97 research outputs found

    Longitudinal Brain Tumor Tracking, Tumor Grading, and Patient Survival Prediction Using MRI

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    This work aims to develop novel methods for brain tumor classification, longitudinal brain tumor tracking, and patient survival prediction. Consequently, this dissertation proposes three tasks. First, we develop a framework for brain tumor segmentation prediction in longitudinal multimodal magnetic resonance imaging (mMRI) scans, comprising two methods: feature fusion and joint label fusion (JLF). The first method fuses stochastic multi-resolution texture features with tumor cell density features, in order to obtain tumor segmentation predictions in follow-up scans from a baseline pre-operative timepoint. 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). With the advantages of feature fusion and label fusion, we achieve state-of-the-art brain tumor segmentation prediction. Second, we propose a deep neural network (DNN) learning-based method for brain tumor type and subtype grading using phenotypic and genotypic data, following the World Health Organization (WHO) criteria. In addition, the classification method integrates a cellularity feature which is derived from the morphology of a pathology image to improve classification performance. The proposed method achieves state-of-the-art performance for tumor grading following the new CNS tumor grading criteria. Finally, we investigate brain tumor volume segmentation, tumor subtype classification, and overall patient survival prediction, and then we propose a new context- aware deep learning method, known as the Context Aware Convolutional Neural Network (CANet). Using the proposed method, we participated in the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) for brain tumor volume segmentation and overall survival prediction tasks. In addition, we also participated in the Radiology-Pathology Challenge 2019 (CPM-RadPath 2019) for Brain Tumor Subtype Classification, organized by the Medical Image Computing & Computer Assisted Intervention (MICCAI) Society. The online evaluation results show that the proposed methods offer competitive performance from their use of state-of-the-art methods in tumor volume segmentation, promising performance on overall survival prediction, and state-of-the-art performance on tumor subtype classification. Moreover, our result was ranked second place in the testing phase of the CPM-RadPath 2019

    Brain tumour genetic network signatures of survival

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    Tumour heterogeneity is increasingly recognized as a major obstacle to therapeutic success across neuro-oncology. Gliomas are characterised by distinct combinations of genetic and epigenetic alterations, resulting in complex interactions across multiple molecular pathways. Predicting disease evolution and prescribing individually optimal treatment requires statistical models complex enough to capture the intricate (epi)genetic structure underpinning oncogenesis. Here, we formalize this task as the inference of distinct patterns of connectivity within hierarchical latent representations of genetic networks. Evaluating multi-institutional clinical, genetic, and outcome data from 4023 glioma patients over 14 years, across 12 countries, we employ Bayesian generative stochastic block modelling to reveal a hierarchical network structure of tumour genetics spanning molecularly confirmed glioblastoma, IDH- wildtype; oligodendroglioma, IDH-mutant and 1p/19q codeleted; and astrocytoma, IDH- mutant. Our findings illuminate the complex dependence between features across the genetic landscape of brain tumours, and show that generative network models reveal distinct signatures of survival with better prognostic fidelity than current gold standard diagnostic categories.Comment: Main article: 52 pages, 1 table, 7 figures. Supplementary material: 13 pages, 11 supplementary figure

    The Era of Radiogenomics in Precision Medicine: An Emerging Approach to Support Diagnosis, Treatment Decisions, and Prognostication in Oncology

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    With the rapid development of new technologies, including artificial intelligence and genome sequencing, radiogenomics has emerged as a state-of-the-art science in the field of individualized medicine. Radiogenomics combines a large volume of quantitative data extracted from medical images with individual genomic phenotypes and constructs a prediction model through deep learning to stratify patients, guide therapeutic strategies, and evaluate clinical outcomes. Recent studies of various types of tumors demonstrate the predictive value of radiogenomics. And some of the issues in the radiogenomic analysis and the solutions from prior works are presented. Although the workflow criteria and international agreed guidelines for statistical methods need to be confirmed, radiogenomics represents a repeatable and cost-effective approach for the detection of continuous changes and is a promising surrogate for invasive interventions. Therefore, radiogenomics could facilitate computer-aided diagnosis, treatment, and prediction of the prognosis in patients with tumors in the routine clinical setting. Here, we summarize the integrated process of radiogenomics and introduce the crucial strategies and statistical algorithms involved in current studies

    Brain Tumor Characterization Using Radiogenomics in Artificial Intelligence Framework

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    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

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

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    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

    Imaging characteristics of H3 K27M histone-mutant diffuse midline glioma in teenagers and adults

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    Background: To assess anatomical and quantitative diffusion-weighted MR imaging features in a recently classified lethal neoplasm, H3 K27M histone-mutant diffuse midline glioma [World Health Organization (WHO) IV]. / Methods: Fifteen untreated gliomas in teenagers and adults (median age 19, range, 14–64) with confirmed H3 K27M histone-mutant genotype were analysed at a national referral centre. Morphological characteristics including tumour epicentre(s), T2/FLAIR and Gadolinium enhancement patterns, calcification, haemorrhage and cyst formation were recorded. Multiple apparent diffusion coefficient (ADCmin, ADCmean) regions of interest were sited in solid tumour and normal appearing white matter (ADCNAWM) using post-processing software (Olea Sphere v2.3, Olea Medical). ADC histogram data (2nd, 5th, 10th percentile, median, mean, kurtosis, skewness) were calculated from volumetric tumour segmentations and tested against the regions of interest (ROI) data (Wilcoxon signed rank test). / Results: The median interval from imaging to tissue diagnosis was 9 (range, 0–74) days. The structural MR imaging findings varied between individuals and within tumours, often featuring signal heterogeneity on all MR sequences. All gliomas demonstrated contact with the brain midline, and 67% exhibited rim-enhancing necrosis. The mean ROI ADCmin value was 0.84 (±0.15 standard deviation, SD) ×10−3 mm2/s. In the largest tumour cross-section (excluding necrosis), an average ADCmean value of 1.12 (±0.25)×10−3 mm2/s was observed. The mean ADCmin/NAWM ratio was 1.097 (±0.149), and the mean ADCmean/NAWM ratio measured 1.466 (±0.299). With the exception of the 2nd centile, no statistical difference was observed between the regional and histogram derived ADC results. / Conclusions: H3 K27M-mutant gliomas demonstrate variable morphology and diffusivity, commonly featuring moderately low ADC values in solid tumour. Regional ADC measurements appeared representative of volumetric histogram data in this study

