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Cardiac shape modeling is a useful computational tool that has provided quantitative insights into the mechanisms underlying dysfunction in heart disease. The manual input and time required to make cardiac shape models, however, limits their clinical utility. Here we present an end-to-end pipeline that uses deep learning for automated view classification, slice selection, phase selection, anatomical landmark localization, and myocardial image segmentation for the automated generation of three-dimensional, biventricular shape models. With this approach, we aim to make cardiac shape modeling a more robust and broadly applicable tool that has processing times consistent with clinical workflows. Cardiovascular magnetic resonance (CMR) images from a cohort of 123 patients with repaired tetralogy of Fallot (rTOF) from two internal sites were used to train and validate each step in the automated pipeline. The complete automated pipeline was tested using CMR images from a cohort of 12 rTOF patients from an internal site and 18 rTOF patients from an external site. Manually and automatically generated shape models from the test set were compared using Euclidean projection distances, global ventricular measurements, and atlas-based shape mode scores. The mean absolute error (MAE) between manually and automatically generated shape models in the test set was similar to the voxel resolution of the original CMR images for end-diastolic models (MAE = 1.9 ± 0.5 mm) and end-systolic models (MAE = 2.1 ± 0.7 mm). Global ventricular measurements computed from automated models were in good agreement with those computed from manual models. The average mean absolute difference in shape mode Z-score between manually and automatically generated models was 0.5 standard deviations for the first 20 modes of a reference statistical shape atlas. Using deep learning, accurate three-dimensional, biventricular shape models can be reliably created. This fully automated end-to-end approach dramatically reduces the manual input required to create shape models, thereby enabling the rapid analysis of large-scale datasets and the potential to deploy statistical atlas-based analyses in point-of-care clinical settings. Training data and networks are available from cardiacatlas.org.

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

The current study proposes an efficient strategy for exploiting the statistical power of cardiac atlases to investigate whether clinically significant variations in ventricular shape are sufficient to explain corresponding differences in ventricular wall motion directly, or if they are indirect markers of altered myocardial mechanical properties. This study was conducted in a cohort of patients with repaired tetralogy of Fallot (rTOF) that face long-term right ventricular (RV) and/or left ventricular (LV) dysfunction as a consequence of adverse remodeling. Features of biventricular end-diastolic (ED) shape associated with RV apical dilation, LV dilation, RV basal bulging, and LV conicity correlated with components of systolic wall motion (SWM) that contribute most to differences in global systolic function. A finite element analysis of systolic biventricular mechanics was employed to assess the effect of perturbations in these ED shape modes on corresponding components of SWM. Perturbations to ED shape modes and myocardial contractility explained observed variation in SWM to varying degrees. In some cases, shape markers were partial determinants of systolic function and, in other cases, they were indirect markers for altered myocardial mechanical properties. Patients with rTOF may benefit from an atlas-based analysis of biventricular mechanics to improve prognosis and gain mechanistic insight into underlying myocardial pathophysiology.

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

Increased availability and access to medical image data has enabled more quantitative approaches to clinical diagnosis, prognosis, and treatment planning for congenital heart disease. Here we present an overview of long-term clinical management of tetralogy of Fallot (TOF) and its intersection with novel computational and data science approaches to discovering biomarkers of functional and prognostic importance. Efforts in translational medicine that seek to address the clinical challenges associated with cardiovascular diseases using personalized and precision-based approaches are then discussed. The considerations and challenges of translational cardiovascular medicine are reviewed, and examples of digital platforms with collaborative, cloud-based, and scalable design are provided.

BackgroundAdverse cardiac remodeling is an important precursor to anthracycline-related cardiac dysfunction, however conventional remodeling indices are limited. We sought to examine the utility of statistical atlas-derived measures of ventricular shape to improve the identification of adverse anthracycline-related remodeling in childhood cancer survivors.MethodsWe analyzed cardiac magnetic resonance imaging from a cross-sectional cohort of 20 childhood cancer survivors who were treated with low (

Single ventricle physiology and palliation via the Fontan operation lead to a series of cardiovascular changes. In addition, organs such as the kidneys and liver have been shown to experience insults and subsequent injury. This has led to routine surveillance of patients. We present findings from a small cohort of patients that was deeply phenotyped to illustrate the need for comprehensive evaluation. A cohort of four Fontan patients with fairly high cardiovascular function was recruited 5-10 years post-Fontan. Patients underwent a rigorous clinical work-up after which a research MRI scan was performed during which (I) data were obtained during exercise to evaluate changes in stroke volume during supine exercise and (II) magnetic resonance angiograms with phase-contrast images were obtained for computational modeling of flows through the Fontan circulation at rest. Clinical measures were consistent with a fairly homogeneous high function cohort (peak oxygen consumption >20 mL/kg/min, robust response to exercise, peak ventilatory efficiency below levels associated with heart failure, MR-derived ejection fraction >50%). Liver evaluation did not reveal clear signs of cirrhosis or extensive fibrosis. However, we observed considerable variability (27-162%) in the increase in stroke index with exercise [100%±64% increase, 53.9±17.4 mL/beat m2 (rest), 101.1±20.7 mL/beat m2, (exercise)]. Computational flow modeling at rest in two patients also showed marked differences in flow distribution and shear stress. We report marked differences in both changes in stroke index during an exercise MRI protocol as well as computational flow patterns at rest suggesting different compensation strategies may be associated with high functioning Fontan patients. The observed heterogeneity illustrates the need for deep phenotyping to capture patient-specific adaptive mechanisms.

