# Predicting isocitrate dehydrogenase status in glioma using hierarchical attention-based deep 3D multiple instance learning

**Authors:** Qinqin Xie, Yongheng Sun, Yuxia Liang, Yu Shang, Haifeng Wang, Fan Wang, Rong Wei, Bin Chen, Ming Zhang, Chen Niu

PMC · DOI: 10.3389/fonc.2025.1665690 · Frontiers in Oncology · 2025-12-18

## TL;DR

This paper introduces a new AI model that can predict a brain tumor marker (IDH status) from MRI scans, avoiding invasive procedures.

## Contribution

A novel hierarchical attention-based deep 3D multiple instance learning framework for non-invasive IDH status prediction in gliomas.

## Key findings

- The HAB-MIL model achieved an AUC of 0.917 on the TCIA dataset and 0.892 on the hospital dataset.
- The model performs comparably to state-of-the-art methods while requiring no pixel-level annotations.
- Multiple instance learning shows strong potential for IDH classification in gliomas.

## Abstract

According to the 2021 WHO classification of tumors of the central nervous system, isocitrate dehydrogenase (IDH) status serve an independent prognostic biomarker and is closely associated with tumor diagnosis and treatment response. At present, the determination of IDH status still relies on invasive surgical procedures.

A total of 345 patients with pathologically confirmed gliomas diagnosed at the First Affiliated Hospital of Xi’an Jiaotong University between October 2019 and October 2024 were retrospectively included, comprising 148 (42.9%) IDH-wild and 197 (57.1%) IDH-mutant. An additional 495 glioma patients were obtained from the public TCIA dataset. Patients were randomly split into training, validation, and test cohorts 6:2:2. A Hierarchical Attention-Based Multiple Instance Learning (HAB-MIL) framework was developed, integrating auxiliary positional encoding into feature maps to capture spatially specific information and generate refined 3D lesion representations. Model performance was evaluated using five-fold cross-validation, with receiver operating characteristic (ROC) curves, area under the curve (AUC), sensitivity, and specificity as assessment metrics.

HAB-MIL achieved competitive performance, with AUCs of 0.917 and 0.892 on the glioma datasets from TCIA and the First Affiliated Hospital of Xi’an Jiaotong University. Additionally, our work achieves results that are comparable to the state-of-the-art methods in TCIA dataset and demonstrates that multiple instance learning has great potential for IDH prediction.

The proposed HAB-MIL achieved IDH classification based on conventional preoperative MRI images, eliminating the need for pixel-level annotations and significantly reducing the annotation burden for doctors.

## Linked entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417]
- **Diseases:** glioma (MONDO:0021042)

## Full-text entities

- **Genes:** IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}
- **Diseases:** tumor (MESH:D009369), glioma (MESH:D005910)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12756022/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12756022/full.md

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Source: https://tomesphere.com/paper/PMC12756022