Construction of 3D MR image-based computer models of pathologic hearts, augmented with histology and optical fluorescence imaging to characterize action potential propagation.

Cardiac computer models can help us understand and predict the propagation of excitation waves (i.e., action potential, AP) in healthy and pathologic hearts. Our broad aim is to develop accurate 3D MR image-based computer models of electrophysiology in large hearts (translatable to clinical applications) and to validate them experimentally. The specific goals of this paper were to match models with maps of the propagation of optical AP on the epicardial surface using large porcine hearts with scars, estimating several parameters relevant to macroscopic reaction-diffusion electrophysiological models. We used voltage-sensitive dyes to image AP in large porcine hearts with scars (three specimens had chronic myocardial infarct, and three had radiofrequency RF acute scars). We first analyzed the main AP waves' characteristics: duration (APD) and propagation under controlled pacing locations and frequencies as recorded from 2D optical images. We further built 3D MR image-based computer models that have information derived from the optical measures, as well as morphologic MRI data (i.e., myocardial anatomy, fiber directions and scar definition). The scar morphology from MR images was validated against corresponding whole-mount histology. We also compared the measured 3D isochronal maps of depolarization to simulated isochrones (the latter replicating precisely the experimental conditions), performing model customization and 3D volumetric adjustments of the local conductivity. Our results demonstrated that mean APD in the border zone (BZ) of the infarct scars was reduced by ~13% (compared to ~318 ms measured in normal zone, NZ), but APD did not change significantly in the thin BZ of the ablation scars. A generic value for velocity ratio (1:2.7) in healthy myocardial tissue was derived from measured values of transverse and longitudinal conduction velocities relative to fibers direction (22 cm/s and 60 cm/s, respectively). The model customization and 3D volumetric adjustment reduced the differences between measurements and simulations; for example, from one pacing location, the adjustment reduced the absolute error in local depolarization times by a factor of 5 (i.e., from 58 ms to 11 ms) in the infarcted heart, and by a factor of 6 (i.e., from 60 ms to 9 ms) in the heart with the RF scar. Moreover, the sensitivity of adjusted conductivity maps to different pacing locations was tested, and the errors in activation times were found to be of approximately 10-12 ms independent of pacing location used to adjust model parameters, suggesting that any location can be used for model predictions.

Fusion of optical imaging and MRI for the evaluation and adjustment of macroscopic models of cardiac electrophysiology: a feasibility study.

The aim of this work was to demonstrate the correspondence between a macroscopic 3D computer model of electrophysiology (i.e., the Aliev-Panfilov model) parametrized with MR data and experimental characterization of action potential propagation in large porcine hearts, ex vivo, using optical methods (based on voltage-sensitive fluorescence). A secondary goal was to use one of these studies to demonstrate an optimized method for regional adjustment of critical model parameters (i.e., adjustment of the local conductivity from the isochronal maps obtained via optical images). There was good agreement between model behaviour and experiment using fusion of optical and MR data, and model parameters from previous work in the literature. Specifically, qualitative comparison between computed and measured activation maps gave good results. Adjustment of the conductivity parameter within 26 regions fitting data from the current experiments in one heart reduced absolute error in local depolarization times by a factor of 3 (i.e. from 30 to 10 ms).