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

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

Fourier-Net+: Leveraging Band-Limited Representation for Efficient 3D Medical Image Registration

U-Net style networks are commonly utilized in unsupervised image registration to predict dense displacement fields, which for high-resolution volumetric image data is a resource-intensive and time-consuming task. To tackle this challenge, we first propose Fourier-Net, which replaces the costly U-Net style expansive path with a parameter-free model-driven decoder. Instead of directly predicting a full-resolution displacement field, our Fourier-Net learns a low-dimensional representation of the displacement field in the band-limited Fourier domain which our model-driven decoder converts to a full-resolution displacement field in the spatial domain. Expanding upon Fourier-Net, we then introduce Fourier-Net+, which additionally takes the band-limited spatial representation of the images as input and further reduces the number of convolutional layers in the U-Net style network's contracting path. Finally, to enhance the registration performance, we propose a cascaded version of Fourier-Net+. We evaluate our proposed methods on three datasets, on which our proposed Fourier-Net and its variants achieve comparable results with current state-of-the art methods, while exhibiting faster inference speeds, lower memory footprint, and fewer multiply-add operations. With such small computational cost, our Fourier-Net+ enables the efficient training of large-scale 3D registration on low-VRAM GPUs. Our code is publicly available at \url{https://github.com/xi-jia/Fourier-Net}.Comment: Under review. arXiv admin note: text overlap with arXiv:2211.1634

CLAIRE -- Parallelized Diffeomorphic Image Registration for Large-Scale Biomedical Imaging Applications

We study the performance of CLAIRE -- a diffeomorphic multi-node, multi-GPU image-registration algorithm, and software -- in large-scale biomedical imaging applications with billions of voxels. At such resolutions, most existing software packages for diffeomorphic image registration are prohibitively expensive. As a result, practitioners first significantly downsample the original images and then register them using existing tools. Our main contribution is an extensive analysis of the impact of downsampling on registration performance. We study this impact by comparing full-resolution registrations obtained with CLAIRE to lower-resolution registrations for synthetic and real-world imaging datasets. Our results suggest that registration at full resolution can yield a superior registration quality -- but not always. For example, downsampling a synthetic image from $1024^3$ to $256^3$ decreases the Dice coefficient from 92% to 79%. However, the differences are less pronounced for noisy or low-contrast high-resolution images. CLAIRE allows us not only to register images of clinically relevant size in a few seconds but also to register images at unprecedented resolution in a reasonable time. The highest resolution considered is CLARITY images of size $2816\times3016\times1162$. To the best of our knowledge, this is the first study on image registration quality at such resolutions.Comment: 32 pages, 9 tables, 8 figure

Combining the Band-Limited Parameterization and Semi-Lagrangian Runge–Kutta Integration for Efficient PDE-Constrained LDDMM

The family of PDE-constrained Large Deformation Diffeomorphic Metric Mapping (LDDMM) methods is emerging as a particularly interesting approach for physically meaningful diffeomorphic transformations. The original combination of Gauss–Newton–Krylov optimization and Runge–Kutta integration shows excellent numerical accuracy and fast convergence rate. However, its most significant limitation is the huge computational complexity, hindering its extensive use in Computational Anatomy applied studies. This limitation has been treated independently by the problem formulation in the space of band-limited vector fields and semi-Lagrangian integration. The purpose of this work is to combine both in three variants of band-limited PDE-constrained LDDMM for further increasing their computational efficiency. The accuracy of the resulting methods is evaluated extensively. For all the variants, the proposed combined approach shows a significant increment of the computational efficiency. In addition, the variant based on the deformation state equation is positioned consistently as the best performing method across all the evaluation frameworks in terms of accuracy and efficiency

Fast Predictive Simple Geodesic Regression

Deformable image registration and regression are important tasks in medical image analysis. However, they are computationally expensive, especially when analyzing large-scale datasets that contain thousands of images. Hence, cluster computing is typically used, making the approaches dependent on such computational infrastructure. Even larger computational resources are required as study sizes increase. This limits the use of deformable image registration and regression for clinical applications and as component algorithms for other image analysis approaches. We therefore propose using a fast predictive approach to perform image registrations. In particular, we employ these fast registration predictions to approximate a simplified geodesic regression model to capture longitudinal brain changes. The resulting method is orders of magnitude faster than the standard optimization-based regression model and hence facilitates large-scale analysis on a single graphics processing unit (GPU). We evaluate our results on 3D brain magnetic resonance images (MRI) from the ADNI datasets.Comment: 19 pages, 10 figures, 13 table