Generative discriminative models for multivariate inference and statistical mapping in medical imaging

This paper presents a general framework for obtaining interpretable multivariate discriminative models that allow efficient statistical inference for neuroimage analysis. The framework, termed generative discriminative machine (GDM), augments discriminative models with a generative regularization term. We demonstrate that the proposed formulation can be optimized in closed form and in dual space, allowing efficient computation for high dimensional neuroimaging datasets. Furthermore, we provide an analytic estimation of the null distribution of the model parameters, which enables efficient statistical inference and p-value computation without the need for permutation testing. We compared the proposed method with both purely generative and discriminative learning methods in two large structural magnetic resonance imaging (sMRI) datasets of Alzheimer's disease (AD) (n=415) and Schizophrenia (n=853). Using the AD dataset, we demonstrated the ability of GDM to robustly handle confounding variations. Using Schizophrenia dataset, we demonstrated the ability of GDM to handle multi-site studies. Taken together, the results underline the potential of the proposed approach for neuroimaging analyses.Comment: To appear in MICCAI 2018 proceeding

Visual Feature Attribution using Wasserstein GANs

Attributing the pixels of an input image to a certain category is an important and well-studied problem in computer vision, with applications ranging from weakly supervised localisation to understanding hidden effects in the data. In recent years, approaches based on interpreting a previously trained neural network classifier have become the de facto state-of-the-art and are commonly used on medical as well as natural image datasets. In this paper, we discuss a limitation of these approaches which may lead to only a subset of the category specific features being detected. To address this problem we develop a novel feature attribution technique based on Wasserstein Generative Adversarial Networks (WGAN), which does not suffer from this limitation. We show that our proposed method performs substantially better than the state-of-the-art for visual attribution on a synthetic dataset and on real 3D neuroimaging data from patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). For AD patients the method produces compellingly realistic disease effect maps which are very close to the observed effects.Comment: Accepted to CVPR 201

SubCMap: subject and condition specific effect maps

Current methods for statistical analysis of neuroimaging data identify condition related structural alterations in the human brain by detecting group differences. They construct detailed maps showing population-wide changes due to a condition of interest. Although extremely useful, methods do not provide information on the subject-specific structural alterations and they have limited diagnostic value because group assignments for each subject are required for the analysis. In this article, we propose SubCMap, a novel method to detect subject and condition specific structural alterations. SubCMap is designed to work without the group assignment information in order to provide diagnostic value. Unlike outlier detection methods, SubCMap detections are condition-specific and can be used to study the effects of various conditions or for diagnosing diseases. The method combines techniques from classification, generalization error estimation and image restoration to the identify the condition-related alterations. Experimental evaluation is performed on synthetically generated data as well as data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Results on synthetic data demonstrate the advantages of SubCMap compared to population-wide techniques and higher detection accuracy compared to outlier detection. Analysis with the ADNI dataset show that SubCMap detections on cortical thickness data well correlate with non-imaging markers of Alzheimer's Disease (AD), the Mini Mental State Examination Score and Cerebrospinal Fluid amyloid-β levels, suggesting the proposed method well captures the inter-subject variation of AD effects

Random Forests Based Group Importance Scores and Their Statistical Interpretation: Application for Alzheimer's Disease

Machine learning approaches have been increasingly used in the neuroimaging field for the design of computer-aided diagnosis systems. In this paper, we focus on the ability of these methods to provide interpretable information about the brain regions that are the most informative about the disease or condition of interest. In particular, we investigate the benefit of group-based, instead of voxel-based, analyses in the context of Random Forests. Assuming a prior division of the voxels into non overlapping groups (defined by an atlas), we propose several procedures to derive group importances from individual voxel importances derived from Random Forests models. We then adapt several permutation schemes to turn group importance scores into more interpretable statistical scores that allow to determine the truly relevant groups in the importance rankings. The good behaviour of these methods is first assessed on artificial datasets. Then, they are applied on our own dataset of FDG-PET scans to identify the brain regions involved in the prognosis of Alzheimer's disease

Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers. DISCUSSION: Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial desig