Noninvasive Molecular Subtyping of Pediatric Low-Grade Glioma with Self-Supervised Transfer Learning

Divyanshu Tak, Zezhong Ye, Anna Zapaischykova, Yining Zha, Aidan Boyd, Sridhar Vajapeyam, Rishi Chopra, Hasaan Hayat, Sanjay Prabhu, Kevin X Liu, Hesham Elhalawani, Ali Nabavizadeh, Ariana Familiar, Adam Resnick, Sabine Mueller, Hugo J W L Aerts, Pratiti Bandopadhayay, Keith Ligon, Daphne Haas-Kogan, Tina PoussaintBenjamin H Kann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Purpose: To develop and externally test a scan-to-prediction deep learning pipeline for noninvasive, MRI-based BRAF mutational status classification for pediatric low-grade glioma. Materials and Methods: This retrospective study included two pediatric low-grade glioma datasets with linked genomic and diagnostic T2-weighted MRI data of patients: Dana-Farber/Boston Children’s Hospital (development dataset, n = 214 [113 (52.8%) male; 104 (48.6%) BRAF wild type, 60 (28.0%) BRAF fusion, and 50 (23.4%) BRAF V600E]) and the Children’s Brain Tumor Network (external testing, n = 112 [55 (49.1%) male; 35 (31.2%) BRAF wild type, 60 (53.6%) BRAF fusion, and 17 (15.2%) BRAF V600E]). A deep learning pipeline was developed to classify BRAF mutational status (BRAF wild type vs BRAF fusion vs BRAF V600E) via a two-stage process: (a) three-di-mensional tumor segmentation and extraction of axial tumor images and (b) section-wise, deep learning–based classification of mutational status. Knowledge-transfer and self-supervised approaches were investigated to prevent model overfitting, with a primary end point of the area under the receiver operating characteristic curve (AUC). To enhance model interpretability, a novel metric, center of mass distance, was developed to quantify the model attention around the tumor. Results: A combination of transfer learning from a pretrained medical imaging–specific network and self-supervised label cross-training (TransferX) coupled with consensus logic yielded the highest classification performance with an AUC of 0.82 (95% CI: 0.72, 0.91), 0.87 (95% CI: 0.61, 0.97), and 0.85 (95% CI: 0.66, 0.95) for BRAF wild type, BRAF fusion, and BRAF V600E, respectively, on internal testing. On external testing, the pipeline yielded an AUC of 0.72 (95% CI: 0.64, 0.86), 0.78 (95% CI: 0.61, 0.89), and 0.72 (95% CI: 0.64, 0.88) for BRAF wild type, BRAF fusion, and BRAF V600E, respectively. Conclusion: Transfer learning and self-supervised cross-training improved classification performance and generalizability for noninvasive pediatric low-grade glioma mutational status prediction in a limited data scenario.

Original languageEnglish
Article numbere230333
JournalRadiology: Artificial Intelligence
Volume6
Issue number3
DOIs
Publication statusPublished - May 2024

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