Machine learning for cryosection pathology predicts the 2021 WHO classification of glioma
Open accessAbstract
Background Timely and accurate intraoperative cryosection evaluations remain the gold standard for guiding surgical treatments for gliomas. However, the tissue-freezing process often generates artifacts that make histologic interpretation difficult. In addition, the 2021 WHO Classification of Tumors of the Central Nervous System incorporates molecular profiles in the diagnostic categories, so standard visual evaluation of cryosections alone cannot completely inform diagnoses based on the new classification system.Methods To address these challenges, we develop the context-aware Cryosection Histopathology Assessment and Review Machine (CHARM) using samples from 1,524 glioma patients from three different patient populations to systematically analyze cryosection slides.Findings Our CHARM models successfully identified malignant cells (AUROC = 0.98 ± 0.01 in the independent validation cohort), distinguished isocitrate dehydrogenase (IDH)-mutant tumors from wild type (AUROC = 0.79-0.82), classified three major types of molecularly defined gliomas (AUROC = 0.88-0.93), and identified the most prevalent subtypes of IDH-mutant tumors (AUROC = 0.89-0.97). CHARM further predicts clinically important genetic alterations in low-grade glioma, including ATRX, TP53, and CIC mutations, CDKN2A/B homozygous deletion, and 1p/19q codeletion via cryosection images.Conclusions Our approaches accommodate the evolving diagnostic criteria informed by molecular studies, provide real-time clinical decision support, and will democratize accurate cryosection diagnoses.Funding Supported in part by the National Institute of General Medical Sciences grant R35GM142879, the Google Research Scholar Award, the Blavatnik Center for Computational Biomedicine Award, the Partners' Innovation Discovery Grant, and the Schlager Family Award for Early Stage Digital Health Innovations.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several studies have shown potential for AI to facilitate intraoperative cancer diagnosis using label-free and cryosectioned tissue samples.
“several studies have demonstrated the potential of using AI to facilitate intraoperative diagnosis (e.g., during surgical resection) using label-free (40,41) and cryosectioned (42,43) tissue samples.”
From Artificial Intelligence in Oncology: Current Landscape, Challenges, and Future Directions (2024) · cites this paper as [42]
Cites
Swin Transformer: Hierarchical Vision Transformer using Shifted Windows
Liu, Z., Lin, Y., Cao, Y., Hu, H., Wei, Y., Zhang, Z., Lin, S., & Guo, B. (2021) · 2021 IEEE/CVF International Conference on Computer Vision (ICCV) · doi:10.1109/iccv48922.2021.00986 · Cited by 35,534 · see citing works
An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale
Dosovitskiy, A., Beyer, L., Kolesnikov, A., Weissenborn, D., Zhai, X., Unterthiner, T., Dehghani, M., Minderer, M., Heigold, G., Gelly, S., et al. (2020) · arXiv · doi:10.48550/arxiv.2010.11929 · Cited by 21,793 · see citing works
The 2021 WHO classification of tumors of the central nervous system: a summary
Louis, D. N., Perry, A., Wesseling, P., Brat, D. J., Cree, I. A., Figarella-Branger, D., Hawkins, C., Ng, H. K., Pfister, S. M., Reifenberger, G., et al. (2021) · Neuro-Oncology · doi:10.1093/neuonc/noab106 · Cited by 12,273 · see citing works
UMAP: Uniform Manifold Approximation and Projection
McInnes, L., Healy, J., Saul, N., & Großberger, L. (2018) · Journal of Open Source Software · doi:10.21105/joss.00861 · Cited by 9,826 · see citing works
Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas
The Cancer Genome Atlas Research Network (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1402121 · Cited by 3,148 · see citing works
Artificial intelligence in healthcare
Yu, K.-H., Beam, A. L., & Kohane, I. S. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0305-z · Cited by 2,817 · see citing works
Self-citationClinical-grade computational pathology using weakly supervised deep learning on whole slide images
Campanella, G., Hanna, M. G., Geneslaw, L., Miraflor, A., Werneck Krauss Silva, V., Busam, K. J., Brogi, E., Reuter, V. E., Klimstra, D. S., & Fuchs, T. J. (2019) · Nature Medicine · doi:10.1038/s41591-019-0508-1 · Cited by 2,799 · see citing works
Data-efficient and weakly supervised computational pathology on whole-slide images
Lu, M. Y., Williamson, D. F. K., Chen, T. Y., Chen, R. J., Barbieri, M., & Mahmood, F. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00682-w · Cited by 2,282 · see citing works
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers
Goodman, A. M., Kato, S., Bazhenova, L., Patel, S. P., Frampton, G. M., Miller, V., Stephens, P. J., Daniels, G. A., & Kurzrock, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0386 · Cited by 2,264 · see citing works
EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood
Weller, M., van den Bent, M., Preusser, M., Le Rhun, E., Tonn, J. C., Minniti, G., Bendszus, M., Balana, C., Chinot, O., Dirven, L., et al. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00447-z · Cited by 2,048 · see citing works
Modern Information Retrieval : A Brief Overview
Singhal, A. (2001) · Cited by 1,520 · see citing works
Kather, J. N., Pearson, A. T., Halama, N., Jäger, D., Krause, J., Loosen, S. H., Marx, A., Boor, P., Tacke, F., Neumann, U. P., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0462-y · Cited by 1,458 · see citing works
GLIOMA EXTENT OF RESECTION AND ITS IMPACT ON PATIENT OUTCOME
Sanai, N., & Berger, M. S. (2008) · Neurosurgery · doi:10.1227/01.neu.0000318159.21731.cf · Cited by 1,323 · see citing works
Yu, K.-H., Zhang, C., Berry, G. J., Altman, R. B., Ré, C., Rubin, D. L., & Snyder, M. (2016) · Nature Communications · doi:10.1038/ncomms12474 · Cited by 972 · see citing works
Self-citationIDH mutation in glioma: molecular mechanisms and potential therapeutic targets
Han, S., Liu, Y., Cai, S. J., Qian, M., Ding, J., Larion, M., Gilbert, M. R., & Yang, C. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0814-x · Cited by 661 · see citing works
Pan-cancer image-based detection of clinically actionable genetic alterations
Kather, J. N., Heij, L. R., Grabsch, H. I., Loeffler, C. M. L., Echle, A., Muti, H. S., Krause, J., Niehues, J., Sommer, K. A. J., Bankhead, P., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0087-6 · Cited by 660 · see citing works
Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis
Fu, Y., Jung, A. W., Viñas, R., González, S., Vöhringer, H. S., Shmatko, A., Yates, L. R., Jimenez‐Liñan, M., Moore, L., & Gerstung, M. (2020) · Nature Cancer · doi:10.1038/s43018-020-0085-8 · Cited by 636 · see citing works
Molinaro, A. M., Hervey‐Jumper, S. L., Morshed, R. A., Young, J. S., Han, S. J., Chunduru, P., Zhang, Y., Phillips, J. J., Shai, A., Lafontaine, M., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2019.6143 · Cited by 634 · see citing works
Oncolytic Viruses in Cancer Treatment
Lawler, S. E., Speranza, M. C., Cho, C., & Chiocca, E. A. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.2064 · Cited by 602 · see citing works
Artificial intelligence and machine learning in clinical development: a translational perspective
Shah, P. P., Kendall, F., Khozin, S., Goosen, R., Hu, J., Laramie, J. M., Ringel, M. S., & Schork, N. J. (2019) · npj Digital Medicine · doi:10.1038/s41746-019-0148-3 · Cited by 498 · see citing works
Incidence of gliomas by anatomic location
Larjavaara, S., Mäntylä, R., Salminen, T. M., et al. (2007) · Neuro-Oncology · doi:10.1215/15228517-2007-016 · Cited by 398 · see citing works
Wiestler, B., Capper, D., Holland-Letz, T., Korshunov, A., von Deimling, A., Pfister, S. M., Platten, M., Weller, M., & Wick, W. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1156-z · Cited by 346 · see citing works
Pekmezci, M., Rice, T., Molinaro, A. M., Walsh, K. M., Decker, P. A., Hansen, H., Sicotte, H., Kollmeyer, T. M., McCoy, L. S., Sarkar, G., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1690-1 · Cited by 319 · see citing works
EGFR heterogeneity and implications for therapeutic intervention in glioblastoma
Eskilsson, E., Røsland, G. V., Solecki, G. M., Wang, Q., Harter, P. N., Graziani, G., Verhaak, R. G. W., Winkler, F., Bjerkvig, R., & Miletić, H. (2017) · Neuro-Oncology · doi:10.1093/neuonc/nox191 · Cited by 308 · see citing works
Appay, R., Dehais, C., Maurage, C., Alentorn, A., Carpentier, C., Colin, C., Ducray, F., Escande, F., Idbaïh, A., Kamoun, A., et al. (2019) · Neuro-Oncology · doi:10.1093/neuonc/noz124 · Cited by 275 · see citing works
Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery
Santagata, S., Eberlin, L. S., Norton, I. H., Calligaris, D., Feldman, D. R., Ide, J. L., Liu, X., Wiley, J. S., Vestal, M. L., Ramkissoon, S. H., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404724111 · Cited by 259 · see citing works
Self-citationErtosun, M. G., & Rubin, D. L. (2015) · PubMed · Cited by 255 · see citing works
Choi, Y. S., Bae, S., Chang, J. H., Kang, S., Kim, S. H., Kim, J., Rim, T. H., Choi, S. H., Jain, R., & Lee, S. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa177 · Cited by 255 · see citing works
Naik, N., Madani, A., Esteva, A., Keskar, N. S., Press, M. F., Ruderman, D., Agus, D. B., & Socher, R. (2020) · Nature Communications · doi:10.1038/s41467-020-19334-3 · Cited by 253 · see citing works
Noorbakhsh, J., Farahmand, S., Foroughi pour, A., Namburi, S., Caruana, D., Rimm, D., Soltanieh-ha, M., Zarringhalam, K., & Chuang, J. H. (2020) · Nature Communications · doi:10.1038/s41467-020-20030-5 · Cited by 206 · see citing works
Hollon, T. C., Jiang, C., Chowdury, A., Nasir-Moin, M., Kondepudi, A., Aabedi, A. A., Adapa, A. R., Al‐Holou, W. N., Heth, J., Sagher, O., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02252-4 · Cited by 192 · see citing works
Hervey‐Jumper, S. L., Zhang, Y., Phillips, J. J., Morshed, R. A., Young, J. S., Mccoy, L. S., Lafontaine, M., Luks, T. L., Ammanuel, S. G., Kakaizada, S., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.21.02929 · Cited by 188 · see citing works
Laleh, N. G., Muti, H. S., Loeffler, C. M. L., Echle, A., Saldanha, O. L., Mahmood, F., Lu, M. Y., Trautwein, C., Langer, R., Dislich, B., et al. (2022) · Medical Image Analysis · doi:10.1016/j.media.2022.102474 · Cited by 186 · see citing works
TransPath: Transformer-Based Self-supervised Learning for Histopathological Image Classification
Wang, X., Yang, S., Zhang, J., Wang, M., Zhang, J., Huang, J., Yang, W., & Han, X. (2021) · Lecture Notes in Computer Science · doi:10.1007/978-3-030-87237-3_18 · Cited by 178 · see citing works
Lu, V. M., O’Connor, K. P., Shah, A. H., Eichberg, D. G., Luther, E., Komotar, R. J., & Ivan, M. E. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03528-2 · Cited by 142 · see citing works
Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients
Tsai, P.-C., Lee, T.-H., Kuo, K.-C., Su, F.-Y., Lee, T.-L. M., Marostica, E., Ugai, T., Zhao, M., Lau, M. C., Väyrynen, J. P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37179-4 · Cited by 136 · see citing works
Self-citationAppay, R., Dehais, C., Colin, C., Alentorn, A., Carpentier, C., Ducray, F., Ibdaih, A., Kamoun, A., Mokhtari, K., Tabouret, E., et al. (2019) · Neuro-Oncology · doi:10.1093/neuonc/noz126.000 · Cited by 126 · see citing works
Jin, L., Shi, F., Chun, Q., Chen, H., Ma, Y., Wu, S., Hameed, N. U. F., Mei, C., Lu, J., Zhang, J., et al. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa163 · Cited by 125 · see citing works
Yu, K., Wang, F., Berry, G. J., Ré, C., Altman, R. B., Snyder, M. P., & Kohane, I. S. (2020) · Journal of the American Medical Informatics Association · doi:10.1093/jamia/ocz230 · Cited by 123 · see citing works
Self-citationAssociation of Omics Features with Histopathology Patterns in Lung Adenocarcinoma
Yu, K., Berry, G. J., Rubin, D. L., Ré, C., Altman, R. B., & Snyder, M. P. (2017) · Cell Systems · doi:10.1016/j.cels.2017.10.014 · Cited by 119 · see citing works
Self-citationHan, W., Qin, L., Bay, C. P., Chen, X., Yu, K., Miskin, N. P., Li, A., Xu, X., & Young, G. S. (2019) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6365 · Cited by 112 · see citing works
Self-citationRapid Intraoperative Molecular Characterization of Glioma
Shankar, G. M., Francis, J. M., Rinne, M. L., Ramkissoon, S. H., Huang, F. W., Venteicher, A. S., Akama‐Garren, E. H., Kang, Y. J., Lelic, N., Kim, J. C., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.0917 · Cited by 88 · see citing works
Self-citationMarostica, E., Barber, R., Denize, T., Kohane, I. S., Signoretti, S., Golden, J. A., & Yu, K. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4119 · Cited by 82 · see citing works
Self-citationYu, K., Hu, V. J., Wang, F., Matulonis, U. A., Mutter, G. L., Golden, J. A., & Kohane, I. S. (2020) · BMC Medicine · doi:10.1186/s12916-020-01684-w · Cited by 71 · see citing works
Self-citationPei, L., Jones, K. A., Shboul, Z. A., Chen, J. Y., & Iftekharuddin, K. M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.668694 · Cited by 64 · see citing works
Recent Advances on the Molecular Pathology of Glial Neoplasms in Children and Adults
Rodríguez, F. J., Vizcaíno, M. A., & Lin, M. (2016) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.05.005 · Cited by 50 · see citing works
Integrative multiomics-histopathology analysis for breast cancer classification
Ektefaie, Y., Yuan, W., Dillon, D. A. R., Lin, N., Golden, J. A., Kohane, I. S., & Yu, K. (2021) · npj Breast Cancer · doi:10.1038/s41523-021-00357-y · Cited by 50 · see citing works
Self-citationThe Misclassification of Diffuse Gliomas: Rates and Outcomes
Iorgulescu, J. B., Torre, M., Harary, M., Smith, T. R., Aizer, A. A., Reardon, D. A., Barnholtz‐Sloan, J. S., & Perry, A. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3101 · Cited by 49 · see citing works
Diagnostic Accuracy of Cytology Smear and Frozen Section in Glioma
Zin, A. A. M., & Zulkarnain, S. (2019) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2019.20.2.321 · Cited by 44 · see citing works
Truong, A. H., Sharmanska, V., Limbӓck-Stanic, C., & Grech‐Sollars, M. (2020) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaa110 · Cited by 39 · see citing works
Classification of brain tumor isocitrate dehydrogenase status using MRI and deep learning
Nalawade, S. S., Murugesan, G. K., Vejdani‐Jahromi, M., Fisicaro, R. A., Yogananda, C. G. B., Wagner, B. C., Mickey, B., Maher, E. A., Pinho, M. C., Fei, B., et al. (2019) · Journal of medical imaging · doi:10.1117/1.jmi.6.4.046003 · Cited by 34 · see citing works
Automated histologic diagnosis of CNS tumors with machine learning
Khalsa, S. S. S., Hollon, T. C., Adapa, A. R., Urias, E., Srinivasan, S., Jairath, N. K., Szczepanski, J. M., Ouillette, P. D., Camelo-Piragua, S. I., & Orringer, D. A. (2020) · CNS Oncology · doi:10.2217/cns-2020-0003 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Towards a general-purpose foundation model for computational pathology
Chen, R. J., Ding, T., Lu, M. Y., Williamson, D. F. K., Jaume, G., Song, A. H., Chen, B., Zhang, A., Shao, D., Shaban, M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02857-3 · Cited by 1,560 · see citing works
A pathology foundation model for cancer diagnosis and prognosis prediction
Wang, X., Zhao, J., Marostica, E., Yuan, W., Jin, J., Zhang, J., Li, R., Tang, H., Wang, K., Li, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07894-z · Cited by 580 · see citing works
Self-citationArtificial Intelligence in Oncology: Current Landscape, Challenges, and Future Directions
Lotter, W., Hassett, M. J., Schultz, N., Kehl, K. L., Van Allen, E. M., & Cerami, E. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1199 · Cited by 196 · see citing works
Medical Artificial Intelligence and Human Values
Yu, K.-H., Healey, E., Leong, T.-Y., Kohane, I. S., & Manrai, A. K. (2024) · New England Journal of Medicine · doi:10.1056/nejmra2214183 · Cited by 149 · see citing works
Self-citation
- Authors
- Nasrallah, M. P., Zhao, J., Tsai, C. C., Meredith, D., Marostica, E., Ligon, K. L., Golden, J. A., & Yu, K.-H.
- Affiliations
- University of Pennsylvania (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Dana-Farber Cancer Institute (US)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Yu, Kun-Hsing
- ORCID
- Venue
- Med
- Publisher
- Elsevier BV
- Published
- 2023-08
- Volume
- 4
- Issue
- 8
- Pages
- 526-540.e4
- ISSN
- 2666-6340 (ISSN-L)
- PMC
- PMC10527821
- OpenAlex
- W4383533409
- Cited by
- 67
- References
- 52
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 18 · 2023: 1
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 376 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Med (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Mass General Brigham Inc
- NIGMS
- Brigham and Women's Hospital
- Harvard Medical School
- Google LLC
- Topics
- Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
- Keywords
- glioma, IDH mutation, glioma molecular classification, ATRX mutation, TP53 mutation, CIC mutation, CDKN2A/B homozygous deletion, 1p/19q codeletion, low-grade glioma, histopathology image analysis, clinical decision support
- MeSH terms
- Machine Learning, Brain Neoplasms, Glioma, Homozygote, Humans, World Health Organization, Sequence Deletion
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review