Embedding MRI information into MRSI data source extraction improves brain tumour delineation in animal models

Glioblastoma is the most frequent malignant intra-cranial tumour. Magnetic resonance imaging is the modality of choice in diagnosis, aggressiveness assessment, and follow-up. However, there are examples where it lacks diagnostic accuracy. Magnetic resonance spectroscopy enables the identification of molecules present in the tissue, providing a precise metabolomic signature. Previous research shows that combining imaging and spectroscopy information results in more accurate outcomes and superior diagnostic value. This study proposes a method to combine them, which builds upon a previous methodology whose main objective is to guide the extraction of sources. To this aim, prior knowledge about class-specific information is integrated into the methodology by setting the metric of a latent variable space where Non-negative Matrix Factorisation is performed. The former methodology, which only used spectroscopy and involved combining spectra from different subjects, was adapted to use selected areas of interest that arise from segmenting the T2-weighted image. Results showed that embedding imaging information into the source extraction (the proposed semi-supervised analysis) improved the quality of the tumour delineation, as compared to those obtained without this information (unsupervised analysis). Both approaches were applied to pre-clinical data, involving thirteen brain tumour-bearing mice, and tested against histopathological data. On results of twenty-eight images, the proposed Semi-Supervised Source Extraction (SSSE) method greatly outperformed the unsupervised one, as well as an alternative semi-supervised approach from the literature, with differences being statistically significant. SSSE has proven successful in the delineation of the tumour, while bringing benefits such as 1) not constricting the metabolomic-based prediction to the image-segmented area, 2) ability to deal with signal-to-noise issues, 3) opportunity to answer specific questions by allowing researchers/radiologists define areas of interest that guide the source extraction, 4) creation of an intra-subject model and avoiding contamination from inter-subject overlaps, and 5) extraction of meaningful, good-quality sources that adds interpretability, conferring validation and better understanding of each case

Computational methods to predict and enhance decision-making with biomedical data.

The proposed research applies machine learning techniques to healthcare applications. The core ideas were using intelligent techniques to find automatic methods to analyze healthcare applications. Different classification and feature extraction techniques on various clinical datasets are applied. The datasets include: brain MR images, breathing curves from vessels around tumor cells during in time, breathing curves extracted from patients with successful or rejected lung transplants, and lung cancer patients diagnosed in US from in 2004-2009 extracted from SEER database. The novel idea on brain MR images segmentation is to develop a multi-scale technique to segment blood vessel tissues from similar tissues in the brain. By analyzing the vascularization of the cancer tissue during time and the behavior of vessels (arteries and veins provided in time), a new feature extraction technique developed and classification techniques was used to rank the vascularization of each tumor type. Lung transplantation is a critical surgery for which predicting the acceptance or rejection of the transplant would be very important. A review of classification techniques on the SEER database was developed to analyze the survival rates of lung cancer patients, and the best feature vector that can be used to predict the most similar patients are analyzed

Deep semi-supervised learning for brain tumor classification

Background: This paper addresses issues of brain tumor, glioma, classification from four modalities of Magnetic Resonance Image (MRI) scans (i.e., T1 weighted MRI, T1 weighted MRI with contrast-enhanced, T2 weighted MRI and FLAIR). Currently, many available glioma datasets often contain some unlabeled brain scans, and many datasets are moderate in size. Methods: We propose to exploit deep semi-supervised learning to make full use of the unlabeled data. Deep CNN features were incorporated into a new graph-based semi-supervised learning framework for learning the labels of the unlabeled data, where a new 3D-2D consistent constraint is added to make consistent classifications for the 2D slices from the same 3D brain scan. A deep-learning classifier is then trained to classify different glioma types using both labeled and unlabeled data with estimated labels. To alleviate the overfitting caused by moderate-size datasets, synthetic MRIs generated by Generative Adversarial Networks (GANs) are added in the training of CNNs. Results: The proposed scheme has been tested on two glioma datasets, TCGA dataset for IDH-mutation prediction (molecular-based glioma subtype classification) and MICCAI dataset for glioma grading. Our results have shown good performance (with test accuracies 86.53% on TCGA dataset and 90.70% on MICCAI dataset). Conclusions: The proposed scheme is effective for glioma IDH-mutation prediction and glioma grading, and its performance is comparable to the state-of-the-art

