Noninvasive Evaluation of the Notch Signaling Pathway via Radiomic Signatures Based on Multiparametric MRI in Association With Biological Functions of Patients With Glioma: A Multi-institutional Study

Abstract

Background: Noninvasive determination of Notch signaling is important for prognostic evaluation and therapeutic intervention in glioma.

Purpose: To predict Notch signaling using multiparametric (mp) MRI radiomics and correlate with biological characteristics in gliomas.

Study type: Retrospective.

Population: A total of 63 patients for model construction and 47 patients from two public databases for external testing.

Field strength/sequence: A 1.5 T and 3.0 T, T1-weighted imaging (T1WI), T2WI, T2 fluid attenuated inversion recovery (FLAIR), contrast-enhanced (CE)-T1WI.

Assessment: Radiomic features were extracted from CE-T1WI, T1WI, T2WI, and T2FLAIR and imaging signatures were selected using a least absolute shrinkage and selection operator. Diagnostic performance was compared between single modality and a combined mpMRI radiomics model. A radiomic-clinical nomogram was constructed incorporating the mpMRI radiomic signature and Karnofsky Performance score. The performance was validated in the test set. The radiomic signatures were correlated with immunohistochemistry (IHC) analysis of downstream Notch pathway components.

Statistical tests: Receiver operating characteristic curve, decision curve analysis (DCA), Pearson correlation, and Hosmer-Lemeshow test. A P value < 0.05 was considered statistically significant.

Results: The radiomic signature derived from the combination of all sequences numerically showed highest area under the curve (AUC) in both training and external test sets (AUCs of 0.857 and 0.823). The radiomics nomogram that incorporated the mpMRI radiomic signature and KPS status resulted in AUCs of 0.891 and 0.859 in the training and test sets. The calibration curves showed good agreement between prediction and observation in both sets (P= 0.279 and 0.170, respectively). DCA confirmed the clinical usefulness of the nomogram. IHC identified Notch pathway inactivation and the expression levels of Hes1 correlated with higher combined radiomic scores (r = -0.711) in Notch1 mutant tumors.

Data conclusion: The mpMRI-based radiomics nomogram may reflect the intratumor heterogeneity associated with downstream biofunction that predicts Notch signaling in a noninvasive manner.

Evidence level: 3 TECHNICAL EFFICACY: Stage 2.

Keywords: Notch signaling pathway; glioma; multiparametric MRI; radiogenomic; radiomic.