Retinal Biomarker Discovery for Dementia in an Elderly Diabetic Population

Dementia is a devastating disease, and has severe implications on affected individuals, their family and wider society. A growing body of literature is studying the association of retinal microvasculature measurement with dementia. We present a pilot study testing the strength of groups of conventional (semantic) and texture-based (non-semantic) measurements extracted from retinal fundus camera images to classify patients with and without dementia. We performed a 500-trial bootstrap analysis with regularized logistic regression on a cohort of 1,742 elderly diabetic individuals (median age 72.2). Age was the strongest predictor for this elderly cohort. Semantic retinal measurements featured in up to 81% of the bootstrap trials, with arterial caliber and optic disk size chosen most often, suggesting that they do complement age when selected together in a classifier. Textural features were able to train classifiers that match the performance of age, suggesting they are potentially a rich source of information for dementia outcome classification

Evaluation of Retinal Image Quality Assessment Networks in Different Color-spaces

Retinal image quality assessment (RIQA) is essential for controlling the quality of retinal imaging and guaranteeing the reliability of diagnoses by ophthalmologists or automated analysis systems. Existing RIQA methods focus on the RGB color-space and are developed based on small datasets with binary quality labels (i.e., `Accept' and `Reject'). In this paper, we first re-annotate an Eye-Quality (EyeQ) dataset with 28,792 retinal images from the EyePACS dataset, based on a three-level quality grading system (i.e., `Good', `Usable' and `Reject') for evaluating RIQA methods. Our RIQA dataset is characterized by its large-scale size, multi-level grading, and multi-modality. Then, we analyze the influences on RIQA of different color-spaces, and propose a simple yet efficient deep network, named Multiple Color-space Fusion Network (MCF-Net), which integrates the different color-space representations at both a feature-level and prediction-level to predict image quality grades. Experiments on our EyeQ dataset show that our MCF-Net obtains a state-of-the-art performance, outperforming the other deep learning methods. Furthermore, we also evaluate diabetic retinopathy (DR) detection methods on images of different quality, and demonstrate that the performances of automated diagnostic systems are highly dependent on image quality.Comment: Accepted by MICCAI 2019. Corrected two typos in Table 1 as: (1) in training set, the number of "Usable + All" should be '1,876'; (2) In testing set, the number of "Total + DR-0" should be '11,362'. Project page: https://github.com/hzfu/Eye

Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

BACKGROUND: Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. METHODS: Retinal microvascular parameters (fractal dimension [FD] - a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background. RESULTS: Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03-1.34 for arterioles and OR 1.24, CI 1.05-1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. CONCLUSIONS: This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.This research was supported by grants from the National Institutes of Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (11/20/03), the British Heart Foundation (PG/09/083) and the Evelyn Trust (09/22). Dr. McBride is supported by the Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine. Dr. Joshi is supported by Chief Scientist Office (ETM/160). Dr. van Beek is supported by the Scottish Imaging Network e a Platform of Scientific Excellence. The work of Dr. Rudd is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation and the Wellcome Trust. Dr. Newby is supported by the British Heart Foundation (CH/09/002). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre are supported by National Health Service Research Scotland through National Health Service Lothian.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ejvs.2015.12.01

Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation.

Objectives: Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection. Methods: Ten volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results: Ten patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion: Stable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection. Trial registration number: NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24

A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features

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

Recovery of Barotrauma Injuries in Chinook Salmon, Oncorhynchus tshawytscha from Exposure to Pile Driving Sound

Juvenile Chinook salmon, Oncorhynchus tshawytscha, were exposed to simulated high intensity pile driving signals to evaluate their ability to recover from barotrauma injuries. Fish were exposed to one of two cumulative sound exposure levels for 960 pile strikes (217 or 210 dB re 1 µPa2·s SELcum; single strike sound exposure levels of 187 or 180 dB re 1 µPa2⋅s SELss respectively). This was followed by an immediate assessment of injuries, or assessment 2, 5, or 10 days post-exposure. There were no observed mortalities from the pile driving sound exposure. Fish exposed to 217 dB re 1 µPa2·s SELcum displayed evidence of healing from injuries as post-exposure time increased. Fish exposed to 210 dB re 1 µPa2·s SELcum sustained minimal injuries that were not significantly different from control fish at days 0, 2, and 10. The exposure to 210 dB re 1 µPa2·s SELcum replicated the findings in a previous study that defined this level as the threshold for onset of injury. Furthermore, these data support the hypothesis that one or two Mild injuries resulting from pile driving exposure are unlikely to affect the survival of the exposed animals, at least in a laboratory environment

Adherence to antidepressant therapy for major depressive patients in a psychiatric hospital in Thailand

Poor adherence to antidepressant therapy is an important barrier to the effective management of major depressive disorder. This study aims to quantify the adherence rate to antidepressant treatment and to determine the pattern of prescriptions of depressed patients in a psychiatric institute in Thailand.This retrospective study used electronic pharmacy data of outpatients aged 15 or older, with a new diagnosis of major depression who received at least one prescription of antidepressants between August 2005 and September 2008. The medication possession ratio (MPR) was used to measure adherence over a 6 month period.1,058 were eligible for study inclusion. The overall adherence (MPR > 80%) in those attending this facility at least twice was 41% but if we assume that all patients who attended only once were non-adherent, adherence may be as low as 23%. Fluoxetine was the most commonly prescribed drug followed by TCAs. A large proportion of cases received more than one drug during one visit or was switched from one drug to another (39%).Adherence to antidepressant therapy for treatment of major depression in Thailand is rather low compared to results of adherence from elsewhere

Retinal microvascular parameters are not associated with reduced renal function in a study of individuals with type 2 diabetes

Abstract The eye provides an opportunistic “window” to view the microcirculation. There is published evidence of an association between retinal microvascular calibre and renal function measured by estimated glomerular filtration rate (eGFR) in individuals with diabetes mellitus. Beyond vascular calibre, few studies have considered other microvascular geometrical features. Here we report novel null findings for measures of vascular spread (vessel fractal dimension), tortuosity, and branching patterns and their relationship with renal function in type 2 diabetes over a mean of 3 years. We performed a nested case-control comparison of multiple retinal vascular parameters between individuals with type 2 diabetes and stable (non-progressors) versus declining (progressors) eGFR across two time points within a subset of 1072 participants from the GoDARTS study cohort. Retinal microvascular were measured using VAMPIRE 3.1 software. In unadjusted analyses and following adjustment for age, gender, systolic blood pressure, HbA1C, and diabetic retinopathy, no associations between baseline retinal vascular parameters and risk of eGFR progression were observed. Cross-sectional analysis of follow-up data showed a significant association between retinal arteriolar diameter and eGFR, but this was not maintained following adjustment. These findings are consistent with a lack of predictive capacity for progressive loss of renal function in type 2 diabetes