3D - Patch Based Machine Learning Systems for Alzheimer’s Disease classification via 18F-FDG PET Analysis

abstract: Alzheimer’s disease (AD), is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. There is growing interest in identifying brain image biomarkers that help evaluate AD risk pre-symptomatically. High-dimensional non-linear pattern classification methods have been applied to structural magnetic resonance images (MRI’s) and used to discriminate between clinical groups in Alzheimers progression. Using Fluorodeoxyglucose (FDG) positron emission tomography (PET) as the pre- ferred imaging modality, this thesis develops two independent machine learning based patch analysis methods and uses them to perform six binary classification experiments across different (AD) diagnostic categories. Specifically, features were extracted and learned using dimensionality reduction and dictionary learning & sparse coding by taking overlapping patches in and around the cerebral cortex and using them as fea- tures. Using AdaBoost as the preferred choice of classifier both methods try to utilize 18F-FDG PET as a biological marker in the early diagnosis of Alzheimer’s . Addi- tional we investigate the involvement of rich demographic features (ApoeE3, ApoeE4 and Functional Activities Questionnaires (FAQ)) in classification. The experimental results on Alzheimer’s Disease Neuroimaging initiative (ADNI) dataset demonstrate the effectiveness of both the proposed systems. The use of 18F-FDG PET may offer a new sensitive biomarker and enrich the brain imaging analysis toolset for studying the diagnosis and prognosis of AD.Dissertation/ThesisThesis Defense PresentationMasters Thesis Computer Science 201

Dealing with heterogeneity in the prediction of clinical diagnosis

Le diagnostic assisté par ordinateur est un domaine de recherche en émergence et se situe à l’intersection de l’imagerie médicale et de l’apprentissage machine. Les données médi- cales sont de nature très hétérogène et nécessitent une attention particulière lorsque l’on veut entraîner des modèles de prédiction. Dans cette thèse, j’ai exploré deux sources d’hétérogénéité, soit l’agrégation multisites et l’hétérogénéité des étiquettes cliniques dans le contexte de l’imagerie par résonance magnétique (IRM) pour le diagnostic de la maladie d’Alzheimer (MA). La première partie de ce travail consiste en une introduction générale sur la MA, l’IRM et les défis de l’apprentissage machine en imagerie médicale. Dans la deuxième partie de ce travail, je présente les trois articles composant la thèse. Enfin, la troisième partie porte sur une discussion des contributions et perspectives fu- tures de ce travail de recherche. Le premier article de cette thèse montre que l’agrégation des données sur plusieurs sites d’acquisition entraîne une certaine perte, comparative- ment à l’analyse sur un seul site, qui tend à diminuer plus la taille de l’échantillon aug- mente. Le deuxième article de cette thèse examine la généralisabilité des modèles de prédiction à l’aide de divers schémas de validation croisée. Les résultats montrent que la formation et les essais sur le même ensemble de sites surestiment la précision du modèle, comparativement aux essais sur des nouveaux sites. J’ai également montré que l’entraînement sur un grand nombre de sites améliore la précision sur des nouveaux sites. Le troisième et dernier article porte sur l’hétérogénéité des étiquettes cliniques et pro- pose un nouveau cadre dans lequel il est possible d’identifier un sous-groupe d’individus qui partagent une signature homogène hautement prédictive de la démence liée à la MA. Cette signature se retrouve également chez les patients présentant des symptômes mod- érés. Les résultats montrent que 90% des sujets portant la signature ont progressé vers la démence en trois ans. Les travaux de cette thèse apportent ainsi de nouvelles con- tributions à la manière dont nous approchons l’hétérogénéité en diagnostic médical et proposent des pistes de solution pour tirer profit de cette hétérogénéité.Computer assisted diagnosis has emerged as a popular area of research at the intersection of medical imaging and machine learning. Medical data are very heterogeneous in nature and therefore require careful attention when one wants to train prediction models. In this thesis, I explored two sources of heterogeneity, multisite aggregation and clinical label heterogeneity, in an application of magnetic resonance imaging to the diagnosis of Alzheimer’s disease. In the process, I learned about the feasibility of multisite data aggregation and how to leverage that heterogeneity in order to improve generalizability of prediction models. Part one of the document is a general context introduction to Alzheimer’s disease, magnetic resonance imaging, and machine learning challenges in medical imaging. In part two, I present my research through three articles (two published and one in preparation). Finally, part three provides a discussion of my contributions and hints to possible future developments. The first article shows that data aggregation across multiple acquisition sites incurs some loss, compared to single site analysis, that tends to diminish as the sample size increase. These results were obtained through semisynthetic Monte-Carlo simulations based on real data. The second article investigates the generalizability of prediction models with various cross-validation schemes. I showed that training and testing on the same batch of sites over-estimates the accuracy of the model, compared to testing on unseen sites. However, I also showed that training on a large number of sites improves the accuracy on unseen sites. The third article, on clinical label heterogeneity, proposes a new framework where we can identify a subgroup of individuals that share a homogeneous signature highly predictive of AD dementia. That signature could also be found in patients with mild symptoms, 90% of whom progressed to dementia within three years. The thesis thus makes new contributions to dealing with heterogeneity in medical diagnostic applications and proposes ways to leverage that heterogeneity to our benefit

