Brain status modeling with non-negative projective dictionary learning

Accurate prediction of individuals’ brain age is critical to establish a baseline for normal brain development. This study proposes to model brain development with a novel non-negative projective dictionary learning (NPDL) approach, which learns a discriminative representation of multi-modal neuroimaging data for predicting brain age. Our approach encodes the variability of subjects in different age groups using separate dictionaries, projecting features into a low-dimensional manifold such that information is preserved only for the corresponding age group. The proposed framework improves upon previous discriminative dictionary learning methods by inc

Development of white matter fiber covariance networks supports executive function in youth

During adolescence, the brain undergoes extensive changes in white matter structure that support cognition. Data-driven approaches applied to cortical surface properties have led the field to understand brain development as a spatially and temporally coordinated mechanism that follows hierarchically organized gradients of change. Although white matter development also appears asynchronous, previous studies have relied largely on anatomical tract-based atlases, precluding a direct assessment of how white matter structure is spatially and temporally coordinated. Harnessing advances in diffusion modeling and machine learning, we identified 14 data-driven patterns of covarying white matter structure in a large sample of youth. Fiber covariance networks aligned with known major tracts, while also capturing distinct patterns of spatial covariance across distributed white matter locations. Most networks showed age-related increases in fiber network properties, which were also related to developmental changes in executive function. This study delineates data-driven patterns of white matter development that support cognition

Generative-Discriminative Low Rank Decomposition for Medical Imaging Applications

In this thesis, we propose a method that can be used to extract biomarkers from medical images toward early diagnosis of abnormalities. Surge of demand for biomarkers and availability of medical images in the recent years call for accurate, repeatable, and interpretable approaches for extracting meaningful imaging features. However, extracting such information from medical images is a challenging task because the number of pixels (voxels) in a typical image is in order of millions while even a large sample-size in medical image dataset does not usually exceed a few hundred. Nevertheless, depending on the nature of an abnormality, only a parsimonious subset of voxels is typically relevant to the disease; therefore various notions of sparsity are exploited in this thesis to improve the generalization performance of the prediction task. We propose a novel discriminative dimensionality reduction method that yields good classification performance on various datasets without compromising the clinical interpretability of the results. This is achieved by combining the modelling strength of generative learning framework and the classification performance of discriminative learning paradigm. Clinical interpretability can be viewed as an additional measure of evaluation and is also helpful in designing methods that account for the clinical prior such as association of certain areas in a brain to a particular cognitive task or connectivity of some brain regions via neural fibres. We formulate our method as a large-scale optimization problem to solve a constrained matrix factorization. Finding an optimal solution of the large-scale matrix factorization renders off-the-shelf solver computationally prohibitive; therefore, we designed an efficient algorithm based on the proximal method to address the computational bottle-neck of the optimization problem. Our formulation is readily extended for different scenarios such as cases where a large cohort of subjects has uncertain or no class labels (semi-supervised learning) or a case where each subject has a battery of imaging channels (multi-channel), \etc. We show that by using various notions of sparsity as feasible sets of the optimization problem, we can encode different forms of prior knowledge ranging from brain parcellation to brain connectivity

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

Predicting clinical variables from neuroimages using fused sparse group lasso

Predictive models in which neuroimage features serve as predictors and a clinical variable is modeled as the outcome are good candidates for clinical application because (1) they can exploit dependencies between predictor variables and thus potentially explain more variability in the outcome than a mass univariate approach, and (2) they allow inference at the individual level, such that a prediction can be obtained for a new individual whose data was not used to train the model. This dissertation proposes methods for neuroimaging prediction models that not only aim for predictive accuracy, but also seek interpretability and potential insight into the underlying pathophysiology of neuropsychiatric disorders. In the first part of this dissertation we propose the fused sparse group lasso penalty, which encourages structured, sparse, interpretable solutions by incorporating prior information about spatial and group structure among voxels. We derive optimization steps for fused sparse group lasso penalized regression using the alternating direction method of multipliers algorithm. With simulation studies, we demonstrate conditions under which fusion and group penalties together outperform either of them alone. We then use fused sparse group lasso to predict continuous measures from resting state magnetic resonance imaging data using the Autism Brain Imaging Data Exchange dataset. In the second part of this dissertation we use fused sparse group lasso to predict age from multimodal neuroimaging data in a sample of cognitively normal adults aged 65 and older. In general, we show how the incorporation of prior information via the fused sparse group lasso penalty can enhance the interpretability of neuroimaging predictive models while also yielding good predictive performance. Public health significance: Psychiatric disorders and neurological diseases such as Alzheimer's present a large public health burden. As of yet, there have been relatively few translations of basic neuroscience findings to clinical applications in psychiatry. Prediction models using neuroimaging data can potentially help clinicians with diagnosis and prediction of prognosis and treatment response. Establishing interpretable neuroimaging-based biomarkers can improve our understanding of the neurobiological mechanisms underlying neuropsychiatric disorders and suggest approaches for prevention and treatment