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Abstract Vessel segmentation in fundus images permits understanding retinal diseases and computing image-based biomarkers. However, manual vessel segmentation is a time-consuming process. Optical coherence tomography angiography (OCT-A) allows direct, non-invasive estimation of retinal vessels. Unfortunately, compared to fundus images, OCT-A cameras are more expensive, less portable, and have a reduced field of view. We present an automated strategy relying on generative adversarial networks to create vascular maps from fundus images without training using manual vessel segmentation maps. Further post-processing used for standard en face OCT-A allows obtaining a vessel segmentation map. We compare our approach to state-of-the-art vessel segmentation algorithms trained on manual vessel segmentation maps and vessel segmentations derived from OCT-A. We evaluate them from an automatic vascular segmentation perspective and as vessel density estimators, i.e., the most common imaging biomarker for OCT-A used in studies. Using OCT-A as a training target over manual vessel delineations yields improved vascular maps for the optic disc area and compares to the best-performing vessel segmentation algorithm in the macular region. This technique could reduce the cost and effort incurred when training vessel segmentation algorithms. To incentivize research in this field, we will make the dataset publicly available to the scientific community.

Abstract There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P

Abstract To investigate the associations between retinal vessel parameters and normal-tension glaucoma (NTG). We conducted a case–control study with a prospective cohort, allowing to record 23 cases of NTG. We matched NTG patient with one primary open-angle glaucoma (POAG) and one control per case by age, systemic hypertension, diabetes, and refraction. Central retinal artery equivalent (CRAE), central retinal venule equivalent (CRVE), Arteriole-To-Venule ratio (AVR), Fractal Dimension and tortuosity of the vascular network were measured using VAMPIRE software. Our sample consisted of 23 NTG, 23 POAG, and 23 control individuals, with a median age of 65 years (25–75th percentile, 56–74). No significant differences were observed in median values for CRAE (130.6 µm (25–75th percentile, 122.8; 137.0) for NTG, 128.4 µm (124.0; 132.9) for POAG, and 135.3 µm (123.3; 144.8) for controls, P = .23), CRVE (172.1 µm (160.0; 188.3), 172.8 µm (163.3; 181.6), and 175.9 µm (167.6; 188.4), P = .43), AVR (0.76, 0.75, 0.74, P = .71), tortuosity and fractal parameters across study groups. Vascular morphological parameters were not significantly associated with retinal nerve fiber layer thickness or mean deviation for the NTG and POAG groups. Our results suggest that vascular dysregulation in NTG does not modify the architecture and geometry of the retinal vessel network.

Optical colonoscopy is the gold standard procedure to detect colorectal cancer, the fourth most common cancer in the United Kingdom. Up to 22%–28% of polyps can be missed during the procedure that is associated with interval cancer. A vision-based autonomous soft endorobot for colonoscopy can drastically improve the accuracy of the procedure by inspecting the colon more systematically with reduced discomfort. A three-dimensional understanding of the environment is essential for robot navigation and can also improve the adenoma detection rate. Monocular depth estimation with deep learning methods has progressed substantially, but collecting ground-truth depth maps remains a challenge as no 3D camera can be fitted to a standard colonoscope. This work addresses this issue by using a self-supervised monocular depth estimation model that directly learns depth from video sequences with view synthesis. In addition, our model accommodates wide field-of-view cameras typically used in colonoscopy and specific challenges such as deformable surfaces, specular lighting, non-Lambertian surfaces, and high occlusion. We performed qualitative analysis on a synthetic data set, a quantitative examination of the colonoscopy training model, and real colonoscopy videos in near real-time.

Abstract Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case–control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.

Abstract The use of 2D alpha-shapes (α-shapes) to quantify morphological features of the retinal microvasculature could lead to imaging biomarkers for proliferative diabetic retinopathy (PDR). We tested our approach using the MESSIDOR dataset that consists of colour fundus photographs from 547 healthy individuals, 149 with mild diabetic retinopathy (DR), 239 with moderate DR, 199 pre-PDR and 53 PDR. The skeleton (centrelines) of the automatically segmented retinal vasculature was represented as an α-shape and the proposed parameters, complexity ( $${Op\alpha }_{min}$$ O p α min ), spread (OpA), global shape (VS) and presence of abnormal angiogenesis (Grad α ) were computed. In cross-sectional analysis, individuals with PDR had a lower $${Op\alpha }_{min}$$ O p α min , OpA and Grad α indicating a vasculature that is more complex, less spread (i.e. dense) and the presence of numerous small vessels. The results show that α-shape parameters characterise vascular abnormalities predictive of PDR (AUC 0.73; 95% CI [0.73 0.74]) and have therefore potential to reveal changes in retinal microvascular morphology.

