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Brain fluid dynamics remains poorly understood with central issues unresolved. In this study, we first review the literature regarding points of controversy, then pilot study if conventional MRI techniques can assess brain fluid outflow pathways and explore potential associations with small vessel disease (SVD). We assessed 19 subjects participating in the Mild Stroke Study 3 who had FLAIR imaging before and 20-30 minutes after intravenous Gadolinium (Gd)-based contrast. Signal intensity (SI) change was assessed semi-quantitatively by placing regions of interest, and qualitatively by a visual scoring system, along dorsal and basal fluid outflow routes. Following i.v. Gd, SI increased substantially along the anterior, middle, and posterior superior sagittal sinus (SSS) (82%, 104%, and 119%, respectively), at basal areas (cribriform plate, 67%; jugular foramina, 72%), and in narrow channels surrounding superficial cortical veins separated from surrounding cerebrospinal fluid (CSF) (96%) (all p < 0.001). The SI increase was associated with higher intraparenchymal perivascular spaces (PVS) scores (Std. Beta 0.71, p = 0.01). Our findings suggests that interstitial fluid drainage is visible on conventional MRI and drains from brain parenchyma via cortical perivenous spaces to dural meningeal lymphatics along the SSS remaining separate from the CSF. An association with parenchymal PVS requires further research, now feasible in humans., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Morphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1 year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1-3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termed cavitation index, as the ratio of the 1-year T1-weighted cavity volume to the baseline RSSI volume on FLAIR. We calculated fractional anisotropy and mean diffusivity (MD) of the RSSI and normal-appearing white matter, and BBB leakage in different tissues on dynamic contrast-enhanced MRI. Amongst 60 patients, at 1-year post-stroke, 44 patients showed some degree of RSSI cavitation on FLAIR, increasing to 50 on T2- and 56 on T1-weighted high-resolution scans, with a median cavitation index of 7% (range, 1-36%). Demographic, clinical, and cerebral small vessel disease features were not associated with the cavitation index. While lower baseline MD of the RSSI (r s  = - 0.371; p = 0.004) and more contrast leakage into CSF (r s  = 0.347; p = 0.007) were associated with the cavitation index in univariable analysis, only BBB leakage in CSF remained independently associated with cavitation (beta = 0.315, p = 0.046). Increased BBB leakage into CSF may indicate worse endothelial dysfunction and increased risk of tissue destruction post RSSI. Although cavitation was common, it only affected a small proportion of the original RSSI.

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71-74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI. We investigated the impact of individual SVD markers (white matter hyperintensity - WMH, microbleeds, lacunes, enlarged perivascular spaces, brain atrophy) as seen on structural brain MRI and of a global SVD score on the patients' performance. A regression model revealed that age, sex, and hypertension significantly explained gait speed. Among SVD markers white matter hyperintensity (WMH) score or volume were additional significant and independent predictors of gait speed in the regression model. A similar association was seen with the global SVD score. Our study confirms a negative impact of SVD-related morphologic brain changes on gait speed in addition to age, sex and hypertension independent from brain atrophy. The presence of WMH seems to be the major driving force for SVD on gait impairment in healthy elderly subjects., Competing Interests: The authors declare no competing financial interests.

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease., (© The Author(s) 2016.)

