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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. [ABSTRACT FROM AUTHOR]

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD.Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group's experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015).Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach.Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use. [ABSTRACT FROM AUTHOR]

Background: The cause of lacunar ischemic stroke, a clinical feature of cerebral small vessel disease (SVD), is largely unknown. Inflammation and endothelial dysfunction have been implicated. Plasma biomarkers could provide mechanistic insights but current data are conflicting. White matter hyperintensities (WMHs) are an important imaging biomarker of SVD. It is unknown if plasma biomarkers add predictive capacity beyond age and vascular risk factors in explaining WMH. Methods: We prospectively recruited patients presenting with non-disabling ischemic stroke, classifying them clinically and with the help of MRI as lacunar or cortical. We measured biomarkers of inflammation, endothelial dysfunction and hemostasis for >1 month after stroke and compared biomarker levels between stroke subtypes. We quantitatively calculated WMH. We used multiple linear regression analysis to model WMH as a function of age, sex, hypertension and smoking (the baseline model). We fitted exploratory models using plasma biomarkers as predictor variables to assess model improvement over baseline. Results: We recruited 125 patients. The lacunar group (n = 65) had lower tissue plasminogen activator (t-PA) levels in unadjusted (7.39 vs. 8.59 ng/ml, p = 0.029) and adjusted (p = 0.035) analyses compared with the cortical group (n = 60). There were no significant differences in the other plasma biomarkers. The results for t-PA were consistent with an updated meta-analysis, although the effect remains non-significant (standardized mean difference -0.08 (95% CI -0.25 to 0.09)). The baseline regression model explained 29% of the variance in quantitative WMH (R ² 0.289). Inflammatory biomarkers showed minor improvement over baseline (R² 0.291), but the other plasma biomarkers did not improve the baseline model. Conclusion: Plasma t-PA levels appear to differ between lacunar and cortical stroke subtypes, late after stroke, independent of age, sex and vascular risk factors and may reflect endothelial dysfunction. Except for a minor additional predictive effect of inflammatory markers, plasma biomarkers do not relate to WMH severity in this small stroke population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: White matter lesions (WML) are commonly seen on brain MRI and are generally considered a marker of tissue damage from cerebral small vessel disease. WML are associated with increasing age and vascular risk factors, but their precise cause is unknown. A role for carotid artery atherothromboemboli has been suggested. If this is the case, more WML would be expected ipsilateral to increasing degrees of carotid stenosis. Methods: We recruited patients with ischaemic stroke from two large, separate prospective stroke studies, assessed with brain MRI and carotid Doppler ultrasound. We scored hemispheric WML visually in periventricular and deep locations. We assessed the association between carotid stenosis asymmetry and WML asymmetry, and vice versa. Further, we assessed the association between carotid stenosis and ipsilateral WML, before and after adjusting for vascular risk factors, and tested associations between ipsilateral and contralateral stenoses and WML. Results: We recruited 247 (Study 1) and 253 (Study 2) patients. In Study 1 and Study 2, 36 (15%) and 29 (11%) patients had ≥50% carotid stenosis, and 27 (11%) and 15 (6%) had ≥70% stenosis, respectively. Carotid stenosis was asymmetric in 28 (11%) and 26 (10%) patients and WML were asymmetric in 22 (9%) and 11 (4%) patients in Study 1 and Study 2, respectively. We found no association between carotid stenosis and ipsilateral WML score, before or after adjusting for vascular risk factors or sidedness, but WML were strongly associated with increasing age (p < 0.001). Conclusion: In two large cohorts of ischaemic stroke patients, we found no association between carotid stenosis and ipsi- or contralateral WML. There is now substantial evidence that atherothromboemboli are unlikely to cause most WML or other forms of cerebral small vessel lesions. Future studies should focus on determining what causes the intrinsic small vessel pathological changes that appear to underlie most WML. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Atheromatous middle cerebral artery (MCA) stenosis could cause lacunar stroke by occluding lenticulostriate artery origins, but atheroma is common, and previous studies lacked suitable controls. We aimed to determine if intracranial atheroma was more common in lacunar than in cortical ischaemic stroke. We recruited patients with lacunar stroke and controls with mild cortical stroke, confirmed the stroke subtype with magnetic resonance imaging and used transcranial Doppler ultrasound imaging to record flow velocity and focal stenoses in the basal intracranial arteries 1 month after stroke. We compared ipsi- and contralateral MCA mean flow velocities between stroke subtypes and tested for associations using linear mixed models. Amongst 67 lacunar and 67 mild cortical strokes, mean age 64 and 67 years, respectively, we found no difference in MCA mean flow velocity between cortical and lacunar patients. Increasing age and white matter lesion scores were independently associated with lower MCA flow velocities (0.2 cms-1 fall in velocity per year increase in age, p = 0.045; 3.75 cms-1 fall in flow velocity per point increase in white matter lesion score, p = 0.004). We found no intracranial arterial stenoses. MCA atheromatous stenosis is unlikely to be a common cause of lacunar stroke in white populations. Falling velocities with increasing white matter lesion scores may reflect progressive brain tissue loss leaving less tissue to supply. