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However, the scale and complexity of volumetric datasets make exhaustive manual review impractical, motivating AI-assisted triage methods to select a small number of high-risk 2D slices for pathologist review. While prior triage models have shown promise, interpretability is poor and performance can be suboptimal, especially in the nascent field of 3D pathology in which labeled data is limited. We present SCOPE, a\n                  <jats:italic>S<\/jats:italic>\n                  egmentation-guided\n                  <jats:italic>C<\/jats:italic>\n                  r\n                  <jats:italic>O<\/jats:italic>\n                  ss-slice\n                  <jats:italic>P<\/jats:italic>\n                  rototyp\n                  <jats:italic>E<\/jats:italic>\n                  learning framework for comprehensive risk assessment of 2D levels within 3D pathology datasets. SCOPE combines (i) clustering-based pretraining on large-scale unlabeled volumetric data to initialize morphology-aware prototypes, (ii) segmentation-derived structural priors from publicly available models to guide proto-type learning, and (iii) cross-slice (2.5D) prototype aggregation across neighboring slices to generate slice-level risk predictions. In prostate and esophageal data cohorts, SCOPE consistently outperforms attention-based and prototype-based multiple instance learning baselines for both binary and multiclass prediction tasks, enabling depth-resolved risk profiling for 3D triage based on morphological prototypes that are interpretable to pathologists.\n                <\/jats:p>","DOI":"10.64898\/2026.07.09.737559","type":"posted-content","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T21:55:15Z","timestamp":1784152515000},"source":"Crossref","is-referenced-by-count":0,"title":["Prototype-based AI triage for 3D pathology"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-199X","authenticated-orcid":false,"given":"Renao","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA, USA"},{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Institute for Data Science in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"},{"name":"Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Ching","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"},{"name":"Department of Bioengineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"},{"name":"Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Almagro-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"},{"name":"Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA, USA"},{"name":"Data Science Program, Dana-Farber Cancer Institute, Boston, MA, USA"},{"name":"Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brenes","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah S.L.","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA, USA"},{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepti M.","family":"Reddi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence D.","family":"True","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priti","family":"Lal","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anant","family":"Madabhushi","sequence":"additional","affiliation":[{"name":"Wallace H. 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