Cerebral Microbleeds and Their Association With Inflammation and Blood-Brain Barrier Leakage in Small Vessel Disease.

Background: How cerebral microbleeds (CMBs) are formed, and how they cause tissue damage is not fully understood, but it has been suggested they are associated with inflammation, and they could also be related to increased blood-brain barrier (BBB) leakage. We investigated the relationship of CMBs with inflammation and BBB leakage in cerebral small vessel disease, and in particular, whether these 2 processes were increased in the vicinity of CMBs.

Methods: In 54 patients with sporadic cerebral small vessel disease presenting with lacunar stroke, we simultaneously assessed microglial activation using the positron emission tomography ligand [11C]PK11195 and BBB leakage using dynamic contrast enhanced magnetic resonance imaging, on a positron emission tomography-magnetic resonance imaging system.

Loss of white matter integrity mediates the association between cortical cerebral microinfarcts and cognitive dysfunction: A longitudinal study.

Cortical cerebral microinfarcts (CMIs) are associated with loss of white matter (WM) integrity and cognitive impairment in cross-sectional studies, while further investigation using longitudinal datasets is required. This study aims to establish the association between cortical CMIs and WM integrity assessed by diffusion-tensor imaging (DTI) measures and to investigate whether DTI measures mediate the relationship between cortical CMIs and cognitive decline. Cortical CMIs were graded on 3T MRI.

MINocyclinE to Reduce inflammation and blood-brain barrier leakage in small Vessel diseAse (MINERVA): A phase II, randomized, double-blind, placebo-controlled experimental medicine trial.

Introduction: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability.

Are central and systemic inflammation associated with fatigue in cerebral small vessel disease?

Background: Fatigue is a common symptom in cerebral small vessel disease (SVD), but its pathogenesis is poorly understood. It has been suggested that inflammation may play a role. We determined whether central (neuro) inflammation and peripheral inflammation were associated with fatigue in SVD.

Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent.

Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease.

Background: Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia.

Methods: In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years.

Immune regulation and blood-brain barrier permeability in cerebral small vessel disease: study protocol of the INflammation and Small Vessel Disease (INSVD) study - a multicentre prospective cohort study.

Introduction: The INflammation and Small Vessel Disease (INSVD) study aims to investigate whether peripheral inflammation, immune (dys)regulation and blood-brain barrier (BBB) permeability relate to disease progression in cerebral small vessel disease (SVD). This research aims to pinpoint specific components of the immune response in SVD relating to disease progression. This could identify biomarkers of SVD progression, as well as potential therapeutic targets to inform the development and repurposing of drugs to reduce or prevent SVD, cognitive decline and vascular dementia.

Apathy After Stroke: Incidence, Symptom Trajectory, and Impact on Quality of Life and Disability.

Background And Objectives: Apathy is one of the most common symptoms following stroke and is often associated with worse functional outcome and poor quality of life (QoL). The trajectory of apathy symptoms has been previously described, and different trajectories have been identified. We determined group and individual changes in apathy symptomatology from the acute phase until 1 year after stroke.

Predicting incident dementia in cerebral small vessel disease: comparison of machine learning and traditional statistical models.

Background: Cerebral small vessel disease (SVD) contributes to 45% of dementia cases worldwide, yet we lack a reliable model for predicting dementia in SVD. Past attempts largely relied on traditional statistical approaches. Here, we investigated whether machine learning (ML) methods improved prediction of incident dementia in SVD from baseline SVD-related features over traditional statistical methods.

The association of diffusion tensor MRI measures of normal appearing white matter and cognition.

Objective: Median and peak height of fractional anisotropy (FA) and mean diffusivity (MD) are diffusion tensor imaging (DTI) markers used to quantify white matter microstructure changes. We examine the association of DTI histogram-derived measures in global normal appearing white matter (NAWM) and cognitive decline in patients with normal cognition and cognitive impairment no dementia from a memory clinic in Singapore.

Methods: A total of 252 patients (mean age: 71.

Reproducibility of regional structural and functional MRI networks in cerebral small vessel disease compared to age matched and stroke-free controls.

Abnormalities in structural and functional MRI connectivity measures have been reported in cerebral small vessel disease (SVD). Previous research has shown that whole-brain structural connectivity was highly reproducible in SVD patients, while whole-brain functional connectivity showed low reproducibility. It remains unclear whether the lower reproducibility of functional networks reported in SVD is due to selective disruption of reproducibility in specific networks or is generalised in patients with SVD.

Prediction of response to thrombolysis in acute stroke using neural network analysis of CT perfusion imaging.

Background: In ischaemic stroke patients undergoing reperfusion therapy, the amount of salvageable tissue, that is, extent of the ischaemic penumbra, predicts the clinical outcomes. CT perfusion (CTP) enables quantification of penumbral tissues to guide decision making, and current programmes have automated its analysis. More advanced machine learning techniques utilising the CTP maps may improve prediction beyond the ischaemic volume measures.

How often does white matter hyperintensity volume regress in cerebral small vessel disease?

