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      Automated detection of a nonperfusion area caused by retinal vein occlusion in optical coherence tomography angiography images using deep learning

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          Abstract

          We aimed to assess the ability of deep learning (DL) and support vector machine (SVM) to detect a nonperfusion area (NPA) caused by retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA) images. The study included 322 OCTA images (normal: 148; NPA owing to RVO: 174 [128 branch RVO images and 46 central RVO images]). Training to construct the DL model using deep convolutional neural network (DNN) algorithms was provided using OCTA images. The SVM used a scikit-learn library with a radial basis function kernel. The area under the curve (AUC), sensitivity and specificity for detecting an NPA were examined. We compared the diagnostic ability (sensitivity, specificity and average required time) between the DNN, SVM and seven ophthalmologists. Heat maps were generated. With regard to the DNN, the mean AUC, sensitivity, specificity and average required time for distinguishing RVO OCTA images with an NPA from normal OCTA images were 0.986, 93.7%, 97.3% and 176.9 s, respectively. With regard to SVM, the mean AUC, sensitivity, and specificity were 0.880, 79.3%, and 81.1%, respectively. With regard to the seven ophthalmologists, the mean AUC, sensitivity, specificity and average required time were 0.962, 90.8%, 89.2%, and 700.6 s, respectively. The DNN focused on the foveal avascular zone and NPA in heat maps. The performance of the DNN was significantly better than that of SVM in all parameters (p < 0.01, all) and that of the ophthalmologists in AUC and specificity ( p < 0.01, all). The combination of DL and OCTA images had high accuracy for the detection of an NPA, and it might be useful in clinical practice and retinal screening.

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          The meaning and use of the area under a receiver operating characteristic (ROC) curve.

          A representation and interpretation of the area under a receiver operating characteristic (ROC) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed ROC curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.
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            Split-spectrum amplitude-decorrelation angiography with optical coherence tomography

            Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.
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              Understanding diagnostic tests 3: Receiver operating characteristic curves.

              The results of many clinical tests are quantitative and are provided on a continuous scale. To help decide the presence or absence of disease, a cut-off point for 'normal' or 'abnormal' is chosen. The sensitivity and specificity of a test vary according to the level that is chosen as the cut-off point. The receiver operating characteristic (ROC) curve, a graphical technique for describing and comparing the accuracy of diagnostic tests, is obtained by plotting the sensitivity of a test on the y axis against 1-specificity on the x axis. Two methods commonly used to establish the optimal cut-off point include the point on the ROC curve closest to (0, 1) and the Youden index. The area under the ROC curve provides a measure of the overall performance of a diagnostic test. In this paper, the author explains how the ROC curve can be used to select optimal cut-off points for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of tests. The ROC curve is obtained by calculating the sensitivity and specificity of a test at every possible cut-off point, and plotting sensitivity against 1-specificity. The curve may be used to select optimal cut-off values for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of different tests.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: Supervision
                Role: MethodologyRole: Validation
                Role: Data curation
                Role: Resources
                Role: Data curation
                Role: Data curation
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 November 2019
                2019
                : 14
                : 11
                : e0223965
                Affiliations
                [1 ] Department of Ophthalmology, Tsukazaki Hospital, Himeji, Japan
                [2 ] Rist Incorporated, Tokyo, Japan
                [3 ] Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
                Newcastle University, UNITED KINGDOM
                Author notes

                Competing Interests: The funder, Rist Incorporated, provided support in the form of salary for author HE. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

                Author information
                http://orcid.org/0000-0003-3956-9352
                Article
                PONE-D-19-11408
                10.1371/journal.pone.0223965
                6837754
                31697697
                1dcd2784-7f64-42a6-8ad5-039433d5671c
                © 2019 Nagasato et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 April 2019
                : 2 October 2019
                Page count
                Figures: 5, Tables: 2, Pages: 14
                Funding
                The funder, Rist Incorporated, provided support in the form of salary for author HE, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Support Vector Machines
                Biology and Life Sciences
                Anatomy
                Head
                Eyes
                Medicine and Health Sciences
                Anatomy
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                Eyes
                Biology and Life Sciences
                Anatomy
                Ocular System
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                Diagnostic Medicine
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                Cardiovascular Imaging
                Angiography
                Research and Analysis Methods
                Imaging Techniques
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                Imaging Techniques
                Diagnostic Radiology
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                Radiology and Imaging
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                Ophthalmology
                Retinal Disorders
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                All relevant data are within the manuscript and its Supporting Information files.

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