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (lacunar stroke and cerebral white matter hyperintensities) is caused by vessel abnormalities of unknown aetiology. Retinal vessels show developmental and pathophysiological similarities to cerebral small vessels and microvessel geometry may influence vascular efficiency. Retinal arteriolar branching angles or coefficients (the ratio of the sum of the cross-sectional areas of the two daughter vessels to the cross-sectional area of the parent vessel at an arteriolar bifurcation) may be associated with cerebral small vessel disease. We performed a cross-sectional observational study in a UK tertiary referral hospital. An experienced stroke physician recruited consecutive patients presenting with lacunar ischaemic stroke with a control group consisting of patients with minor cortical ischaemic stroke. We performed brain magnetic resonance imaging to assess the recent infarct and periventricular and deep white matter hyperintensities. We subtyped stroke with clinical and radiological findings. We took digital retinal photographs to assess retinal arteriolar branching coefficients and branching angles using a semi-automated technique. Two hundred and five patients were recruited (104 lacunar stroke, 101 cortical stroke), mean age 68-years (standard deviation 12). With multivariate analysis, increased branching coefficient was associated with periventricular white matter hyperintensities ( P=0·006) and ischaemic heart disease ( P<0·001), and decreased branching coefficient with deep white matter hyperintensities ( P=0·003), but not with lacunar stroke subtype ( P=0·96). We found no associations with retinal branching angles. Retinal arteriolar geometry differs between cerebral small vessel phenotypes. Further research is needed to ascertain the clinical significance of these findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diffusion-weighted (DWI) MRI is recommended in UK guidelines to evaluate minor strokes, yet can produce negative results. OBJECTIVE: The authors determined the rate of negative MRI (including DWI) and associated features in patients presenting to hospital with minor strokes. METHODS: The authors performed a prospective observational cross-sectional study in a teaching hospital of patients with a clinical diagnosis of ischaemic lacunar or minor cortical stroke. The authors performed MRI (DWI, T2, fluid-attenuated inversion recovery (FLAIR), T2* and T1) as soon as possible after presentation. The authors used multivariate analysis to determine predictors of negative DWI and MRI (all sequences). Gold standard for clinical diagnosis of stroke was the opinion of an expert panel. RESULTS: The authors recruited 246 patients, mean age 68.1 years (SD 11.6 years), 162 were males (66%), and the median NIHSS was 2 (range 0 to 8). The median time from stroke onset to MR scan was 12 days (IQR 4–27 days). Eighty-one patients (33%) did not show any ischaemia on DWI. Sixty patients (24%) did not show the recent infarct on MRI (DWI/T2/FLAIR). With multivariate analysis, less severe stroke, younger age, female gender and increased time from stroke onset to scan were associated with negative DWI. With multivariate analysis, younger age and female gender were associated with negative MRI (DWI or T2 or FLAIR) scans. CONCLUSIONS: There is a high rate of negative MRI and DWI among patients with minor stroke (a third) which has important management and research implications. A negative MRI or DWI does not exclude the diagnosis of stroke. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is a cause of stroke and dementia. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) are developmentally related to brain microvessels. We quantified retinal vessel density (VD) and branching complexity, investigating relationships with SVD lesions, white matter integrity on diffusion tensor imaging (DTI) and cerebrovascular reactivity (CVR) to CO2 in patients with minor stroke. We enrolled 123 patients (mean age 68.1 ± SD 9.9 years), 115 contributed retinal data. Right (R) and left (L) eyes are reported. After adjusting for age, eye disease, diabetes, blood pressure and image quality, lower VD remained associated with higher mean diffusivity (MD) (standardized β; R −0.16 [95%CI −0.32 to −0.01]) and lower CVR (L 0.17 [0.03 to 0.31] and R 0.19 [0.02 to 0.36]) in normal appearing white matter (NAWM). Sparser branching remained associated with sub-visible white matter damage shown by higher MD (R −0.24 [−0.08 to −0.40]), lower fractional anisotropy (FA) (L 0.17 [0.01 to 0.33]), and lower CVR (R 0.20 [0.02 to 0.38]) in NAWM. OCTA-derived metrics provide evidence of microvessel abnormalities that may underpin SVD lesions in the brain. [ABSTRACT FROM AUTHOR]

Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild ischemic stroke patients. We studied cross-sectional associations between PSMD and cognition at both 3-months (N = 229) and 1-year (N = 173) post-stroke, adjusted for premorbid IQ, sex, age, stroke severity and disability, as well as the association between baseline PSMD and 1-year cognition. At baseline, (mean age = 65.9 years (SD = 11.1); 34% female), lower Montreal Cognitive Assessment (MoCA) scores were associated with older age, lower premorbid IQ and higher stroke severity, but not with PSMD (βstandardized = −0.116, 95% CI −0.241, 0.009; p = 0.069). At 1-year, premorbid IQ, older age, higher stroke severity and higher PSMD (βstandardized = −0.301, 95% CI −0.434, −0.168; p < 0.001) were associated with lower MoCA. Higher baseline PSMD was associated with lower 1-year MoCA (βstandardized = −0.182, 95% CI −0.308, −0.056; p = 0.005). PSMD becomes more associated with global cognition at 1-year post-stroke, possibly once acute effects have settled. Additionally, PSMD in the subacute phase after a mild stroke could help predict long-term cognitive impairment. [ABSTRACT FROM AUTHOR]

• Raised signal in CSF on FLAIR may indicate raised CSF protein or debris. • Inferior frontal sulcal hyperintensities (IFSH) were associated with ageing. • IFSH were associated with PVS score in centrum semiovale in stroke patients. Raised signal in cerebrospinal fluid (CSF) on fluid-attenuated inversion recovery (FLAIR) may indicate raised CSF protein or debris and is seen in inferior frontal sulci on routine MRI. To explore its clinical relevance, we assessed the association of inferior frontal sulcal hyperintensities (IFSH) on FLAIR with demographics, risk factors, and small vessel disease markers in three cohorts (healthy volunteers, n=44; mild stroke patients, n=105; older community-dwelling participants from Lothian birth cohort 1936, n=101). We collected detailed clinical data, scanned all subjects on the same 3T MRI scanner and 3-dimensional FLAIR sequence and developed a scale to rate IFSH. In adjusted analyses, the IFSH score increased with age (per 10-year increase; OR 1.69; 95% CI, 1.42-2.02), and perivascular spaces score in centrum semiovale in stroke patients (OR 1.73; 95% CI, 1.13-2.69). Since glymphatic CSF clearance declines with age and drains partially via the cribriform plate to the nasal lymphatics, IFSH on 3T MRI may be a non-invasive biomarker of altered CSF clearance and justifies further research in larger, more diverse samples. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936 (n = 603); and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study (n = 155). Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32–0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease. [ABSTRACT FROM AUTHOR]

No biological system or structure is likely to be perfectly symmetrical, or have identical right and left forms. This review explores the evidence for eye and visual pathway asymmetry, in health and in disease, and attempts to provide guidance for those studying the structure and function of the visual system, where recognition of symmetry or asymmetry may be essential. The principal question with regards to asymmetry is not 'are the eyes the same?', for some degree of asymmetry is pervasive, but 'when are they importantly different?'. Knowing if right and left eyes are 'importantly different' could have significant consequences for deciding whether right or left eyes are included in an analysis or for examining the association between a phenotype and ocular parameter. The presence of significant asymmetry would also have important implications for the design of normative databases of retinal and optic nerve metrics. In this review, we highlight not only the universal presence of asymmetry, but provide evidence that some elements of the visual system are inherently more asymmetric than others, pointing to the need for improved normative data to explain sources of asymmetry and their impact on determining associations with genetic, environmental or health-related factors and ultimately in clinical practice. [ABSTRACT FROM AUTHOR]

Background Acute lacunar ischaemic stroke, white matter hyperintensities, and lacunes are all features of cerebral small vessel disease. It is unclear why some small vessel disease lesions present with acute stroke symptoms, whereas others typically do not. Aim To test if lesion location could be one reason why some small vessel disease lesions present with acute stroke, whereas others accumulate covertly. Methods We identified prospectively patients who presented with acute lacunar stroke symptoms with a recent small subcortical infarct confirmed on magnetic resonance diffusion imaging. We compared the distribution of the acute infarcts with that of white matter hyperintensity and lacunes using computational image mapping methods. Results In 188 patients, mean age 67 ± standard deviation 12 years, the lesions that presented with acute lacunar ischaemic stroke were located in or near the main motor and sensory tracts in (descending order): posterior limb of the internal capsule (probability density 0·2/mm3), centrum semiovale (probability density = 0·15/mm3), medial lentiform nucleus/lateral thalamus (probability density = 0·09/mm3), and pons (probability density = 0·02/mm3). Most lacunes were in the lentiform nucleus (probability density = 0·01-0·04/mm3) or external capsule (probability density = 0·05/mm3). Most white matter hyperintensities were in centrum semiovale (except for the area affected by the acute symptomatic infarcts), external capsules, basal ganglia, and brainstem, with little overlap with the acute symptomatic infarcts (analysis of variance, P < 0·01). Conclusions Lesions that present with acute lacunar ischaemic stroke symptoms may be more likely noticed by the patient through affecting the main motor and sensory tracts, whereas white matter hyperintensity and asymptomatic lacunes mainly affect other areas. Brain location could at least partly explain the symptomatic vs. covert development of small vessel disease. [ABSTRACT FROM AUTHOR]

