A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (n=126) or stroke (n=28) over a 10-year period were age and gender matched with controls subjects (n=528; case:control matching, ≈1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation ( P =0.02 unadjusted) and decreased retinal arteriolar tortuosity ( P =0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality ( P =0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure ( P =0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk. <s> BIB001 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Background Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. Methods Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. Results After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P trend = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P trend = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). Conclusion Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons. <s> BIB002 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> BACKGROUND AND PURPOSE ::: The retinal and cerebral vasculature share similar anatomic, physiological, and embryological characteristics. We reviewed the literature, focusing particularly on recent population-based studies, to examine the relationship between retinal signs and stroke. Summary of Review- Hypertensive retinopathy signs (eg, focal retinal arteriolar narrowing, arterio-venous nicking) were associated with prevalent stroke, incident stroke, and stroke mortality, independent of blood pressure and other cerebrovascular risk factors. Diabetic retinopathy signs (eg, microaneurysms, hard exudates) were similarly associated with incident stroke and stroke mortality. Retinal arteriolar emboli were associated with stroke mortality but not incident stroke. There were fewer studies on the association of other retinal signs such as retinal vein occlusion and age-related macular degeneration with stroke, and the results were less consistent. ::: ::: ::: CONCLUSIONS ::: Many retinal conditions are associated with stroke, reflecting possible concomitant pathophysiological processes affecting both the eye and the brain. However, the incremental value of a retinal examination for prediction of future stroke risk remains to be determined. <s> BIB003 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> This paper describes REVIEW, a new retinal vessel reference dataset. This dataset includes 16 images with 193 vessel segments, demonstrating a variety of pathologies and vessel types. The vessel edges are marked by three observers using a special drawing tool. The paper also describes the algorithm used to process these segments to produce vessel profiles, against which vessel width measurement algorithms can be assessed. Recommendations are given for use of the dataset in performance assessment. REVIEW can be downloaded from http://ReviewDB.lincoln.ac.uk. <s> BIB004 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> 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. <s> BIB005 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> This paper presents an algorithm for segmenting and measuring retinal vessels, by growing a "Ribbon of Twins" active contour model, which uses two pairs of contours to capture each vessel edge, while maintaining width consistency. The algorithm is initialized using a generalized morphological order filter to identify approximate vessels centerlines. Once the vessel segments are identified the network topology is determined using an implicit neural cost function to resolve junction configurations. The algorithm is robust, and can accurately locate vessel edges under difficult conditions, including noisy blurred edges, closely parallel vessels, light reflex phenomena, and very fine vessels. It yields precise vessel width measurements, with subpixel average width errors. We compare the algorithm with several benchmarks from the literature, demonstrating higher segmentation sensitivity and more accurate width measurement. <s> BIB006 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Objectives: Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Methods: Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2–4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Results: Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20–4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14–6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31–5.86) compared to those without FAN. Conclusions: Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors. GLOSSARY: AVN: arteriovenous nicking CI: confidence interval CRAE: central retinal artery equivalent CRVE: central retinal vein equivalent FAN: focal arteriolar narrowing HR: hazard ratio NIHSS: NIH Stroke Scale OAW: opacification of the arteriolar wall TOAST: Trial of ORG 10172 in Acute Stroke <s> BIB007 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Many studies have shown that hypertensive ocular funduscopic abnormalities are clearly related to stroke, even after controlling for level of blood pressure and other vascular risk factors. Retinal abnormalities indicative of a breakdown of the blood-retina barrier confer a greater increase in risk for stroke than sclerotic