Pattern recognition and pharmacokinetic methods on DCE-MRI data for tumor hypoxia mapping in sarcoma

The main purpose of this study is to analyze the intrinsic tumor physiologic characteristics in patients with sarcoma through model-free analysis of dynamic contrast enhanced MR imaging data (DCE-MRI). Clinical data were collected from three patients with two different types of histologically proven sarcomas who underwent conventional and advanced MRI examination prior to excision. An advanced matrix factorization algorithm has been applied to the data, resulting in the identification of the principal time-signal uptake curves of DCE-MRI data, which were used to characterize the physiology of the tumor area, described by three different perfusion patterns i.e. hypoxic, well-perfused and necrotic one. The performance of the algorithm was tested by applying different initialization approaches with subsequent comparison of their results. The algorithm was proven to be robust and led to the consistent segmentation of the tumor area in three regions of different perfusion, i.e. well- perfused, hypoxic and necrotic. Results from the model-free approach were compared with a widely used pharmacokinetic (PK) model revealing significant correlations

Image Analysis for the Life Sciences - Computer-assisted Tumor Diagnostics and Digital Embryomics

Current research in the life sciences involves the analysis of such a huge amount of image data that automatization is required. This thesis presents several ways how pattern recognition techniques may contribute to improved tumor diagnostics and to the elucidation of vertebrate embryonic development. Chapter 1 studies an approach for exploiting spatial context for the improved estimation of metabolite concentrations from magnetic resonance spectroscopy imaging (MRSI) data with the aim of more robust tumor detection, and compares against a novel alternative. Chapter 2 describes a software library for training, testing and validating classification algorithms that estimate tumor probability based on MRSI. It allows flexible adaptation towards changed experimental conditions, classifier comparison and quality control without need for expertise in pattern recognition. Chapter 3 studies several models for learning tumor classifiers that allow for the common unreliability of human segmentations. For the first time, models are used for this task that additionally employ the objective image information. Chapter 4 encompasses two contributions to an image analysis pipeline for automatically reconstructing zebrafish embryonic development based on time-resolved microscopy: Two approaches for nucleus segmentation are experimentally compared, and a procedure for tracking nuclei over time is presented and evaluated

Integration of magnetic resonance spectroscopic imaging into the radiotherapy treatment planning

L'objectif de cette thèse est de proposer de nouveaux algorithmes pour surmonter les limitations actuelles et de relever les défis ouverts dans le traitement de l'imagerie spectroscopique par résonance magnétique (ISRM). L'ISRM est une modalité non invasive capable de fournir la distribution spatiale des composés biochimiques (métabolites) utilisés comme biomarqueurs de la maladie. Les informations fournies par l'ISRM peuvent être utilisées pour le diagnostic, le traitement et le suivi de plusieurs maladies telles que le cancer ou des troubles neurologiques. Cette modalité se montre utile en routine clinique notamment lorsqu'il est possible d'en extraire des informations précises et fiables. Malgré les nombreuses publications sur le sujet, l'interprétation des données d'ISRM est toujours un problème difficile en raison de différents facteurs tels que le faible rapport signal sur bruit des signaux, le chevauchement des raies spectrales ou la présence de signaux de nuisance. Cette thèse aborde le problème de l'interprétation des données d'ISRM et la caractérisation de la rechute des patients souffrant de tumeurs cérébrales. Ces objectifs sont abordés à travers une approche méthodologique intégrant des connaissances a priori sur les données d'ISRM avec une régularisation spatio-spectrale. Concernant le cadre applicatif, cette thèse contribue à l'intégration de l'ISRM dans le workflow de traitement en radiothérapie dans le cadre du projet européen SUMMER (Software for the Use of Multi-Modality images in External Radiotherapy) financé par la Commission européenne (FP7-PEOPLE-ITN).The aim of this thesis is to propose new algorithms to overcome the current limitations and to address the open challenges in the processing of magnetic resonance spectroscopic imaging (MRSI) data. MRSI is a non-invasive modality able to provide the spatial distribution of relevant biochemical compounds (metabolites) commonly used as biomarkers of disease. Information provided by MRSI can be used as a valuable insight for the diagnosis, treatment and follow-up of several diseases such as cancer or neurological disorders. Obtaining accurate and reliable information from in vivo MRSI signals is a crucial requirement for the clinical utility of this technique. Despite the numerous publications on the topic, the interpretation of MRSI data is still a challenging problem due to different factors such as the low signal-to-noise ratio (SNR) of the signals, the overlap of spectral lines or the presence of nuisance components. This thesis addresses the problem of interpreting MRSI data and characterizing recurrence in tumor brain patients. These objectives are addressed through a methodological approach based on novel processing methods that incorporate prior knowledge on the MRSI data using a spatio-spectral regularization. As an application, the thesis addresses the integration of MRSI into the radiotherapy treatment workflow within the context of the European project SUMMER (Software for the Use of Multi-Modality images in External Radiotherapy) founded by the European Commission (FP7-PEOPLE-ITN framework)