ObjectivePatients with diabetes have an increased risk of dementia. Improved prediction of dementia is an important goal in developing future prevention strategies. Diabetic retinopathy screening (DRS) photographs may be a convenient source of imaging biomarkers of brain health. We therefore investigated the association of retinal vascular measures (RVMs) from DRS photographs in patients with type 2 diabetes with dementia risk.Research Design and MethodsRVMs were obtained from 6,111 patients in the GoDARTS bioresource (635 incident cases) using VAMPIRE software. Their association, independent of Apo E4 genotype and clinical parameters, was determined for incident all cause dementia (ACD) and separately Alzheimer's disease (AD) and vascular dementia (VD). We used Cox’s proportional hazards with competing risk of death without dementia. The potential value of RVMs to increase the accuracy of risk prediction was evaluated.ResultsIncreased retinal arteriolar fractal dimension associated with increased risk of ACD (csHR 1.17; 1.08–1.26) and AD (HR 1.33; 1.16–1.52), whereas increased venular fractal dimension (FDV) was associated with reduced risk of AD (csHR 0.85; 0.74–0.96). Conversely, FDV was associated with increased risk of VD (csHR 1.22; 1.07–1.40). Wider arteriolar calibre was associated with a reduced risk of ACD (csHR 0.9; 0.83–0.98) and wider venular calibre was associated with a reduced risk of AD (csHR 0.87; 0.78–0.97). Accounting for competing risk did not substantially alter these findings. RVMs significantly increased the accuracy of prediction.ConclusionsConventional DRS photographs could enhance stratifying patients with diabetes at increased risk of dementia facilitating the development of future prevention strategies.

Cortical bone microstructure assessment in biological and forensic anthropology can assist with the estimation of age-at-death and animal-human differentiation, for example. Osteonal structures within cortical bone are the key feature under analysis, with osteon frequency and metric parameters providing crucial information for the assessment. Currently, the histomorphological assessment consists of a time-consuming manual process for which specific training is required. Our work investigates the feasibility of automatic analysis of human bone microstructure images through the application of deep learning. In this paper, we use a U-Net architecture to address the semantic segmentation of such images into three classes: intact osteons, fragmentary osteons, and background. Data augmentation was used to avoid overfitting. We evaluated our fully automatic approach using a sample of 99 microphotographs. The contours of intact and fragmentary osteons were traced manually to provide ground truth. The Dice coefficients were 0.73 for intact osteons, 0.38 for fragmented osteons, and 0.81 for background, giving an average of 0.64. The Dice coefficient of the binary classification osteon-background was 0.82. Although further refinement of the initial model and tests with larger datasets are needed, this study provides, to the best of our knowledge, the first proof of concept for the use of computer vision and deep learning for differentiating both intact and fragmentary osteons in human cortical bone. This approach has the potential to widen and facilitate the use of histomorphological assessment in the biological and forensic anthropology communities.

Abstract Microcirculatory dysfunction occurs early in cardiovascular disease (CVD) development. Acute myocardial infarction (MI) is a late consequence of CVD. The conjunctival microcirculation is readily-accessible for quantitative assessment and has not previously been studied in MI patients. We compared the conjunctival microcirculation of acute MI patients and age/sex-matched healthy controls to determine if there were differences in microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. Results are for all vessels as they were not sub-classified into arterioles or venules. The conjunctival microcirculation was assessed in 56 controls and 59 inpatients with a presenting diagnosis of MI. Mean vessel diameter for the controls was 21.41 ± 7.57 μm compared to 22.32 ± 7.66 μm for the MI patients (p

Abstract 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

Abstract Introduction We test whether measures of the retinal vasculature are associated with cognitive functioning and cognitive change. Methods Retinal images from a narrow‐age cohort were analyzed using Vessel Assessment and Measurement Platform for Images of the Retina, producing a comprehensive range of quantitative measurements of the retinal vasculature, at mean age 72.5 years (SD = 0.7). Cognitive ability and change were measured using a battery of multiple measures of memory, visuospatial, processing speed, and crystallized cognitive abilities at mean ages 73, 76, and 79 years. We applied multivariate growth curve models to test the association between retinal vascular measurements with cognitive abilities and their changes. Results Almost all associations were nonsignificant. In our most parsimonious model, venular asymmetry factor was associated with speed at age 73. Discussion Our null findings suggest that the quantitative retinal parameters applied in this study are not significantly associated with cognitive functioning or cognitive change.