retinal changes. Similar retinal changes also have a positive relationship with stroke mortality. Hypertensive ocular fundus abnormalities are also reported to be associated with an increased risk for cognitive impairment, cerebral atrophy, progression of MRI-defined white matter lesions, and subclinical infarction. Recent advances in fundus photography allow for improved accuracy and consistency in interpretation of funduscopic lesions, and improve the feasibility of screening for these abnormalities in at-risk patient populations. Evaluating the ocular fundus for signs of hypertensive retinopathy, in combination with an assessment of the presence or absence of other known vascular risk factors, may allow clinicians to further individualize a risk profile for stroke to each individual patient, thus permitting more accurate risk stratification and, potentially, guiding treatment strategies. <s> BIB008 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> A reliable and accurate method to measure the width of retinal blood vessel in fundus photography is proposed in this paper. Our approach is based on a graph-theoretic algorithm. The two boundaries of the same blood vessel are segmented simultaneously by converting the two-boundary segmentation problem into a two-slice, three-dimension surface segmentation problem, which is further converted into the problem of computing a minimum closed set in a node-weighted graph. An initial segmentation is generated from a vessel probability image. Two datasets from the REVIEW database were used to assess the performance of proposed method. This algorithm is robust and is able to produce accurate measurements. <s> BIB009 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> This paper proposes an algorithm to measure the width of retinal vessels in fundus photographs using graph-based algorithm to segment both vessel edges simultaneously. First, the simultaneous two-boundary segmentation problem is modeled as a two-slice, 3-D surface segmentation problem, which is further converted into the problem of computing a minimum closed set in a node-weighted graph. An initial segmentation is generated from a vessel probability image. We use the REVIEW database to evaluate diameter measurement performance. The algorithm is robust and estimates the vessel width with subpixel accuracy. The method is used to explore the relationship between the average vessel width and the distance from the optic disc in 600 subjects. <s> BIB010 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Background and Purpose—Small-vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to the risk of stroke. We examined the relationship of retinal signs with incident stroke in a multiethnic cohort. Methods—The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from 6 US communities between 2000 and 2002. Of the participants, 4849 (71.2%) had fundus photography performed in 2002 to 2004. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein, carotid artery intima-media thickness, and coronary artery calcium were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates. Results—After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke ... <s> BIB011 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Study of retinal blood vessel features, especially the caliber, has been widely used for risk level assessment of certain disease conditions. In this work a vessel diameter measurement technique based on Gaussian modeling has been proposed. This method adaptively combines a series of second and higher order Gaussians to model the vessel profile and uses the sigma parameter of the best fitted Generalized Gaussians to the boundaries, to measure the vessel caliber. One advantage of this technique is that, unlike other methods, it does not assume the vessel profile as a symmetrical Gaussian-like shape with similar blurriness levels at the edges. The technique has been tested on 580 cross-sections from normal and pathological public datasets with mixed quality fundus images. Comparison was made against two gold standard techniques and a ground truth obtained manually by three experts to sub-pixel accuracy. <s> BIB012 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Although assessment of hypertensive retinopathy signs has been recommended for determining end-organ damage and stratifying vascular risk in persons with hypertension, its value remains unclear. In this study, we examine whether hypertensive retinopathy predicts the long-term risk of stroke in those with hypertension. A total of 2907 participants with hypertension aged 50 to 73 years at the 1993 to 1995 examination, who had gradable retinal photographs, no history of diabetes mellitus, stroke, and coronary heart disease at baseline and data on incident stroke, were included from the Atherosclerosis Risk in Communities (ARIC) Study. Retinal photographs were assessed for hypertensive retinopathy signs and classified as none, mild, and moderate/severe. Incident events of any stroke, cerebral infarction, and hemorrhagic stroke were identified and validated. After a mean follow-up period of 13.0 years, 165 persons developed incident stroke (146 cerebral infarctions and 15 hemorrhagic