Machine-Learning-Based Radiomics for Classifying Glioma Grade from Magnetic Resonance Images of the Brain

Grading of gliomas is a piece of critical information related to prognosis and survival. Classifying glioma grade by semantic radiological features is subjective, requires multiple MRI sequences, is quite complex and clinically demanding, and can very often result in erroneous radiological diagnosis. We used a radiomics approach with machine learning classifiers to determine the grade of gliomas. Eighty-three patients with histopathologically proven gliomas underwent MRI of the brain. Whenever available, immunohistochemistry was additionally used to augment the histopathological diagnosis. Segmentation was performed manually on the T2W MR sequence using the TexRad texture analysis softwareTM, Version 3.10. Forty-two radiomics features, which included first-order features and shape features, were derived and compared between high-grade and low-grade gliomas. Features were selected by recursive feature elimination using a random forest algorithm method. The classification performance of the models was measured using accuracy, precision, recall, f1 score, and area under the curve (AUC) of the receiver operating characteristic curve. A 10-fold cross-validation was adopted to separate the training and the test data. The selected features were used to build five classifier models: support vector machine, random forest, gradient boost, naive Bayes, and AdaBoost classifiers. The random forest model performed the best, achieving an AUC of 0.81, an accuracy of 0.83, f1 score of 0.88, a recall of 0.93, and a precision of 0.85 for the test cohort. The results suggest that machine-learning-based radiomics features extracted from multiparametric MRI images can provide a non-invasive method for predicting glioma grades preoperatively. In the present study, we extracted the radiomics features from a single cross-sectional image of the T2W MRI sequence and utilized these features to build a fairly robust model to classify low-grade gliomas from high-grade gliomas (grade 4 gliomas)

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

Radiomics MRI Phenotyping with Machine Learning to Predict the Grade of Lower-Grade Gliomas: A Study Focused on Nonenhancing Tumors

OBJECTIVE: To assess whether radiomics features derived from multiparametric MRI can predict the tumor grade of lower-grade gliomas (LGGs; World Health Organization grade II and grade III) and the nonenhancing LGG subgroup. MATERIALS AND METHODS: Two-hundred four patients with LGGs from our institutional cohort were allocated to training (n = 136) and test (n = 68) sets. Postcontrast T1-weighted images, T2-weighted images, and fluid-attenuated inversion recovery images were analyzed to extract 250 radiomics features. Various machine learning classifiers were trained using the radiomics features to predict the glioma grade. The trained classifiers were internally validated on the institutional test set and externally validated on a separate cohort (n = 99) from The Cancer Genome Atlas (TCGA). Classifier performance was assessed by determining the area under the curve (AUC) from receiver operating characteristic curve analysis. An identical process was performed in the nonenhancing LGG subgroup (institutional training set, n = 73; institutional test set, n = 37; and TCGA cohort, n = 37) to predict the glioma grade. RESULTS: The performance of the best classifier was good in the internal validation set (AUC, 0.85) and fair in the external validation set (AUC, 0.72) to predict the LGG grade. For the nonenhancing LGG subgroup, the performance of the best classifier was good in the internal validation set (AUC, 0.82), but poor in the external validation set (AUC, 0.68). CONCLUSION: Radiomics feature-based classifiers may be useful to predict LGG grades. However, radiomics classifiers may have a limited value when applied to the nonenhancing LGG subgroup in a TCGA cohort.ope

Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis

We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon–Mann–Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873–0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705–0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas

Classification of the glioma grading using radiomics analysis

Background Grading of gliomas is critical information related to prognosis and survival. We aimed to apply a radiomics approach using various machine learning classifiers to determine the glioma grading. Methods We considered 285 (high grade n = 210, low grade n = 75) cases obtained from the Brain Tumor Segmentation 2017 Challenge. Manual annotations of enhancing tumors, non-enhancing tumors, necrosis, and edema were provided by the database. Each case was multi-modal with T1-weighted, T1-contrast enhanced, T2-weighted, and FLAIR images. A five-fold cross validation was adopted to separate the training and test data. A total of 468 radiomics features were calculated for three types of regions of interest. The minimum redundancy maximum relevance algorithm was used to select features useful for classifying glioma grades in the training cohort. The selected features were used to build three classifier models of logistics, support vector machines, and random forest classifiers. The classification performance of the models was measured in the training cohort using accuracy, sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve. The trained classifier models were applied to the test cohort. Results Five significant features were selected for the machine learning classifiers and the three classifiers showed an average AUC of 0.9400 for training cohorts and 0.9030 (logistic regression 0.9010, support vector machine 0.8866, and random forest 0.9213) for test cohorts. Discussion Glioma grading could be accurately determined using machine learning and feature selection techniques in conjunction with a radiomics approach. The results of our study might contribute to high-throughput computer aided diagnosis system for gliomas

Brain Tumor Characterization Using Radiogenomics in Artificial Intelligence Framework

Brain tumor characterization (BTC) is the process of knowing the underlying cause of brain tumors and their characteristics through various approaches such as tumor segmentation, classification, detection, and risk analysis. The substantial brain tumor characterization includes the identification of the molecular signature of various useful genomes whose alteration causes the brain tumor. The radiomics approach uses the radiological image for disease characterization by extracting quantitative radiomics features in the artificial intelligence (AI) environment. However, when considering a higher level of disease characteristics such as genetic information and mutation status, the combined study of “radiomics and genomics” has been considered under the umbrella of “radiogenomics”. Furthermore, AI in a radiogenomics’ environment offers benefits/advantages such as the finalized outcome of personalized treatment and individualized medicine. The proposed study summarizes the brain tumor’s characterization in the prospect of an emerging field of research, i.e., radiomics and radiogenomics in an AI environment, with the help of statistical observation and risk-of-bias (RoB) analysis. The PRISMA search approach was used to find 121 relevant studies for the proposed review using IEEE, Google Scholar, PubMed, MDPI, and Scopus. Our findings indicate that both radiomics and radiogenomics have been successfully applied aggressively to several oncology applications with numerous advantages. Furthermore, under the AI paradigm, both the conventional and deep radiomics features have made an impact on the favorable outcomes of the radiogenomics approach of BTC. Furthermore, risk-of-bias (RoB) analysis offers a better understanding of the architectures with stronger benefits of AI by providing the bias involved in them

Computational Modeling for Abnormal Brain Tissue Segmentation, Brain Tumor Tracking, and Grading

This dissertation proposes novel texture feature-based computational models for quantitative analysis of abnormal tissues in two neurological disorders: brain tumor and stroke. Brain tumors are the cells with uncontrolled growth in the brain tissues and one of the major causes of death due to cancer. On the other hand, brain strokes occur due to the sudden interruption of the blood supply which damages the normal brain tissues and frequently causes death or persistent disability. Clinical management of these brain tumors and stroke lesions critically depends on robust quantitative analysis using different imaging modalities including Magnetic Resonance (MR) and Digital Pathology (DP) images. Due to uncontrolled growth and infiltration into the surrounding tissues, the tumor regions appear with a significant texture variation in the static MRI volume and also in the longitudinal imaging study. Consequently, this study developed computational models using novel texture features to segment abnormal brain tissues (tumor, and stroke lesions), tracking the change of tumor volume in longitudinal images, and tumor grading in MR images. Manual delineation and analysis of these abnormal tissues in large scale is tedious, error-prone, and often suffers from inter-observer variability. Therefore, efficient computational models for robust segmentation of different abnormal tissues is required to support the diagnosis and analysis processes. In this study, brain tissues are characterized with novel computational modeling of multi-fractal texture features for multi-class brain tumor tissue segmentation (BTS) and extend the method for ischemic stroke lesions in MRI. The robustness of the proposed segmentation methods is evaluated using a huge amount of private and public domain clinical data that offers competitive performance when compared with that of the state-of-the-art methods. Further, I analyze the dynamic texture behavior of tumor volume in longitudinal imaging and develop post-processing frame-work using three-dimensional (3D) texture features. These post-processing methods are shown to reduce the false positives in the BTS results and improve the overall segmentation result in longitudinal imaging. Furthermore, using this improved segmentation results the change of tumor volume has been quantified in three types such as stable, progress, and shrinkage as observed by the volumetric changes of different tumor tissues in longitudinal images. This study also investigates a novel non-invasive glioma grading, for the first time in literature, that uses structural MRI only. Such non-invasive glioma grading may be useful before an invasive biopsy is recommended. This study further developed an automatic glioma grading scheme using the invasive cell nuclei morphology in DP images for cross-validation with the same patients. In summary, the texture-based computational models proposed in this study are expected to facilitate the clinical management of patients with the brain tumors and strokes by automating large scale imaging data analysis, reducing human error, inter-observer variability, and producing repeatable brain tumor quantitation and grading

