Correcting bias in cardiac geometries derived from multimodal images using spatiotemporal mapping.

Cardiovascular imaging studies provide a multitude of structural and functional data to better understand disease mechanisms. While pooling data across studies enables more powerful and broader applications, performing quantitative comparisons across datasets with varying acquisition or analysis methods is problematic due to inherent measurement biases specific to each protocol. We show how dynamic time warping and partial least squares regression can be applied to effectively map between left ventricular geometries derived from different imaging modalities and analysis protocols to account for such differences. To demonstrate this method, paired real-time 3D echocardiography (3DE) and cardiac magnetic resonance (CMR) sequences from 138 subjects were used to construct a mapping function between the two modalities to correct for biases in left ventricular clinical cardiac indices, as well as regional shape. Leave-one-out cross-validation revealed a significant reduction in mean bias, narrower limits of agreement, and higher intraclass correlation coefficients for all functional indices between CMR and 3DE geometries after spatiotemporal mapping. Meanwhile, average root mean squared errors between surface coordinates of 3DE and CMR geometries across the cardiac cycle decreased from 7 ± 1 to 4 ± 1 mm for the total study population. Our generalised method for mapping between time-varying cardiac geometries obtained using different acquisition and analysis protocols enables the pooling of data between modalities and the potential for smaller studies to leverage large population databases for quantitative comparisons.

Biventricular shape modes discriminate pulmonary valve replacement in tetralogy of Fallot better than imaging indices.

Current indications for pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (rTOF) rely on cardiovascular magnetic resonance (CMR) image-based indices but are inconsistently applied, lead to mixed outcomes, and remain debated. This study aimed to test the hypothesis that specific markers of biventricular shape may discriminate differences between rTOF patients who did and did not require subsequent PVR better than standard imaging indices. In this cross-sectional retrospective study, biventricular shape models were customized to CMR images from 84 rTOF patients. A statistical atlas of end-diastolic shape was constructed using principal component analysis. Multivariate regression was used to quantify shape mode and imaging index associations with subsequent intervention status (PVR, n = 48 vs. No-PVR, n = 36), while accounting for confounders. Clustering analysis was used to test the ability of the most significant shape modes and imaging indices to discriminate PVR status as evaluated by a Matthews correlation coefficient (MCC). Geometric strain analysis was also conducted to assess shape mode associations with systolic function. PVR status correlated significantly with shape modes associated with right ventricular (RV) apical dilation and left ventricular (LV) dilation (p < 0.01), RV basal bulging and LV conicity (p < 0.05), and pulmonary valve dilation (p < 0.01). PVR status also correlated significantly with RV ejection fraction (p < 0.05) and correlated marginally with LV end-systolic volume index (p < 0.07). Shape modes discriminated subsequent PVR better than standard imaging indices (MCC = 0.49 and MCC = 0.28, respectively) and were significantly associated with RV and LV radial systolic strain. Biventricular shape modes discriminated differences between patients who did and did not require subsequent PVR better than standard imaging indices in current use. These regional features of cardiac morphology may provide insight into adaptive vs. maladaptive types of structural remodeling and point toward an improved quantitative, patient-specific assessment tool for clinical use.

Super-resolution 4D flow MRI to quantify aortic regurgitation using computational fluid dynamics and deep learning.

Changes in cardiovascular hemodynamics are closely related to the development of aortic regurgitation (AR), a type of valvular heart disease. Metrics derived from blood flows are used to indicate AR onset and evaluate its severity. These metrics can be non-invasively obtained using four-dimensional (4D) flow magnetic resonance imaging (MRI), where accuracy is primarily dependent on spatial resolution. However, insufficient resolution often results from limitations in 4D flow MRI and complex aortic regurgitation hemodynamics. To address this, computational fluid dynamics simulations were transformed into synthetic 4D flow MRI data and used to train a variety of neural networks. These networks generated super-resolution, full-field phase images with an upsample factor of 4. Results showed decreased velocity error, high structural similarity scores, and improved learning capabilities from previous work. Further validation was performed on two sets of in vivo 4D flow MRI data and demonstrated success in de-noising flow images. This approach presents an opportunity to comprehensively analyse AR hemodynamics in a non-invasive manner.

Multi-Ethnic Study of Atherosclerosis: Relationship between Left Ventricular Shape at Cardiac MRI and 10-year Outcomes.

