CHeart: A Conditional Spatio-Temporal Generative Model for Cardiac Anatomy

Two key questions in cardiac image analysis are to assess the anatomy and motion of the heart from images; and to understand how they are associated with non-imaging clinical factors such as gender, age and diseases. While the first question can often be addressed by image segmentation and motion tracking algorithms, our capability to model and to answer the second question is still limited. In this work, we propose a novel conditional generative model to describe the 4D spatio-temporal anatomy of the heart and its interaction with non-imaging clinical factors. The clinical factors are integrated as the conditions of the generative modelling, which allows us to investigate how these factors influence the cardiac anatomy. We evaluate the model performance in mainly two tasks, anatomical sequence completion and sequence generation. The model achieves a high performance in anatomical sequence completion, comparable to or outperforming other state-of-the-art generative models. In terms of sequence generation, given clinical conditions, the model can generate realistic synthetic 4D sequential anatomies that share similar distributions with the real data.

Data-driven generation of 4D velocity profiles in the aneurysmal ascending aorta

Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoracic aortic aneurysms (ATAA). To accurately reproduce hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements still makes researchers resort to idealized BCs. In this study we generated and thoroughly characterized a large dataset of synthetic 4D aortic velocity profiles suitable to be used as BCs for CFD simulations. 4D flow MRI scans of 30 subjects with ATAA were processed to extract cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated. Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors. We built a data-driven generative model of 4D aortic velocity profiles, suitable to be used in computational studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set.

Nesterov Accelerated ADMM for Fast Diffeomorphic Image Registration

Deterministic approaches using iterative optimisation have been historically successful in diffeomorphic image registration (DiffIR). Although these approaches are highly accurate, they typically carry a significant computational burden. Recent developments in stochastic approaches based on deep learning have achieved sub-second runtimes for DiffIR with competitive registration accuracy, offering a fast alternative to conventional iterative methods. In this paper, we attempt to reduce this difference in speed whilst retaining the performance advantage of iterative approaches in DiffIR. We first propose a simple iterative scheme that functionally composes intermediate non-stationary velocity fields to handle large deformations in images whilst guaranteeing diffeomorphisms in the resultant deformation. We then propose a convex optimisation model that uses a regularisation term of arbitrary order to impose smoothness on these velocity fields and solve this model with a fast algorithm that combines Nesterov gradient descent and the alternating direction method of multipliers (ADMM). Finally, we leverage the computational power of GPU to implement this accelerated ADMM solver on a 3D cardiac MRI dataset, further reducing runtime to less than 2 seconds. In addition to producing strictly diffeomorphic deformations, our methods outperform both state-of-the-art deep learning-based and iterative DiffIR approaches in terms of dice and Hausdorff scores, with speed approaching the inference time of deep learning-based methods.

Joint Semi-supervised 3D Super-Resolution and Segmentation with Mixed Adversarial Gaussian Domain Adaptation

Optimising the analysis of cardiac structure and function requires accurate 3D representations of shape and motion. However, techniques such as cardiac magnetic resonance imaging are conventionally limited to acquiring contiguous cross-sectional slices with low through-plane resolution and potential inter-slice spatial misalignment. Super-resolution in medical imaging aims to increase the resolution of images but is conventionally trained on features from low resolution datasets and does not super-resolve corresponding segmentations. Here we propose a semi-supervised multi-task generative adversarial network (Gemini-GAN) that performs joint super-resolution of the images and their labels using a ground truth of high resolution 3D cines and segmentations, while an unsupervised variational adversarial mixture autoencoder (V-AMA) is used for continuous domain adaptation. Our proposed approach is extensively evaluated on two transnational multi-ethnic populations of 1,331 and 205 adults respectively, delivering an improvement on state of the art methods in terms of Dice index, peak signal to noise ratio, and structural similarity index measure. This framework also exceeds the performance of state of the art generative domain adaptation models on external validation (Dice index 0.81 vs 0.74 for the left ventricle). This demonstrates how joint super-resolution and segmentation, trained on 3D ground-truth data with cross-domain generalization, enables robust precision phenotyping in diverse populations.

