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

Mixed-effects shape models for estimating longitudinal changes in anatomy

pre-prin

Splines for diffeomorphisms

This paper develops a method for higher order parametric regression on diffeomorphisms for image regression. We present a principled way to de ne curves with nonzero acceleration and nonzero jerk. This work extends methods based on geodesics which have been developed during the last decade for computational anatomy in the large deformation diffeomorphic image analysis framework. In contrast to previously proposed methods to capture image changes over time, such as geodesic regression, the proposed method can capture more complex spatio-temporal deformations. We take a variational approach that is governed by an underlying energy formulation, which respects the non at geometry of diffeomorphisms. Such an approach of minimal energy curve estimation also provides a physical analogy to particle motion under a varying force eld. This gives rise to the notion of the quadratic, the cubic and the piecewise cubic splines on the manifold of diffeomorphisms. The variational formulation of splines also allows for the use of temporal control points to control spline behavior. This necessitates the development of a shooting formulation for splines. The initial conditions of our proposed shooting polynomial paths in diffeomorphisms are analogous to the Euclidean polynomial coeffcients. We experimentally demonstrate the effectiveness of using the parametric curves both for synthesizing polynomial paths and for regression of imaging data. The performance of the method is compared to geodesic regression

Geodesic shape regression with multiple geometries and sparse parameters

International audienceMany problems in medicine are inherently dynamic processes which include the aspect of change over time, such as childhood development, aging, and disease progression. From medical images, numerous geometric structures can be extracted with various representations, such as landmarks, point clouds, curves, and surfaces. Different sources of geometry may characterize different aspects of the anatomy, such as fiber tracts from DTI and subcortical shapes from structural MRI, and therefore require a modeling scheme which can include various shape representations in any combination. In this paper, we present a geodesic regression model in the large deformation (LDDMM) framework applicable to multi-object complexes in a variety of shape representations. Our model decouples the deformation parameters from the specific shape representations, allowing the complexity of the model to reflect the nature of the shape changes, rather than the sampling of the data. As a consequence, the sparse representation of diffeomorphic flow allows for the straightforward embedding of a variety of geometry in different combinations, which all contribute towards the estimation of a single deformation of the ambient space. Additionally, the sparse representation along with the geodesic constraint results in a compact statistical model of shape change by a small number of parameters defined by the user. Experimental validation on multi-object complexes demonstrate robust model estimation across a variety of parameter settings. We further demonstrate the utility of our method to support the analysis of derived shape features, such as volume, and explore shape model extrapolation. Our method is freely available in the software package deformetrica which can be downloaded at www.deformetrica.org

Functional Data Analysis of Amplitude and Phase Variation

The abundance of functional observations in scientific endeavors has led to a significant development in tools for functional data analysis (FDA). This kind of data comes with several challenges: infinite-dimensionality of function spaces, observation noise, and so on. However, there is another interesting phenomena that creates problems in FDA. The functional data often comes with lateral displacements/deformations in curves, a phenomenon which is different from the height or amplitude variability and is termed phase variation. The presence of phase variability artificially often inflates data variance, blurs underlying data structures, and distorts principal components. While the separation and/or removal of phase from amplitude data is desirable, this is a difficult problem. In particular, a commonly used alignment procedure, based on minimizing the $\mathbb{L}^2$ norm between functions, does not provide satisfactory results. In this paper we motivate the importance of dealing with the phase variability and summarize several current ideas for separating phase and amplitude components. These approaches differ in the following: (1) the definition and mathematical representation of phase variability, (2) the objective functions that are used in functional data alignment, and (3) the algorithmic tools for solving estimation/optimization problems. We use simple examples to illustrate various approaches and to provide useful contrast between them.Comment: Published at http://dx.doi.org/10.1214/15-STS524 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Doctor of Philosophy