Background Left ventricular (LV) subclinical remodeling is associated with adverse outcomes and indicates mechanisms of disease development. Standard metrics such as LV mass and volumes may not capture the full range of remodeling. Purpose To quantify the relationship between LV three-dimensional shape at MRI and incident cardiovascular events over 10 years. Materials and Methods In this retrospective study, 5098 participants from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease underwent cardiac MRI from 2000 to 2002. LV shape models were automatically generated using a machine learning workflow. Event-specific remodeling signatures were computed using partial least squares regression, and random survival forests were used to determine which features were most associated with incident heart failure (HF), coronary heart disease (CHD), and cardiovascular disease (CVD) events over a 10-year follow-up period. The discrimination improvement of adding LV shape to traditional cardiovascular risk factors, coronary artery calcium scores, and N-terminal pro-brain natriuretic peptide levels was assessed using the index of prediction accuracy and time-dependent area under the receiver operating characteristic curve (AUC). Kaplan-Meier survival curves were used to illustrate the ability of remodeling signatures to predict the end points. Results Overall, 4618 participants had sufficient three-dimensional MRI information to generate patient-specific LV models (mean age, 60.6 years ± 9.9 [SD]; 2540 women). Among these participants, 147 had HF, 317 had CHD, and 455 had CVD events. The addition of LV remodeling signatures to traditional cardiovascular risk factors improved the mean AUC for 10-year survival prediction and achieved better performance than LV mass and volumes; HF (AUC, 0.83 ± 0.01 and 0.81 ± 0.01, respectively; P < .05), CHD (AUC, 0.77 ± 0.01 and 0.75 ± 0.01, respectively; P < .05), and CVD (AUC, 0.78 ± 0.0 and 0.76 ± 0.0, respectively; P < .05). Kaplan-Meier analysis demonstrated that participants with high-risk HF remodeling signatures had a 10-year survival rate of 56% compared with 95% for those with low-risk scores. Conclusion Left ventricular event-specific remodeling signatures were more predictive of heart failure, coronary heart disease, and cardiovascular disease events over 10 years than standard mass and volume measures and enable an automatic personalized medicine approach to tracking remodeling. © RSNA, 2022 Online supplemental material is available for this article.

Le Cœur en Sabot: shape associations with adverse events in repaired tetralogy of Fallot.

BACKGROUND: Maladaptive remodelling mechanisms occur in patients with repaired tetralogy of Fallot (rToF) resulting in a cycle of metabolic and structural changes. Biventricular shape analysis may indicate mechanisms associated with adverse events independent of pulmonary regurgitant volume index (PRVI). We aimed to determine novel remodelling patterns associated with adverse events in patients with rToF using shape and function analysis. METHODS: Biventricular shape and function were studied in 192 patients with rToF (median time from TOF repair to baseline evaluation 13.5 years). Linear discriminant analysis (LDA) and principal component analysis (PCA) were used to identify shape differences between patients with and without adverse events. Adverse events included death, arrhythmias, and cardiac arrest with median follow-up of 10 years. RESULTS: LDA and PCA showed that shape characteristics pertaining to adverse events included a more circular left ventricle (LV) (decreased eccentricity), dilated (increased sphericity) LV base, increased right ventricular (RV) apical sphericity, and decreased RV basal sphericity. Multivariate LDA showed that the optimal discriminative model included only RV apical ejection fraction and one PCA mode associated with a more circular and dilated LV base (AUC = 0.77). PRVI did not add value, and shape changes associated with increased PRVI were not predictive of adverse outcomes. CONCLUSION: Pathological remodelling patterns in patients with rToF are significantly associated with adverse events, independent of PRVI. Mechanisms related to incident events include LV basal dilation with a reduced RV apical ejection fraction.

Right-left ventricular shape variations in tetralogy of Fallot: associations with pulmonary regurgitation.

BACKGROUND: Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. METHODS: In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8-24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. RESULTS: PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). CONCLUSION: A biventricular atlas of rTOF patients quantified multivariate relationships between left-right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.

An Implementation of Patient-Specific Biventricular Mechanics Simulations With a Deep Learning and Computational Pipeline.

