Singular geodesic coordinates for representing diffeomorphic maps in computational anatomy, with application to the morphometry of early Alzheimer's disease in the medial temporal lobe

In this work we develop novel algorithms for building one to one correspondences between anatomical forms by providing a sparse representation of dense registration information. These sparse parameterizations of complex high dimensional data allow robustness in the face of noise and anomalies, and a platform for inference that is effective in the face of multiple comparisons. We review background in the theory of generating smooth, invertible transformations (the diffeomorphism group), and build our parameterization as a function supported on surfaces bounding anatomical structures of interest. We show how dimensionality can be reduced even further and still provide a rich family of mappings using principal component analysis or Laplace Beltrami eigenfunctions supported on the surface. We develop algorithms for surface matching and image matching within this model, and demonstrate the desired robustness by working with published large neuroimaging datasets that include many low quality examples. Finally we turn to addressing challenges associated with some specific data types: images with multiple labels, and longitudinal data. We use the mapping tools developed to draw conclusions about the progression of early Alzheimer's disease in the medial temporal lobe

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

Anatomical Image Series Analysis in the Computational Anatomy Random Orbit Model

Serially acquired medical imagery plays an important role in the computational study of human anatomy. In this work, we describe the development of novel algorithms set in the large deformation diffeomorphic metric mapping framework for analyzing serially acquired imagery of two general types: spatial image series and temporal image series. In the former case, a critical step in the analysis of neural connectivity from serially-sectioned brain histology data is the reconstruction of spatially distorted image volumes and registration into a common coordinate space. In the latter case, computational methods are required for building low dimensional representations of the infinite dimensional shape space standard to computational anatomy. Here, we review the vast body of work related to volume reconstruction and atlas-mapping of serially-sectioned data as well as diffeomorphic methods for longitudinal data and we position our work relative to these in the context of the computational anatomy random orbit model. We show how these two problems are embedded as extensions to the classic random orbit model and use it to both enforce diffeomorphic conditions and analyze the distance metric associated to diffeomorphisms. We apply our new algorithms to histology and MRI datasets to study the structure, connectivity, and pathological degeneration of the brain

Control Theory: On the Way to New Application Fields

Control theory is an interdisciplinary field that is located at the crossroads of pure and applied mathematics with systems engineering and the sciences. Recently, deep interactions are emerging with new application areas, such as systems biology, quantum control and information technology. In order to address the new challenges posed by the new application disciplines, a special focus of this workshop has been on the interaction between control theory and mathematical systems biology. To complement these more biology oriented focus, a series of lectures in this workshop was devoted to the control of networks of systems, fundamentals of nonlinear control systems, model reduction and identification, algorithmic aspects in control, as well as open problems in control

Geodesics, Parallel Transport & One-parameter Subgroups for Diffeomorphic Image Registration

International audienceComputational anatomy aims at developing models to understand the anatomical variability of organs and tissues. A widely used and validated instrument for comparing the anatomy in medical images is non-linear diffeomorphic registration which is based on a rich mathematical background. For instance, the "large deformation diffeomorphic metric mapping" (LDDMM) framework defines a Riemannian setting by providing a right invariant metric on the tangent spaces, and solves the registration problem by computing geodesics parametrized by time-varying velocity fields. A simpler alternative based on stationary velocity fields (SVF) has been proposed, using the one-parameter subgroups from Lie groups theory. In spite of its better computational efficiency, the geometrical setting of the SVF is more vague, especially regarding the relationship between one-parameter subgroups and geodesics. In this work, we detail the properties of finite dimensional Lie groups that highlight the geometric foundations of one-parameter subgroups. We show that one can define a proper underlying geometric structure (an affine manifold) based on the canonical Cartan connections, for which tne-parameter subgroups and their translations are geodesics. This geometric structure is perfectly compatible with all the group operations (left, right composition and inversion), contrarily to left- (or right-) invariant Riemannian metrics. Moreover, we derive closed-form expressions for the parallel transport. Then, we investigate the generalization of such properties to infinite dimensional Lie groups. We suggest that some of the theoretical objections might actually be ruled out by the practical implementation of both the LDDMM and the SVF frameworks for image registration. This leads us to a more practical study comparing the parameterization (initial velocity field) of metric and Cartan geodesics in the specific optimization context of longitudinal and inter-subject image registration.Our experimental results suggests that stationarity is a good approximation for longitudinal deformations, while metric geodesics notably differ from stationary ones for inter-subject registration, which involves much larger and non-physical deformations. Then, we turn to the practical comparison of five parallel transport techniques along oneparameter subgroups. Our results point out the fundamental role played by the numerical implementation, which may hide the theoretical differences between the different schemes. Interestingly, even if the parallel transport generally depends on the path used, an experiment comparing the Cartan parallel transport along the one-parameter subgroup and the LDDMM (metric) geodesics from inter-subject registration suggests that our parallel transport methods are not so sensitive to the path