Learning a Model-Driven Variational Network for Deformable Image Registration

Data-driven deep learning approaches to image registration can be less accurate than conventional iterative approaches, especially when training data is limited. To address this whilst retaining the fast inference speed of deep learning, we propose VR-Net, a novel cascaded variational network for unsupervised deformable image registration. Using the variable splitting optimization scheme, we first convert the image registration problem, established in a generic variational framework, into two sub-problems, one with a point-wise, closed-form solution while the other one is a denoising problem. We then propose two neural layers (i.e. warping layer and intensity consistency layer) to model the analytical solution and a residual U-Net to formulate the denoising problem (i.e. generalized denoising layer). Finally, we cascade the warping layer, intensity consistency layer, and generalized denoising layer to form the VR-Net. Extensive experiments on three (two 2D and one 3D) cardiac magnetic resonance imaging datasets show that VR-Net outperforms state-of-the-art deep learning methods on registration accuracy, while maintains the fast inference speed of deep learning and the data-efficiency of variational model.

Explainable Shape Analysis through Deep Hierarchical Generative Models: Application to Cardiac Remodeling

Quantification of anatomical shape changes still relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of heart conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled hearts when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set. More importantly, it enabled the visualisation in three-dimensions of the most discriminative anatomical features between the two conditions. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging.

3D High-Resolution Cardiac Segmentation Reconstruction from 2D Views using Conditional Variational Autoencoders

Accurate segmentation of heart structures imaged by cardiac MR is key for the quantitative analysis of pathology. High-resolution 3D MR sequences enable whole-heart structural imaging but are time-consuming, expensive to acquire and they often require long breath holds that are not suitable for patients. Consequently, multiplanar breath-hold 2D cine sequences are standard practice but are disadvantaged by lack of whole-heart coverage and low through-plane resolution. To address this, we propose a conditional variational autoencoder architecture able to learn a generative model of 3D high-resolution left ventricular (LV) segmentations which is conditioned on three 2D LV segmentations of one short-axis and two long-axis images. By only employing these three 2D segmentations, our model can efficiently reconstruct the 3D high-resolution LV segmentation of a subject. When evaluated on 400 unseen healthy volunteers, our model yielded an average Dice score of $87.92 \pm 0.15$ and outperformed competing architectures.

Deep learning cardiac motion analysis for human survival prediction

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrell's C-index) was significantly higher (p < .0001) for our model C=0.73 (95$\%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$\%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival.

Learning-Based Quality Control for Cardiac MR Images

The effectiveness of a cardiovascular magnetic resonance (CMR) scan depends on the ability of the operator to correctly tune the acquisition parameters to the subject being scanned and on the potential occurrence of imaging artefacts such as cardiac and respiratory motion. In the clinical practice, a quality control step is performed by visual assessment of the acquired images: however, this procedure is strongly operator-dependent, cumbersome and sometimes incompatible with the time constraints in clinical settings and large-scale studies. We propose a fast, fully-automated, learning-based quality control pipeline for CMR images, specifically for short-axis image stacks. Our pipeline performs three important quality checks: 1) heart coverage estimation, 2) inter-slice motion detection, 3) image contrast estimation in the cardiac region. The pipeline uses a hybrid decision forest method - integrating both regression and structured classification models - to extract landmarks as well as probabilistic segmentation maps from both long- and short-axis images as a basis to perform the quality checks. The technique was tested on up to 3000 cases from the UK Biobank as well as on 100 cases from the UK Digital Heart Project, and validated against manual annotations and visual inspections performed by expert interpreters. The results show the capability of the proposed pipeline to correctly detect incomplete or corrupted scans (e.g. on UK Biobank, sensitivity and specificity respectively 88% and 99% for heart coverage estimation, 85% and 95% for motion detection), allowing their exclusion from the analysed dataset or the triggering of a new acquisition.