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.

Diffuse low-grade gliomas (LGG) have been reclassified based on molecular mutations, which require invasive tumor tissue sampling. Tissue sampling by biopsy may be limited by sampling error, whereas non-invasive imaging can evaluate the entirety of a tumor. This study presents a non-invasive analysis of low-grade gliomas using imaging features based on the updated classification. We introduce molecular (MGMT methylation, IDH mutation, 1p/19q co-deletion, ATRX mutation, and TERT mutations) prediction methods of low-grade gliomas with imaging. Imaging features are extracted from magnetic resonance imaging data and include texture features, fractal and multi-resolution fractal texture features, and volumetric features. Training models include nested leave-one-out crossvalidation to select features, train the model, and estimate model performance. The prediction models of MGMT methylation, IDH mutations, 1p/19q co-deletion, ATRX mutation, and TERT mutations achieve a test performance AUC of 0.83 ± 0.04, 0.84 ± 0.03, 0.80 ± 0.04, 0.70 ± 0.09, and 0.82 ± 0.04, respectively. Furthermore, our analysis shows that the fractal features have a significant effect on the predictive performance of MGMT methylation IDH mutations, 1p/19q co-deletion, and ATRX mutations. The performance of our prediction methods indicates the potential of correlating computed imaging features with LGG molecular mutations types and identifies candidates that may be considered potential predictive biomarkers of LGG molecular classification. Diffuse low-grade gliomas (LGG) are World Health Organization (WHO) Grade II and III gliomas. They are infiltrative in their nature and arising from glial cells (astrocytes or oligodendrocytes) of the central nervous system (CNS) 1,2. Recurrence and malicious progression are possible because of the difficulty in complete tumor resection 3. A group of these tumors may also develop into glioblastoma (GBM). An updated classification of diffuse LGG was included in the 2016 WHO Classification of Tumors of the CNS 4. The new classification of the diffuse LGG depends on the genetic driver mutations (IDH mutations, 1p/19q co-deletion, TERT mutations, and ATRX mutations). This new classification correlates well with patients' treatment and survival, for example, oligodendroglioma, defined by the 1p/19q co-deletion, are associated with longer survival compared to astrocytoma, which do not harbor the 1p/19q co-deletion 5. Molecular mutations are determined using invasive methods by obtaining usable tissue samples that have an increase in proliferation and neovascularization 6. Tissue sampling may also be associated with high cost, morbidity, and even mortality 7 , and depending on the sample, may undersample tumor components, especially in heterogeneous tumors. Consequently, developing alternative methods and non-invasively classify diffuse LGG into its different subtypes using imaging features and machine learning techniques have emerged as a promising body of research. In this work, we propose a non-invasive imaging-based...

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel glioma analytical method that, for the first time in the literature, integrates a cellularity feature derived from the digital analysis of brain histopathology images integrated with molecular features following the latest WHO criteria. We first propose a novel over-segmentation strategy for region-of-interest (ROI) selection in large histopathology whole slide images (WSIs). A Deep Neural Network (DNN)-based classification method then fuses molecular features with cellularity features to improve tumor classification performance. We evaluate the proposed method with 549 patient cases from The Cancer Genome Atlas (TCGA) dataset for evaluation. The cross validated classification accuracies are 93.81% for lower-grade glioma (LGG) and high-grade glioma (HGG) using a regular DNN, and 73.95% for LGG II and LGG III using a residual neural network (ResNet) DNN, respectively. Our experiments suggest that the type of deep learning has a significant impact on tumor subtype discrimination between LGG II vs. LGG III. These results outperform state-of-the-art methods in classifying LGG II vs. LGG III and offer competitive performance in distinguishing LGG vs. HGG in the literature. In addition, we also investigate molecular subtype classification using pathology images and cellularity information. Finally, for the first time in literature this work shows promise for cellularity quantification to predict brain tumor grading for LGGs with IDH mutations.

A glioma grading method using conventional structural magnetic resonance image (MRI) and molecular data from patients is proposed. The noninvasive grading of glioma tumors is obtained using multiple radiomic texture features including dynamic texture analysis, multifractal detrended fluctuation analysis, and multiresolution fractal Brownian motion in structural MRI. The proposed method is evaluated using two multicenter MRI datasets: (1) the brain tumor segmentation (BRATS-2017) challenge for high-grade versus low-grade (LG) and (2) the cancer imaging archive (TCIA) repository for glioblastoma (GBM) versus LG glioma grading. The grading performance using MRI is compared with that of digital pathology (DP) images in the cancer genome atlas (TCGA) data repository. The results show that the mean area under the receiver operating characteristic curve (AUC) is 0.88 for the BRATS dataset. The classification of tumor grades using MRI and DP images in TCIA/TCGA yields mean AUC of 0.90 and 0.93, respectively. This work further proposes and compares tumor grading performance using molecular alterations (IDH1/2 mutations) along with MRI and DP data, following the most recent World Health Organization grading criteria, respectively. The overall grading performance demonstrates the efficacy of the proposed noninvasive glioma grading approach using structural MRI.

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