Multimodal Ensemble Fusion Deep Learning Using Histopathological Images and Clinical Data for Glioma Subtype Classification.

Glioma is the most common malignant tumor of the central nervous system, and diffuse Glioma is classified as grades II-IV by world health organization (WHO). In the the cancer genome atlas (TCGA) Glioma dataset, grade II and III Gliomas are classified as low-grade glioma (LGG), and grade IV Gliomas as glioblastoma multiforme (GBM). In clinical practice, the survival and treatment process with Glioma patients depends on properly diagnosing the subtype. With this background, there has been much research on Glioma over the years. Among these researches, the origin and evolution of whole slide images (WSIs) have led to many attempts to support diagnosis by image analysis. On the other hand, due to the disease complexities of Glioma patients, multimodal analysis using various types of data rather than a single data set has been attracting attention. In our proposed method, multiple deep learning models are used to extract features from histopathology images, and the features of the obtained images are concatenated with those of the clinical data in a fusion approach. Then, we perform patch-level classification by machine learning (ML) using the concatenated features. Based on the performances of the deep learning models, we ensemble feature sets from top three models and perform further classifications. In the experiments with our proposed ensemble fusion AI (EFAI) approach using WSIs and clinical data of diffuse Glioma patients on TCGA dataset, the classification accuracy of the proposed multimodal ensemble fusion method is 0.936 with an area under the curve (AUC) value of 0.967 when tested on a balanced dataset of 240 GBM, 240 LGG patients. On an imbalanced dataset of 141 GBM, 242 LGG patients the proposed method obtained the accuracy of 0.936 and AUC of 0.967. Our proposed ensemble fusion approach significantly outperforms the classification using only histopathology images alone with deep learning models. Therefore, our approach can be used to support the diagnosis of Glioma patients and can lead to better diagnosis.