Hyperparameter optimisation and validation of registration algorithms for measuring regional ventricular deformation using retrospective gated computed tomography images.

Recent dose reduction techniques have made retrospective computed tomography (CT) scans more applicable and extracting myocardial function from cardiac computed tomography (CCT) images feasible. However, hyperparameters of generic image intensity-based registration techniques, which are used for tracking motion, have not been systematically optimised for this modality. There is limited work on their validation for measuring regional strains from retrospective gated CCT images and open-source software for motion analysis is not widely available. We calculated strain using our open-source platform by applying an image registration warping field to a triangulated mesh of the left ventricular endocardium. We optimised hyperparameters of two registration methods to track the wall motion. Both methods required a single semi-automated segmentation of the left ventricle cavity at end-diastolic phase. The motion was characterised by the circumferential and longitudinal strains, as well as local area change throughout the cardiac cycle from a dataset of 24 patients. The derived motion was validated against manually annotated anatomical landmarks and the calculation of strains were verified using idealised problems. Optimising hyperparameters of registration methods allowed tracking of anatomical measurements with a mean error of 6.63% across frames, landmarks, and patients, comparable to an intra-observer error of 7.98%. Both registration methods differentiated between normal and dyssynchronous contraction patterns based on circumferential strain ([Formula: see text], [Formula: see text]). To test whether a typical 10 temporal frames sampling of retrospective gated CCT datasets affects measuring cardiac mechanics, we compared motion tracking results from 10 and 20 frames datasets and found a maximum error of [Formula: see text]. Our findings show that intensity-based registration techniques with optimal hyperparameters are able to accurately measure regional strains from CCT in a very short amount of time. Furthermore, sufficient sensitivity can be achieved to identify heart failure patients and left ventricle mechanics can be quantified with 10 reconstructed temporal frames. Our open-source platform will support increased use of CCT for quantifying cardiac mechanics.

Standardised computed tomographic assessment of left atrial morphology and tissue thickness in humans.

AIMS: Left atrial (LA) remodelling is a common feature of many cardiovascular pathologies and is a sensitive marker of adverse cardiovascular outcomes. The aim of this study was to establish normal ranges for LA parameters derived from coronary computed tomographic angiography (CCTA) imaging using a standardised image processing pipeline to establish normal ranges in a previously described cohort. METHODS: CCTA imaging from 193 subjects recruited to the Budapest GLOBAL twin study was analysed. Indexed LA cavity volume (LACVi), LA surface area (LASAi), wall thickness and LA tissue volume (LATVi) were calculated. Wall thickness maps were combined into an atlas. Indexed LA parameters were compared with clinical variables to identify early markers of pathological remodelling. RESULTS: LACVi is similar between sexes (31 ml/m2 v 30 ml/m2) and increased in hypertension (33 ml/m2 v 29 ml/m2, p = 0.009). LASAi is greater in females than males (47.8 ml/m2 v 45.8 ml/m2 male, p = 0.031). Median LAWT was 1.45 mm. LAWT was lowest at the inferior portion of the posterior LA wall (1.14 mm) and greatest in the septum (median = 2.0 mm) (p < 0.001). Conditions known to predispose to the development of AF were not associated with differences in tissue thickness. CONCLUSIONS: The reported LACVi, LASAi, LATVi and tissue thickness derived from CCTA may serve as reference values for this age group and clinical characteristics for future studies. Increased LASAi in females in the absence of differences in LACVi or LATVi may indicate differential LA shape changes between the sexes. AF predisposing conditions, other than sex, were not associated with detectable changes in LAWT.Clinical trial registration:http://www.ClinicalTrials.gov/NCT01738828.

The impact of wall thickness and curvature on wall stress in patient-specific electromechanical models of the left atrium.