strokes). After adjusting for age, sex, blood pressure, and other risk factors, persons with moderate hypertensive retinopathy were more likely to have stroke (moderate versus no retinopathy: multivariable hazard ratios, 2.37 [95% confidence interval, 1.39–4.02]). In participants with hypertension on medication with good control of blood pressure, hypertensive retinopathy was related to an increased risk of cerebral infarction (mild retinopathy: hazard ratio, 1.96 [95% confidence interval, 1.09–3.55]; and moderate retinopathy: hazard ratio, 2.98 [95% confidence interval, 1.01–8.83]). Hypertensive retinopathy predicts the long-term risk of stroke, independent of blood pressure, even in treated patients with hypertension with good hypertension control. Retinal photographic assessment of hypertensive retinopathy signs may be useful for assessment of stroke risk. <s> BIB013 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> An improved scheme for contour detection with better performance measure has been proposed in this paper. A 9x9 Laplacian and Gaussian (LOG) filter has been proposed. The present study has shown that the gradient images obtained by the 9x9 LOG mask appears to be much clearer with sharp and prominent edges than those obtained through 5x5 LOG filter. The method has been applied to a number of digital images and better performance measure of contour detection has been achieved. <s> BIB014 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Diabetic retinopathy is one of the leading disabling chronic diseases, and one of the leading causes of preventable blindness in the world. Early diagnosis of diabetic retinopathy enables timely treatment and in order to achieve it a major effort will have to be invested into screening programs and especially into automated screening programs. For automated screening programs to work robustly a representative fundus image database is required. In this paper we give an overview of currently available databases and present a new diabetic retinopathy database. Our database is to our knowledge the first and only database which has diabetic retinopathy pathologies and major fundus structures annotated for every image from the database which makes it perfect for design and evaluation of currently available and new image processing algorithms for early detection of diabetic retinopathy using color fundus images. <s> BIB015 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Retinal images provide early signs of diabetic retinopathy, glaucoma, and hypertension. These signs can be investigated based on microaneurysms or smaller vessels. The diagnostic biomarkers are the change of vessel widths and angles especially at junctions, which are investigated using the vessel segmentation or tracking. Vessel paths may also be interrupted; crossings and bifurcations may be disconnected. This paper addresses a novel contextual method based on the geometry of the primary visual cortex (V1) to study these difficulties. We have analyzed the specific problems at junctions with a connectivity kernel obtained as the fundamental solution of the Fokker-Planck equation, which is usually used to represent the geometrical structure of multi-orientation cortical connectivity. Using the spectral clustering on a large local affinity matrix constructed by both the connectivity kernel and the feature of intensity, the vessels are identified successfully in a hierarchical topology each representing an individual perceptual unit. <s> BIB016 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. <s> BIB017 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Abstract This work is part of an ongoing project aimed to generate synthetic retinal fundus images. This paper concentrates on the generation of synthetic vascular networks with realistic shape and texture characteristics. An example-based method, the Active Shape Model, is used to synthesize reliable vessels’ shapes. An approach based on Kalman Filtering combined with an extension of the Multiresolution Hermite vascular cross-section model has been developed for the simulation of vessels’ textures. The proposed method is able to generate realistic synthetic vascular networks with morphological properties that guarantee the correct flow of the blood and the oxygenation of the retinal surface observed by fundus cameras. The validity of our synthetic retinal images is demonstrated by qualitative assessment and quantitative analysis. <s> BIB018 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Background —Narrower retinal arterioles and wider retinal venules have been associated with negative cardiovascular outcomes. We investigated whether retinal vessel calibers are associated with cardiovascular outcomes in long-term follow-up and provide incremental value over the 2013 American College of Cardiology/American Heart Association pooled cohort equations (PCE) in predicting Atherosclerotic Cardiovascular Disease Events (ASCVE). ::: ::: Methods —10,470 men and women without prior ASCVE or heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) study underwent retinal photography at visit 3 (1993-1995). ::: ::: Results —During a mean follow up of 16 years, there were 