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      OCT-Derived Radiomic Features Predict Anti–VEGF Response and Durability in Neovascular Age-Related Macular Degeneration

      research-article
      , PhD 1 , 2 , , MD 1 , , BA 1 , , BA 1 , , PharmD 3 , , PhD 3 , , MD 1 , 4 , , PhD 2 , 5 , , , MD 1 , 4 , ,
      Ophthalmology Science
      Elsevier
      OCT, Radiomics, Wet age-related macular degeneration, AMD, age-related macular degeneration, AUC, area under the receiver operating characteristic curve, AUC-PRC, area under the precision recall curve, IAI, intravitreal aflibercept injection, ILM, internal limiting membrane, IRF, intraretinal fluid, ML, machine learning, mRmR, minimum redundancy maximum relevance, nAMD, neovascular age-related macular degeneration, QDA, quadratic discriminant analysis, RFI, retinal fluid index, RPE, retinal pigment epithelium, SHRM, subretinal hyperreflective material, SRF, subretinal fluid, SRFI, subretinal fluid index, 3D, 3-dimensional, TRFI, total retinal fluid index

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          Abstract

          Purpose

          No established biomarkers currently exist for therapeutic efficacy and durability of anti–VEGF therapy in neovascular age-related macular degeneration (nAMD). This study evaluated radiomic-based quantitative OCT biomarkers that may be predictive of anti-VEGF treatment response and durability.

          Design

          Assessment of baseline biomarkers using machine learning (ML) classifiers to predict tolerance to anti-VEGF therapy.

          Participants

          Eighty-one participants with treatment-naïve nAMD from the OSPREY study, including 15 super responders (patients who achieved and maintained retinal fluid resolution) and 66 non–super responders (patients who did not achieve or maintain retinal fluid resolution).

          Methods

          A total of 962 texture-based radiomic features were extracted from fluid, subretinal hyperreflective material (SHRM), and different retinal tissue compartments of OCT scans. The top 8 features, chosen by the minimum redundancy maximum relevance feature selection method, were evaluated using 4 ML classifiers in a cross-validated approach to distinguish between the 2 patient groups. Longitudinal assessment of changes in different texture-based radiomic descriptors (delta-texture features) between baseline and month 3 also was performed to evaluate their association with treatment response. Additionally, 8 baseline clinical parameters and a combination of baseline OCT, delta-texture features, and the clinical parameters were evaluated in a cross-validated approach in terms of association with therapeutic response.

          Main Outcome Measures

          The cross-validated area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to validate the classifier performance.

          Results

          The cross-validated AUC by the quadratic discriminant analysis classifier was 0.75 ± 0.09 using texture-based baseline OCT features. The delta-texture features within different OCT compartments between baseline and month 3 yielded an AUC of 0.78 ± 0.08. The baseline clinical parameters sub–retinal pigment epithelium volume and intraretinal fluid volume yielded an AUC of 0.62 ± 0.07. When all the baseline, delta, and clinical features were combined, a statistically significant improvement in the classifier performance (AUC, 0.81 ± 0.07) was obtained.

          Conclusions

          Radiomic-based quantitative assessment of OCT images was shown to distinguish between super responders and non–super responders to anti-VEGF therapy in nAMD. The baseline fluid and SHRM delta-texture features were found to be most discriminating across groups.

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          Most cited references44

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            The Image Biomarker Standardization Initiative: Standardized Quantitative Radiomics for High-Throughput Image-based Phenotyping

            Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features. Results Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI). Conclusion A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuhl and Truhn in this issue.
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              Radiomics: the process and the challenges.

              "Radiomics" refers to the extraction and analysis of large amounts of advanced quantitative imaging features with high throughput from medical images obtained with computed tomography, positron emission tomography or magnetic resonance imaging. Importantly, these data are designed to be extracted from standard-of-care images, leading to a very large potential subject pool. Radiomics data are in a mineable form that can be used to build descriptive and predictive models relating image features to phenotypes or gene-protein signatures. The core hypothesis of radiomics is that these models, which can include biological or medical data, can provide valuable diagnostic, prognostic or predictive information. The radiomics enterprise can be divided into distinct processes, each with its own challenges that need to be overcome: (a) image acquisition and reconstruction, (b) image segmentation and rendering, (c) feature extraction and feature qualification and (d) databases and data sharing for eventual (e) ad hoc informatics analyses. Each of these individual processes poses unique challenges. For example, optimum protocols for image acquisition and reconstruction have to be identified and harmonized. Also, segmentations have to be robust and involve minimal operator input. Features have to be generated that robustly reflect the complexity of the individual volumes, but cannot be overly complex or redundant. Furthermore, informatics databases that allow incorporation of image features and image annotations, along with medical and genetic data, have to be generated. Finally, the statistical approaches to analyze these data have to be optimized, as radiomics is not a mature field of study. Each of these processes will be discussed in turn, as well as some of their unique challenges and proposed approaches to solve them. The focus of this article will be on images of non-small-cell lung cancer. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Ophthalmol Sci
                Ophthalmol Sci
                Ophthalmology Science
                Elsevier
                2666-9145
                18 May 2022
                December 2022
                18 May 2022
                : 2
                : 4
                : 100171
                Affiliations
                [1 ]The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
                [2 ]Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio
                [3 ]Novartis Pharmaceuticals, East Hanover, New Jersey
                [4 ]Vitreoretinal Service, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
                [5 ]Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, Ohio
                Author notes
                []Correspondence: Justis P. Ehlers, MD, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk i32, Cleveland, OH 44195. ehlersj@ 123456ccf.org
                [∗]

                Both authors contributed equally as senior authors.

                Article
                S2666-9145(22)00060-4 100171
                10.1016/j.xops.2022.100171
                9754979
                36531588
                2fb64045-ce49-4299-afa9-61d32f953f44
                © 2022 by the American Academy of Ophthalmology.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 January 2022
                : 15 April 2022
                : 12 May 2022
                Categories
                Original Articles

                oct,radiomics,wet age-related macular degeneration,amd, age-related macular degeneration,auc, area under the receiver operating characteristic curve,auc-prc, area under the precision recall curve,iai, intravitreal aflibercept injection,ilm, internal limiting membrane,irf, intraretinal fluid,ml, machine learning,mrmr, minimum redundancy maximum relevance,namd, neovascular age-related macular degeneration,qda, quadratic discriminant analysis,rfi, retinal fluid index,rpe, retinal pigment epithelium,shrm, subretinal hyperreflective material,srf, subretinal fluid,srfi, subretinal fluid index,3d, 3-dimensional,trfi, total retinal fluid index

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