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

Discrete Riemannian Calculus and A Posteriori Error Control on Shape Spaces

In this thesis, a novel discrete approximation of the curvature tensor on Riemannian manifolds is derived, efficient methods to interpolate and extrapolate images in the context of the time discrete metamorphosis model are analyzed, and an a posteriori error estimator for the binary Mumford–Shah model is examined. Departing from the variational time discretization on (possibly infinite-dimensional) Riemannian manifolds originally proposed by Rumpf and Wirth, in which a consistent time discrete approximation of geodesic curves, the logarithm, the exponential map and parallel transport is analyzed, we construct the discrete curvature tensor and prove its convergence under certain smoothness assumptions. To this end, several time discrete parallel transports are applied to suitably rescaled tangent vectors, where each parallel transport is computed using Schild’s ladder. The associated convergence proof essentially relies on multiple Taylor expansions incorporating symmetry and scaling relations. In several numerical examples we validate this approach for surfaces. The by now classical flow of diffeomorphism approach allows the transport of image intensities along paths in time, which are characterized by diffeomorphisms, and the brightness of each image particle is assumed to be constant along each trajectory. As an extension, the metamorphosis model proposed by Trouvé, Younes and coworkers allows for intensity variations of the image particles along the paths, which is reflected by an additional penalization term appearing in the energy functional that quantifies the squared weak material derivative. Taking into account the aforementioned time discretization, we propose a time discrete metamorphosis model in which the associated time discrete path energy consists of the sum of squared L2-mismatch functionals of successive square-integrable image intensity functions and a regularization functional for pairwise deformations. Our main contributions are the existence proof of time discrete geodesic curves in the context of this model, which are defined as minimizers of the time discrete path energy, and the proof of the Mosco-convergence of a suitable interpolation of the time discrete to the time continuous path energy with respect to the L2-topology. Using an alternating update scheme as well as a multilinear finite element respectively cubic spline discretization for the images and deformations allows to efficiently compute time discrete geodesic curves. In several numerical examples we demonstrate that time discrete geodesics can be robustly computed for gray-scale and color images. Taking into account the time discretization of the metamorphosis model we define the discrete exponential map in the space of images, which allows image extrapolation of arbitrary length for given weakly differentiable initial images and variations. To this end, starting from a suitable reformulation of the Euler–Lagrange equations characterizing the one-step extrapolation a fixed point iteration is employed to establish the existence of critical points of the Euler–Lagrange equations provided that the initial variation is small in L2. In combination with an implicit function type argument requiring H1-closeness of the initial variation one can prove the local existence as well as the local uniqueness of the discrete exponential map. The numerical algorithm for the one-step extrapolation is based on a slightly modified fixed point iteration using a spatial Galerkin scheme to obtain the optimal deformation associated with the unknown image, from which the unknown image itself can be recovered. To prove the applicability of the proposed method we compute the extrapolated image path for real image data. A common tool to segment images and shapes into multiple regions was developed by Mumford and Shah. The starting point to derive a posteriori error estimates for the binary Mumford–Shah model, which is obtained by restricting the original model to two regions, is a uniformly convex and non-constrained relaxation of the binary model following the work by Chambolle and Berkels. In particular, minimizers of the binary model can be exactly recovered from minimizers of the relaxed model via thresholding. Then, applying duality techniques proposed by Repin and Bartels allows deriving a consistent functional a posteriori error estimate for the relaxed model. Afterwards, an a posteriori error estimate for the original binary model can be computed incorporating a suitable cut-out argument in combination with the functional error estimate. To calculate minimizers of the relaxed model on an adaptive mesh described by a quadtree structure, we employ a primal-dual as well as a purely dual algorithm. The quality of the error estimator is analyzed for different gray-scale input images

Groupwise non-rigid registration for automatic construction of appearance models of the human craniofacial complex for analysis, synthesis and simulation

Finally, a novel application of 3D appearance modelling is proposed: a faster than real-time algorithm for statistically constrained quasi-mechanical simulation. Experiments demonstrate superior realism, achieved in the proposed method by employing statistical appearance models to drive the simulation, in comparison with the comparable state-of-the-art quasi-mechanical approaches.EThOS - Electronic Theses Online ServiceGBUnited Kingdo