1779 incident CHD events, 548 ischemic strokes, 1395 HF events and 2793 deaths. Rates of all outcomes were higher in those with wider retinal venules and narrower retinal arterioles. Subjects with wider retinal venules [hazard ratio (HR) 1.13 (95% CI: 1.08-1.18), HR 1.18 (1.07-1.31) and HR 1.10 (1.00-1.20) per standard deviation (SD) increase] and narrower retinal arterioles [HR 1.06 (1.01-1.11), HR 1.14 (1.03-1.26) and HR 1.13 (1.03-1.24) per SD decrease] had a higher risk of death and stroke in both sexes as well as incident CHD in women but not men (interaction p=0.02) after adjustment for the PCE risk-score variables. The association between retinal vessel caliber and HF was non-significant after adjustment for systolic blood pressure. Among women with PCE-predicted 10-year ASCVE risk 5%). ::: ::: Conclusions —Narrower retinal arterioles and wider retinal venules conferred long-term risk of mortality and ischemic stroke in both genders and CHD in women. These measures serve as an inexpensive, reproducible biomarker that added incremental value to current practice guidelines in ASCVE risk prediction in low-risk women. <s> BIB019 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Background ::: To compare retinal vessel oxygenation and vessel caliber in primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal controls, as well as between eyes of asymmetrical glaucoma severity. <s> BIB020 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Purpose ::: To examine associations between retinal vascular geometry (tortuosity, branching coefficient [BC] and length–diameter ratio [LDR]) and diabetic proliferative retinopathy (PDR), nephropathy, and peripheral neuropathy in patients with type 1 diabetes mellitus (T1DM). <s> BIB021 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> This paper proposes the use of an adaptive model to measure the width of retinal vessels in fundus photographs. It is based on the hypothesis that the Higuchi's dimension of the cross-section is proportional to the vessel diameter. This approach does not require image segmentation and binarization of the vessels and therefore is suitable for machine based measurements. The model is developed using a synthetic image of the vessel of known diameter and added noise. As a first step, the vessel cross-section profiles were manually obtained and analyzed using Higuchi's fractal dimension method. A 3D model was formed using the relationship between Higuchi's dimension, vessel diameter and noise variance. This model was then evaluated using expert annotated REVIEW public database and solved for the vessel diameter for performance evaluation. The result showed a good agreement with state of the art techniques. The model is background noise tolerant, estimates the vessel width with subpixel precision and does not require manual intervention. <s> BIB022 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Automatic artery/vein (A/V) classification is one of the important topics in retinal image analysis. It allows the researchers to investigate the association between biomarkers and disease progression on a huge amount of data for arteries and veins separately. Recent proposed methods, which employ contextual information of vessels to achieve better A/V classification accuracy, still rely on the performance of pixel-wise classification, which has received limited attention in recent years. In this paper, we show that these classification methods can be markedly improved. We propose a new normalization technique for extracting four new features which are associated with the lightness reflection of vessels. The accuracy of a linear discriminate analysis classifier is used to validate these features. Accuracy rates of 85.1, 86.9 and 90.6% were obtained on three datasets using only local information. Based on the introduced features, the advanced graph-based methods will achieve a better performance on A/V classification. <s> BIB023 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Aim: To evaluate a new algorithm to detect the optic disc in retinal fundus images on a number of publicly available datasets. Optic Disc detection is an important first step in many automated algorithms, either to be masked out of future processing or for the use in optic disc related disease such as glaucoma and papilledema. Methods: We propose a new method for optic disc detection that converts the retinal image into a graph and exploits vessel enhancement methods to calculate edge weights in finding the shortest path between pairs of points on the periphery of the image. The line segment with the maximum number of shortest paths is considered the optic disc location, with refinement from a combination template matching approach in the found region. The method was tested on three publicly available datasets: DRIVE, DIARETDB1, and Messidor consisting of 40, 89, and 1200 images. All images were acquired at a 45°-50° field of view. Results: The method achieves an accuracy of 100, 98.88, and 99.42% on the DRIVE, DIARETDB1, and Messidor databases respectively. Conclusions: The method performs as well or better than state-of-the-art methods on these datasets. Processing takes an average of 32 seconds (+-1.2) to detect the optic disc, with 26 of those seconds used for the vessel enhancement process. The accuracy over a wide variety of images shows that the method is robust and would be optimal for retinal analysis systems that perform vessel enhancement as part of their processing. <s> BIB024 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> To determine the association between retinal vasculature changes and stroke.MEDLINE and EMBASE were searched for relevant human studies to September 2015 that investigated the association between retinal vasculature changes and the prevalence or incidence of stroke; the studies were independently examined for their qualities. Data on clinical characteristics and calculated summary odds ratios (ORs) were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, and adjusted for key variables.Nine cases were included in the study comprising 20 659 patients, 1178 of whom were stroke patients. The retinal microvascular morphological markers used were hemorrhage, microaneurysm, vessel caliber, arteriovenous nicking, and fractal dimension. OR of retinal arteriole narrowing and retinal arteriovenous nicking and stroke was 1.42 and 1.91, respectively, indicating that a small-caliber retinal arteriole and retinal arteriovenous nicking were associated with stroke. OR of retinal hemorrhage and retinal microaneurysm and stroke was 3.21 and 3.83, respectively, indicating that retinal microvascular lesions were highly associated with stroke. Results also showed that retinal fractal dimension reduction was associated with stroke (OR: 2.28 for arteriole network, OR: 1.80 for venular network).Retinal vasculature changes have a specific relationship to stroke, which is promising evidence for the prediction of stroke using computerized retinal vessel analysis. <s> BIB025 </s> A Review on the Extraction of Quantitative Retinal Microvascular Image Feature <s> Introduction <s> Several clinical studies reveal the relationship between alterations in the topologies of the human retinal blood vessel, the outcrop and the disease evolution, such as diabetic retinopathy, hypertensive retinopathy, and macular degeneration. Indeed, the detection of these vascular changes always has gaps. In addition, the manual steps are slow, which may be subjected to a bias of the perceiver. However, we can overcome these troubles using computer algorithms that are quicker and more accurate. This paper presents and investigates a novel method for measuring the blood vessel diameter in the retinal image. The proposed method is based on a thresholding segmentation and thinning step, followed by the characteristic point determination step by the Douglas-Peucker algorithm. Thereafter, it uses the active contours to detect vessel contour. Finally, Heron's Formula is applied to assure the calculation of vessel diameter. The obtained results for six sample images showed that the proposed method generated less errors compared to other techniques, which confirms the high performance of the proposed method. <s> BIB026
One of the most important subfields of biomedical engineering is the analysis of fundus retinal images. Analysis of the human fundus eye images has become the key point for diagnosing the various pathologies of retinal vasculature. Furthermore, image analysis provides a simple and noninvasive visualization of the retinal blood vessels in those high risk ophthalmologic medical conditions BIB001  BIB016 . The fundus retinal images are directly captured from human eye that includes some other landmarks like microcirculation system of the retina, macula, optic disc, fovea, microaneurysm, and exudates BIB023 . This cost-effective, simple image acquisition system can be used in the large-scale screening programs and retinal image analysis developing mathematical and computational techniques. In addition, physicians can benefit from this technique as to objectively assess abnormal symptoms such as vessel tortuosity, vessel width, bifurcation angles, branching angles, and vessel caliber. All these features are useful for early detection of hypertensive and diabetic retinopathy, macular degeneration, acute stroke, neovascular glaucoma, and some other cardiovascular diseases BIB001 BIB016 BIB024 BIB018 BIB019 BIB020 BIB021 . Some distinct changes in the retinal microvasculature are recognized as the preindicator of subsequent vascular incidents like ischemic stroke or acute stroke BIB007 . It was 2 Computational and Mathematical Methods in Medicine found in many types of research that there is a clear relationship between the ocular funduscopic abnormalities and acute stroke even though the blood pressure and other vascular risk factors are in control BIB008 . According to the study of BIB011 with a multiethnic cohort, retinal arteriolar narrowing and retinopathy of diabetic free people have an association with increased risk of acute stroke. But the Cardiovascular Health Study stated that there is no association between retinal arteriolar caliber (diameter) and stroke but rather there is a close association between stroke and the larger venular caliber (diameter) BIB002 . Rotterdam cohort study also came into a decision after a long-term observation