Purpose: We sought to assess the feasibility, reproducibility, and accuracy of conventional and newer echocardiographic measures of right ventricular (RV) systolic function in adolescent and young adult childhood cancer survivors treated with anthracyclines. Methods: Echocardiography and cardiac magnetic resonance imaging (CMR) were acquired ≤60 days apart in prospectively recruited survivors and RV functional measures were quantitated by blinded observers. Repeat quantitation was performed in a subset to evaluate reproducibility. For each echocardiographic measure, Spearman correlations with CMR measures were calculated, and values in participants with CMR RV ejection fraction (RVEF) ≥48% and RVEF <48% were compared using two sample Wilcoxon rank‐sum tests. Results: Among 58 participants, mean age was 18.2 years (range 13.1–25.2) and five participants had CMR RVEF <48%. Intra‐ and inter‐observer coefficients of variation were 8.2%–10.1% and 10.5%–12.0% for adjusted automated strain measures, and 5.2%–8.7% and 2.7% for 3D RVEF, respectively. No echocardiographic measures were significantly correlated with CMR RVEF; only tricuspid annular plane systolic excursion was correlated with CMR RV stroke volume (r =.392, p =.003). Participants with RV dysfunction had worse automated global longitudinal strain (−20.3% vs. −23.9%, p =.007) and free wall longitudinal strain (−23.7% vs. −26.7%, p =.09). Conclusions: Echocardiographic strain and 3D RV function measurements were feasible and reproducible in at‐risk childhood cancer survivors. Although not associated with CMR RVEF in this population with predominantly normal RV function, automated strain measurements were more abnormal in participants with RV dysfunction, suggesting potential clinical utility of these measures. [ABSTRACT FROM AUTHOR]

Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133-3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8-2.4 %], whereas mortality was 0.28 % (95 % CI 0.18-0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age

The hybrid magnetic resonance (MR)/X-ray suite (XMR) is a recently introduced imaging solution that provides new possibilities for guidance of cardiovascular catheterization procedures. We have previously described and validated a technique based on optical tracking to register MR and X-ray images obtained from the sliding table XMR configuration. The aim of our recent work was to extend our technique by providing an improved calibration stage, real-time guidance during cardiovascular catheterization procedures, and further off-line analysis for mapping cardiac electrical data to patient anatomy. Specially designed optical trackers and a dedicated calibration object have resulted in a single calibration step that can be efficiently checked and updated before each procedure. All X-ray distortion model has been implemented that allows for distortion correction for arbitrary c-arm orientations. During procedures, the guidance system provides a real-time combined MR/X-ray image display consisting of live X-ray images with registered recently acquired MR derived anatomy. It is also possible to reconstruct the location of catheters seen during X-ray imaging in the MR derived patient anatomy. We have applied our registration technique to 13 cardiovascular catheterization procedures. Our system has been used for the real-time guidance of ten radiofrequency ablations and one aortic stent implantation. We demonstrate the real-time guidance using two exemplar cases. In a further two cases we show how off-line analysis of registered image data, acquired during electrophysiology study procedures, has been used to map cardiac electrical measurements to patient anatomy for two different types of mapping catheters. The cardiologists that have used the guidance system suggest that real-time XMR guidance could have substantial value in difficult interventional and electrophysiological procedures, potentially reducing procedure time and delivered radiation dose. Also, the ability to map measured electrical data to patient specific anatomy provides improved visualization and a path to investigation of cardiac electromechanical models. Index Terms--Cardiovascular intervention, interventional navigation, XMR systems, 2D-3D registration.

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method. pulmonary hypertension; nitric oxide; magnetic resonance imaging

We describe a registration and tracking technique to integrate cardiac X-ray images and cardiac magnetic resonance (MR) images acquired from a combined X-ray and MR interventional suite (XMR). Optical tracking is used to determine the transformation matrices relating MR image coordinates and X-ray image coordinates. Calibration of X-ray projection geometry and tracking of the X-ray C-arm and table enable three-dimensional (3-D) reconstruction of vessel centerlines and catheters from bi-plane X-ray views. We can, therefore, combine single X-ray projection images with registered projection MR images from a volume acquisition, and we can also display 3-D reconstructions of catheters within a 3-D or multi-slice MR volume. Registration errors were assessed using phantom experiments. Errors in the combined projection images (two-dimensional target registration error--TRE) were found to be 2.4 to 4.2 mm, and the errors in the integrated volume representation (3-D TRE) were found to be 4.6 to 5.1 mm. These errors are clinically acceptable for alignment of images of the great vessels and the chambers of the heart. Results are shown for two patients. The first involves overlay of a catheter used for invasive pressure measurements on an MR volume that provides anatomical context. The second involves overlay of invasive electrode catheters (including a basket catheter) on a tagged MR volume in order to relate electrophysiology to myocardial motion in a patient with an arrhythmia. Visual assessment of these results suggests the errors were of a similar magnitude to those obtained in the phantom measurements. Index Terms--2-D-3-D registration, cardiovascular intervention, optical tracking, XMR systems.