The left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA using patient-specific anatomical FE meshes with rule-based myofiber directions. The models of the LA were passively inflated to 10mmHg followed by simulation of the contraction phase of the atrial cardiac cycle. The FE models predicted maximum LA volumes of 156.5 mL, 99.3 mL and 83.4 mL and ejection fractions of 36.9%, 32.0% and 25.2%. The median wall thickness in the 3 cases was calculated as [Formula: see text] mm, [Formula: see text] mm, and [Formula: see text] mm. The median curvature was determined as [Formula: see text] [Formula: see text], [Formula: see text], and [Formula: see text]. Following passive inflation, the correlation of wall stress with the inverse of wall thickness and curvature was 0.55-0.62 and 0.20-0.25, respectively. At peak contraction, the correlation of wall stress with the inverse of wall thickness and curvature was 0.38-0.44 and 0.16-0.34, respectively. In the LA, the 1st principal Cauchy stress is more dependent on wall thickness than curvature during passive inflation and both correlations decrease during active contraction. This emphasizes the importance of including the heterogeneous wall thickness in electromechanical FE simulations of the LA. Overall, simulation results and sensitivity analyses show that in complex atrial anatomy it is unlikely that a simple anatomical-based law can be used to estimate local wall stress, demonstrating the importance of FE analyses.

Personalized computational modeling of left atrial geometry and transmural myofiber architecture.

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by complete absence of coordinated atrial contraction and is associated with an increased morbidity and mortality. Personalized computational modeling provides a novel framework for integrating and interpreting the role of atrial electrophysiology (EP) including the underlying anatomy and microstructure in the development and sustenance of AF. Coronary computed tomography angiography data were segmented using a statistics-based approach and the smoothed voxel representations were discretized into high-resolution tetrahedral finite element (FE) meshes. To estimate the complex left atrial myofiber architecture, individual fiber fields were generated according to morphological data on the endo- and epicardial surfaces based on local solutions of Laplace's equation and transmurally interpolated to tetrahedral elements. The influence of variable transmural microstructures was quantified through EP simulations on 3 patients using 5 different fiber interpolation functions. Personalized geometrical models included the heterogeneous thickness distribution of the left atrial myocardium and subsequent discretization led to high-fidelity tetrahedral FE meshes. The novel algorithm for automated incorporation of the left atrial fiber architecture provided a realistic estimate of the atrial microstructure and was able to qualitatively capture all important fiber bundles. Consistent maximum local activation times were predicted in EP simulations using individual transmural fiber interpolation functions for each patient suggesting a negligible effect of the transmural myofiber architecture on EP. The established modeling pipeline provides a robust framework for the rapid development of personalized model cohorts accounting for detailed anatomy and microstructure and facilitates simulations of atrial EP.

Lesion Index-Guided Ablation Facilitates Continuous, Transmural, and Durable Lesions in a Porcine Recovery Model.

BACKGROUND: The Lesion Index (LSI) is a proprietary algorithm from Abbott Medical combining contact force, radiofrequency application duration, and radiofrequency current. It can be displayed during ablation with the TactiCath contact force catheter. The LSI Index was designed to provide real-time lesion formation feedback and is hypothesized to estimate the lesion diameter. METHODS AND RESULTS: Before ablation, animals underwent cardiac computed tomography to assess atrial tissue thickness. Ablation lines (n=2-3 per animal) were created in the right atrium of 7 Göttingen mini pigs with point lesions (25 W). Within each line of ablation, the catheter tip was moved a prescribed distance (D/mm) according to 1 of 3 strategies: D=LSI+0 mm; D=LSI+2 mm; or D=LSI+4 mm. Two weeks after ablation, serial sections of targeted atrial tissue were examined histologically to identify gaps in transmural ablation. LSI-guided lines had a lower incidence of histological gaps (4 gaps in 69 catheter moves, 5.8%) than LSI+2 mm lines (7 gaps in 33 catheter moves, 21.2%) and LSI+4 mm lines (15 gaps in 23 catheter moves, 65.2%, P<0.05 versus D=LSI). ΔLSI was calculated retrospectively as the distance between 2 adjacent lesions above the mean LSI of the 2 lesions. ΔLSI values of ≤1.5 were associated with no gaps in transmural ablation. CONCLUSIONS: In this model of chronic atrial ablation, delivery of uninterrupted transmural linear lesions may be facilitated by using LSI to guide catheter movement. When ΔLSI between adjacent lesions is ≤1.5 mm, no gaps in atrial linear lesions should be expected.

Cardiac CT assessment of tissue thickness at the ostium of the left atrial appendage predicts acute success of radiofrequency ablation.

BACKGROUND: Tissue thickness at the site of ablation is a determinant of lesion transmurality. We reported the feasibility, safety, and efficacy of longstanding persistent atrial fibrillation ablation, incorporating deliberate left atrial appendage (LAA) isolation and occlusion, and identified systematic differences in ostial LAA tissue thickness in a matched cohort of cadaveric specimens. METHODS: Preprocedural cardiac computed tomography (CCT) scans were acquired from 22 patients undergoing LAA isolation and subsequent occlusion. Using a novel CCT wall thickness algorithm, LAA ostial wall thickness was assessed in vivo, compared with measurements from the cadaveric specimens, and analyzed for differences between regions that demonstrated acute electrical reconnection and those that did not. RESULTS: Mean tissue thickness calculated for each LAA ostial quadrant was 2.1 (±0.6) mm (anterior quadrant), 1.9 (±0.4) mm (superior quadrant), 1.5 (±0.4) mm (posterior quadrant), and 1.8 (±0.7) mm (inferior quadrant). Tissue was significantly thicker in the anterior (P  =  0.004) and superior quadrants (P  =  0.014) than the posterior quadrant. Higher thickness measurements were recorded from quadrants demonstrated to be thicker from histology. Tissue was significantly thicker in regions that demonstrated acute electrical reconnection (1.9 (±0.6) mm) when compared with those that did not (1.6 (±0.5) mm) (P  =  0.008). CONCLUSIONS: CCT imaging may be used to detect differences in wall thickness at different atrial locations and success of LAA ablation may be affected by local tissue thickness. Atrial wall thickness may need to be considered as a metric to guide titration of radiofrequency energy for safe and successful ablation.

A method for incorporating three-dimensional residual stretches/stresses into patient-specific finite element simulations of arteries.

The existence of residual stresses in human arteries has long been shown experimentally. Researchers have also demonstrated that residual stresses have a significant effect on the distribution of physiological stresses within arterial tissues, and hence on their development, e.g., stress-modulated remodeling. Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to construct in vivo patient-specific geometries and thus to study specific, clinically relevant problems in arterial mechanics via FE simulations. Classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations start from unloaded, stress-free reference configurations while the boundary-value problem of interest represents a loaded geometry and includes residual stresses. We present a pragmatic methodology to simultaneously account for both (i) the three-dimensional (3-D) residual stress distributions in the arterial tissue layers, and (ii) the equilibrium of the in vivo patient-specific geometry with the known boundary conditions. We base our methodology on analytically determined residual stress distributions (Holzapfel and Ogden, 2010, J. R. Soc. Interface 7, 787-799) and calibrate it using data on residual deformations (Holzapfel et al., 2007, Ann. Biomed. Eng. 35, 530-545). We demonstrate our methodology on three patient-specific FE simulations calibrated using experimental data. All data employed here are generated from human tissues - both the aorta and thrombus, and their respective layers - including the geometries determined from magnetic resonance images, and material properties and 3-D residual stretches determined from mechanical experiments. We study the effect of 3-D residual stresses on the distribution of physiological stresses in the aortic layers (intima, media, adventitia) and the layers of the intraluminal thrombus (luminal, medial, abluminal) by comparing three types of FE simulations: (i) conventional calculations; (ii) calculations accounting only for prestresses; (iii) calculations including both 3-D residual stresses and prestresses. Our results show that including residual stresses in patient-specific simulations of arterial tissues significantly impacts both the global (organ-level) deformations and the stress distributions within the arterial tissue (and its layers). Our method produces circumferential Cauchy stress distributions that are more uniform through the tissue thickness (i.e., smaller stress gradients in the local radial directions) compared to both the conventional and prestressing calculations. Such methods, combined with appropriate experimental data, aim at increasing the accuracy of classical FE analyses for patient-specific studies in computational biomechanics and may lead to increased clinical application of simulation tools.

Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour.

Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software.