Deep nested level sets: Fully automated segmentation of cardiac MR images in patients with pulmonary hypertension

In this paper we introduce a novel and accurate optimisation method for segmentation of cardiac MR (CMR) images in patients with pulmonary hypertension (PH). The proposed method explicitly takes into account the image features learned from a deep neural network. To this end, we estimate simultaneous probability maps over region and edge locations in CMR images using a fully convolutional network. Due to the distinct morphology of the heart in patients with PH, these probability maps can then be incorporated in a single nested level set optimisation framework to achieve multi-region segmentation with high efficiency. The proposed method uses an automatic way for level set initialisation and thus the whole optimisation is fully automated. We demonstrate that the proposed deep nested level set (DNLS) method outperforms existing state-of-the-art methods for CMR segmentation in PH patients

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 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 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. We will share the code and the trained generative model at https://github.com/MengyunQ/CHeart

Joint analysis of clinical risk factors and 4D cardiac motion for survival prediction using a hybrid deep learning network

In this work, a novel approach is proposed for joint analysis of high dimensional time-resolved cardiac motion features obtained from segmented cardiac MRI and low dimensional clinical risk factors to improve survival prediction in heart failure. Different methods are evaluated to find the optimal way to insert conventional covariates into deep prediction networks. Correlation analysis between autoencoder latent codes and covariate features is used to examine how these predictors interact. We believe that similar approaches could also be used to introduce knowledge of genetic variants to such survival networks to improve outcome prediction by jointly analysing cardiac motion traits with inheritable risk factors

Automatic 3D bi-ventricular segmentation of cardiac images by a shape-refined multi-task deep learning approach

Deep learning approaches have achieved state-of-the-art performance in cardiac magnetic resonance (CMR) image segmentation. However, most approaches have focused on learning image intensity features for segmentation, whereas the incorporation of anatomical shape priors has received less attention. In this paper, we combine a multi-task deep learning approach with atlas propagation to develop a shape-constrained bi-ventricular segmentation pipeline for short-axis CMR volumetric images. The pipeline first employs a fully convolutional network (FCN) that learns segmentation and landmark localisation tasks simultaneously. The architecture of the proposed FCN uses a 2.5D representation, thus combining the computational advantage of 2D FCNs networks and the capability of addressing 3D spatial consistency without compromising segmentation accuracy. Moreover, the refinement step is designed to explicitly enforce a shape constraint and improve segmentation quality. This step is effective for overcoming image artefacts (e.g. due to different breath-hold positions and large slice thickness), which preclude the creation of anatomically meaningful 3D cardiac shapes. The proposed pipeline is fully automated, due to network's ability to infer landmarks, which are then used downstream in the pipeline to initialise atlas propagation. We validate the pipeline on 1831 healthy subjects and 649 subjects with pulmonary hypertension. Extensive numerical experiments on the two datasets demonstrate that our proposed method is robust and capable of producing accurate, high-resolution and anatomically smooth bi-ventricular 3D models, despite the artefacts in input CMR volumes

Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning

Aims: Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements. / Methods and results: One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform—greatest in the septum with more pronounced changes in males than females (wall thickness regression: −13 ± 3.6 vs. −6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [−37 (interquartile range −88 to −2) vs. −1 (−24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02). / Conclusion: In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification

Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy

ABSTRACT Background International guidelines for variant interpretation in Mendelian disease set stringent criteria to report a variant as (likely) pathogenic, prioritising control of false positive rate over test sensitivity and diagnostic yield. Genetic testing is also more likely informative in individuals with well-characterised variants from extensively studied European-ancestry populations. Inherited cardiomyopathies are relatively common Mendelian diseases that allow empirical calibration and assessment of this framework. Results We compared rare variants in large hypertrophic cardiomyopathy (HCM) cohorts to reference populations to identify variant classes with high prior likelihoods of pathogenicity, as defined by etiological fraction (EF). Analysis of variant distribution identified regions in which variants are significantly enriched in cases and variant location was a better discriminator of pathogenicity than generic computational functional prediction algorithms. Non-truncating variant classes with an EF≥0.95, and therefore clinically actionable, were identified in 5 established HCM genes. Applying this approach leads to an estimated 14-20% increase in cases with actionable HCM variants. Conclusions When found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent, unbiased and equitable approach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorporate such evidence in a quantitative and transparent manner