We aimed to compare measurements from three of the most widely used software packages in the literature and to generate conversion algorithms for measurement of the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) between SIVA and IVAN and between SIVA and VAMPIRE. We analyzed 223 retinal photographs from 133 human participants using both SIVA, VAMPIRE and IVAN independently for computing CRAE and CRVE. Agreement between measurements was assessed using Bland–Altman plots and intra-class correlation coefficients. A conversion algorithm between measurements was carried out using linear regression, and validated using bootstrapping and root-mean-square error. The agreement between VAMPIRE and IVAN was poor to moderate: The mean difference was 20.2 µm (95% limits of agreement, LOA, −12.2–52.6 µm) for CRAE and 21.0 µm (95% LOA, −17.5–59.5 µm) for CRVE. The agreement between VAMPIRE and SIVA was also poor to moderate: the mean difference was 36.6 µm (95% LOA, −12.8–60.4 µm) for CRAE, and 40.3 µm (95% LOA, 5.6–75.0 µm) for CRVE. The agreement between IVAN and SIVA was good to excellent: the mean difference was 16.4 µm (95% LOA, −4.25–37.0 µm) for CRAE, and 19.3 µm (95% LOA, 0.09–38.6 µm) for CRVE. We propose an algorithm converting IVAN and VAMPIRE measurements into SIVA-estimated measurements, which could be used to homogenize sets of vessel measurements obtained with different software packages.

The aim of this prospective study was to compare retinal vascular diameter measurements taken from standard fundus images and adaptive optics (AO) images. We analysed retinal images of twenty healthy subjects with 45-degree funduscopic colour photographs (CR-2 Canon fundus camera, Canon™) and adaptive optics (AO) fundus images (rtx1 camera, Imagine Eyes®). Diameters were measured using three software applications: the VAMPIRE (Vessel Assessment and Measurement Platform for Images of the REtina) annotation tool, IVAN (Interactive Vessel ANalyzer) for funduscopic colour photographs, and AO_Detect_Artery™ for AO images. For the arterial diameters, the mean difference between AO_Detect_Artery™ and IVAN was 9.1 µm (−27.4 to 9.2 µm, p = 0.005) and the measurements were significantly correlated (r = 0.79). The mean difference between AO_Detect_Artery™ and VAMPIRE annotation tool was 3.8 µm (−34.4 to 26.8 µm, p = 0.16) and the measurements were poorly correlated (r = 0.12). For the venous diameters, the mean difference between the AO_Detect_Artery™ and IVAN was 3.9 µm (−40.9 to 41.9 µm, p = 0.35) and the measurements were highly correlated (r = 0.83). The mean difference between the AO_Detect_Artery™ and VAMPIRE annotation tool was 0.4 µm (−17.44 to 25.3 µm, p = 0.91) and the correlations were moderate (r = 0.41). We found that the VAMPIRE annotation tool, an entirely manual software, is accurate for the measurement of arterial and venular diameters, but the correlation with AO measurements is poor. On the contrary, IVAN, a semi-automatic software tool, presents slightly greater differences with AO imaging, but the correlation is stronger. Data from arteries should be considered with caution, since IVAN seems to significantly under-estimate arterial diameters.

ObjectiveChanges to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.MethodsWe retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal–annular arteriole:venule ratio (NA-AVR), a novel combined parameter.ResultsLeft and right eyes were analysed from 440 participants (aged 50–59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).ConclusionsSemiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.

Background: Perivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people. Methods: We analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors. Results: In 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=−0.170, count β=−0.184, p

Abstract Introduction Advanced machine learning methods might help to identify dementia risk from neuroimaging, but their accuracy to date is unclear. Methods We systematically reviewed the literature, 2006 to late 2016, for machine learning studies differentiating healthy aging from dementia of various types, assessing study quality, and comparing accuracy at different disease boundaries. Results Of 111 relevant studies, most assessed Alzheimer's disease versus healthy controls, using AD Neuroimaging Initiative data, support vector machines, and only T1‐weighted sequences. Accuracy was highest for differentiating Alzheimer's disease from healthy controls and poor for differentiating healthy controls versus mild cognitive impairment versus Alzheimer's disease or mild cognitive impairment converters versus nonconverters. Accuracy increased using combined data types, but not by data source, sample size, or machine learning method. Discussion Machine learning does not differentiate clinically relevant disease categories yet. More diverse data sets, combinations of different types of data, and close clinical integration of machine learning would help to advance the field.

Abstract Background The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured‐light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input. Methods Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days. Results The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case). Conclusion The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environments.