Feature-Guided Deep Radiomics for Glioblastoma Patient Survival Prediction

Glioblastoma is recognized as World Health Organization (WHO) grade IV glioma with an aggressive growth pattern. The current clinical practice in diagnosis and prognosis of Glioblastoma using MRI involves multiple steps including manual tumor sizing. Accurate identification and segmentation of multiple abnormal tissues within tumor volume in MRI is essential for precise survival prediction. Manual tumor and abnormal tissue detection and sizing are tedious, and subject to inter-observer variability. Consequently, this work proposes a fully automated MRI-based glioblastoma and abnormal tissue segmentation, and survival prediction framework. The framework includes radiomics feature-guided deep neural network methods for tumor tissue segmentation; followed by survival regression and classification using these abnormal tumor tissue segments and other relevant clinical features. The proposed multiple abnormal tumor tissue segmentation step effectively fuses feature-based and feature-guided deep radiomics information in structural MRI. The survival prediction step includes two representative survival prediction pipelines that combine different feature selection and regression approaches. The framework is evaluated using two recent widely used benchmark datasets from Brain Tumor Segmentation (BraTS) global challenges in 2017 and 2018. The best overall survival pipeline in the proposed framework achieves leave-one-out cross-validation (LOOCV) accuracy of 0.73 for training datasets and 0.68 for validation datasets, respectively. These training and validation accuracies for tumor patient survival prediction are among the highest reported in literature. Finally, a critical analysis of radiomics features and efficacy of these features in segmentation and survival prediction performance is presented as lessons learned

Model-Based Approach for Diffuse Glioma Classification, Grading, and Patient Survival Prediction

The work in this dissertation proposes model-based approaches for molecular mutations classification of gliomas, grading based on radiomics features and genomics, and prediction of diffuse gliomas clinical outcome in overall patient survival. Diffuse gliomas are types of Central Nervous System (CNS) brain tumors that account for 25.5% of primary brain and CNS tumors and originate from the supportive glial cells. In the 2016 World Health Organization’s (WHO) criteria for CNS brain tumor, a major reclassification of the diffuse gliomas is presented based on gliomas molecular mutations and the growth behavior. Currently, the status of molecular mutations is determined by obtaining viable regions of tumor tissue samples. However, an increasing need to non-invasively analyze the clinical outcome of tumors requires careful modeling and co-analysis of radiomics (i.e., imaging features) and genomics (molecular and proteomics features). The variances in diffuse Lower-grade gliomas (LGG), which are demonstrated by their heterogeneity, can be exemplified by radiographic imaging features (i.e., radiomics). Therefore, radiomics may be suggested as a crucial non-invasive marker in the tumor diagnosis and prognosis. Consequently, we examine radiomics extracted from the multi-resolution fractal representations of the tumor in classifying the molecular mutations of diffuse LGG non-invasively. The proposed radiomics in the decision-tree-based ensemble machine learning molecular prediction model confirm the efficacy of these fractal features in glioma prediction. Furthermore, this dissertation proposes a novel non-invasive statistical model to classify and predict LGG molecular mutations based on radiomics and count-based genomics data. The performance results of the proposed statistical model indicate that fusing radiomics to count-based genomics improves the performance of mutations prediction. Furthermore, the radiomics-based glioblastoma survival prediction framework is proposed in this work. The survival prediction framework includes two survival prediction pipelines that combine different feature selection and regression approaches. The framework is evaluated using two recent widely used benchmark datasets from Brain Tumor Segmentation (BraTS) challenges in 2017 and 2018. The first survival prediction pipeline offered the best overall performance in the 2017 Challenge, and the second survival prediction pipeline offered the best performance using the validation dataset. In summary, in this work, we develop non-invasive computational and statistical models based on radiomics and genomics to investigate overall survival, tumor progression, and the molecular classification in diffuse gliomas. The methods discussed in our study are important steps towards a non-invasive approach to diffuse brain tumor classification, grading, and patient survival prediction that may be recommended prior to invasive tissue sampling in a clinical setting

