Sudip Ghate

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

The aim of this paper was to compare several in-vivo electrophysiological (EP) characteristics measured in a swine model of chronic infarct, with those predicted by simple 3-D MRI-based computer models built from ex-vivo scans (voxel size <;1 mm3). Specifically, we recorded electroanatomical voltage maps (EAVM) in six animals, and ECG waves during induction of arrhythmia in two of these cases. The infarct heterogeneities (dense scar and border zone) as well as fiber directions were estimated using diffusion weighted DW-MRI. We found a good correspondence (r = 0.9) between scar areas delineated on the EAVM and MRI maps. For theoretical predictions, we used a simple two-variable macroscopic model and computed the propagation of action potential after application of a train of stimuli, with location and timing replicating the stimulation protocol used in the in-vivo EP study. Simulation results are exemplified for two hearts: one with noninducible ventricular tachycardia (VT), and another with a macroreentrant VT (for the latter, the average predicted VT cycle length was 273 ms, compared to a recorded VT of 250 ms).

Intrinsic Contrast for Characterization of Acute Radiofrequency Ablation Lesions

Background—Both intrinsic contrast (T1 and T2 relaxation and the equilibrium magnetization) and contrast agent (gadolinium)–enhanced MRI are used to visualize and evaluate acute radiofrequency ablation lesions. However, current methods are imprecise in delineating lesion extent shortly after the ablation. Methods and Results—Fifteen lesions were created in the endocardium of 13 pigs. A multicontrast inversion recovery steady state free precession imaging method was used to delineate the acute ablation lesions, exploiting T1-weighted contrast. T2 and Mo* maps were also created from fast spin echo data in a subset of pigs (n=5) to help characterize the change in intrinsic contrast in the lesions. Gross pathology was used as reference for the lesion size comparison, and the lesion structures were confirmed with histological data. In addition, a colorimetric iron assay was used to measure ferric and ferrous iron content in the lesions and the healthy myocardium in a subset of pigs (n=2). The lesion sizes measured in inversion recovery steady state free precession images were highly correlated with the extent of lesion core identified in gross pathology. Magnetic resonance relaxometry showed that the radiofrequency ablation procedure changes the intrinsic T1 value in the lesion core and the intrinsic T2 in the edematous region. Furthermore, the T1 shortening appeared to be correlated with the presence of ferric iron, which may have been associated with metmyoglobin and methemoglobin in the lesions. Conclusions—The study suggests that T1 contrast may be able to separate necrotic cores from the surrounding edematous rims in acute radiofrequency ablation lesions.

The Feasibility of Endocardial Propagation Mapping Using Magnetic Resonance Guidance in a Swine Model, and Comparison With Standard Electroanatomic Mapping

The introduction of electroanatomic mapping (EAM) has improved the understanding of the substrate of ventricular tachycardia. EAM systems are used to delineate scar regions responsible for the arrhythmia by creating voltage or activation time maps. Previous studies have identified the benefits of creating MR-guided voltage maps; however, in some cases voltage maps may not identify regions of slow propagation that can cause the reentrant tachycardia. In this study, we obtained local activation time maps and analyzed propagation properties by performing MR-guided mapping of the porcine left ventricle while pacing from the right ventricle. Anatomical and myocardial late gadolinium enhancement images were used for catheter navigation and identification of scar regions. Our MR-guided mapping procedure showed qualitative correspondence to conventional clinical EAM systems in healthy pigs and demonstrated altered propagation in endocardial infarct models.

Postinfarction Ventricular Tachycardia Substrate Characterization: A Comparison Between Late Enhancement Magnetic Resonance Imaging and Voltage Mapping Using an MR-Guided Electrophysiology System

