Multidirectional and Topography-based Dynamic-scale Varifold Representations with Application to Matching Developing Cortical Surfaces

The human cerebral cortex is marked by great complexity as well as substantial dynamic changes during early postnatal development. To obtain a fairly comprehensive picture of its age-induced and/or disorder-related cortical changes, one needs to match cortical surfaces to one another, while maximizing their anatomical alignment. Methods that geodesically shoot surfaces into one another as currents (a distribution of oriented normals) and varifolds (a distribution of non-oriented normals) provide an elegant Riemannian framework for generic surface matching and reliable statistical analysis. However, both conventional current and varifold matching methods have two key limitations. First, they only use the normals of the surface to measure its geometry and guide the warping process, which overlooks the importance of the orientations of the inherently convoluted cortical sulcal and gyral folds. Second, the ‘conversion’ of a surface into a current or a varifold operates at a fixed scale under which geometric surface details will be neglected, which ignores the dynamic scales of cortical foldings. To overcome these limitations and improve varifold-based cortical surface registration, we propose two different strategies. The first strategy decomposes each cortical surface into its normal and tangent varifold representations, by integrating principal curvature direction field into the varifold matching framework, thus providing rich information of the orientation of cortical folding and better characterization of the complex cortical geometry. The second strategy explores the informative cortical geometric features to perform a dynamic-scale measurement of the cortical surface that depends on the local surface topography (e.g., principal curvature), thereby we introduce the concept of a topography-based dynamic-scale varifold. We tested the proposed varifold variants for registering 12 pairs of dynamically developing cortical surfaces from 0 to 6 months of age. Both variants improved the matching accuracy in terms of closeness to the target surface and the goodness of alignment with regional anatomical boundaries, when compared with three state-of-the-art methods: (1) diffeomorphic spectral matching, (2) conventional current-based surface matching, and (3) conventional varifold-based surface matching

Combining spatial priors and anatomical information for fMRI detection

In this paper, we analyze Markov Random Field (MRF) as a spatial regularizer in fMRI detection. The low signal-to-noise ratio (SNR) in fMRI images presents a serious challenge for detection algorithms, making regularization necessary to achieve good detection accuracy. Gaussian smoothing, traditionally employed to boost SNR, often produces over-smoothed activation maps. Recently, the use of MRF priors has been suggested as an alternative regularization approach. However, solving for an optimal configuration of the MRF is NP-hard in general. In this work, we investigate fast inference algorithms based on the Mean Field approximation in application to MRF priors for fMRI detection. Furthermore, we propose a novel way to incorporate anatomical information into the MRF-based detection framework and into the traditional smoothing methods. Intuitively speaking, the anatomical evidence increases the likelihood of activation in the gray matter and improves spatial coherency of the resulting activation maps within each tissue type. Validation using the receiver operating characteristic (ROC) analysis and the confusion matrix analysis on simulated data illustrates substantial improvement in detection accuracy using the anatomically guided MRF spatial regularizer. We further demonstrate the potential benefits of the proposed method in real fMRI signals of reduced length. The anatomically guided MRF regularizer enables significant reduction of the scan length while maintaining the quality of the resulting activation maps.National Institutes of Health (U.S.) (National Institute for Biomedical Imaging and Bioengineering (U.S.)/National Alliance for Medical Image Computing (U.S.) Grant U54-EB005149)National Science Foundation (U.S.) (Grant IIS 9610249)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Biomedical Informatics Research Network Grant U24-RR021382)National Institutes of Health (U.S.) (National Center for Research Resources (U.S.)/Neuroimaging Analysis Center (U.S.) Grant P41-RR13218)National Institutes of Health (U.S.) (National Institute of Neurological Disorders and Stroke (U.S.) Grant R01-NS051826)National Science Foundation (U.S.) (CAREER Grant 0642971)National Science Foundation (U.S.). Graduate Research FellowshipNational Center for Research Resources (U.S.) (FIRST-BIRN Grant)Neuroimaging Analysis Center (U.S.

