{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T12:30:17Z","timestamp":1763728217394,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Federal Ministry for Economic Affairs and Engery","doi-asserted-by":"publisher","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NeuroCure Clinical Research Center (NCRC)","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}]},{"name":"German Federal Ministry for Education and Research","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}]},{"DOI":"10.13039\/501100006360","name":"German Federal Ministry for Economic Affairs and Climate Action","doi-asserted-by":"publisher","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}],"id":[{"id":"10.13039\/501100006360","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH R01","doi-asserted-by":"publisher","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Open Access Publication Fund of Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}]},{"name":"German Research Foundation (DFG)","award":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"],"award-info":[{"award-number":["03EFEBE079","BD_03EUEBE079","EXC-2049\u2013390688087","BMBF 13N15432","ZF4741901CR9","EY027929"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Imaging"],"abstract":"<jats:p>Reliable biomarkers quantifying neurodegeneration and neuroinflammation in central nervous system disorders such as Multiple Sclerosis, Alzheimer\u2019s dementia or Parkinson\u2019s disease are an unmet clinical need. Intraretinal layer thicknesses on macular optical coherence tomography (OCT) images are promising noninvasive biomarkers querying neuroretinal structures with near cellular resolution. However, changes are typically subtle, while tissue gradients can be weak, making intraretinal segmentation a challenging task. A robust and efficient method that requires no or minimal manual correction is an unmet need to foster reliable and reproducible research as well as clinical application. Here, we propose and validate a cascaded two-stage network for intraretinal layer segmentation, with both networks being compressed versions of U-Net (CCU-INSEG). The first network is responsible for retinal tissue segmentation from OCT B-scans. The second network segments eight intraretinal layers with high fidelity. At the post-processing stage, we introduce Laplacian-based outlier detection with layer surface hole filling by adaptive non-linear interpolation. Additionally, we propose a weighted version of focal loss to minimize the foreground\u2013background pixel imbalance in the training data. We train our method using 17,458 B-scans from patients with autoimmune optic neuropathies, i.e., multiple sclerosis, and healthy controls. Voxel-wise comparison against manual segmentation produces a mean absolute error of 2.3 \u03bcm, outperforming current state-of-the-art methods on the same data set. Voxel-wise comparison against external glaucoma data leads to a mean absolute error of 2.6 \u03bcm when using the same gold standard segmentation approach, and 3.7 \u03bcm mean absolute error in an externally segmented data set. In scans from patients with severe optic atrophy, 3.5% of B-scan segmentation results were rejected by an experienced grader, whereas this was the case in 41.4% of B-scans segmented with a graph-based reference method. The validation results suggest that the proposed method can robustly segment macular scans from eyes with even severe neuroretinal changes.<\/jats:p>","DOI":"10.3390\/jimaging8050139","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T08:34:29Z","timestamp":1652776469000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Intraretinal Layer Segmentation Using Cascaded Compressed U-Nets"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-8442","authenticated-orcid":false,"given":"Sunil Kumar","family":"Yadav","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"},{"name":"Nocturne GmbH, 10119 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-9476","authenticated-orcid":false,"given":"Rahele","family":"Kafieh","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"}]},{"given":"Hanna Gwendolyn","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-9027","authenticated-orcid":false,"given":"Josef","family":"Kauer-Bonin","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"},{"name":"Nocturne GmbH, 10119 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-8904","authenticated-orcid":false,"given":"Kouros","family":"Nouri-Mahdavi","sequence":"additional","affiliation":[{"name":"Glaucoma Division, Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA"}]},{"given":"Vahid","family":"Mohammadzadeh","sequence":"additional","affiliation":[{"name":"Glaucoma Division, Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA"}]},{"given":"Lynn","family":"Shi","sequence":"additional","affiliation":[{"name":"Glaucoma Division, Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA"}]},{"given":"Ella Maria","family":"Kadas","sequence":"additional","affiliation":[{"name":"Nocturne GmbH, 10119 Berlin, Germany"}]},{"given":"Friedemann","family":"Paul","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"},{"name":"Department of Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10098 Berlin, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-5387","authenticated-orcid":false,"given":"Seyedamirhosein","family":"Motamedi","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"}]},{"given":"Alexander Ulrich","family":"Brandt","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Max Delbr\u00fcck Center for Molecular Medicine and Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 13125 Berlin, Germany"},{"name":"Department of Neurology, University of California Irvine, Irvine, CA 92697, USA"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1126\/science.1957169","article-title":"Optical coherence 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