Open-radiomics: A Collection of Standardized Datasets and a Technical Protocol for Reproducible Radiomics Machine Learning Pipelines

Purpose: As an important branch of machine learning pipelines in medical imaging, radiomics faces two major challenges namely reproducibility and accessibility. In this work, we introduce open-radiomics, a set of radiomics datasets along with a comprehensive radiomics pipeline based on our proposed technical protocol to investigate the effects of radiomics feature extraction on the reproducibility of the results. Materials and Methods: Experiments are conducted on BraTS 2020 open-source Magnetic Resonance Imaging (MRI) dataset that includes 369 adult patients with brain tumors (76 low-grade glioma (LGG), and 293 high-grade glioma (HGG)). Using PyRadiomics library for LGG vs. HGG classification, 288 radiomics datasets are formed; the combinations of 4 MRI sequences, 3 binWidths, 6 image normalization methods, and 4 tumor subregions. Random Forest classifiers were used, and for each radiomics dataset the training-validation-test (60%/20%/20%) experiment with different data splits and model random states was repeated 100 times (28,800 test results) and Area Under Receiver Operating Characteristic Curve (AUC) was calculated. Results: Unlike binWidth and image normalization, tumor subregion and imaging sequence significantly affected performance of the models. T1 contrast-enhanced sequence and the union of necrotic and the non-enhancing tumor core subregions resulted in the highest AUCs (average test AUC 0.951, 95% confidence interval of (0.949, 0.952)). Although 28 settings and data splits yielded test AUC of 1, they were irreproducible. Conclusion: Our experiments demonstrate the sources of variability in radiomics pipelines (e.g., tumor subregion) can have a significant impact on the results, which may lead to superficial perfect performances that are irreproducible

Deep Learning versus Classical Regression for Brain Tumor Patient Survival Prediction

Deep learning for regression tasks on medical imaging data has shown promising results. However, compared to other approaches, their power is strongly linked to the dataset size. In this study, we evaluate 3D-convolutional neural networks (CNNs) and classical regression methods with hand-crafted features for survival time regression of patients with high grade brain tumors. The tested CNNs for regression showed promising but unstable results. The best performing deep learning approach reached an accuracy of 51.5% on held-out samples of the training set. All tested deep learning experiments were outperformed by a Support Vector Classifier (SVC) using 30 radiomic features. The investigated features included intensity, shape, location and deep features. The submitted method to the BraTS 2018 survival prediction challenge is an ensemble of SVCs, which reached a cross-validated accuracy of 72.2% on the BraTS 2018 training set, 57.1% on the validation set, and 42.9% on the testing set. The results suggest that more training data is necessary for a stable performance of a CNN model for direct regression from magnetic resonance images, and that non-imaging clinical patient information is crucial along with imaging information.Comment: Contribution to The International Multimodal Brain Tumor Segmentation (BraTS) Challenge 2018, survival prediction tas