Deep Learning Methods for Classification of Glioma and its Molecular Subtypes

Diagnosis and timely treatment play an important role in\ua0preventing brain tumor growth. Clinicians are unable to reliablypredict LGG molecular subtypes from magnetic resonance imaging (MRI) without taking biopsy. Accurate diagnosis prior to surgery would be important. Recently, non-invasive classification methods such as deep learning have shown promising outcome in prediction of glioma-subtypes based upon pre-operative brain scans. However, it needs large amount of annotated medical data on tumors. This thesis investigates methods on the problem of data scarcity, specifically for molecular LGG-subtypes. The focus of this thesis is on two challenges for improving the classification performance of gliomas and its molecular subtypes using MRIs; data augmentation and domain mapping to overcome the lack of data and using data with unavailable GT annotation to tackle the issue of tedious task of manually marking tumor boundaries. Data augmentation includes generating synthetic MR images to enlarge the training data using Generative Adversarial Networks (GANs). Another type of GAN, CycleGAN, is used to enlarge the data size by mapping data from different domains to a target domain. A multi-stream Convolutional Autoencoder (CAE) classifier is proposed with a 2-stage training strategy. To enable MRI data to be used without tumor annotation, ellipse bounding box is proposed that gives comparable classification performance. The thesis comprises of papers addressing the challenging problems of data scarcity and lacking of tumor annotation. These proposed methods can benefit the future research in bringing machine learning tools into clinical practice for non-invasive diagnostics that would assist surgeons and patients in the shared decision making process

Deep Learning Methods for Classification of Gliomas and Their Molecular Subtypes, From Central Learning to Federated Learning

The most common type of brain cancer in adults are gliomas. Under the updated 2016 World Health Organization (WHO) tumor classification in central nervous system (CNS), identification of molecular subtypes of gliomas is important. For low grade gliomas (LGGs), prediction of molecular subtypes by observing magnetic resonance imaging (MRI) scans might be difficult without taking biopsy. With the development of machine learning (ML) methods such as deep learning (DL), molecular based classification methods have shown promising results from MRI scans that may assist clinicians for prognosis and deciding on a treatment strategy. However, DL requires large amount of training datasets with tumor class labels and tumor boundary annotations. Manual annotation of tumor boundary is a time consuming and expensive process.The thesis is based on the work developed in five papers on gliomas and their molecular subtypes. We propose novel methods that provide improved performance. \ua0The proposed methods consist of a multi-stream convolutional autoencoder (CAE)-based classifier, a deep convolutional generative adversarial network (DCGAN) to enlarge the training dataset, a CycleGAN to handle domain shift, a novel federated learning (FL) scheme to allow local client-based training with dataset protection, and employing bounding boxes to MRIs when tumor boundary annotations are not available.Experimental results showed that DCGAN generated MRIs have enlarged the original training dataset size and have improved the classification performance on test sets. CycleGAN showed good domain adaptation on multiple source datasets and improved the classification performance. The proposed FL scheme showed a slightly degraded performance as compare to that of central learning (CL) approach while protecting dataset privacy. Using tumor bounding boxes showed to be an alternative approach to tumor boundary annotation for tumor classification and segmentation, with a trade-off between a slight decrease in performance and saving time in manual marking by clinicians. The proposed methods may benefit the future research in bringing DL tools into clinical practice for assisting tumor diagnosis and help the decision making process

Domain Mapping and Deep Learning from Multiple MRI Clinical Datasets for Prediction of Molecular Subtypes in Low Grade Gliomas

Brain tumors, such as low grade gliomas (LGG), are molecularly classified which require the surgical collection of tissue samples. The pre-surgical or non-operative identification of LGG molecular type could improve patient counseling and treatment decisions. However, radiographic approaches to LGG molecular classification are currently lacking, as clinicians are unable to reliably predict LGG molecular type using magnetic resonance imaging (MRI) studies. Machine learning approaches may improve the prediction of LGG molecular classification through MRI, however, the development of these techniques requires large annotated data sets. Merging clinical data from different hospitals to increase case numbers is needed, but the use of different scanners and settings can affect the results and simply combining them into a large dataset often have a significant negative impact on performance. This calls for efficient domain adaption methods. Despite some previous studies on domain adaptations, mapping MR images from different datasets to a common domain without affecting subtitle molecular-biomarker information has not been reported yet. In this paper, we propose an effective domain adaptation method based on Cycle Generative Adversarial Network (CycleGAN). The dataset is further enlarged by augmenting more MRIs using another GAN approach. Further, to tackle the issue of brain tumor segmentation that requires time and anatomical expertise to put exact boundary around the tumor, we have used a tight bounding box as a strategy. Finally, an efficient deep feature learning method, multi-stream convolutional autoencoder (CAE) and feature fusion, is proposed for the prediction of molecular subtypes (1p/19q-codeletion and IDH mutation). The experiments were conducted on a total of 161 patients consisting of FLAIR and T1 weighted with contrast enhanced (T1ce) MRIs from two different institutions in the USA and France. The proposed scheme is shown to achieve the test accuracy of\ua074.81%\ua0on 1p/19q codeletion and\ua081.19%\ua0on IDH mutation, with marked improvement over the results obtained without domain mapping. This approach is also shown to have comparable performance to several state-of-the-art methods