Radiomic Features to Predict Overall Survival Time for Patients with Glioblastoma Brain Tumors Based on Machine Learning and Deep Learning Methods

Machine Learning (ML) methods including Deep Learning (DL) Methods have been employed in the medical field to improve diagnosis process and patient’s prognosis outcomes. Glioblastoma multiforme is an extremely aggressive Glioma brain tumor that has a poor survival rate. Understanding the behavior of the Glioblastoma brain tumor is still uncertain and some factors are still unrecognized. In fact, the tumor behavior is important to decide a proper treatment plan and to improve a patient’s health. The aim of this dissertation is to develop a Computer-Aided-Diagnosis system (CADiag) based on ML/DL methods to automatically estimate the Overall Survival Time (OST) for patients with Glioblastoma brain tumors from medical imaging and non-imaging data. This system is developed to enhance and speed-up the diagnosis process, as well as to increase understanding of the behavior of Glioblastoma brain tumors. The proposed OST prediction system is developed based on a classification process to categorize a GBM patient into one of the following three survival time groups: short-term (months), mid-term (10-15 months), and long-term (\u3e15 months). The Brain Tumor Segmentation challenge (BraTS) dataset is used to develop the automatic OST prediction system. This dataset consists of multimodal preoperative Magnetic Resonance Imaging (mpMRI) data, and clinical data. The training data is relatively small in size to train an accurate OST prediction model based on DL method. Therefore, traditional ML methods such as Support Vector Machine (SVM), Neural Network, K-Nearest Neighbor (KNN), Decision Tree (DT) were used to develop the OST prediction model for GBM patients. The main contributions in the perspective of ML field include: developing and evaluating five novel radiomic feature extraction methods to produce an automatic and reliable OST prediction system based on classification task. These methods are volumetric, shape, location, texture, histogram-based, and DL features. Some of these radiomic features can be extracted directly from MRI images, such as statistical texture features and histogram-based features. However, preprocessing methods are required to extract automatically other radiomic features from MRI images such as the volume, shape, and location information of the GBM brain tumors. Therefore, a three-dimension (3D) segmentation DL model based on modified U-Net architecture is developed to identify and localize the three glioma brain tumor subregions, peritumoral edematous/invaded tissue (ED), GD-enhancing tumor (ET), and the necrotic tumor core (NCR), in multi MRI scans. The segmentation results are used to calculate the volume, location and shape information of a GBM tumor. Two novel approaches based on volumetric, shape, and location information, are proposed and evaluated in this dissertation. To improve the performance of the OST prediction system, information fusion strategies based on data-fusion, features-fusion and decision-fusion are involved. The best prediction model was developed based on feature fusions and ensemble models using NN classifiers. The proposed OST prediction system achieved competitive results in the BraTS 2020 with accuracy 55.2% and 55.1% on the BraTS 2020 validation and test datasets, respectively. In sum, developing automatic CADiag systems based on robust features and ML methods, such as our developed OST prediction system, enhances the diagnosis process in terms of cost, accuracy, and time. Our OST prediction system was evaluated from the perspective of the ML field. In addition, preprocessing steps are essential to improve not only the quality of the features but also boost the performance of the prediction system. To test the effectiveness of our developed OST system in medical decisions, we suggest more evaluations from the perspective of biology and medical decisions, to be then involved in the diagnosis process as a fast, inexpensive and automatic diagnosis method. To improve the performance of our developed OST prediction system, we believe it is required to increase the size of the training data, involve multi-modal data, and/or provide any uncertain or missing information to the data (such as patients\u27 resection statuses, gender, etc.). The DL structure is able to extract numerous meaningful low-level and high-level radiomic features during the training process without any feature type nominations by researchers. We thus believe that DL methods could achieve better predictions than ML methods if large size and proper data is available