Parameterised patient-specific models of the heart enable quantitative analysis of cardiac function as well as estimation of regional stress and intrinsic tissue stiffness. However, the development of personalised models and subsequent simulations have often required lengthy manual setup, from image labelling through to generating the finite element model and assigning boundary conditions. Recently, rapid patient-specific finite element modelling has been made possible through the use of machine learning techniques. In this paper, utilising multiple neural networks for image labelling and detection of valve landmarks, together with streamlined data integration, a pipeline for generating patient-specific biventricular models is applied to clinically-acquired data from a diverse cohort of individuals, including hypertrophic and dilated cardiomyopathy patients and healthy volunteers. Valve motion from tracked landmarks as well as cavity volumes measured from labelled images are used to drive realistic motion and estimate passive tissue stiffness values. The neural networks are shown to accurately label cardiac regions and features for these diverse morphologies. Furthermore, differences in global intrinsic parameters, such as tissue anisotropy and normalised active tension, between groups illustrate respective underlying changes in tissue composition and/or structure as a result of pathology. This study shows the successful application of a generic pipeline for biventricular modelling, incorporating artificial intelligence solutions, within a diverse cohort.

Right Ventricular Flow Vorticity Relationships With Biventricular Shape in Adult Tetralogy of Fallot.

Remodeling in adults with repaired tetralogy of Fallot (rToF) may occur due to chronic pulmonary regurgitation, but may also be related to altered flow patterns, including vortices. We aimed to correlate and quantify relationships between vorticity and ventricular shape derived from atlas-based analysis of biventricular shape. Adult rToF (n = 12) patients underwent 4D flow and cine MRI imaging. Vorticity in the RV was computed after noise reduction using a neural network. A biventricular shape atlas built from 95 rToF patients was used to derive principal component modes, which were associated with vorticity and pulmonary regurgitant volume (PRV) using univariate and multivariate linear regression. Univariate analysis showed that indexed PRV correlated with 3 modes (r = -0.55,-0.50, and 0.6, all p < 0.05) associated with RV dilatation and an increase in basal bulging, apical bulging and tricuspid annulus tilting with more severe regurgitation, as well as a smaller LV and paradoxical movement of the septum. RV outflow and inflow vorticity were also correlated with these modes. However, total vorticity over the whole RV was correlated with two different modes (r = -0.62,-0.69, both p < 0.05). Higher vorticity was associated with both RV and LV shape changes including longer ventricular length, a larger bulge beside the tricuspid valve, and distinct tricuspid tilting. RV flow vorticity was associated with changes in biventricular geometry, distinct from associations with PRV. Flow vorticity may provide additional mechanistic information in rToF remodeling. Both LV and RV shapes are important in rToF RV flow patterns.

Deep Learning Analysis of Cardiac MRI in Legacy Datasets: Multi-Ethnic Study of Atherosclerosis.

The Multi-Ethnic Study of Atherosclerosis (MESA), begun in 2000, was the first large cohort study to incorporate cardiovascular magnetic resonance (CMR) to study the mechanisms of cardiovascular disease in over 5,000 initially asymptomatic participants, and there is now a wealth of follow-up data over 20 years. However, the imaging technology used to generate the CMR images is no longer in routine use, and methods trained on modern data fail when applied to such legacy datasets. This study aimed to develop a fully automated CMR analysis pipeline that leverages the ability of machine learning algorithms to enable extraction of additional information from such a large-scale legacy dataset, expanding on the original manual analyses. We combined the original study analyses with new annotations to develop a set of automated methods for customizing 3D left ventricular (LV) shape models to each CMR exam and build a statistical shape atlas. We trained VGGNet convolutional neural networks using a transfer learning sequence between two-chamber, four-chamber, and short-axis MRI views to detect landmarks. A U-Net architecture was used to detect the endocardial and epicardial boundaries in short-axis images. The landmark detection network accurately predicted mitral valve and right ventricular insertion points with average error distance <2.5 mm. The agreement of the network with two observers was excellent (intraclass correlation coefficient >0.9). The segmentation network produced average Dice score of 0.9 for both myocardium and LV cavity. Differences between the manual and automated analyses were small, i.e., <1.0 ± 2.6 mL/m2 for indexed LV volume, 3.0 ± 6.4 g/m2 for indexed LV mass, and 0.6 ± 3.3% for ejection fraction. In an independent atlas validation dataset, the LV atlas built from the fully automated pipeline showed similar statistical relationships to an atlas built from the manual analysis. Hence, the proposed pipeline is not only a promising framework to automatically assess additional measures of ventricular function, but also to study relationships between cardiac morphologies and future cardiac events, in a large-scale population study.

WSSNet: Aortic Wall Shear Stress Estimation Using Deep Learning on 4D Flow MRI.

