, retinal signs predicted WM disease and lacunar infarcts 18 years later. Novel to this study, we found that retinal signs related to arteriolar damage also predicted loss of white matter microvascular integrity measured using DTI.

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Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease: A systematic review

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16631756 ◽

2016 ◽

Vol 36 (5) ◽

pp. 833-841 ◽

Cited By ~ 31

Author(s):

Gordon W Blair ◽

Fergus N Doubal ◽

Michael J Thrippleton ◽

Ian Marshall ◽

Joanna M Wardlaw

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Cerebrovascular Reactivity ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease

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.

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Pathological Correlates of White Matter Hyperintensities on Magnetic Resonance Imaging

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000366411 ◽

2014 ◽

Vol 39 (1-2) ◽

pp. 92-104 ◽

Cited By ~ 38

Author(s):

Yong Soo Shim ◽

Dong-Won Yang ◽

Catherine M. Roe ◽

Mary A. Coats ◽

Tammie L. Benzinger ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Blood Vessels ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease ◽

Postmortem Brain Tissue

Background/Aims: We investigated the histopathological correlates of white matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD) or cerebrovascular disease, and in aged controls. Methods: We reviewed 57 participants who had neuropathology and in whom neuroimaging was done. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small-vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs was investigated in 14 participants. The variables included: demyelination of the deep and periventricular white matter (WM), atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman's rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. Results: The severity of arteriosclerosis was correlated with the volume of periventricular hyperintensity (PVH) estimated by magnetic resonance imaging. Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs, and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. Conclusion: WMHs are consistent with small-vessel disease and increase the tissue water content. We found no association between WMHs and the thickness of small blood vessels. © 2014 S. Karger AG, Basel

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PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease

Stroke ◽

10.1161/strokeaha.120.032054 ◽

2021 ◽

Author(s):

Hugh S. Markus ◽

Marco Egle ◽

Iain D. Croall ◽

Hasan Sari ◽

Usman Khan ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Blood Pressure ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease

Background and Purpose: In cerebral small vessel disease, cerebral blood flow and autoregulation are impaired and therefore excessive blood pressure reduction could possibly accelerate white matter damage and worsen outcome. The trial determined, in severe symptomatic cerebral small vessel disease, whether intensive blood pressure lowering resulted in progression of white matter damage assessed using diffusion tensor imaging. Methods: Randomized, parallel, multicenter controlled, blinded-outcomes clinical trial. One hundred eleven participants with magnetic resonance imaging confirmed symptomatic lacunar infarct and confluent white matter hyperintensities and were recruited and randomized to standard (systolic=130–140 mmHg) (N=56) or intensive (systolic<125 mmHg) (N=55) blood pressure targets. The primary end point was change in diffusion tensor imaging white matter mean diffusivity peak height between baseline and 24 months. Secondary end points were other magnetic resonance imaging markers and cognition. Results: Patients were mean 68 years and 60% male. Mean (SD) blood pressure reduced by −15.3 (15.4) and −23.1 (22.04) mm Hg in the standard/intensive groups, respectively ( P <0.001). There was no difference between treatment groups for the primary end point: standard, adjusted mean (SE)=12.5×10 −3 (0.2×10 −3 ); intensive, 12.5×10 −3 (0.2×10 −3 ), P =0.92. In the whole population over 24 months follow-up, there was a significant deterioration in white matter microstructure but no detectable decrease in cognition. Conclusions: Intensive blood pressure lowering in severe cerebral small vessel disease was not associated with progression of white matter damage on diffusion tensor imaging or magnetic resonance imaging. In a multicentre study setting over 2 years, multimodal diffusion tensor imaging-magnetic resonance imaging was more sensitive to detecting change than cognitive testing. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN37694103.

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A longitudinal magnetic resonance imaging study of neurodegenerative and small vessel disease, and clinical cognitive trajectories in non demented patients with transient ischemic attack: the PREVENT study

BMC Geriatrics ◽

10.1186/s12877-018-0858-4 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 3

Author(s):

Sana Tariq ◽

Christopher D. d’Esterre ◽

Tolulope T. Sajobi ◽

Eric E. Smith ◽

Richard Stewart Longman ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Transient Ischemic Attack ◽

Small Vessel Disease ◽

Imaging Study ◽

Small Vessel ◽

Magnetic Resonance Imaging Study ◽

Resonance Imaging ◽

Vessel Disease ◽

Ischemic Attack

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Risk factors for small-vessel disease revealed by magnetic resonance imaging of the brain.

Nosotchu ◽

10.3995/jstroke.18.10 ◽

1996 ◽

Vol 18 (1) ◽

pp. 10-18

Author(s):

Tatsuo Kohriyama ◽

Shinya Yamaguchi ◽

Eiji Tanaka ◽

Yasuhiro Yamamura ◽

Shigenobu Nakamura

Keyword(s):

Magnetic Resonance Imaging ◽

Risk Factors ◽

Magnetic Resonance ◽

Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease ◽

The Brain

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Association of Key Magnetic Resonance Imaging Markers of Cerebral Small Vessel Disease With Hematoma Volume and Expansion in Patients With Lobar and Deep Intracerebral Hemorrhage

JAMA Neurology ◽

10.1001/jamaneurol.2016.2619 ◽

2016 ◽

Vol 73 (12) ◽

pp. 1440 ◽

Cited By ~ 27

Author(s):

Gregoire Boulouis ◽

Ellis S. van Etten ◽

Andreas Charidimou ◽

Eitan Auriel ◽

Andrea Morotti ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Intracerebral Hemorrhage ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Hematoma Volume ◽

Vessel Disease ◽

Imaging Markers

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Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

European Stroke Journal ◽

10.1177/2396987320929617 ◽

2020 ◽

pp. 239698732092961

Author(s):

Una Clancy ◽

Daniela Jaime Garcia ◽

Michael S Stringer ◽

Michael J Thrippleton ◽

Maria C Valdés-Hernández ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Risk Factors ◽

Magnetic Resonance ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease ◽

Stroke Study ◽

Mild Stroke

Background Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood–brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood–brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543. Summary Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy.

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