Cerebral blood flow in small vessel disease: A systematic review and meta-analysis

Shi, Yulu; Thrippleton, Michael J.; Makin, Stephen; Marshall, Ian; Geerlings, Mirjam I.; Craen, Anton J. M. de; Buchem, Mark A. van; Wardlaw, Joanna M.

doi:10.1177/0271678x16662891

Cited by 227 publications

(278 citation statements)

References 45 publications

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“…A pathological report has associated WMH with demyelination and axonal loss, and clinical studies have shown associations between WMH and progressive cognitive impairment and increased risk of dementia . Although previous studies reported globally reduced CBF in cerebral SVD patients with greater WMHs, the k w changes in 19 subjects with potential SVD were not significantly associated with CBF changes in this study. Subjects recruited in this study are in the early stages of WMH development (average WMH volume is 2.6 cm 3 ), and its association with k w will provide important opportunities to prevent brain damage attributed to SVD at the earliest stages and ameliorate cognitive impairment.…”

Section: Discussioncontrasting

confidence: 86%

Mapping water exchange across the blood–brain barrier using 3D diffusion‐prepared arterial spin labeled perfusion MRI

Shao

Samantha

Casey

et al. 2018

Magnetic Resonance in Med

158

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Purpose To present a novel MR pulse sequence and modeling algorithm to quantify the water exchange rate (kw) across the blood–brain barrier (BBB) without contrast, and to evaluate its clinical utility in a cohort of elderly subjects at risk of cerebral small vessel disease (SVD). Methods A diffusion preparation module with spoiling of non–Carr‐Purcell‐Meiboom‐Gill signals was integrated with pseudo‐continuous arterial spin labeling (pCASL) and 3D gradient and spin echo (GRASE) readout. The tissue/capillary fraction of the arterial spin labeling (ASL) signal was separated by appropriate diffusion weighting (b = 50 s/mm2). kw was quantified using a single‐pass approximation (SPA) model with total generalized variation (TGV) regularization. Nineteen elderly subjects were recruited and underwent 2 MRIs to evaluate the reproducibility of the proposed technique. Correlation analysis was performed between kw and vascular risk factors, Clinical Dementia Rating (CDR) scale, neurocognitive assessments, and white matter hyperintensity (WMH). Results The capillary/tissue fraction of ASL signal can be reliably differentiated with the diffusion weighting of b = 50 s/mm2, given ~100‐fold difference between the (pseudo‐)diffusion coefficients of the 2 compartments. Good reproducibility of kw measurements (intraclass correlation coefficient = 0.75) was achieved. Average kw was 105.0 ± 20.6, 109.6 ± 18.9, and 94.1 ± 19.6 min–1 for whole brain, gray and white matter. kw was increased by 28.2%/19.5% in subjects with diabetes/hypercholesterolemia. Significant correlations between kw and vascular risk factors, CDR, executive/memory function, and the Fazekas scale of WMH were observed. Conclusion A diffusion prepared 3D GRASE pCASL sequence with TGV regularized SPA modeling was proposed to measure BBB water permeability noninvasively with good reproducibility. kw may serve as an imaging marker of cerebral SVD and associated cognitive impairment.

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Section: Discussioncontrasting

confidence: 86%

Mapping water exchange across the blood–brain barrier using 3D diffusion‐prepared arterial spin labeled perfusion MRI

Shao

Samantha

Casey

et al. 2018

Magnetic Resonance in Med

158

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“…Consistent with the microstructural abnormalities, a recent meta‐analysis showed that overall cerebral blood flow was low in regions that developed WMH (Shi et al . ).…”

