Uncertainty Quantification, Image Synthesis and Deformation Prediction for Image Registration

Image registration is essential for medical image analysis to provide spatial correspondences. It is a difficult problem due to the modeling complexity of image appearance and the computational complexity of the deformable registration models. Thus, several techniques are needed: Uncertainty measurements of the high-dimensional parameter space of the registration methods for the evaluation of the registration result; Registration methods for registering healthy medical images to pathological images with large appearance changes; Fast registration prediction techniques for uni-modal and multi-modal images. This dissertation addresses these problems and makes the following contributions: 1) A frame- work for uncertainty quantification of image registration results is proposed. The proposed method for uncertainty quantification utilizes a low-rank Hessian approximation to evaluate the variance/co- variance of the variational Gaussian distribution of the registration parameters. The method requires significantly less storage and computation time than computing the Hessian via finite difference while achieving excellent approximation accuracy, facilitating the computation of the variational approximation; 2) An image synthesis deep network for pathological image registration is developed. The network transforms a pathological image into a ‘quasi-normal’ image, making registrations more accurate; 3) A patch-based deep learning framework for registration parameter prediction using image appearances only is created. The network is capable of accurately predicting the initial momentum for the Large Deformation Diffeomorphic Metric Mapping (LDDMM) model for both uni-modal and multi-modal registration problems, while increasing the registration speed by at least an order of magnitude compared with optimization-based approaches and maintaining the theoretical properties of LDDMM. Applications of the methods include 1) Uncertainty quantification of LDDMM for 2D and 3D medical image registrations, which could be used for uncertainty-based image smoothing and subsequent analysis; 2) Quasi-normal image synthesis for the registration of brain images with tumors with potential extensions to other image registration problems with pathologies and 3) deformation prediction for various brain datasets and T1w/T2w magnetic resonance images (MRI), which could be incorporated into other medical image analysis tasks such as fast multi-atlas image segmentation, fast geodesic image regression, fast atlas construction and fast user-interactive registration refinement.Doctor of Philosoph

Partial Differential Equation-Constrained Diffeomorphic Registration from Sum of Squared Differences to Normalized Cross-Correlation, Normalized Gradient Fields, and Mutual Information: A Unifying Framework; 35632143

This work proposes a unifying framework for extending PDE-constrained Large Deformation Diffeomorphic Metric Mapping (PDE-LDDMM) with the sum of squared differences (SSD) to PDE-LDDMM with different image similarity metrics. We focused on the two best-performing variants of PDE-LDDMM with the spatial and band-limited parameterizations of diffeomorphisms. We derived the equations for gradient-descent and Gauss-Newton-Krylov (GNK) optimization with Normalized Cross-Correlation (NCC), its local version (lNCC), Normalized Gradient Fields (NGFs), and Mutual Information (MI). PDE-LDDMM with GNK was successfully implemented for NCC and lNCC, substantially improving the registration results of SSD. For these metrics, GNK optimization outperformed gradient-descent. However, for NGFs, GNK optimization was not able to overpass the performance of gradient-descent. For MI, GNK optimization involved the product of huge dense matrices, requesting an unaffordable memory load. The extensive evaluation reported the band-limited version of PDE-LDDMM based on the deformation state equation with NCC and lNCC image similarities among the best performing PDE-LDDMM methods. In comparison with benchmark deep learning-based methods, our proposal reached or surpassed the accuracy of the best-performing models. In NIREP16, several configurations of PDE-LDDMM outperformed ANTS-lNCC, the best benchmark method. Although NGFs and MI usually underperformed the other metrics in our evaluation, these metrics showed potentially competitive results in a multimodal deformable experiment. We believe that our proposed image similarity extension over PDE-LDDMM will promote the use of physically meaningful diffeomorphisms in a wide variety of clinical applications depending on deformable image registration