Background And Objectives: It has been suggested that white matter hyperintensity lesions (WMHs), which typically progress over time, can also regress, and that this might be associated with favorable cognitive performance. We determined the prevalence of WMH regression in patients with cerebral small vessel disease (SVD) and examined which demographic, clinical, and radiological markers were associated with this regression.

Methods: We used semi-automated lesion marking methods to quantify WMH volume at multiple timepoints in three cohorts with symptomatic SVD; two with moderate-to-severe symptomatic SVD (the SCANS observational cohort and the control arm of the PRESERVE interventional trial) and one with mild-to-moderate SVD (the RUN DMC observational cohort).

Do Regions of Increased Inflammation Progress to New White Matter Hyperintensities?: A Longitudinal Positron Emission Tomography-Magnetic Resonance Imaging Study.

Background: Recent studies have demonstrated increased microglial activation using C-PK11195 positron emission tomography imaging, indicating central nervous system inflammation, in cerebral small vessel disease. However, whether such areas of neuroinflammation progress to tissue damage is uncertain. We determined whether white matter destined to become white matter hyperintensities (WMH) at 1 year had evidence of altered inflammation at baseline.

Visualisation of lenticulostriate arteries using contrast-enhanced time-of-flight magnetic resonance angiography at 7 Tesla.

7 Tesla-field-strength (7 T) Magnetic Resonance Imaging allows the small perforating arteries in the brain to be visualised, and this modality may allow visualisation of the arterial pathology in cerebral small vessel disease. Most studies have used standard Time-of-Flight (ToF) Magnetic Resonance Angiography (MRA). Whether the use of contrast enhancement improves perforating artery visualisation at 7 T remains unclear.

Association of Vascular Risk Factors and Genetic Factors With Penetrance of Variants Causing Monogenic Stroke.

Importance: It is uncertain whether typical variants causing monogenic stroke are associated with cerebrovascular disease in the general population and why the phenotype of these variants varies so widely.

Objective: To determine the frequency of pathogenic variants in the 3 most common monogenic cerebral small vessel diseases (cSVD) and their associations with prevalent and incident stroke and dementia.

Design, Setting, And Participants: This cohort study is a multicenter population-based study of data from UK Biobank participants recruited in 2006 through 2010, with the latest follow-up in September 2021.

MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol.

Background: Cerebral small vessel disease (SVD) is a common cause of stroke and cognitive impairment. Recent data has implicated neuroinflammation and increased blood-brain barrier (BBB) permeability in its pathogenesis, but whether such processes are causal and can be therapeutically modified is uncertain. In a rodent model of SVD, minocycline was associated with reduced white matter lesions, inflammation and BBB permeability.

Genome-wide association study of the human brain functional connectome reveals strong vascular component underlying global network efficiency.

Complex brain networks play a central role in integrating activity across the human brain, and such networks can be identified in the absence of any external stimulus. We performed 10 genome-wide association studies of resting state network measures of intrinsic brain activity in up to 36,150 participants of European ancestry in the UK Biobank. We found that the heritability of global network efficiency was largely explained by blood oxygen level-dependent (BOLD) resting state fluctuation amplitudes (RSFA), which are thought to reflect the vascular component of the BOLD signal.

Determining the OPTIMAL DTI analysis method for application in cerebral small vessel disease.

Background: DTI is sensitive to white matter (WM) microstructural damage and has been suggested as a surrogate marker for phase 2 clinical trials in cerebral small vessel disease (SVD). The study's objective is to establish the best way to analyse the diffusion-weighted imaging data in SVD for this purpose. The ideal method would be sensitive to change and predict dementia conversion, but also straightforward to implement and ideally automated.

Central obesity is selectively associated with cerebral gray matter atrophy in 15,634 subjects in the UK Biobank.

Background: Obesity is a risk factor for both cardiovascular disease and dementia, but the mechanisms underlying this association are not fully understood. We examined associations between obesity, including estimates of central obesity using different modalities, with brain gray matter (GM) volume in the UK Biobank, a large population-based cohort study.

Methods: To determine relationships between obesity and the brain we used brain MRI, abdominal MRI, dual-energy X-ray absorptiometry (DXA), and bioelectric whole-body impedance.

Automated Detection of Candidate Subjects With Cerebral Microbleeds Using Machine Learning.

Cerebral microbleeds (CMBs) appear as small, circular, well defined hypointense lesions of a few mm in size on T2-weighted gradient recalled echo (T2-GRE) images and appear enhanced on susceptibility weighted images (SWI). Due to their small size, contrast variations and other mimics (e.g.

Prevalence and Risk Factors of Cerebral Microbleeds: Analysis From the UK Biobank.

Background And Objectives: To determine the prevalence of and risk factors for cerebral microbleeds (CMBs) at different locations in a large healthy community population.

Methods: A total of 8,159 participants from the UK Biobank with MRI scans suitable for CMB analysis were included. Brain susceptibility-weighted imaging data were acquired on 2 identical 3.

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

[Figure: see text].

Association of common genetic variants with brain microbleeds: A genome-wide association study.

Objective: To identify common genetic variants associated with the presence of brain microbleeds (BMBs).

Methods: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel.