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Pediatric brain tumor classification using digital pathology and deep learning: Evaluation of SOTA methods on a multi-center Swedish cohort
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0002-7582-1706
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.ORCID iD: 0000-0001-8921-431X
Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.ORCID iD: 0009-0001-8127-0867
Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0002-8857-5698
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2026 (English)In: Brain Pathology, ISSN 1015-6305, Vol. 36, no 1, article id e70029Article in journal (Refereed) Published
Abstract [en]

Brain tumors are the most common solid tumors in children and young adults, but the scarcity of large histopathology datasets has limited the application of computational pathology in this group. This study implements two weakly supervised multiple-instance learning (MIL) approaches on patch features obtained from state-of-the-art histology-specific foundation models to classify pediatric brain tumors in hematoxylin and eosin whole slide images (WSIs) from a multi-center Swedish cohort. WSIs from 540 subjects (age 8.5 ± 4.9 years) diagnosed with brain tumors were gathered from the six Swedish university hospitals. Instance (patch)-level features were obtained from WSIs using three pre-trained feature extractors: ResNet50, UNI, and CONCH. Instances were aggregated using attention-based MIL (ABMIL) or clustering-constrained attention MIL (CLAM) for patient-level classification. Models were evaluated on three classification tasks based on the hierarchical classification of pediatric brain tumors: tumor category, family, and type. Model generalization was assessed by training on data from two of the centers and testing on data from four other centers. Model interpretability was evaluated through attention mapping. The highest classification performance was achieved using UNI features and ABMIL aggregation, with Matthew's correlation coefficient of 0.76 ± 0.04, 0.63 ± 0.04, and 0.60 ± 0.05 for tumor category, family, and type classification, respectively. When evaluating generalization, models utilizing UNI and CONCH features outperformed those using ResNet50. However, the drop in performance from the in-site to out-of-site testing was similar across feature extractors. These results show the potential of state-of-the-art computational pathology methods in diagnosing pediatric brain tumors at different hierarchical levels with fair generalizability on a multi-center national dataset.

Place, publisher, year, edition, pages
John Wiley & Sons, 2026. Vol. 36, no 1, article id e70029
Keywords [en]
Deep learning, artificial intelligence, Cancer, Pediatric brain tumor, digital pathology
National Category
Medical Imaging Cancer and Oncology Pediatrics
Identifiers
URN: urn:nbn:se:liu:diva-208705DOI: 10.1111/bpa.70029ISI: 001519965600001PubMedID: 40589103Scopus ID: 2-s2.0-105009437454OAI: oai:DiVA.org:liu-208705DiVA, id: diva2:1907021
Funder
Swedish Childhood Cancer Foundation, MT2021-0011, MT2022-0013Linköpings universitet, Cocozza 2022Linköpings universitet, Cancer Strength AreaVinnova, AIDA (2022-2222)Region Östergötland, ALF, 974566Wallenberg Foundations, Wallenberg Center for Molecular Medicine
Note

Funding Agencies|Linkoeping University's Cancer Strength Area; ALF Grants, Region Ostergoetland [974566]; Vinnova via Medtech4Health and Analytic Imaging Diagnostics Arena [2222]; Swedish Childhood Cancer Fund [MT2021-0011, MT2022-0013]; Joanna Cocozza's Foundation for Children's Medical Research

Available from: 2024-10-21 Created: 2024-10-21 Last updated: 2025-12-18Bibliographically approved
In thesis
1. Deep learning for medical image analysis in cancer diagnosis
Open this publication in new window or tab >>Deep learning for medical image analysis in cancer diagnosis
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Medical imaging is one of the cornerstones of clinical diagnosis, providing insights into the anatomy and physiology of organs and tissues for screening, initial diagnosis, treatment planning, and follow-up. Utilizing both invasive and non-invasive techniques, medical imaging employs various contrast mechanisms to capture details of the tissue structure and the functionality of biological systems at different spatial and temporal resolutions, and dimensionalities. The ever-growing volume of medical image data driven by screening programs, digitalization, and the push towards precision medicine has highlighted the need for automatic image analysis methods to reduce the workload of healthcare personnel in reviewing these images.

Deep learning (DL), a subset of artificial intelligence (AI), comprises of methods that learn representations from data to perform various predictive tasks. Although DL was introduced in the mid-1960s, it has only been successfully applied for computer vision tasks in the past two decades, becoming the standard method for natural image processing. Additionally, the versatility of DL in processing data from diverse sources (such as speech, text, and climate) has encouraged its application in the medical domain as well.

This thesis explores the application of DL-based methods for medical image analysis, focusing on cancer diagnosis at various treatment planning stages, including preoperative, intraoperative, and postoperative procedures. Methods were developed and applied to three medical imaging modalities: optical coherence tomography (OCT) for intraoperative diagnosis, magnetic resonance imaging (MRI) for pre-operative diagnosis and radiotherapy treatment planning, and histopathology whole-slide images (WSI) for postoperative final diagnosis, addressing tasks such as detection, semantic segmentation, and classification for thyroid diseases and pediatric and adult brain tumors.

In summary, the outcomes of this thesis highlight the potential of deep learning-based methods for medical image analysis in the context of cancer diagnosis. These works demonstrate the versatility of deep learning in processing medical images from various sources and at different spatial resolutions and dimensionalities. Appropriate dataset curation, method validation and interpretation, and translational research are needed to promote the integration of deep learning-powered tools in the clinic.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2024. p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 2408
Keywords
Medical imaging, Cancer diagnosis, Deep learning
National Category
Medical Imaging
Identifiers
urn:nbn:se:liu:diva-208602 (URN)10.3384/9789180757805 (DOI)9789180757799 (ISBN)9789180757805 (ISBN)
Public defence
2024-11-27, Belladonna, Building 511, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2024-10-17 Created: 2024-10-17 Last updated: 2025-02-09Bibliographically approved

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Tampu, Iulian EmilNyman, PerSpyretos, ChristoforosBlystad, IdaLundberg, PeterHaj-Hosseini, Neda

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Tampu, Iulian EmilNyman, PerSpyretos, ChristoforosBlystad, IdaSandgren, JohannaLundberg, PeterHaj-Hosseini, Neda
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Division of Biomedical EngineeringCenter for Medical Image Science and Visualization (CMIV)Faculty of Science & EngineeringDivision of Diagnostics and Specialist MedicineFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhusDepartment of Radiology in LinköpingMedical radiation physics
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