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Automatic Quantification of Ki-67 Labeling Index in Pediatric Brain Tumors Using Qupath
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0009-0001-8127-0867
Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.ORCID iD: 0000-0002-9845-1410
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. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0001-8921-431X
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The quantification of the Ki-67 labeling index (LI) is critical for assessing tumor proliferation and prognosis in tumors, yet manual scoring remains a common practice. This study presents an automated workflow for Ki-67 scoring in whole slide images (WSIs) using an Apache Groovy code script for QuPath, complemented by a Python-based post-processing script, providing cell density maps and summary tables. The tissue and cell segmentation are performed using StarDist, a deep learning model, and adaptive thresholding to classify Ki-67 positive and negative nuclei. The pipeline was applied to a cohort of 632 pediatric brain tumor cases with 734 Ki-67-stained WSIs from the Children’s Brain Tumor Network. Medulloblastoma showed the highest Ki-67 LI(median: 19.84), followed by atypical teratoid rhabdoid tumor (median: 19.36). Moderate values were observed in brainstem glioma-diffuse intrinsic pontine glioma (median: 11.50), high-grade glioma (grades 3 & 4) (median: 9.50), and ependymoma (median: 5.88). Lower indices were foundin meningioma (median: 1.84), while the lowest were seen in low-grade glioma (grades 1 & 2)(median: 0.85), dysembryoplastic neuroepithelial tumor (median: 0.63), and ganglioglioma (median:0.50). The results aligned with the consensus of the oncology, demonstrating a significant correlationin Ki-67 LI across most of the tumor families/types, with high malignancy tumors showing thehighest proliferation indices and lower malignancy tumors exhibiting lower Ki-67 LI. The automated approach facilitates the assessment of large amounts of Ki-67 WSIs in research settings.

Keywords [en]
pediatric, brain, tumor, histopathology, immunohistochemistry, Ki-67, image analysis
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Other Medical Engineering Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-213640DOI: 10.1101/2025.05.09.25327292OAI: oai:DiVA.org:liu-213640DiVA, id: diva2:1958628
Funder
Swedish Childhood Cancer Foundation, MT-0013Linköpings universitet, Cancer Strength AreaLinköpings universitet, Joanna CocozzaMedical Research Council of Southeast Sweden (FORSS), FORSS-1011571Available from: 2025-05-15 Created: 2025-05-15 Last updated: 2026-01-14Bibliographically approved

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Spyretos, ChristoforosPardo Ladino, Juan ManuelBlomstrand, HakonNyman, PerSnödahl, OscarElander, NilsHaj-Hosseini, Neda

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Spyretos, ChristoforosPardo Ladino, Juan ManuelBlomstrand, HakonNyman, PerSnödahl, OscarElander, NilsHaj-Hosseini, Neda
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Division of Biomedical EngineeringFaculty of Science & EngineeringCenter for Medical Image Science and Visualization (CMIV)Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesClinical pathologyDivision of Diagnostics and Specialist MedicineH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhusDepartment of Radiology in LinköpingDepartment of Oncology
Other Medical EngineeringCancer and Oncology

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