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

Abstract

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.

Correspondence Between Simple 3-D MRI-Based Computer Models and In-Vivo EP Measurements in Swine With Chronic Infarctions

“…For the VT-inducible heart, the average predicted VT cycle length was slightly longer (by 23 ms) compared to the recorded cycle length, possibly due to input model parameters assigned to different zones. However, we demonstrated in [13] very good correspondence between our classification and the extent of scars in histological images. Also, in a recent study, we reported good agreement between infarct classifications obtained using contrast-enhanced MRI methods (clinically used) and the DW method.…”

“…Some input values for model parameters were taken from our recent optical imaging ex-vivo study [13] in infarcted swine hearts, and they were assigned by zones. The restitution curves in that study were generated by plotting APD90 (ms) versus cycle length, (CL in ms), at different pacing frequencies (e.g., in the normal zone, measured APD90 = 0.218 × CL +151 and computed APD90 = 0.213 × CL +160).…”

Cartan Frame Analysis of Hearts with Infarcts

“…Studies have been trying to determine the consequences of myocardial infarctions in small (rat [41]) hearts and larger (porcine [43,27]) hearts. In these studies it was shown that acute infarction led to a decrease in regional wall thickness and an increased radius of curvature, mostly in the border zone (BZ) -which is the zone close to the dense scar region but with a more heterogeneous nature due to the persistence of surviving blood vessels that continue to supply oxygen to isolated cells.…”

A 3D MRI-Based Cardiac Computer Model to Study Arrhythmia and Its In-vivo Experimental Validation

“…The MR parameters were given in our previous EP studies [12,14], together with the methodology regarding the construction of the 3D model from apparent diffusion coefficient (ADC) maps, which were next used to segment the heart into three zones: healthy tissue, BZ and infarct scar. Surface meshes were then created for each heart from the 3D anatomy MR scan, and volumetric tetrahedral meshes were generated with TetGen package.…”

“…For instance, the value in the anisotropy ratio is set to 0.14 for a wave propagating almost 2.7 times as fast along the fiber as in the transverse direction. The input values for model parameters were taken from our recent optical fluorescence imaging study performed in infarct hearts [14], and these values were assigned per zone (i.e., infarct, BZ and healthy) and are given in Table 1. Specifically, the values for a (tuning the duration of AP), k (tuning the up-stroke of AP) and the normalized conductivity d were set as in Table 1 (note that a and k values in the scar zone are similarly set like those for BZ, but are in fact irrelevant because the scar is unexcitable, thus d is to 0 (i.e., the AP wave does not propagate through the scar).…”