Brainlesion: Glioma, Multiple Sclerosis, Stroke and Traumatic Brain Injuries

This two-volume set LNCS 12962 and 12963 constitutes the thoroughly refereed proceedings of the 7th International MICCAI Brainlesion Workshop, BrainLes 2021, as well as the RSNA-ASNR-MICCAI Brain Tumor Segmentation (BraTS) Challenge, the Federated Tumor Segmentation (FeTS) Challenge, the Cross-Modality Domain Adaptation (CrossMoDA) Challenge, and the challenge on Quantification of Uncertainties in Biomedical Image Quantification (QUBIQ). These were held jointly at the 23rd Medical Image Computing for Computer Assisted Intervention Conference, MICCAI 2020, in September 2021. The 91 revised papers presented in these volumes were selected form 151 submissions. Due to COVID-19 pandemic the conference was held virtually. This is an open access book

Synergizing human-machine intelligence: Visualizing, labeling, and mining the electronic health record

We live in a world where data surround us in every aspect of our lives. The key challenge for humans and machines is how we can make better use of such data. Imagine what would happen if you were to have intelligent machines that could give you insight into the data. Insight that will enable you to better 1) reason about, 2) learn, and 3) understand the underlying phenomena that produced the data. The possibilities of combined human-machine intelligence are endless and will impact our lives in ways we can not even imagine today. Synergistic human-machine intelligence aims to facilitate the analytical reasoning and inference process of humans by creating machines that maximize a human's ability to 1) reason about, 2) learn, and 3) understand large, complex, and heterogeneous data. Combined human-machine intelligence is a powerful symbiosis of mutual benefit, in which we depend on the computational capabilities of the machine for the tasks we are not good at, and the machine requires human intervention for the tasks it performs poorly on. This relationship provides a compelling alternative to either approach in isolation for solving today's and tomorrow's arising data challenges. In his regard, this dissertation proposes a diverse analytical framework that leverages synergistic human-machine intelligence to maximize a human's ability to better 1) reason about, 2) learn, and 3) understand different biomedical imaging and healthcare data present in the patient's electronic health record (EHR). Correspondingly, we approach the data analyses problem from the 1) visualization, 2) labeling, and 3) mining perspective and demonstrate the efficacy of our analytics on specific application scenarios and various data domains. In the first part of this dissertation we explore the question how we can build intelligent imaging analytics that are commensurate with human capabilities and constraints, specifically for optimizing data visualization and automated labeling workflows. Our journey starts with heuristic rule-based analytical models that are derived from task-specific human knowledge. From this experience, we move on to data-driven analytics, where we adapt and combine the intelligence of the model based on prior information provided by the human and synthetic knowledge learned from partial data observations. Within this realm, we propose a novel Bayesian transductive Markov random field model that requires minimal human intervention and is able to cope with scarce label information to learn and infer object shapes in complex spatial, multimodal, spatio-temporal, and longitudinal data. We then study the question how machines can learn discriminative object representations from dense human provided label information by investigating learning and inference mechanisms that make use of deep learning architectures. The developed analytics can aid visualization and labeling tasks, which enables the interpretation and quantification of clinically relevant image information. The second part explores the question how we can build data-driven analytics for exploratory analysis in longitudinal event data that are commensurate with human capabilities and constraints. We propose human-intuitive analytics that enable the representation and discovery of interpretable event patterns to ease knowledge absorption and comprehension of the employed analytics model and the underlying data. We propose a novel doubly-constrained convolutional sparse-coding framework that learns interpretable and shift-invariant latent temporal event patterns. We apply the model to mine complex event data in EHRs. By mapping the event space to heterogeneous patient encounters in the EHR we explore the linkage between healthcare resource utilization (HRU) in relation to disease severity. This linkage may help to better understand how disease specific co-morbidities and their clinical attributes incur different HRU patterns. Such insight helps to characterize the patient's care history, which then enables the comparison against clinical practice guidelines, the discovery of prevailing practices based on common HRU group patterns, and the identification of outliers that might indicate poor patient management