Purpose: Perivascular spaces (PVS) are associated with ageing, cerebral small vessel disease, inflammation and increased blood brain barrier permeability. Most studies to date use visual rating scales to assess PVS, but these are prone to observer variation., Methods: We developed a semi-automatic computational method that extracts PVS on bilateral ovoid basal ganglia (BG) regions on intensity-normalised T2-weighted magnetic resonance images. It uses Analyze™10.0 and was applied to 100 mild stroke patients' datasets. We used linear regression to test association between BGPVS count, volume and visual rating scores; and between BGPVS count & volume, white matter hyperintensity (WMH) rating scores (periventricular: PVH; deep: DWMH) & volume, atrophy rating scores and brain volume., Results: In the 100 patients WMH ranged from 0.4 to 119ml, and total brain tissue volume from 0.65 to 1.45l. BGPVS volume increased with BGPVS count (67.27, 95%CI [57.93 to 76.60], p<0.001). BGPVS count was positively associated with WMH visual rating (PVH: 2.20, 95%CI [1.22 to 3.18], p<0.001; DWMH: 1.92, 95%CI [0.99 to 2.85], p<0.001), WMH volume (0.065, 95%CI [0.034 to 0.096], p<0.001), and whole brain atrophy visual rating (1.01, 95%CI [0.49 to 1.53], p<0.001). BGPVS count increased as brain volume (as % of ICV) decreased (-0.33, 95%CI [-0.53 to -0.13], p=0.002)., Comparison With Existing Method: BGPVS count and volume increased with the overall increase of BGPVS visual scores (2.11, 95%CI [1.36 to 2.86] for count and 0.022, 95%CI [0.012 to 0.031] for volume, p<0.001). Distributions for PVS count and visual scores were also similar., Conclusions: This semi-automatic method is applicable to clinical protocols and offers quantitative surrogates for PVS load. It shows good agreement with a visual rating scale and confirmed that BGPVS are associated with WMH and atrophy measurements., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lacunar strokes account for 25% of ischaemic strokes, but their precise aetiology is unknown. Similarities between the retinal and cerebral small vessels mean that clarification of the exact relationship between retinal microvascular abnormalities and stroke, and particularly with stroke subtypes, may aid understanding of the aetiology of lacunar stroke and stroke risk., Methods: A systematic review of the literature was performed by searching Medline and Embase to October 2007 for studies in humans that investigated the association between retinal microvascular abnormalities and prevalent or incident stroke. Data and calculated summary risk ratios (sRR) were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, adjusted for key variables. 37 papers from 22 different studies were included with 62 975 subjects (mean age 62 years) among whom there were 2893 strokes. Stroke identification and diagnosis methods varied., Results: Retinopathy was associated with incident stroke (sRR 2.1, 95% CI 1.7 to 2.6) and prevalent stroke (sRR 2.5, 95% CI 1.4 to 4.3). Incident stroke was also associated with retinal artery embolism (sRR 2.9, 95% CI 1.6 to 5.1) and venular widening (sRR 1.4, 95% CI 1.1 to 1.7). There was significant heterogeneity between studies for some associations. There were no data on retinal microvascular abnormalities and haemorrhagic versus ischaemic stroke or ischaemic stroke subtypes., Conclusions: Retinal microvascular abnormalities are associated with stroke, but more data are required to clarify associations between specific types of retinal microvascular abnormality and stroke, as well as between different stroke subtypes. Future retinal-stroke studies should concentrate on carefully diagnosing and accurately sub-typing ischaemic stroke.

Background and Purpose: If the diagnostic and prognostic significance of brain microbleeds (BMBs) are to be investigated and used for these purposes in clinical practice, observer variation in BMB assessment must be minimized., Methods: Two doctors used a pilot rating scale to describe the number and distribution of BMBs (round, low-signal lesions, <10 mm diameter on gradient echo MRI) among 264 adults with stroke or TIA. They were blinded to clinical data and their counterpart's ratings. Disagreements were adjudicated by a third observer, who informed the development of a new Brain Observer MicroBleed Scale (BOMBS), which was tested in a separate cohort of 156 adults with stroke., Results: In the pilot study, agreement about the presence of >/=1 BMB in any location was moderate (kappa=0.44; 95% CI, 0.32-0.56), but agreement was worse in lobar locations (kappa=0.44; 95% CI, 0.30-0.58) than in deep (kappa=0.62; 95% CI, 0.48-0.76) or posterior fossa locations (kappa=0.66; 95% CI, 0.47-0.84). Using BOMBS, agreement about the presence of >/=1 BMB improved in any location (kappa=0.68; 95% CI, 0.49-0.86) and in lobar locations (kappa=0.78; 95% CI, 0.60-0.97)., Conclusions: Interrater reliability concerning the presence of BMBs was moderate to good, and could be improved with the use of the BOMBS rating scale, which takes into account the main sources of interrater disagreement identified by our pilot scale.