A Statistical Model for Simultaneous Template Estimation, Bias Correction, and Registration of 3D Brain Images

Template estimation plays a crucial role in computational anatomy since it provides reference frames for performing statistical analysis of the underlying anatomical population variability. While building models for template estimation, variability in sites and image acquisition protocols need to be accounted for. To account for such variability, we propose a generative template estimation model that makes simultaneous inference of both bias fields in individual images, deformations for image registration, and variance hyperparameters. In contrast, existing maximum a posterori based methods need to rely on either bias-invariant similarity measures or robust image normalization. Results on synthetic and real brain MRI images demonstrate the capability of the model to capture heterogeneity in intensities and provide a reliable template estimation from registration

Uncertainty quantification in non-rigid image registration via stochastic gradient Markov chain Monte Carlo

We develop a new Bayesian model for non-rigid registration of three-dimensional medical images, with a focus on uncertainty quantification. Probabilistic registration of large images with calibrated uncertainty estimates is difficult for both computational and modelling reasons. To address the computational issues, we explore connections between the Markov chain Monte Carlo by backpropagation and the variational inference by backpropagation frameworks, in order to efficiently draw samples from the posterior distribution of transformation parameters. To address the modelling issues, we formulate a Bayesian model for image registration that overcomes the existing barriers when using a dense, high-dimensional, and diffeomorphic transformation parametrisation. This results in improved calibration of uncertainty estimates. We compare the model in terms of both image registration accuracy and uncertainty quantification to VoxelMorph, a state-of-the-art image registration model based on deep learning

A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed locally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The generative model is first estimated on a control population, then, for each subject, the markers are computed for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolution. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are more located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quiet high. In this context, the model can be used to generate plausible morphological trajectories associated with the disease. Our method gives two interpretable scalar imaging biomarkers assessing the effects of aging and disease on brain morphology at the individual and population level. These markers confirm an acceleration of apparent aging for Alzheimer's subjects and can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.Comment: NeuroImage, Elsevier, In pres

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

Image registration via stochastic gradient markov chain monte carlo

We develop a fully Bayesian framework for non-rigid registration of three-dimensional medical images, with a focus on uncertainty quantification. Probabilistic registration of large images along with calibrated uncertainty estimates is difficult for both computational and modelling reasons. To address the computational issues, we explore connections between the Markov chain Monte Carlo by backprop and the variational inference by backprop frameworks in order to efficiently draw thousands of samples from the posterior distribution. Regarding the modelling issues, we carefully design a Bayesian model for registration to overcome the existing barriers when using a dense, high-dimensional, and diffeomorphic parameterisation of the transformation. This results in improved calibration of uncertainty estimates

Learning Conditional Deformable Templates with Convolutional Networks

We develop a learning framework for building deformable templates, which play a fundamental role in many image analysis and computational anatomy tasks. Conventional methods for template creation and image alignment to the template have undergone decades of rich technical development. In these frameworks, templates are constructed using an iterative process of template estimation and alignment, which is often computationally very expensive. Due in part to this shortcoming, most methods compute a single template for the entire population of images, or a few templates for specific sub-groups of the data. In this work, we present a probabilistic model and efficient learning strategy that yields either universal or conditional templates, jointly with a neural network that provides efficient alignment of the images to these templates. We demonstrate the usefulness of this method on a variety of domains, with a special focus on neuroimaging. This is particularly useful for clinical applications where a pre-existing template does not exist, or creating a new one with traditional methods can be prohibitively expensive. Our code and atlases are available online as part of the VoxelMorph library at http://voxelmorph.csail.mit.edu.Comment: NeurIPS 2019: Neural Information Processing Systems. Keywords: deformable templates, conditional atlases, diffeomorphic image registration, probabilistic models, neuroimagin

Stochastic Algorithm For Parameter Estimation For Dense Deformable Template Mixture Model

Estimating probabilistic deformable template models is a new approach in the fields of computer vision and probabilistic atlases in computational anatomy. A first coherent statistical framework modelling the variability as a hidden random variable has been given by Allassonni\`ere, Amit and Trouv\'e in [1] in simple and mixture of deformable template models. A consistent stochastic algorithm has been introduced in [2] to face the problem encountered in [1] for the convergence of the estimation algorithm for the one component model in the presence of noise. We propose here to go on in this direction of using some "SAEM-like" algorithm to approximate the MAP estimator in the general Bayesian setting of mixture of deformable template model. We also prove the convergence of this algorithm toward a critical point of the penalised likelihood of the observations and illustrate this with handwritten digit images

CLAIRE: Scalable GPU-Accelerated Algorithms for Diffeomorphic Image Registration in 3D

We present our work on scalable, GPU-accelerated algorithms for diffeomorphic image registration. The associated software package is termed CLAIRE. Image registration is a non-linear inverse problem. It is about computing a spatial mapping from one image of the same object or scene to another. In diffeomorphic image registration, the set of admissible spatial transformations is restricted to maps that are smooth, one-to-one, and have a smooth inverse. We formulate diffeomorphic image registration as a variational problem governed by transport equations. We use an inexact, globalized (Gauss--)Newton--Krylov method for numerical optimization. We consider semi-Lagrangian methods for numerical time integration. Our solver features mixed-precision, hardware-accelerated computational kernels for optimal computational throughput. We use the message-passing interface for distributed-memory parallelism and deploy our code on modern high-performance computing architectures. Our solver allows us to solve clinically relevant problems in under four seconds on a single GPU. It can also be applied to large-scale 3D imaging applications with data that is discretized on meshes with billions of voxels. We demonstrate that our numerical framework yields high-fidelity results in only a few seconds, even if we search for an optimal regularization parameter

Gaussian Process Morphable Models

Statistical shape models (SSMs) represent a class of shapes as a normal distribution of point variations, whose parameters are estimated from example shapes. Principal component analysis (PCA) is applied to obtain a low-dimensional representation of the shape variation in terms of the leading principal components. In this paper, we propose a generalization of SSMs, called Gaussian Process Morphable Models (GPMMs). We model the shape variations with a Gaussian process, which we represent using the leading components of its Karhunen-Loeve expansion. To compute the expansion, we make use of an approximation scheme based on the Nystrom method. The resulting model can be seen as a continuous analogon of an SSM. However, while for SSMs the shape variation is restricted to the span of the example data, with GPMMs we can define the shape variation using any Gaussian process. For example, we can build shape models that correspond to classical spline models, and thus do not require any example data. Furthermore, Gaussian processes make it possible to combine different models. For example, an SSM can be extended with a spline model, to obtain a model that incorporates learned shape characteristics, but is flexible enough to explain shapes that cannot be represented by the SSM. We introduce a simple algorithm for fitting a GPMM to a surface or image. This results in a non-rigid registration approach, whose regularization properties are defined by a GPMM. We show how we can obtain different registration schemes,including methods for multi-scale, spatially-varying or hybrid registration, by constructing an appropriate GPMM. As our approach strictly separates modelling from the fitting process, this is all achieved without changes to the fitting algorithm. We show the applicability and versatility of GPMMs on a clinical use case, where the goal is the model-based segmentation of 3D forearm images