Regression uncertainty on the Grassmannian

Trends in longitudinal or cross-sectional studies over time are often captured through regression models. In their simplest manifestation, these regression models are formulated in ℝn. However, in the context of imaging studies, the objects of interest which are to be regressed are frequently best modeled as elements of a Riemannian manifold. Regression on such spaces can be accomplished through geodesic regression. This paper develops an approach to compute confidence intervals for geodesic regression models. The approach is general, but illustrated and specifically developed for the Grassmann manifold, which allows us, e.g., to regress shapes or linear dynamical systems. Extensions to other manifolds can be obtained in a similar manner. We demonstrate our approach for regression with 2D/3D shapes using synthetic and real data

Efficient algorithms for geodesic shooting in diffeomorphic image registration

Diffeomorphic image registration is a common problem in medical image analysis. Here, one searches for a diffeomorphic deformation that maps one image (the moving or template image) onto another image (the fixed or reference image). We can formulate the search for such a map as a PDE constrained optimization problem. These types of problems are computationally expensive. This gives rise to the need for efficient algorithms. After introducing the PDE constrained optimization problem, we derive the first and second order optimality conditions. We discretize the problem using a pseudo-spectral discretization in space and consider Heun's method and the semi-Lagrangian method for the time integration of the PDEs that appear in the optimality system. To solve this optimization problem, we consider an L-BFGS and an inexact Gauss-Newton-Krylov method. To reduce the cost of solving the linear system that arises in Newton-type methods, we investigate different preconditioners. They exploit the structure of the Hessian, and use algorithms to efficiently compute an approximation to its inverse. Further, we build the preconditioners on a coarse grid to further reduce computational costs. The different methods are evaluated for two-dimensional image data (real and synthetic). We study the spectrum of the different building blocks that appear in the Hessian. It is demonstrated that low rank preconditioners are able to significantly reduce the number of iterations needed to solve the linear system in Newton-type optimizers. We then compare different optimization methods based on their overall performance. This includes the accuracy and time-to-solution. L-BFGS turns out to be the best method, in terms of runtime, if we solve solving for large gradient tolerances. If we are interested in computing accurate solutions with a small gradient norm, an inexact Gauss-Newton-Krylov optimizer with the regularization term as preconditioner performs best

TOWARD SOLVING GROUPWISE MEDICAL IMAGE ANALYSIS PROBLEMS WITH DEEP LEARNING

Image regression, atlas building, and multi-atlas segmentation are three groupwise medical image analysis problems extended from image registration. These three problems are challenging because of the difficulty in establishing spatial correspondences and the associated high computational cost. Specifically, most previous methods are computationally costly as they are optimization-based approaches. Hence fast and accurate approaches are highly desirable. This dissertation addresses the following problems concerning the three groupwise medical im- age analysis problems: (1) fast and reliable geodesic regression for image time series; (2) joint atlas building and diffeomorphic registration learning; (3) efficient and accurate label fusion for multi-atlas segmentation; and (4) spatially localized probability calibration for semantic segmentation networks. Specifically, the contributions in this thesis are as follows: (1) A fast predictive simple geodesic regression approach is proposed to capture the frequently subtle deformation trends of longitudinal image data. (2) A new deep learning model that jointly builds an atlas and learns the diffeomorphic registrations in both the atlas-to-image and the image-to-atlas directions is developed. (3) A novel deep learning label fusion method (VoteNet) that locally identifies sets of trustworthy atlases is presented; and several ways to improve the performance under the VoteNet based multi-atlas segmentation framework are explored. (4) A learning-based local temperature scaling method that predicts a separate temperature scale for each pixel/voxel is designed. The resulting post-processing approach is accuracy preserving and is theoretically guaranteed to be effective.Doctor of Philosoph