Purpose: To assess the suitability of retinal images held in the UK Biobank - the largest retinal data repository in a prospective population-based cohort - for computer assisted vascular morphometry, generating measures that are commonly investigated as candidate biomarkers of systemic disease. Methods: Non-mydriatic fundus images from both eyes of 2,690 participants - people with a self-reported history of myocardial infarction (n=1,345) and a matched control group (n=1,345) - were analysed using VAMPIRE software. These images were drawn from those of 68,554 UK Biobank participants who underwent retinal imaging at recruitment. Four operators were trained in the use of the software to measure retinal vascular tortuosity and bifurcation geometry. Results: Total operator time was approximately 360 hours (4 minutes per image). 2,252 (84%) of participants had at least one image of sufficient quality for the software to process, i.e. there was sufficient detection of retinal vessels in the image by the software to attempt the measurement of the target parameters. 1,604 (60%) of participants had an image of at least one eye that was adequately analysed by the software, i.e. the measurement protocol was successfully completed. Increasing age was associated with a reduced proportion of images that could be processed (p=0.0004) and analysed (p<0.0001). Cases exhibited more acute arteriolar branching angles (p=0.02) as well as lower arteriolar and venular tortuosity (p<0.0001). Conclusions: A proportion of the retinal images in UK Biobank are of insufficient quality for automated analysis. However, the large size of the UK Biobank means that tens of thousands of images are available and suitable for computational analysis. Parametric information measured from the retinas of participants with suspected cardiovascular disease was significantly different to that measured from a matched control group. [ABSTRACT FROM AUTHOR]

Abstract: There is growing interest in investigating the role of subtle changes in blood–brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences. [Copyright &y& Elsevier]

Abstract: Visual neglect is a common, yet frequently overlooked, neurological disorder following stroke characterized by a deficit in attention and appreciation of stimuli on the contralesional side of the body. It has a profound functional impact on affected individuals. A assessment and management of this condition are hindered, however, by the lack of professional awareness and clinical guidelines. Recent evidence suggests that the underlying deficit in visual attention is due to a disrupted internalized representation of the outer world rather than a disorder of sensory inputs. Dysfunction of the cortical domains and white-matter tracts, as well as inter-hemispheric imbalance, have been implicated in the various manifestations of visual neglect. Optimal diagnosis requires careful history-taking from the patient, family, and friends, in addition to clinical assessment with the line bisection test, the star cancellation test, and the Catherine Bergego Scale. Early recognition and prompt rehabilitation employing a multidisciplinary approach is desirable. Although no treatment has been definitively shown to be of benefit, those with promise include prism adaptation, visual scanning therapy, and virtual reality–based techniques. Further high quality research to seek optimum short- and long-term rehabilitative strategies for visual neglect is required. [Copyright &y& Elsevier]

Cardiovascular diseases are a public health concern; they remain the leading cause of morbidity and mortality in patients with type 2 diabetes. Phenotypic information available from retinal fundus images and clinical measurements, in addition to genomic data, can identify relevant biomarkers of cardiovascular health. In this study, we assessed whether such biomarkers stratified risks of major adverse cardiac events (MACE). A retrospective analysis was carried out on an extract from the Tayside GoDARTS bioresource of participants with type 2 diabetes (n = 3,891). A total of 519 features were incorporated, summarising morphometric properties of the retinal vasculature, various single nucleotide polymorphisms (SNPs), as well as routine clinical measurements. After imputing missing features, a predictive model was developed on a randomly sampled set (n = 2,918) using L1-regularised logistic regression (lasso). The model was evaluated on an independent set (n = 973) and its performance associated with overall hazard rate after censoring (log-rank p < 0.0001), suggesting that multimodal features were able to capture important knowledge for MACE risk assessment. We further showed through a bootstrap analysis that all three sources of information (retinal, genetic, routine clinical) offer robust signal. Particularly robust features included: tortuousity, width gradient, and branching point retinal groupings; SNPs known to be associated with blood pressure and cardiovascular phenotypic traits; age at imaging; clinical measurements such as blood pressure and high density lipoprotein. This novel approach could be used for fast and sensitive determination of future risks associated with MACE. [ABSTRACT FROM AUTHOR]