dissertationThe statistical study of anatomy is one of the primary focuses of medical image analysis. It is well-established that the appropriate mathematical settings for such analyses are Riemannian manifolds and Lie group actions. Statistically defined atlases, in which a mean anatomical image is computed from a collection of static three-dimensional (3D) scans, have become commonplace. Within the past few decades, these efforts, which constitute the field of computational anatomy, have seen great success in enabling quantitative analysis. However, most of the analysis within computational anatomy has focused on collections of static images in population studies. The recent emergence of large-scale longitudinal imaging studies and four-dimensional (4D) imaging technology presents new opportunities for studying dynamic anatomical processes such as motion, growth, and degeneration. In order to make use of this new data, it is imperative that computational anatomy be extended with methods for the statistical analysis of longitudinal and dynamic medical imaging. In this dissertation, the deformable template framework is used for the development of 4D statistical shape analysis, with applications in motion analysis for individualized medicine and the study of growth and disease progression. A new method for estimating organ motion directly from raw imaging data is introduced and tested extensively. Polynomial regression, the staple of curve regression in Euclidean spaces, is extended to the setting of Riemannian manifolds. This polynomial regression framework enables rigorous statistical analysis of longitudinal imaging data. Finally, a new diffeomorphic model of irrotational shape change is presented. This new model presents striking practical advantages over standard diffeomorphic methods, while the study of this new space promises to illuminate aspects of the structure of the diffeomorphism group

Doctor of Philosophy in Computing

dissertationAn important area of medical imaging research is studying anatomical diffeomorphic shape changes and detecting their relationship to disease processes. For example, neurodegenerative disorders change the shape of the brain, thus identifying differences between the healthy control subjects and patients affected by these diseases can help with understanding the disease processes. Previous research proposed a variety of mathematical approaches for statistical analysis of geometrical brain structure in three-dimensional (3D) medical imaging, including atlas building, brain variability quantification, regression, etc. The critical component in these statistical models is that the geometrical structure is represented by transformations rather than the actual image data. Despite the fact that such statistical models effectively provide a way for analyzing shape variation, none of them have a truly probabilistic interpretation. This dissertation contributes a novel Bayesian framework of statistical shape analysis for generic manifold data and its application to shape variability and brain magnetic resonance imaging (MRI). After we carefully define the distributions on manifolds, we then build Bayesian models for analyzing the intrinsic variability of manifold data, involving the mean point, principal modes, and parameter estimation. Because there is no closed-form solution for Bayesian inference of these models on manifolds, we develop a Markov Chain Monte Carlo method to sample the hidden variables from the distribution. The main advantages of these Bayesian approaches are that they provide parameter estimation and automatic dimensionality reduction for analyzing generic manifold-valued data, such as diffeomorphisms. Modeling the mean point of a group of images in a Bayesian manner allows for learning the regularity parameter from data directly rather than having to set it manually, which eliminates the effort of cross validation for parameter selection. In population studies, our Bayesian model of principal modes analysis (1) automatically extracts a low-dimensional, second-order statistics of manifold data variability and (2) gives a better geometric data fit than nonprobabilistic models. To make this Bayesian framework computationally more efficient for high-dimensional diffeomorphisms, this dissertation presents an algorithm, FLASH (finite-dimensional Lie algebras for shooting), that hugely speeds up the diffeomorphic image registration. Instead of formulating diffeomorphisms in a continuous variational problem, Flash defines a completely new discrete reparameterization of diffeomorphisms in a low-dimensional bandlimited velocity space, which results in the Bayesian inference via sampling on the space of diffeomorphisms being more feasible in time. Our entire Bayesian framework in this dissertation is used for statistical analysis of shape data and brain MRIs. It has the potential to improve hypothesis testing, classification, and mixture models

Symmetric diffeomorphic modeling of longtudinal structural MRI

This technology report describes the longitudinal registration approach that we intend to incorporate into SPM12. It essentially describes a group-wise intra-subject modeling framework, which combines diffeomorphic and rigid-body registration, incorporating a correction for the intensity inhomogeneity artifact usually seen in MRI data. Emphasis is placed on achieving internal consistency and accounting for many of the mathematical subtleties that most implementations overlook. The implementation was evaluated using examples from the OASIS Longitudinal MRI Data in Non-demented and Demented Older Adults