Restauration d'images en IRM anatomique pour l'étude préclinique des marqueurs du vieillissement cérébral

Les maladies neurovasculaires et neurodégénératives liées à l'âge sont en forte augmentation. Alors que ces changements pathologiques montrent des effets sur le cerveau avant l'apparition de symptômes cliniques, une meilleure compréhension du processus de vieillissement normal du cerveau aidera à distinguer l'impact des pathologies connues sur la structure régionale du cerveau. En outre, la connaissance des schémas de rétrécissement du cerveau dans le vieillissement normal pourrait conduire à une meilleure compréhension de ses causes et peut-être à des interventions réduisant la perte de fonctions cérébrales associée à l'atrophie cérébrale. Par conséquent, ce projet de thèse vise à détecter les biomarqueurs du vieillissement normal et pathologique du cerveau dans un modèle de primate non humain, le singe marmouset (Callithrix Jacchus), qui possède des caractéristiques anatomiques plus proches de celles des humains que de celles des rongeurs. Cependant, les changements structurels (par exemple, de volumes, d'épaisseur corticale) qui peuvent se produire au cours de leur vie adulte peuvent être minimes à l'échelle de l'observation. Dans ce contexte, il est essentiel de disposer de techniques d'observation offrant un contraste et une résolution spatiale suffisamment élevés et permettant des évaluations détaillées des changements morphométriques du cerveau associé au vieillissement. Cependant, l'imagerie de petits cerveaux dans une plateforme IRM 3T dédiée à l'homme est une tâche difficile car la résolution spatiale et le contraste obtenus sont insuffisants par rapport à la taille des structures anatomiques observées et à l'échelle des modifications attendues. Cette thèse vise à développer des méthodes de restauration d'image pour les images IRM précliniques qui amélioreront la robustesse des algorithmes de segmentation. L'amélioration de la résolution spatiale des images à un rapport signal/bruit constant limitera les effets de volume partiel dans les voxels situés à la frontière entre deux structures et permettra une meilleure segmentation tout en augmentant la reproductibilité des résultats. Cette étape d'imagerie computationnelle est cruciale pour une analyse morphométrique longitudinale fiable basée sur les voxels et l'identification de marqueurs anatomiques du vieillissement cérébral en suivant les changements de volume dans la matière grise, la matière blanche et le liquide cérébral.Age-related neurovascular and neurodegenerative diseases are increasing significantly. While such pathological changes show effects on the brain before clinical symptoms appear, a better understanding of the normal aging brain process will help distinguish known pathologies' impact on regional brain structure. Furthermore, knowledge of the patterns of brain shrinkage in normal aging could lead to a better understanding of its causes and perhaps to interventions reducing the loss of brain functions. Therefore, this thesis project aims to detect normal and pathological brain aging biomarkers in a non-human primate model, the marmoset monkey (Callithrix Jacchus) which possesses anatomical characteristics more similar to humans than rodents. However, structural changes (e.g., volumes, cortical thickness) that may occur during their adult life may be minimal with respect to the scale of observation. In this context, it is essential to have observation techniques that offer sufficiently high contrast and spatial resolution and allow detailed assessments of the morphometric brain changes associated with aging. However, imaging small brains in a 3T MRI platform dedicated to humans is a challenging task because the spatial resolution and the contrast obtained are insufficient compared to the size of the anatomical structures observed and the scale of the xpected changes with age. This thesis aims to develop image restoration methods for preclinical MR images that will improve the robustness of the segmentation algorithms. Improving the resolution of the images at a constant signal-to-noise ratio will limit the effects of partial volume in voxels located at the border between two structures and allow a better segmentation while increasing the results' reproducibility. This computational imaging step is crucial for a reliable longitudinal voxel-based morphometric analysis and for the identification of anatomical markers of brain aging by following the volume changes in gray matter, white matter and cerebrospinal fluid