MRI-based machine learning models predict the malignant biological behavior of meningioma
Authors: Li Maoyuan , Liu Luzhou , Qi Jie , Qiao Ying , Zeng Hanrui , Jiang Wen , Zhu Rui , Chen Fujian , Huang Huan , Wu Shaoping 
Published: September 2023

Abstract
Background
The WHO grade and Ki-67 index are independent indices used to evaluate the malignant biological behavior of meningioma. This study aims to develop MRI-based machine learning models to predict the malignant biological behavior of meningioma from the perspective of the WHO grade, Ki-67 index, and their combination.

Methods
This multicenter, retrospective study included 313 meningioma patients, of which 70 were classified as high-grade (WHO II/III) and 243 as low-grade (WHO I). The Ki-67 expression was classified into low-expression (n = 216) and high-expression (n = 97) groups with a threshold of 5%. Among them, there were 128 patients with malignant biological behavior whose WHO grade or Ki-67 index increased either or both. Data from Center A and B are were utilized for model development, while data from Center C and D were used for external validation. Radiomic features were extracted from the maximum cross-sectional area (2D) region of Interest (ROI) and the whole tumor volume (3D) ROI using different paraments from the T1, T2-weighted, and T1 contrast-enhanced sequences (T1CE), followed by five independent feature selections and eight classifiers. 240 prediction models were constructed to predict the WHO grade, Ki-67 index and their combination respectively. Models were evaluated by cross-validation in training set (n = 224). Suitable models were chosen by comparing the cross-validation (CV) area under the curves (AUC) and their relative standard deviations (RSD). Clinical and radiological features were collected and analyzed; meaningful features were combined with radiomic features to establish the clinical-radiological-radiomic (CRR) models. The receiver operating characteristic (ROC) analysis was used to evaluate those models in validation set. Radiomic models and CRR models were compared by Delong test.

Results
1218 and 1781 radiomic features were extracted from 2D ROI and 3D ROI of each sequence. The selected grade, Ki-67 index and their combination radiomic models were T1CE-2D-LASSO-LR, T1CE-3D-LASSO-NB, and T1CE-2D-LASSO-LR, with cross-validated AUCs on the training set were 0.857, 0.798, and 0.888, the RSDs were 0.06, 0.09, and 0.05, the validation set AUCs were 0.829, 0.752, and 0.904, respectively. Heterogeneous enhancement was found to be associated with high grade and Ki-67 status, while surrounding invasion was associated with the high grade status, peritumoral edema and cerebrospinal fluid space surrounding tumor were correlated with the high Ki-67 status. The Delong test showed that these significant radiological features did not significantly improve the predictive performance. The AUCs for CRR models predicting grade, Ki-67 index, and their combination in the validation set were 0.821, 0.753, and 0.906, respectively.

Conclusions
This study demonstrated that MRI-based machine learning models could effectively predict the grade, Ki-67 index of meningioma. Models considering these two indices might be valuable for improving the predictive sensitivity and comprehensiveness of prediction of malignant biological behavior of meningioma.