A Multivariate Surface-Based Analysis of the Putamen in Premature Newborns: Regional Differences within the Ventral Striatum

Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamo-cortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiato-thalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates. © 2013 Shi et al

Unified Heat Kernel Regression for Diffusion, Kernel Smoothing and Wavelets on Manifolds and Its Application to Mandible Growth Modeling in CT Images

We present a novel kernel regression framework for smoothing scalar surface data using the Laplace-Beltrami eigenfunctions. Starting with the heat kernel constructed from the eigenfunctions, we formulate a new bivariate kernel regression framework as a weighted eigenfunction expansion with the heat kernel as the weights. The new kernel regression is mathematically equivalent to isotropic heat diffusion, kernel smoothing and recently popular diffusion wavelets. Unlike many previous partial differential equation based approaches involving diffusion, our approach represents the solution of diffusion analytically, reducing numerical inaccuracy and slow convergence. The numerical implementation is validated on a unit sphere using spherical harmonics. As an illustration, we have applied the method in characterizing the localized growth pattern of mandible surfaces obtained in CT images from subjects between ages 0 and 20 years by regressing the length of displacement vectors with respect to the template surface.Comment: Accepted in Medical Image Analysi

CLASSIFICATION OF NEUROANATOMICAL STRUCTURES BASED ON NON-EUCLIDEAN GEOMETRIC OBJECT PROPERTIES

Studying the observed morphological differences in neuroanatomical structures between individuals with neurodevelopmental disorders and a control group of typically developing individuals has been an important objective. Researchers study the differences with two goals: to assist an accurate diagnosis of the disease and to gain insights into underlying mechanisms of the disease that cause such changes. Shape classification is commonly utilized in such studies. An effective classification is difficult because it requires 1) a choice of an object model that can provide rich geometric object properties (GOPs) relevant for a given classification task, and 2) a choice of a statistical classification method that accounts for the non-Euclidean nature of GOPs. I lay out my methodological contributions to address the aforementioned challenges in the context of early diagnosis and detection of Autism Spectrum Disorder (ASD) in infants based on shapes of hippocampi and caudate nuclei; morphological deviations in these structures between individuals with ASD and typically developing individuals have been reported in the literature. These contributions respectively lead to 1) an effective modeling of shapes of objects of interest and 2) an effective classification. As the first contribution for modeling shapes of objects, I propose a method to obtain a set of skeletal models called s-reps from a set of 3D objects. First, the method iteratively deforms the object surface via Mean Curvature Flow (MCF) until the deformed surface is approximately ellipsoidal. Then, an s-rep of the approximate ellipsoid is obtained analytically. Finally, the ellipsoid s-rep is deformed via a series of inverse MCF transformations. The method has two important properties: 1) it is fully automatic, and 2) it yields a set of s-reps with good correspondence across the set. The method is shown effective in generating a set of s-reps for a few neuroanatomical structures. As the second contribution with respect to modeling shapes of objects, I introduce an extension to the current s-rep for representing an object with a narrowing sharp tail. This includes a spoke interpolation method for interpolating a discrete s-rep of an object with a narrowing sharp tail into a continuous object. This extension is necessary for representing surface geometry of objects whose boundary has a singular point. I demonstrate that this extension allows appropriate surface modeling of a narrowing sharp tail region of the caudate nucleus. In addition, I show that the extension is beneficial in classifying autistic and non-autistic infants at high risk of ASD based on shapes of caudate nuclei. As the first contribution with respect to statistical methods, I propose a novel shape classification framework that uses the s-rep to capture rich localized geometric descriptions of an object, a statistical method called Principal Nested Spheres (PNS) analysis to handle the non-Euclidean s-rep GOPs, and a classification method called Distance Weighted Discrimination (DWD). I evaluate the effectiveness of the proposed method in classifying autistic and non-autistic infants based on either hippocampal shapes or caudate shapes in terms of the Area Under the ROC curve (AUC). In addition, I show that the proposed method is superior to commonly used shape classification methods in the literature. As my final methodological contribution, I extend the proposed shape classification method to perform the classifcation task based on temporal shape differences. DWD learns a class separation direction based on the temporal shape differences that are obtained by taking differences of the temporal pair of Euclideanized s-reps. In the context of early diagnosis and detection of ASD in young infants, the proposed temporal shape difference classification produces some interesting results; the temporal differences in shapes of hippocampi and caudate nuclei do not seem to be as predictive as the cross-sectional shape of these structures alone.Doctor of Philosoph

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Computational Anatomy for Multi-Organ Analysis in Medical Imaging: A Review

The medical image analysis field has traditionally been focused on the development of organ-, and disease-specific methods. Recently, the interest in the development of more 20 comprehensive computational anatomical models has grown, leading to the creation of multi-organ models. Multi-organ approaches, unlike traditional organ-specific strategies, incorporate inter-organ relations into the model, thus leading to a more accurate representation of the complex human anatomy. Inter-organ relations are not only spatial, but also functional and physiological. Over the years, the strategies 25 proposed to efficiently model multi-organ structures have evolved from the simple global modeling, to more sophisticated approaches such as sequential, hierarchical, or machine learning-based models. In this paper, we present a review of the state of the art on multi-organ analysis and associated computation anatomy methodology. The manuscript follows a methodology-based classification of the different techniques 30 available for the analysis of multi-organs and multi-anatomical structures, from techniques using point distribution models to the most recent deep learning-based approaches. With more than 300 papers included in this review, we reflect on the trends and challenges of the field of computational anatomy, the particularities of each anatomical region, and the potential of multi-organ analysis to increase the impact of 35 medical imaging applications on the future of healthcare.Comment: Paper under revie

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

Doctor of Philosophy

dissertationStatistical analysis of time dependent imaging data is crucial for understanding normal anatomical development as well as disease progression. The most promising studies are of longitudinal design, where repeated observations are obtained from the same subjects. Analysis in this case is challenging due to the difficulty in modeling longitudinal changes, such as growth, and comparing changes across different populations. In any case, the study of anatomical change over time has the potential to further our understanding of many dynamic processes. What is needed are accurate computational models to capture, describe, and quantify anatomical change over time. Anatomical shape is encoded in a variety of representations, such as medical imaging data and derived geometric information extracted as points, curves, and/or surfaces. By considering various shape representations embedded into the same ambient space as a shape complex, either in 2D or 3D, we obtain a more comprehensive description of the anatomy than provided by an single isolated shape. In this dissertation, we develop spatiotemporal models of anatomical change designed to leverage multiple shape representations simultaneously. Rather than study directly the geometric changes to a shape itself, we instead consider how the ambient space deforms, which allows all embedded shapes to be included simultaneously in model estimation. Around this idea, we develop two complementary spatiotemporal models: a flexible nonparametric model designed to capture complex anatomical trajectories, and a generative model designed as a compact statistical representation of anatomical change. We present several ways spatiotemporal models can support the statistical analysis of scalar measurements, such as volume, extracted from shape. Finally, we cover the statistical analysis of higher dimensional shape features to take better advantage of the rich morphometric information provided by shape, as well as the trajectory of change captured by spatiotemporal models