A general skull stripping of multiparametric brain MRIs using 3D convolutional neural network.

Accurate skull stripping facilitates following neuro-image analysis. For computer-aided methods, the presence of brain skull in structural magnetic resonance imaging (MRI) impacts brain tissue identification, which could result in serious misjudgments, specifically for patients with brain tumors. Though there are several existing works on skull stripping in literature, most of them either focus on healthy brain MRIs or only apply for a single image modality. These methods may be not optimal for multiparametric MRI scans. In the paper, we propose an ensemble neural network (EnNet), a 3D convolutional neural network (3DCNN) based method, for brain extraction on multiparametric MRI scans (mpMRIs). We comprehensively investigate the skull stripping performance by using the proposed method on a total of 15 image modality combinations. The comparison shows that utilizing all modalities provides the best performance on skull stripping. We have collected a retrospective dataset of 815 cases with/without glioblastoma multiforme (GBM) at the University of Pittsburgh Medical Center (UPMC) and The Cancer Imaging Archive (TCIA). The ground truths of the skull stripping are verified by at least one qualified radiologist. The quantitative evaluation gives an average dice score coefficient and Hausdorff distance at the 95th percentile, respectively. We also compare the performance to the state-of-the-art methods/tools. The proposed method offers the best performance.The contributions of the work have five folds: first, the proposed method is a fully automatic end-to-end for skull stripping using a 3D deep learning method. Second, it is applicable for mpMRIs and is also easy to customize for any MRI modality combination. Third, the proposed method not only works for healthy brain mpMRIs but also pre-/post-operative brain mpMRIs with GBM. Fourth, the proposed method handles multicenter data. Finally, to the best of our knowledge, we are the first group to quantitatively compare the skull stripping performance using different modalities. All code and pre-trained model are available at: https://github.com/plmoer/skull_stripping_code_SR .

A weakly supervised deep learning-based method for glioma subtype classification using WSI and mpMRIs.

Accurate glioma subtype classification is critical for the treatment management of patients with brain tumors. Developing an automatically computer-aided algorithm for glioma subtype classification is challenging due to many factors. One of the difficulties is the label constraint. Specifically, each case is simply labeled the glioma subtype without precise annotations of lesion regions information. In this paper, we propose a novel hybrid fully convolutional neural network (CNN)-based method for glioma subtype classification using both whole slide imaging (WSI) and multiparametric magnetic resonance imagings (mpMRIs). It is comprised of two methods: a WSI-based method and a mpMRIs-based method. For the WSI-based method, we categorize the glioma subtype using a 2D CNN on WSIs. To overcome the label constraint issue, we extract the truly representative patches for the glioma subtype classification in a weakly supervised fashion. For the mpMRIs-based method, we develop a 3D CNN-based method by analyzing the mpMRIs. The mpMRIs-based method consists of brain tumor segmentation and classification. Finally, to enhance the robustness of the predictions, we fuse the WSI-based and mpMRIs-based results guided by a confidence index. The experimental results on the validation dataset in the competition of CPM-RadPath 2020 show the comprehensive judgments from both two modalities can achieve better performance than the ones by solely using WSI or mpMRIs. Furthermore, our result using the proposed method ranks the third place in the CPM-RadPath 2020 in the testing phase. The proposed method demonstrates a competitive performance, which is creditable to the success of weakly supervised approach and the strategy of label agreement from multi-modality data.

QU-BraTS: MICCAI BraTS 2020 Challenge on Quantifying Uncertainty in Brain Tumor Segmentation - Analysis of Ranking Scores and Benchmarking Results.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at https://github.com/RagMeh11/QU-BraTS.

Deep Neural Network Analysis of Pathology Images With Integrated Molecular Data for Enhanced Glioma Classification and Grading.

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.

Context aware deep learning for brain tumor segmentation, subtype classification, and survival prediction using radiology images.

A brain tumor is an uncontrolled growth of cancerous cells in the brain. Accurate segmentation and classification of tumors are critical for subsequent prognosis and treatment planning. This work proposes context aware deep learning for brain tumor segmentation, subtype classification, and overall survival prediction using structural multimodal magnetic resonance images (mMRI). We first propose a 3D context aware deep learning, that considers uncertainty of tumor location in the radiology mMRI image sub-regions, to obtain tumor segmentation. We then apply a regular 3D convolutional neural network (CNN) on the tumor segments to achieve tumor subtype classification. Finally, we perform survival prediction using a hybrid method of deep learning and machine learning. To evaluate the performance, we apply the proposed methods to the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) dataset for tumor segmentation and overall survival prediction, and to the dataset of the Computational Precision Medicine Radiology-Pathology (CPM-RadPath) Challenge on Brain Tumor Classification 2019 for tumor classification. We also perform an extensive performance evaluation based on popular evaluation metrics, such as Dice score coefficient, Hausdorff distance at percentile 95 (HD95), classification accuracy, and mean square error. The results suggest that the proposed method offers robust tumor segmentation and survival prediction, respectively. Furthermore, the tumor classification results in this work is ranked at second place in the testing phase of the 2019 CPM-RadPath global challenge.

Longitudinal brain tumor segmentation prediction in MRI using feature and label fusion.

This work proposes a novel framework for brain tumor segmentation prediction in longitudinal multi-modal MRI scans, comprising two methods; feature fusion and joint label fusion (JLF). The first method fuses stochastic multi-resolution texture features with tumor cell density feature to obtain tumor segmentation predictions in follow-up timepoints using data from baseline pre-operative timepoint. The cell density feature is obtained by solving the 3D reaction-diffusion equation for biophysical tumor growth modelling using the Lattice-Boltzmann method. The second method utilizes JLF to combine segmentation labels obtained from (i) the stochastic texture feature-based and Random Forest (RF)-based tumor segmentation method; and (ii) another state-of-the-art tumor growth and segmentation method, known as boosted Glioma Image Segmentation and Registration (GLISTRboost, or GB). We quantitatively evaluate both proposed methods using the Dice Similarity Coefficient (DSC) in longitudinal scans of 9 patients from the public BraTS 2015 multi-institutional dataset. The evaluation results for the feature-based fusion method show improved tumor segmentation prediction for the whole tumor(DSC WT = 0.314, p = 0.1502), tumor core (DSC TC = 0.332, p = 0.0002), and enhancing tumor (DSC ET = 0.448, p = 0.0002) regions. The feature-based fusion shows some improvement on tumor prediction of longitudinal brain tumor tracking, whereas the JLF offers statistically significant improvement on the actual segmentation of WT and ET (DSC WT = 0.85 ± 0.055, DSC ET = 0.837 ± 0.074), and also improves the results of GB. The novelty of this work is two-fold: (a) exploit tumor cell density as a feature to predict brain tumor segmentation, using a stochastic multi-resolution RF-based method, and (b) improve the performance of another successful tumor segmentation method, GB, by fusing with the RF-based segmentation labels.

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.

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI.

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. In order to model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

ISLES 2015 - A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI.

Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).