Enlarged Training Dataset by Pairwise GANs for Molecular-Based Brain Tumor Classification

This paper addresses issues of brain tumor subtype classification using Magnetic Resonance Images (MRIs) from different scanner modalities like T1 weighted, T1 weighted with contrast-enhanced, T2 weighted and FLAIR images. Currently most available glioma datasets are relatively moderate in size,and often accompanied with incomplete MRIs in different modalities. To tackle the commonly encountered problems of insufficiently large brain tumor datasets and incomplete modality of image for deep learning, we propose to add augmented brain MR images to enlarge the training dataset by employing a pairwise Generative Adversarial Network (GAN) model. The pairwise GAN is able to generate synthetic MRIs across different modalities. To achieve the patient-level diagnostic result, we propose a post-processing strategy to combine the slice-level glioma subtype classification results by majority voting. A two-stage course-to-fine training strategy is proposed to learn the glioma feature using GAN-augmented MRIs followed by real MRIs. To evaluate the effectiveness of the proposed scheme, experiments have been conducted on a brain tumor dataset for classifying glioma molecular subtypes: isocitrate dehydrogenase 1 (IDH1) mutation and IDH1 wild-type. Our results on the dataset have shown good performance (with test accuracy 88.82%). Comparisons with several state-of-the-art methods are also included

Brain Tumor Classification Using a Combination of Variational Autoencoders and Generative Adversarial Networks

Brain tumors are a pernicious cancer with one of the lowest five-year survival rates. Neurologists often use magnetic resonance imaging (MRI) to diagnose the type of brain tumor. Automated computer-assisted tools can help them speed up the diagnosis process and reduce the burden on the health care systems. Recent advances in deep learning for medical imaging have shown remarkable results, especially in the automatic and instant diagnosis of various cancers. However, we need a large amount of data (images) to train the deep learning models in order to obtain good results. Large public datasets are rare in medicine. This paper proposes a framework based on unsupervised deep generative neural networks to solve this limitation. We combine two generative models in the proposed framework: variational autoencoders (VAEs) and generative adversarial networks (GANs). We swap the encoder–decoder network after initially training it on the training set of available MR images. The output of this swapped network is a noise vector that has information of the image manifold, and the cascaded generative adversarial network samples the input from this informative noise vector instead of random Gaussian noise. The proposed method helps the GAN to avoid mode collapse and generate realistic-looking brain tumor magnetic resonance images. These artificially generated images could solve the limitation of small medical datasets up to a reasonable extent and help the deep learning models perform acceptably. We used the ResNet50 as a classifier, and the artificially generated brain tumor images are used to augment the real and available images during the classifier training. We compared the classification results with several existing studies and state-of-the-art machine learning models. Our proposed methodology noticeably achieved better results. By using brain tumor images generated artificially by our proposed method, the classification average accuracy improved from 72.63% to 96.25%. For the most severe class of brain tumor, glioma, we achieved 0.769, 0.837, 0.833, and 0.80 values for recall, specificity, precision, and F1-score, respectively. The proposed generative model framework could be used to generate medical images in any domain, including PET (positron emission tomography) and MRI scans of various parts of the body, and the results show that it could be a useful clinical tool for medical experts

Machine Learning Methods for Image Analysis in Medical Applications, from Alzheimer\u27s Disease, Brain Tumors, to Assisted Living

Healthcare has progressed greatly nowadays owing to technological advances, where machine learning plays an important role in processing and analyzing a large amount of medical data. This thesis investigates four healthcare-related issues (Alzheimer\u27s disease detection, glioma classification, human fall detection, and obstacle avoidance in prosthetic vision), where the underlying methodologies are associated with machine learning and computer vision. For Alzheimer’s disease (AD) diagnosis, apart from symptoms of patients, Magnetic Resonance Images (MRIs) also play an important role. Inspired by the success of deep learning, a new multi-stream multi-scale Convolutional Neural Network (CNN) architecture is proposed for AD detection from MRIs, where AD features are characterized in both the tissue level and the scale level for improved feature learning. Good classification performance is obtained for AD/NC (normal control) classification with test accuracy 94.74%. In glioma subtype classification, biopsies are usually needed for determining different molecular-based glioma subtypes. We investigate non-invasive glioma subtype prediction from MRIs by using deep learning. A 2D multi-stream CNN architecture is used to learn the features of gliomas from multi-modal MRIs, where the training dataset is enlarged with synthetic brain MRIs generated by pairwise Generative Adversarial Networks (GANs). Test accuracy 88.82% has been achieved for IDH mutation (a molecular-based subtype) prediction. A new deep semi-supervised learning method is also proposed to tackle the problem of missing molecular-related labels in training datasets for improving the performance of glioma classification. In other two applications, we also address video-based human fall detection by using co-saliency-enhanced Recurrent Convolutional Networks (RCNs), as well as obstacle avoidance in prosthetic vision by characterizing obstacle-related video features using a Spiking Neural Network (SNN). These investigations can benefit future research, where artificial intelligence/deep learning may open a new way for real medical applications