    The real-time molecular characterisation of human brain tumours during surgery using Rapid Evaporative Ionization Mass Spectrometry [REIMS] and Raman spectroscopy: a platform for precision medicine in neurosurgery

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    Aim: To investigate new methods for the chemical detection of tumour tissue during neurosurgery. Rationale: Surgeons operating on brain tumours currently lack the ability to directly and immediately assess the presence of tumour tissue to help guide resection. Through developing a first in human application of new technology we hope to demonstrate the proof of concept that chemical detection of tumour tissue is possible. It will be further demonstrated that information can be obtained to potentially aid treatment decisions. This new technology could, therefore, become a platform for more effective surgery and introducing precision medicine to Neurosurgery. Methods: Molecular analysis was performed using Raman spectroscopy and Rapid Evaporative Ionization Mass Spectrometry (REIMS). These systems were first developed for use in brain surgery. A single centre prospective observational study of both modalities was designed involving a total of 75 patients undergoing craniotomy and resection of a range of brain tumours. A neuronavigation system was used to register spectral readings in 3D space. Precise intraoperative readings from different tumour zones were taken and compared to matched core biopsy samples verified by routine histopathology. Results: Multivariate statistics including PCA/LDA analysis was used to analyse the spectra obtained and compare these to the histological data. The systems identified normal versus tumour tissue, tumour grade, tumour type, tumour density and tissue status of key markers of gliomagenesis. Conclusions: The work in this thesis provides proof of concept that useful real time intraoperative spectroscopy is possible. It can integrate well with the current operating room setup to provide key information which could potentially enhance surgical safety and effectiveness in increasing extent of resection. The ability to group tissue samples with respect to genomic data opens up the possibility of using this information during surgery to speed up treatment, escalate/deescalate surgery in specific phenotypic groups to introduce precision medicine to Neurosurgery.Open Acces

    MRI-based classification of IDH mutation and 1p/19q codeletion status of gliomas using a 2.5D hybrid multi-task convolutional neural network

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    Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status are important prognostic markers for glioma. Currently, they are determined using invasive procedures. Our goal was to develop artificial intelligence-based methods to non-invasively determine these molecular alterations from MRI. For this purpose, pre-operative MRI scans of 2648 patients with gliomas (grade II-IV) were collected from Washington University School of Medicine (WUSM; n = 835) and publicly available datasets viz. Brain Tumor Segmentation (BraTS; n = 378), LGG 1p/19q (n = 159), Ivy Glioblastoma Atlas Project (Ivy GAP; n = 41), The Cancer Genome Atlas (TCGA; n = 461), and the Erasmus Glioma Database (EGD; n = 774). A 2.5D hybrid convolutional neural network was proposed to simultaneously localize the tumor and classify its molecular status by leveraging imaging features from MR scans and prior knowledge features from clinical records and tumor location. The models were tested on one internal (TCGA) and two external (WUSM and EGD) test sets. For IDH, the best-performing model achieved areas under the receiver operating characteristic (AUROC) of 0.925, 0.874, 0.933 and areas under the precision-recall curves (AUPRC) of 0.899, 0.702, 0.853 on the internal, WUSM, and EGD test sets, respectively. For 1p/19q, the best model achieved AUROCs of 0.782, 0.754, 0.842, and AUPRCs of 0.588, 0.713, 0.782, on those three data-splits, respectively. The high accuracy of the model on unseen data showcases its generalization capabilities and suggests its potential to perform a 'virtual biopsy' for tailoring treatment planning and overall clinical management of gliomas

    Advanced imaging and artificial intelligence for diagnostic and prognostic biomarkers in glioblastoma

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    Conventional magnetic resonance imaging (MRI) has a pivotal role in diagnosis and post-treatment management of glioblastoma, however it has limitations. This work investigates the use of advanced MRI techniques that assess the tumour microenvironment, and artificial intelligence (AI) techniques that compute quantitative features, as potential imaging biomarkers in key clinical issues faced by clinicians, through several retrospective studies. Results show that advanced multiparametric MRI is superior to current standard-of-care imaging for the diagnosis of glioblastoma, and in treatment response assessment. Results of AI techniques on pre-operative imaging show the ability to differentiate between glioblastoma and metastasis with an accuracy of 88.7%, prediction of overall survival with a high level of accuracy, and stratification of patients into high- and low-level groups of MGMT promoter methylation with accuracies between 45-67%. In the early post-treatment phase, AI analysis of imaging can distinguish between disease progression and pseudoprogression with an accuracy of 73.7%, compared to neuroradiologist accuracy of 32.9%. Integrating these techniques into routine clinical practice is essential to improve patient outcomes. Further work is required to validate advanced imaging and AI biomarkers, towards the longer-term goal of using these as clinical decision support tools, to benefit patients with glioblastoma and other brain tumours
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