that the retinal venular diameter is associated with any stroke or ischemic stroke BIB017 . The authors of BIB013 examined the association of hypertensive retinopathy with the risk of stroke in their population base study. Retinal microvascular abnormalities like microaneurysm, arteriovenous nicking, haemorrhages, and vessel caliber are considered as associative to the stroke and indicative of death from stroke and IHD (Ischemic Heart Diseases) BIB001 . A population-based study collaborating with Beaver Dam Eye Study (BDES) of BIB001 revealed that increased diameter ratio was associated with increased stroke mortality (P = 0.02 unadjusted). The paper BIB025 searched MEDLINE and EMBASE to find out the relation between microvascular changes of retinal microvasculature and prevalence or incident of stroke. In the study of BIB025 20659 patients were involved, 1178 patients of them had stroke, and they found the Odd Ratio (OR) of stroke and retinal arteriolar narrowing and AV nicking was 1.42 and 1.91, respectively, which indicated that these abnormalities are slightly associated with stroke. Microvascular lesions like microaneurysm and haemorrhages which were found as highly associated with stroke as their OR were 3.83 and 3.21, respectively, and the OR between stroke and arteriole narrowing and venular network are 2.28 and 1.80 indicated the association of these abnormalities with stroke BIB025 . A cohort study of Asian Malay persons consisting of 3189 patients, free from prevalent stroke at baseline, revealed that 51 (1.93%) participants had an incident stroke event that could be predicted by analyzing the microvascular changes of retinal vasculature  . Prevalent and incident stroke have the association with retinopathy and venular widening BIB005 . Retinal vessel widening is also the predictor of hypertensive retinopathy which also has an association with stroke BIB003 . Many techniques have been developed using image processing principle to measure the vessel diameter of retinal microvasculature. Suppose some of the available vessel diameter measurement techniques are based on Linear Discriminant Analysis (LDA), image gradient segmentation technique (ARG) for vessel edge detection, using active contour BIB026 BIB006 BIB014 , mask creation BIB026 , graph-theoretic method BIB009 BIB010 Multistep Regression Method (Higher order Gaussian modeling) BIB012 , Adaptive Higuchi's Dimension BIB022 , and so on. There are several datasets for fundus retinal images that are publicly available for the researchers from all over the world. High-Resolution Fundus Image Database (HRFID) and Digital Retinal Images for Vessel Extraction (DRIVE) are two kinds of publicly open datasets that can be accessed by the researchers BIB018 BIB015 . Researchers from digital image processing discipline can use images from these datasets as the raw materials for their experiment. REVIEW (Retinal Vessel Image set for Estimation of Width) is another publicly available standard dataset that includes various normal and pathological retinal images for the evaluation of the algorithm for retinal vessel diameter measurement. REVIEW dataset includes 16 images with 193 vessel segments that demonstrate the different types of pathologies and vessel types and this dataset consists of four subsets which are HRIS (HighResolution Image Set), VDIS (Vascular Disease Image), CLRIS (Central Light Reflex Image Set), and KPIS (Kick Point Image) BIB004 . This review is focused mainly on the retinal vessel diameter measurement algorithms, applications of image processing technique, to provide an overview of the recent advancement in measuring the diameter of the retinal blood vessel. In biomedical engineering, the existing retinal image analysis methods are still dependent on a bulk of human observers. The blood vessel diameter measurement methods are also not fully automated. There is limited published work on automation of blood vessel diameter measurement. For medical diagnosing systems, maximum precision is a must for detecting the diseases as it is one of the most sensitive issues for proper diagnosing. This review is a prestep of our future work of shaping a novel, automated, and computeraided algorithm to measure the diameter of the retinal blood vessel with maximum accuracy. In the following sections of this paper, we briefly discussed the abnormalities of retinal microvascular features, responsible for stroke and the circumstantial scenario of the existing methods for analyzing these abnormalities. Here we emphasized to manifest especially the retinal blood vessel diameter measurement techniques as it is one of the most important markers of prevalent and incident stroke. The basic principle of digital image processing and a general digital image processing procedure for extracting the features of the retinal image containing image acquisition, grey-scale image, image enhancement, restoration, segmentation, registration and vessel extraction subsection are also described in this paper in a cabalistic manner. The arising challenges of present retinal image processing techniques for measuring the blood vessel diameter and the future scopes of this field are also explained in this paper.