Wall shear stress (WSS) is an important contributor to vessel wall remodeling and atherosclerosis. However, image-based WSS estimation from 4D Flow MRI underestimates true WSS values, and the accuracy is dependent on spatial resolution, which is limited in 4D Flow MRI. To address this, we present a deep learning algorithm (WSSNet) to estimate WSS trained on aortic computational fluid dynamics (CFD) simulations. The 3D CFD velocity and coordinate point clouds were resampled into a 2D template of 48 × 93 points at two inward distances (randomly varied from 0.3 to 2.0 mm) from the vessel surface ("velocity sheets"). The algorithm was trained on 37 patient-specific geometries and velocity sheets. Results from 6 validation and test cases showed high accuracy against CFD WSS (mean absolute error 0.55 ± 0.60 Pa, relative error 4.34 ± 4.14%, 0.92 ± 0.05 Pearson correlation) and noisy synthetic 4D Flow MRI at 2.4 mm resolution (mean absolute error 0.99 ± 0.91 Pa, relative error 7.13 ± 6.27%, and 0.79 ± 0.10 Pearson correlation). Furthermore, the method was applied on in vivo 4D Flow MRI cases, effectively estimating WSS from standard clinical images. Compared with the existing parabolic fitting method, WSSNet estimates showed 2-3 × higher values, closer to CFD, and a Pearson correlation of 0.68 ± 0.12. This approach, considering both geometric and velocity information from the image, is capable of estimating spatiotemporal WSS with varying image resolution, and is more accurate than existing methods while still preserving the correct WSS pattern distribution.

Artificial Intelligence in Cardiac Imaging With Statistical Atlases of Cardiac Anatomy.

In many cardiovascular pathologies, the shape and motion of the heart provide important clues to understanding the mechanisms of the disease and how it progresses over time. With the advent of large-scale cardiac data, statistical modeling of cardiac anatomy has become a powerful tool to provide automated, precise quantification of the status of patient-specific heart geometry with respect to reference populations. Powered by supervised or unsupervised machine learning algorithms, statistical cardiac shape analysis can be used to automatically identify and quantify the severity of heart diseases, to provide morphometric indices that are optimally associated with clinical factors, and to evaluate the likelihood of adverse outcomes. Recently, statistical cardiac atlases have been integrated with deep neural networks to enable anatomical consistency of cardiac segmentation, registration, and automated quality control. These combinations have already shown significant improvements in performance and avoid gross anatomical errors that could make the results unusable. This current trend is expected to grow in the near future. Here, we aim to provide a mini review highlighting recent advances in statistical atlasing of cardiac function in the context of artificial intelligence in cardiac imaging.

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.

Independent Left Ventricular Morphometric Atlases Show Consistent Relationships with Cardiovascular Risk Factors: A UK Biobank Study.

Left ventricular (LV) mass and volume are important indicators of clinical and pre-clinical disease processes. However, much of the shape information present in modern imaging examinations is currently ignored. Morphometric atlases enable precise quantification of shape and function, but there has been no objective comparison of different atlases in the same cohort. We compared two independent LV atlases using MRI scans of 4547 UK Biobank participants: (i) a volume atlas derived by automatic non-rigid registration of image volumes to a common template, and (ii) a surface atlas derived from manually drawn epicardial and endocardial surface contours. The strength of associations between atlas principal components and cardiovascular risk factors (smoking, diabetes, high blood pressure, high cholesterol and angina) were quantified with logistic regression models and five-fold cross validation, using area under the ROC curve (AUC) and Akaike Information Criterion (AIC) metrics. Both atlases exhibited similar principal components, showed similar relationships with risk factors, and had stronger associations (higher AUC and lower AIC) than a reference model based on LV mass and volume, for all risk factors (DeLong p < 0.05). Morphometric variations associated with each risk factor could be quantified and visualized and were similar between atlases. UK Biobank LV shape atlases are robust to construction method and show stronger relationships with cardiovascular risk factors than mass and volume.

Atlas-Based Computational Analysis of Heart Shape and Function in Congenital Heart Disease.

Approximately 1% of all babies are born with some form of congenital heart defect. Many serious forms of CHD can now be surgically corrected after birth, which has led to improved survival into adulthood. However, many patients require serial monitoring to evaluate progression of heart failure and determine timing of interventions. Accurate multidimensional quantification of regional heart shape and function is required for characterizing these patients. A computational atlas of single ventricle and biventricular heart shape and function enables quantification of remodeling in terms of z scores in relation to specific reference populations. Progression of disease can then be monitored effectively by longitudinal evaluation of z scores. A biomechanical analysis of cardiac function in relation to population variation enables investigation of the underlying mechanisms for developing pathology. Here, we summarize recent progress in this field, with examples in single ventricle and biventricular congenital pathologies.