Visual Exploration And Information Analytics Of High-Dimensional Medical Images

Data visualization has transformed how we analyze increasingly large and complex data sets. Advanced visual tools logically represent data in a way that communicates the most important information inherent within it and culminate the analysis with an insightful conclusion. Automated analysis disciplines - such as data mining, machine learning, and statistics - have traditionally been the most dominant fields for data analysis. It has been complemented with a near-ubiquitous adoption of specialized hardware and software environments that handle the storage, retrieval, and pre- and postprocessing of digital data. The addition of interactive visualization tools allows an active human participant in the model creation process. The advantage is a data-driven approach where the constraints and assumptions of the model can be explored and chosen based on human insight and confirmed on demand by the analytic system. This translates to a better understanding of data and a more effective knowledge discovery. This trend has become very popular across various domains, not limited to machine learning, simulation, computer vision, genetics, stock market, data mining, and geography. In this dissertation, we highlight the role of visualization within the context of medical image analysis in the field of neuroimaging. The analysis of brain images has uncovered amazing traits about its underlying dynamics. Multiple image modalities capture qualitatively different internal brain mechanisms and abstract it within the information space of that modality. Computational studies based on these modalities help correlate the high-level brain function measurements with abnormal human behavior. These functional maps are easily projected in the physical space through accurate 3-D brain reconstructions and visualized in excellent detail from different anatomical vantage points. Statistical models built for comparative analysis across subject groups test for significant variance within the features and localize abnormal behaviors contextualizing the high-level brain activity. Currently, the task of identifying the features is based on empirical evidence, and preparing data for testing is time-consuming. Correlations among features are usually ignored due to lack of insight. With a multitude of features available and with new emerging modalities appearing, the process of identifying the salient features and their interdependencies becomes more difficult to perceive. This limits the analysis only to certain discernible features, thus limiting human judgments regarding the most important process that governs the symptom and hinders prediction. These shortcomings can be addressed using an analytical system that leverages data-driven techniques for guiding the user toward discovering relevant hypotheses. The research contributions within this dissertation encompass multidisciplinary fields of study not limited to geometry processing, computer vision, and 3-D visualization. However, the principal achievement of this research is the design and development of an interactive system for multimodality integration of medical images. The research proceeds in various stages, which are important to reach the desired goal. The different stages are briefly described as follows: First, we develop a rigorous geometry computation framework for brain surface matching. The brain is a highly convoluted structure of closed topology. Surface parameterization explicitly captures the non-Euclidean geometry of the cortical surface and helps derive a more accurate registration of brain surfaces. We describe a technique based on conformal parameterization that creates a bijective mapping to the canonical domain, where surface operations can be performed with improved efficiency and feasibility. Subdividing the brain into a finite set of anatomical elements provides the structural basis for a categorical division of anatomical view points and a spatial context for statistical analysis. We present statistically significant results of our analysis into functional and morphological features for a variety of brain disorders. Second, we design and develop an intelligent and interactive system for visual analysis of brain disorders by utilizing the complete feature space across all modalities. Each subdivided anatomical unit is specialized by a vector of features that overlap within that element. The analytical framework provides the necessary interactivity for exploration of salient features and discovering relevant hypotheses. It provides visualization tools for confirming model results and an easy-to-use interface for manipulating parameters for feature selection and filtering. It provides coordinated display views for visualizing multiple features across multiple subject groups, visual representations for highlighting interdependencies and correlations between features, and an efficient data-management solution for maintaining provenance and issuing formal data queries to the back end

Altered EEG Oscillatory Brain Networks During Music-Listening in Major Depression

To examine the electrophysiological underpinnings of the functional networks involved in music listening, previous approaches based on spatial independent component analysis (ICA) have recently been used to ongoing electroencephalography (EEG) and magnetoencephalography (MEG). However, those studies focused on healthy subjects, and failed to examine the group-level comparisons during music listening. Here, we combined group-level spatial Fourier ICA with acoustic feature extraction, to enable group comparisons in frequency-specific brain networks of musical feature processing. It was then applied to healthy subjects and subjects with major depressive disorder (MDD). The music-induced oscillatory brain patterns were determined by permutation correlation analysis between individual time courses of Fourier-ICA components and musical features. We found that (1) three components, including a beta sensorimotor network, a beta auditory network and an alpha medial visual network, were involved in music processing among most healthy subjects; and that (2) one alpha lateral component located in the left angular gyrus was engaged in music perception in most individuals with MDD. The proposed method allowed the statistical group comparison, and we found that: (1) the alpha lateral component was activated more strongly in healthy subjects than in the MDD individuals, and that (2) the derived frequency-dependent networks of musical feature processing seemed to be altered in MDD participants compared to healthy subjects. The proposed pipeline appears to be valuable for studying disrupted brain oscillations in psychiatric disorders during naturalistic paradigms.Peer reviewe