Advances in Analysis and Exploration in Medical Imaging

With an ever increasing life expectancy, we see a concomitant increase in diseases capable of disrupting normal cognitive processes. Their diagnoses are difficult, and occur usually after daily living activities have already been compromised. This dissertation proposes machine learning methods for the study of the neurological implications of brain lesions. It addresses the analysis and exploration of medical imaging data, with particular emphasis to (f)MRI. Two main research directions are proposed. In the first, a brain tissue segmentation approach is detailed. In the second, a document mining framework, applied to reports of neuroscientific studies, is described. Both directions are based on retrieving consistent information from multi-modal data. A contribution in this dissertation is the application of a semi-supervised method, discriminative clustering, to identify different brain tissues and their partial volume information. The proposed method relies on variations of tissue distributions in multi-spectral MRI, and reduces the need for a priori information. This methodology was successfully applied to the study of multiple sclerosis and age related white matter diseases. It was also showed that early-stage changes of normal-appearing brain tissue can already predict decline in certain cognitive processes. Another contribution in this dissertation is in neuroscience meta-research. One limitation in neuroimage processing relates to data availability. Through document mining of neuroscientific reports, using images as source of information, one can harvest research results dealing with brain lesions. The context of such results can be extracted from textual information, allowing for an intelligent categorisation of images. This dissertation proposes new principles, and a combination of several techniques to the study of published fMRI reports. These principles are based on a number of distance measures, to compare various brain activity sites. Application to studies of the default mode network validated the proposed approach. The aforementioned methodologies rely on clustering approaches. When dealing with such strategies, most results depend on the choice of initialisation and parameter settings. By defining distance measures that search for clusters of consistent elements, one can estimate a degree of reliability for each data grouping. In this dissertation, it is shown that such principles can be applied to multiple runs of various clustering algorithms, allowing for a more robust estimation of data agglomeration

Multimodal MRI characterization of visual word recognition: an integrative view

228 p.The ventral occipito-temporal (vOT) association cortex contributes significantly to recognize different types of visual patterns. It is widely accepted that a subset of this circuitry, including the visual word form area (VWFA), becomes trained to perform the task of rapidly identifying word forms. An important open question is the computational role of this circuitry: To what extent is part of a bottom-up hierarchical processing of information on visual word recognition and/or is involved in processing top-down signals from higher-level language regions. This doctoral dissertation thesis proposal is aimed at characterizing the vOT reading circuitry using behavioral, functional, structural and quantitative MRI indexes, and linking its computations to the other two important regions within the language network: the posterior parietal cortex (pPC) and the inferior frontal gyrus (IFG). Results revealed that two distinct word-responsive areas can be segregated in the vOT: one responsible for visual feature extraction that is connected to the intraparietal sulcus via the vertical occipital fasciculus and a second one responsible for semantic processing that is connected to the angular gyrus via the posterior arcuate fasciculus and to the IFG via the anterior arcuate fasciculus. Importantly, reading behavior was predicted by functional activation in regions identified along the vOT, pPC and IFG, as well as by structural properties of the white matter fiber tracts linking them. The present work constitutes a critical step in the creation of a highly detailed characterization of the early stages of reading at the individual-subject level and to establish a baseline model and parameter range that might serve to clarify functional and structural differences between typical, poor and atypical readers.BCBL: basque center on cognition, brain and languag

Novel Semi-Supervised Learning Models to Balance Data Inclusivity and Usability in Healthcare Applications

abstract: Semi-supervised learning (SSL) is sub-field of statistical machine learning that is useful for problems that involve having only a few labeled instances with predictor (X) and target (Y) information, and abundance of unlabeled instances that only have predictor (X) information. SSL harnesses the target information available in the limited labeled data, as well as the information in the abundant unlabeled data to build strong predictive models. However, not all the included information is useful. For example, some features may correspond to noise and including them will hurt the predictive model performance. Additionally, some instances may not be as relevant to model building and their inclusion will increase training time and potentially hurt the model performance. The objective of this research is to develop novel SSL models to balance data inclusivity and usability. My dissertation research focuses on applications of SSL in healthcare, driven by problems in brain cancer radiomics, migraine imaging, and Parkinson’s Disease telemonitoring. The first topic introduces an integration of machine learning (ML) and a mechanistic model (PI) to develop an SSL model applied to predicting cell density of glioblastoma brain cancer using multi-parametric medical images. The proposed ML-PI hybrid model integrates imaging information from unbiopsied regions of the brain as well as underlying biological knowledge from the mechanistic model to predict spatial tumor density in the brain. The second topic develops a multi-modality imaging-based diagnostic decision support system (MMI-DDS). MMI-DDS consists of modality-wise principal components analysis to incorporate imaging features at different aggregation levels (e.g., voxel-wise, connectivity-based, etc.), a constrained particle swarm optimization (cPSO) feature selection algorithm, and a clinical utility engine that utilizes inverse operators on chosen principal components for white-box classification models. The final topic develops a new SSL regression model with integrated feature and instance selection called s2SSL (with “s2” referring to selection in two different ways: feature and instance). s2SSL integrates cPSO feature selection and graph-based instance selection to simultaneously choose the optimal features and instances and build accurate models for continuous prediction. s2SSL was applied to smartphone-based telemonitoring of Parkinson’s Disease patients.Dissertation/ThesisDoctoral Dissertation Industrial Engineering 201

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202