Section: Neuroimaging In Manmentioning

confidence: 97%

White matter degeneration in vascular and other ageing‐related dementias

Hase

Horsburgh

Ihara

et al. 2018

Journal of Neurochemistry

154

147

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Advances in neuroimaging have enabled greater understanding of the progression of cerebral degenerative processes associated with ageing-related dementias. Leukoaraiosis or rarefied white matter (WM) originally described on computed tomography is one of the most prominent changes which occurs in older age. White matter hyperintensities (WMH) evident on magnetic resonance imaging have become commonplace to describe WM changes in relation to cognitive dysfunction, types of stroke injury, cerebral small vessel disease and neurodegenerative disorders including Alzheimer's disease. Substrates of WM degeneration collectively include myelin loss, axonal abnormalities, arteriolosclerosis and parenchymal changes resulting from lacunar infarcts, microinfarcts, microbleeds and perivascular spacing. WM cells incorporating astrocytes, oligodendrocytes, pericytes and microglia are recognized as key cellular components of the gliovascular unit. They respond to ongoing pathological processes in different ways leading to disruption of the gliovascular unit. The most robust alterations involve oligodendrocyte loss and astrocytic clasmatodendrosis with displacement of the water channel protein, aquaporin 4. These modifications likely precede arteriolosclerosis and capillary degeneration and involve tissue oedema, breach of the blood-brain barrier and induction of a chronic hypoxic state in the deep WM. Several pathophysiological mechanisms are proposed to explain how WM changes commencing with haemodynamic changes within the vascular system impact on cognitive dysfunction. Animal models simulating cerebral hypoperfusion in man have paved the way for several translational opportunities. Various compounds with variable efficacies have been tested to reduce oxidative stress, inflammation and blood-brain barrier damage in the WM. Our review demonstrates that WM degeneration encompasses multiple substrates and therefore more than one pharmacological approach is necessary to preserve axonal function and prevent cognitive impairment. Keywords: astrocytes, blood-brain barrier, post-stroke dementia, stroke, vascular dementia, white matter. Ageing-related cognitive impairment involves multiple substrates affecting brain structure and function. Neuroimaging evidence shows that white matter (WM) changes are associated with various clinical, sensorimotor, lifestyle, behavioural and cognitive abnormalities, particularly related to the small vessel disease (SVD) syndrome (Pantoni 2010).

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“…In a pathology study (n=15), no incomplete infarct was found in WMH 29. Though many cross-sectional studies have found low cerebral blood flow (CBF) to be associated with higher WMH burden, the causality between low CBF and WMH is unclear 35. A longitudinal study (n=575) showed that more severe baseline WMH predated CBF decline over time rather than falling CBF predating WMH progression 36.…”

Section: Introductionmentioning

confidence: 99%

Update on cerebral small vessel disease: a dynamic whole-brain disease

2016

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Cerebral small vessel disease (CSVD) is a very common neurological disease in older people. It causes stroke and dementia, mood disturbance and gait problems. Since it is difficult to visualise CSVD pathologies in vivo, the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities, lacunar ischaemic stroke, lacunes, microbleeds, visible perivascular spaces and many haemorrhagic strokes. However, variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies. A standardised use of terms should be encouraged in CSVD research. These CSVD features have long been regarded as different lesions, but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore, owing to its diffuse nature, CSVD should be regarded as a ‘whole-brain disease’. Single antiplatelet (for acute lacunar ischaemic stroke) and management of traditional risk factors still remain the most important therapeutic and preventive approach, due to limited understanding of pathophysiology in CSVD. Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD. Epidemiology of CSVD might differ in Asian compared with Western populations (where most results and guidelines about CSVD and stroke originate), but more community-based data and clear stratification of stroke types are required to address this.

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Cerebral blood flow in small vessel disease: A systematic review and meta-analysis

Cited by 227 publications

References 45 publications

Mapping water exchange across the blood–brain barrier using 3D diffusion‐prepared arterial spin labeled perfusion MRI

Mapping water exchange across the blood–brain barrier using 3D diffusion‐prepared arterial spin labeled perfusion MRI

White matter degeneration in vascular and other ageing‐related dementias

Update on cerebral small vessel disease: a dynamic whole-brain disease

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