Doctor of Philosophy in Computing

dissertationStatistical shape analysis has emerged as an important tool for the quantitative analysis of anatomy in many medical imaging applications. The correspondence based approach to evaluate shape variability is a popular method, based on comparing configurations of carefully placed landmarks on each shape. In recent years, methods for automatic placement of landmarks have enhanced the ability of this approach to capture statistical properties of shape populations. However, biomedical shapes continue to present considerable difficulties in automatic correspondence optimization due to inherent geometric complexity and the need to correlate shape change with underlying biological parameters. This dissertation addresses these technical difficulties and presents improved shape correspondence models. In particular, this dissertation builds on the particle-based modeling (PBM) framework described by Joshua Cates' 2010 Ph.D. dissertation. In the PBM framework, correspondences are modeled as a set of dynamic points or a particle system, positioned automatically on shape surfaces by optimizing entropy contained in the model, with the idea of balancing model simplicity against accuracy of the particle system representation of shapes. This dissertation is a collection of four papers that extend the PBM framework to include shape regression and longitudinal analysis and also adds new methods to improve modeling of complex shapes. It also includes a summary of two applications from the field of orthopaedics. Technical details of the PBM framework are provided in Chapter 2, after which the first topic related to the study of shape change over time is addressed (Chapters 3 and 4). In analyses of normative growth or disease progression, shape regression models allow characterization of the underlying biological process while also facilitating comparison of a sample against a normative model. The first paper introduces a shape regression model into the PBM framework to characterize shape variability due to an underlying biological parameter. It further confirms the statistical significance of this relationship via systematic permutation testing. Simple regression models are, however, not sufficient to leverage information provided by longitudinal studies. Longitudinal studies collect data at multiple time points for each participant and have the potential to provide a rich picture of the anatomical changes occurring during development, disease progression, or recovery. The second paper presents a linear-mixed-effects (LME) shape model in order to fully leverage the high-dimensional, complex features provided by longitudinal data. The parameters of the LME shape model are estimated in a hierarchical manner within the PBM framework. The topic of geometric complexity present in certain biological shapes is addressed next (Chapters 5 and 6). Certain biological shapes are inherently complex and highly variable, inhibiting correspondence based methods from producing a faithful representation of the average shape. In the PBM framework, use of Euclidean distances leads to incorrect particle system interactions while a position-only representation leads to incorrect correspondences around sharp features across shapes. The third paper extends the PBM framework to use efficiently computed geodesic distances and also adds an entropy term based on the surface normal. The fourth paper further replaces the position-only representation with a more robust distance-from-landmark feature in the PBM framework to obtain isometry invariant correspondences. Finally, the above methods are applied to two applications from the field of orthopaedics. The first application uses correspondences across an ensemble of human femurs to characterize morphological shape differences due to femoroacetabular impingement. The second application involves an investigation of the short bone phenotype apparent in mouse models of multiple osteochondromas. Metaphyseal volume deviations are correlated with deviations in length to quantify the effect of cancer toward the apparent shortening of long bones (femur, tibia-fibula) in mouse models

The development and application of structural priors for diffuse optical imaging in infants from newborn to two years of age

This thesis describes the development and application of age-appropriate structural priors to improve the localisation accuracy of diffuse optical tomography (DOT) approaches in infants aged from birth to two years of age. Knowledge of the target cranial anatomy, known as a structural prior, is required to produce three-dimensional images localising concentration changes to the cortex. A structural prior would ideally be subject-specific, i.e. derived from structural magnetic resonance imaging (MRI) data from each specific subject. Requiring a structural scan from every infant participant, however, is not feasible and undermines many of the benefits of DOT. A review was conducted to catalogue available infant structural MRI data, and selected data was then used to produce structural priors for infants aged 1- to 24-months. Conventional analyses using functional near-infrared spectroscopy (fNIRS) implicitly assume that head size and array position are constant across infants. Using DOT, the validity of assuming these parameters constant in a longitudinal infant cohort was investigated. The results show that this assumption is reasonable at the group-level in infants aged 5- to 12-months but becomes less valid for smaller group sizes. A DOT approach was determined to illicit more subtle effects of activation, particularly for smaller group sizes and expected responses. Using state-of-the-art MRI data from the Developing Human Connectome Project, a database of structural priors of the neonatal head was produced for infants aged pre-term to term-equivalent age. A leave-one-out approach was used to determine how best to find a match between a given infant and a model from the database, and how best to spatially register the model to minimise the anatomical and localisation errors relative to subject-specific anatomy. Model selection based on the 10/20 scalp positions was determined to be the best method (of those based on external features of the head) to minimise these errors