Comparison of T1 mapping techniques for ECV quantification. histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR

BACKGROUND: Myocardial extracellular volume (ECV) is elevated in fibrosis or infiltration and can be quantified by measuring the haematocrit with pre and post contrast T1 at sufficient contrast equilibrium. Equilibrium CMR (EQ-CMR), using a bolus-infusion protocol, has been shown to provide robust measurements of ECV using a multibreath-hold T1 pulse sequence. Newer, faster sequences for T1 mapping promise whole heart coverage and improved clinical utility, but have not been validated. METHODS: Multibreathhold T1 quantification with heart rate correction and single breath-hold T1 mapping using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) were used in equilibrium contrast CMR to generate ECV values and compared in 3 ways.Firstly, both techniques were compared in a spectrum of disease with variable ECV expansion (n=100, 50 healthy volunteers, 12 patients with hypertrophic cardiomyopathy, 18 with severe aortic stenosis, 20 with amyloid). Secondly, both techniques were correlated to human histological collagen volume fraction (CVF%, n=18, severe aortic stenosis biopsies). Thirdly, an assessment of test:retest reproducibility of the 2 CMR techniques was performed 1 week apart in individuals with widely different ECVs (n=10 healthy volunteers, n=7 amyloid patients). RESULTS: More patients were able to perform ShMOLLI than the multibreath-hold technique (6% unable to breath-hold). ECV calculated by multibreath-hold T1 and ShMOLLI showed strong correlation (r(2)=0.892), little bias (bias -2.2%, 95%CI -8.9% to 4.6%) and good agreement (ICC 0.922, range 0.802 to 0.961, p<0.0001). ECV correlated with histological CVF% by multibreath-hold ECV (r(2)= 0.589) but better by ShMOLLI ECV (r(2)= 0.685). Inter-study reproducibility demonstrated that ShMOLLI ECV trended towards greater reproducibility than the multibreath-hold ECV, although this did not reach statistical significance (95%CI -4.9% to 5.4% versus 95%CI -6.4% to 7.3% respectively, p=0.21). CONCLUSIONS: ECV quantification by single breath-hold ShMOLLI T1 mapping can measure ECV by EQ-CMR across the spectrum of interstitial expansion. It is procedurally better tolerated, slightly more reproducible and better correlates with histology compared to the older multibreath-hold FLASH techniques

3D Cardiac Shape Prediction with Deep Neural Networks: Simultaneous Use of Images and Patient Metadata

Large prospective epidemiological studies acquire cardiovascular magnetic resonance (CMR) images for pre-symptomatic populations and follow these over time. To support this approach, fully automatic large-scale 3D analysis is essential. In this work, we propose a novel deep neural network using both CMR images and patient metadata to directly predict cardiac shape parameters. The proposed method uses the promising ability of statistical shape models to simplify shape complexity and variability together with the advantages of convolutional neural networks for the extraction of solid visual features. To the best of our knowledge, this is the first work that uses such an approach for 3D cardiac shape prediction. We validated our proposed CMR analytics method against a reference cohort containing 500 3D shapes of the cardiac ventricles. Our results show broadly significant agreement with the reference shapes in terms of the estimated volume of the cardiac ventricles, myocardial mass, 3D Dice, and mean and Hausdorff distance

Fully Automated Myocardial Strain Estimation from Cardiovascular MRI–tagged Images Using a Deep Learning Framework in the UK Biobank

Purpose: To demonstrate the feasibility and performance of a fully automated deep learning framework to estimate myocardial strain from short-axis cardiac magnetic resonance tagged images. Methods and Materials: In this retrospective cross-sectional study, 4508 cases from the UK Biobank were split randomly into 3244 training and 812 validation cases, and 452 test cases. Ground truth myocardial landmarks were defined and tracked by manual initialization and correction of deformable image registration using previously validated software with five readers. The fully automatic framework consisted of 1) a convolutional neural network (CNN) for localization, and 2) a combination of a recurrent neural network (RNN) and a CNN to detect and track the myocardial landmarks through the image sequence for each slice. Radial and circumferential strain were then calculated from the motion of the landmarks and averaged on a slice basis. Results: Within the test set, myocardial end-systolic circumferential Green strain errors were -0.001 +/- 0.025, -0.001 +/- 0.021, and 0.004 +/- 0.035 in basal, mid, and apical slices respectively (mean +/- std. dev. of differences between predicted and manual strain). The framework reproduced significant reductions in circumferential strain in diabetics, hypertensives, and participants with previous heart attack. Typical processing time was ~260 frames (~13 slices) per second on an NVIDIA Tesla K40 with 12GB RAM, compared with 6-8 minutes per slice for the manual analysis. Conclusions: The fully automated RNNCNN framework for analysis of myocardial strain enabled unbiased strain evaluation in a high-throughput workflow, with similar ability to distinguish impairment due to diabetes, hypertension, and previous heart attack.Comment: accepted in Radiology Cardiothoracic Imagin

Characterizing the hypertensive cardiovascular phenotype in the UK Biobank

Aims: To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations. Methods and results: We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control. Conclusion: Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control

Right ventricular shape and function: cardiovascular magnetic resonance reference morphology and biventricular risk factor morphometrics in UK Biobank

