Abstract

Simple SummarySignificant efforts have been put toward developing MRI-based radiogenomics for IDH status subtyping predictions; however, in the vast majority of these approaches, the external validation sets are absent. Another limitation in current studies is the lack of explainability in radiomics models, which hampers clinical trust and translation. Motivated by these challenges, we proposed a multicenter DSC–MRI-based radiomics study based on an independent exploratory set, which was externally validated on two independent cohorts, for IDH mutation status prediction. Our results demonstrated that DSC–MRI radiogenomics in gliomas, coupled with dynamic-based image standardization techniques, hold the potential to provide (a) increased predictive performance by offering models that generalize well, (b) reasoning behind the IDH mutation status predictions, and (c) interpretability of the radiomics features’ impacts in model performance.To address the current lack of dynamic susceptibility contrast magnetic resonance imaging (DSC–MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutations in gliomas, we present a multicenter study that featured an independent exploratory set for radiomics model development and external validation using two independent cohorts. The maximum performance of the IDH mutation status prediction on the validation set had an accuracy of 0.544 (Cohen’s kappa: 0.145, F1-score: 0.415, area under the curve-AUC: 0.639, sensitivity: 0.733, specificity: 0.491), which significantly improved to an accuracy of 0.706 (Cohen’s kappa: 0.282, F1-score: 0.474, AUC: 0.667, sensitivity: 0.6, specificity: 0.736) when dynamic-based standardization of the images was performed prior to the radiomics. Model explainability using local interpretable model-agnostic explanations (LIME) and Shapley additive explanations (SHAP) revealed potential intuitive correlations between the IDH–wildtype increased heterogeneity and the texture complexity. These results strengthened our hypothesis that DSC–MRI radiogenomics in gliomas hold the potential to provide increased predictive performance from models that generalize well and provide understandable patterns between IDH mutation status and the extracted features toward enabling the clinical translation of radiogenomics in neuro-oncology.

Highlights

  • Gliomas consist of a heterogeneous group of tumors and account for the majority of malignant primary brain tumors [1]

  • In an effort to address all the concerns stated above, this study aimed to explore the potential of dynamic susceptibility contrast magnetic resonance imaging (DSC–MRI)-based radiomics to predict isocitrate dehydrogenase (IDH) mutation status in gliomas

  • The present study developed a postprocessing phase using Shapley additive explanations (SHAP) [31] and local interpretable model-agnostic explanations (LIME) [32] methodologies to provide reasoning behind the IDH mutation status predictions and interpret the impact of each radiomics feature in the model’s performance

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Summary

Introduction

Gliomas consist of a heterogeneous group of tumors and account for the majority of malignant primary brain tumors [1]. Histological grading and classification into low- and high-grade gliomas [2] has been limited in deciphering the heterogeneous treatment response and survival of glioma patients [3], apart from predicting worse clinical outcomes in patients with glioblastoma [4]. Molecular and genetic analyses yielded distinct biochemical and genetic traits of glioma subgroups beyond histological grading [3]. The identification of an IDH mutation in low- and high-grade gliomas and its role in gliomagenesis elucidate the progression of low-grade glioma (LGG) to an IDH-mutant, “secondary”. While IDH-mutant tumors are favored for their improved clinical outcomes, their IDH-mutant counterparts are characterized by a dismal prognosis, irrespective of histological grading [7]. Due to its propensity to stratify glioma patients, IDH mutations were identified in the recent world health organization (WHO)

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