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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.

In cardiac magnetic resonance (CMR) imaging, a 3D high-resolution segmentation of the heart is essential for detailed description of its anatomical structures. However, due to the limit of acquisition duration and respiratory/cardiac motion, stacks of multi-slice 2D images are acquired in clinical routine. The segmentation of these images provides a low-resolution representation of cardiac anatomy, which may contain artefacts caused by motion. Here we propose a novel latent optimisation framework that jointly performs motion correction and super resolution for cardiac image segmentations. Given a low-resolution segmentation as input, the framework accounts for inter-slice motion in cardiac MR imaging and super-resolves the input into a high-resolution segmentation consistent with input. A multi-view loss is incorporated to leverage information from both short-axis view and long-axis view of cardiac imaging. To solve the inverse problem, iterative optimisation is performed in a latent space, which ensures the anatomical plausibility. This alleviates the need of paired low-resolution and high-resolution images for supervised learning. Experiments on two cardiac MR datasets show that the proposed framework achieves high performance, comparable to state-of-the-art super-resolution approaches and with better cross-domain generalisability and anatomical plausibility., Comment: The paper is early accepted to MICCAI 2021. The codes are available at https://github.com/shuowang26/SRHeart

Quantification of anatomical shape changes currently 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 many 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 left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging., Comment: Accepted for publication in IEEE Transactions on Medical Imaging (TMI)

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., Comment: Accepted in IEEE International Symposium on Biomedical Imaging (ISBI 2019)

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.

In the clinical routine, short axis (SA) cine cardiac MR (CMR) image stacks are acquired during multiple subsequent breath-holds. If the patient cannot consistently hold the breath at the same position, the acquired image stack will be affected by inter-slice respiratory motion and will not correctly represent the cardiac volume, introducing potential errors in the following analyses and visualisations. We propose an approach to automatically correct inter-slice respiratory motion in SA CMR image stacks. Our approach makes use of probabilistic segmentation maps (PSMs) of the left ventricular (LV) cavity generated with decision forests. PSMs are generated for each slice of the SA stack and rigidly registered in-plane to a target PSM. If long axis (LA) images are available, PSMs are generated for them and combined to create the target PSM; if not, the target PSM is produced from the same stack using a 3D model trained from motion-free stacks. The proposed approach was tested on a dataset of SA stacks acquired from 24 healthy subjects (for which anatomical 3D cardiac images were also available as reference) and compared to two techniques which use LA intensity images and LA segmentations as targets, respectively. The results show the accuracy and robustness of the proposed approach in motion compensation., Comment: Accepted for publication at MICCAI 2018. arXiv admin note: text overlap with arXiv:1803.09354

Alterations in the geometry and function of the heart define well-established causes of cardiovascular disease. However, current approaches to the diagnosis of cardiovascular diseases often rely on subjective human assessment as well as manual analysis of medical images. Both factors limit the sensitivity in quantifying complex structural and functional phenotypes. Deep learning approaches have recently achieved success for tasks such as classification or segmentation of medical images, but lack interpretability in the feature extraction and decision processes, limiting their value in clinical diagnosis. In this work, we propose a 3D convolutional generative model for automatic classification of images from patients with cardiac diseases associated with structural remodeling. The model leverages interpretable task-specific anatomic patterns learned from 3D segmentations. It further allows to visualise and quantify the learned pathology-specific remodeling patterns in the original input space of the images. This approach yields high accuracy in the categorization of healthy and hypertrophic cardiomyopathy subjects when tested on unseen MR images from our own multi-centre dataset (100%) as well on the ACDC MICCAI 2017 dataset (90%). We believe that the proposed deep learning approach is a promising step towards the development of interpretable classifiers for the medical imaging domain, which may help clinicians to improve diagnostic accuracy and enhance patient risk-stratification., Comment: Accepted at MICCAI 2018

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.

MOTIVATION: Left ventricular (LV) hypertrophy is a strong predictor of cardiovascular outcomes, but its genetic regulation remains largely unexplained. Conventional phenotyping relies on manual calculation of LV mass and wall thickness, but advanced cardiac image analysis presents an opportunity for high-throughput mapping of genotype-phenotype associations in three dimensions (3D). RESULTS: High-resolution cardiac magnetic resonance images were automatically segmented in 1,124 healthy volunteers to create a 3D shape model of the heart. Mass univariate regression was used to plot a 3D effect-size map for the association between wall thickness and a set of predictors at each vertex in the mesh. The vertices where a significant effect exists were determined by applying threshold-free cluster enhancement to boost areas of signal with spatial contiguity. Experiments on simulated phenotypic signals and SNP replication show that this approach offers a substantial gain in statistical power for cardiac genotype-phenotype associations while providing good control of the false discovery rate. This framework models the effects of genetic variation throughout the heart and can be automatically applied to large population cohorts. AVAILABILITY: The proposed approach has been coded in an R package freely available at https://doi.org/10.5281/zenodo.834610 together with the clinical data used in this work., Comment: 14 pages, 11 figures. Version accepted by Bioinformatics (Sept 2017). Includes Supplementary Materials

Incorporation of prior knowledge about organ shape and location is key to improve performance of image analysis approaches. In particular, priors can be useful in cases where images are corrupted and contain artefacts due to limitations in image acquisition. The highly constrained nature of anatomical objects can be well captured with learning based techniques. However, in most recent and promising techniques such as CNN based segmentation it is not obvious how to incorporate such prior knowledge. State-of-the-art methods operate as pixel-wise classifiers where the training objectives do not incorporate the structure and inter-dependencies of the output. To overcome this limitation, we propose a generic training strategy that incorporates anatomical prior knowledge into CNNs through a new regularisation model, which is trained end-to-end. The new framework encourages models to follow the global anatomical properties of the underlying anatomy (e.g. shape, label structure) via learned non-linear representations of the shape. We show that the proposed approach can be easily adapted to different analysis tasks (e.g. image enhancement, segmentation) and improve the prediction accuracy of the state-of-the-art models. The applicability of our approach is shown on multi-modal cardiac datasets and public benchmarks. Additionally, we demonstrate how the learned deep models of 3D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies., Comment: Published in IEEE Transactions on Medical Imaging (Aug 2017)