Background The associations between cardiovascular disease (CVD) risk factors and the biventricular geometry of the right ventricle (RV) and left ventricle (LV) have been difficult to assess, due to subtle and complex shape changes. We sought to quantify reference RV morphology as well as biventricular variations associated with common cardiovascular risk factors. Methods A biventricular shape atlas was automatically constructed using contours and landmarks from 4329 UK Biobank cardiovascular magnetic resonance (CMR) studies. A subdivision surface geometric mesh was customized to the contours using a diffeomorphic registration algorithm, with automatic correction of slice shifts due to differences in breath-hold position. A reference sub-cohort was identified consisting of 630 participants with no CVD risk factors. Morphometric scores were computed using linear regression to quantify shape variations associated with four risk factors (high cholesterol, high blood pressure, obesity and smoking) and three disease factors (diabetes, previous myocardial infarction and angina). Results The atlas construction led to an accurate representation of 3D shapes at end-diastole and end-systole, with acceptable fitting errors between surfaces and contours (average error less than 1.5 mm). Atlas shape features had stronger associations than traditional mass and volume measures for all factors (p < 0.005 for each). High blood pressure was associated with outward displacement of the LV free walls, but inward displacement of the RV free wall and thickening of the septum. Smoking was associated with a rounder RV with inward displacement of the RV free wall and increased relative wall thickness. Conclusion Morphometric relationships between biventricular shape and cardiovascular risk factors in a large cohort show complex interactions between RV and LV morphology. These can be quantified by z-scores, which can be used to study the morphological correlates of disease

Multi-input and dataset-invariant adversarial learning (MDAL) for left and right-ventricular coverage estimation in cardiac MRI

Cardiac functional parameters, such as, the Ejection Fraction (EF) and Cardiac Output (CO) of both ventricles, are most immediate indicators of normal/abnormal cardiac function. To compute these parameters, accurate measurement of ventricular volumes at end-diastole (ED) and end-systole (ES) are required. Accurate volume measurements depend on the correct identification of basal and apical slices in cardiac magnetic resonance (CMR) sequences that provide full coverage of both left (LV) and right (RV) ventricles. This paper proposes a novel adversarial learning (AL) approach based on convolutional neural networks (CNN) that detects and localizes the basal/apical slices in an image volume independently of image-acquisition parameters, such as, imaging device, magnetic field strength, variations in protocol execution, etc. The proposed model is trained on multiple cohorts of different provenance, and learns image features from different MRI viewing planes to learn the appearance and predict the position of the basal and apical planes. To the best of our knowledge, this is the first work tackling the fully automatic detection and position regression of basal/apical slices in CMR volumes in a dataset-invariant manner. We achieve this by maximizing the ability of a CNN to regress the position of basal/apical slices within a single dataset, while minimizing the ability of a classifier to discriminate image features between different data sources. Our results show superior performance over state-of-the-art methods

Automatic Assessment of Full Left Ventricular Coverage in Cardiac Cine Magnetic Resonance Imaging With Fisher-Discriminative 3-D CNN

Cardiac magnetic resonance (CMR) images play a growing role in the diagnostic imaging of cardiovascular diseases. Full coverage of the left ventricle (LV), from base to apex, is a basic criterion for CMR image quality and is necessary for accurate measurement of cardiac volume and functional assessment. Incomplete coverage of the LV is identified through visual inspection, which is time consuming and usually done retrospectively in the assessment of large imaging cohorts. This paper proposes a novel automatic method for determining LV coverage from CMR images by using Fisher-discriminative three-dimensional (FD3D) convolutional neural networks (CNNs). In contrast to our previous method employing 2-D CNNs, this approach utilizes spatial contextual information in CMR volumes, extracts more representative high-level features, and enhances the discriminative capacity of the baseline 2-D CNN learning framework, thus, achieving superior detection accuracy. A two-stage framework is proposed to identify missing basal and apical slices in measurements of CMR volume. First, the FD3D CNN extracts high-level features from the CMR stacks. These image representations are then used to detect the missing basal and apical slices. Compared to the traditional 3-D CNN strategy, the proposed FD3D CNN minimizes within-class scatter and maximizes between-class scatter. We performed extensive experiments to validate the proposed method on more than 5000 independent volumetric CMR scans from the UK Biobank study, achieving low error rates for missing basal/apical slice detection (4.9%/4.6%). The proposed method can also be adopted for assessing LV coverage for other types of CMR image data

Improving cardiac MRI convolutional neural network segmentation on small training datasets and dataset shift: A continuous kernel cut approach

Cardiac magnetic resonance imaging (MRI) provides a wealth of imaging biomarkers for cardiovascular disease care and segmentation of cardiac structures is required as a first step in enumerating these biomarkers. Deep convolutional neural networks (CNNs) have demonstrated remarkable success in image segmentation but typically require large training datasets and provide suboptimal results that require further improvements. Here, we developed a way to enhance cardiac MRI multi-class segmentation by combining the strengths of CNN and interpretable machine learning algorithms. We developed a continuous kernel cut segmentation algorithm by integrating normalized cuts and continuous regularization in a unified framework. The high-order formulation was solved through upper bound relaxation and a continuous max-flow algorithm in an iterative manner using CNN predictions as inputs. We applied our approach to two representative cardiac MRI datasets across a wide range of cardiovascular pathologies. We comprehensively evaluated the performance of our approach for two CNNs trained with various small numbers of training cases, tested on the same and different datasets. Experimental results showed that our approach improved baseline CNN segmentation by a large margin, reduced CNN segmentation variability substantially, and achieved excellent segmentation accuracy with minimal extra computational cost. These results suggest that our approach provides a way to enhance the applicability of CNN by enabling the use of smaller training datasets and improving the segmentation accuracy and reproducibility for cardiac MRI segmentation in research and clinical patient care