Geodesic analysis in Kendall’s shape space with epidemiological applications

We analytically determine Jacobi fields and parallel transports and compute geodesic regression in Kendall’s shape space. Using the derived expressions, we can fully leverage the geometry via Riemannian optimization and thereby reduce the computational expense by several orders of magnitude over common, nonlinear constrained approaches. The methodology is demonstrated by performing a longitudinal statistical analysis of epidemiological shape data. As an example application, we have chosen 3D shapes of knee bones, reconstructed from image data of the Osteoarthritis Initiative. Comparing subject groups with incident and developing osteoarthritis versus normal controls, we find clear differences in the temporal development of femur shapes. This paves the way for early prediction of incident knee osteoarthritis, using geometry data alone

A Probabilistic Approach To Non-Rigid Medical Image Registration

Non-rigid image registration is an important tool for analysing morphometric differences in subjects with Alzheimer's disease from structural magnetic resonance images of the brain. This thesis describes a novel probabilistic approach to non-rigid registration of medical images, and explores the benefits of its use in this area of neuroimaging. Many image registration approaches have been developed for neuroimaging. The vast majority suffer from two limitations: Firstly, the trade-off between image fidelity and regularisation requires selection. Secondly, only a point-estimate of the mapping between images is inferred, overlooking the presence of uncertainty in the estimation. This thesis introduces a novel probabilistic non-rigid registration model and inference scheme. This framework allows the inference of the parameters that control the level of regularisation, and data fidelity in a data-driven fashion. To allow greater flexibility, this model is extended to allow the level of data fidelity to vary across space. A benefit of this approach, is that the registration can adapt to anatomical variability and other image acquisition differences. A further advantage of the proposed registration framework is that it provides an estimate of the distribution of probable transformations. Additional novel contributions of this thesis include two proposals for exploiting the estimated registration uncertainty. The first of these estimates a local image smoothing filter, which is based on the registration uncertainty. The second approach incorporates the distribution of transformations into an ensemble learning scheme for statistical prediction. These techniques are integrated into standard frameworks for morphometric analysis, and are demonstrated to improve the ability to distinguish subjects with Alzheimer's disease from healthy controls

New Directions for Contact Integrators

Contact integrators are a family of geometric numerical schemes which guarantee the conservation of the contact structure. In this work we review the construction of both the variational and Hamiltonian versions of these methods. We illustrate some of the advantages of geometric integration in the dissipative setting by focusing on models inspired by recent studies in celestial mechanics and cosmology.Comment: To appear as Chapter 24 in GSI 2021, Springer LNCS 1282

Landmark Localization, Feature Matching and Biomarker Discovery from Magnetic Resonance Images

The work presented in this thesis proposes several methods that can be roughly divided into three different categories: I) landmark localization in medical images, II) feature matching for image registration, and III) biomarker discovery in neuroimaging. The first part deals with the identification of anatomical landmarks. The motivation stems from the fact that the manual identification and labeling of these landmarks is very time consuming and prone to observer errors, especially when large datasets must be analyzed. In this thesis we present three methods to tackle this challenge: A landmark descriptor based on local self-similarities (SS), a subspace building framework based on manifold learning and a sparse coding landmark descriptor based on data-specific learned dictionary basis. The second part of this thesis deals with finding matching features between a pair of images. These matches can be used to perform a registration between them. Registration is a powerful tool that allows mapping images in a common space in order to aid in their analysis. Accurate registration can be challenging to achieve using intensity based registration algorithms. Here, a framework is proposed for learning correspondences in pairs of images by matching SS features and random sample and consensus (RANSAC) is employed as a robust model estimator to learn a deformation model based on feature matches. Finally, the third part of the thesis deals with biomarker discovery using machine learning. In this section a framework for feature extraction from learned low-dimensional subspaces that represent inter-subject variability is proposed. The manifold subspace is built using data-driven regions of interest (ROI). These regions are learned via sparse regression, with stability selection. Also, probabilistic distribution models for different stages in the disease trajectory are estimated for different class populations in the low-dimensional manifold and used to construct a probabilistic scoring function.Open Acces