Catheter ablation of ventricular tachycardia (VT) is preceded by characterization of the myocardial substrate via electroanatomical voltage mapping (EAVM). The purpose of this study was to characterize the relationship between chronic myocardial fibrotic scar detected by multicontrast late enhancement (MCLE) MRI and by EAVM obtained using an MR-guided electrophysiology system, with a final aim to better understand how these measures may improve identification of potentially arrhythmogenic substrates. Real-time MR-guided EAVM was performed in six chronically infarcted animals in a 1.5T MR system. The MCLE images were analyzed to identify the location and extent of the fibrotic infarct. Voltage maps of the left ventricle (LV) were created with an average of 231 ± 35 points per LV. Correlation analysis was conducted between bipolar voltage and three MR parameters (infarct transmurality, tissue categorization into healthy and scar classes, and normalized relaxation rate R1*). In general, tissue regions classified as scar by normalized R1* values were well correlated with locations with low bipolar voltage values. Moreover, our results demonstrate that MRI information (transmurality, tissue classification, and relaxation rate) can accurately predict areas of myocardial fibrosis identified with bipolar voltage mapping, as demonstrated by ROC analysis. MCLE can help overcome limitations of bipolar voltage mapping including long durations and lower spatial discrimination and may help identify the sites within scars, which are commonly believed to trigger arrhythmic events in postinfarction patients.

Evaluating the extent of acute radiofrequency ablation lesions in the heart using an inversion recovery SSFP sequence

Methods 15 lesions were created in the endocardium of 13 pigs using approved animal protocols. NGE IR-SSFP and T2-w black-blood (double IR-FSE) images were acquired in <60min after ablation. Then, Gd-DTPA (Magnevist, 0.2 mmol/kg) was injected and LGE images were acquired repeatedly over one hour. Gross pathology was used as the reference for lesion size measurements. Two regions were measured in this reference: the pale “inner” lesion core and the “outer” lesion border including the dark rim on pathology (see Results).

Exploring intrinsic MR signal relaxation in acute RF ablation lesions using T2 mapping and IR-SSFP CINE imaging

Background Cardiac MR has been used successfully in RF ablation therapies for arrhythmias, both for procedural planning and for post-ablation lesion imaging. Non-enhanced imaging, though it has a lower SNR, has advantages over Gdenhanced techniques mainly because contrast kinetics and dosage issues are avoided. Previously T2-weighted imaging was found to be more sensitive than T1-weighted imaging [1]. In this study, we performed non-enhanced T2 mapping and an inversion-prepared SSFP CINE imaging to characterize intrinsic relaxation behavior in acute lesions.

A 3D MRI-based cardiac computer model to study arrhythmia and its in-vivo experimental validation

The aim of this work was to develop a simple and fast 3D MRI-based computer model of arrhythmia inducibility in porcine hearts with chronic infarct scar, and to further validate it using electrophysiology (EP) measures obtained in-vivo. The heart model was built from MRI scans (with voxel size smaller than 1mm3) and had fiber directions extracted from diffusion tensor DT-MRI. We used a macroscopic model that calculates the propagation of action potential (AP) after application of a train of stimuli, with location and timing replicating precisely the stimulation protocol used in the in-vivo EP study. Simulation results were performed for two infarct hearts: one with noninducible and the other with inducible ventricular tachycardia (VT), successfully predicting the study outcome like in the in-vivo cases; for the inducible heart, the average predicted VT cycle length was 273ms, compared to a recorded VT of approximately 250ms. We also generated synthetic fibers for each heart and found the associated helix angle whose transmural variation (in healthy zones) from endo- to epicardium gave the smallest difference (i.e., approx. 41°) when compared to the helix angle corresponding to fibers from DW-MRI. Mean differences between activation times computed using DT-MRI fibers and using synthetic fibers for the two hearts were 6 ms and 11 ms, respectively.

Analysis of Activation-Recovery Intervals from Intra-cardiac Electrograms in a Pre-clinical Chronic Model of Myocardial Infarction

Mapping of intracardiac electrical signals is a well-established clinical method used to identify the foci of abnormal heart rhythms associated with chronic myocardial infarct (a major cause of death). These foci reside in the ‘border zone’ (BZ) between healthy tissue and dense collagenous scar, and are the targets of ablation therapy. In this work we analyzed detailed features of the electrical signals recorded in a translational animal model of chronic infarct. Specifically, activation maps and bipolar voltages were recorded in vivo from 6 pigs at ~5 weeks following infarct creation, as well as 6 control (normal) pigs. Endocardial and epicardial maps were obtained during normal sinus rhythm and/or pacing conditions via X-ray guided catheter-based mapping using an electro-anatomical CARTO system. The depolarization and repolarization maps were derived through manual annotation of electro-cardiogram waves, where the peak of the QRS wave marked the time of depolarization and the peak of the T wave marked the recovery time. Then, at each recording point, activation-recovery intervals ARIs (clinical surrogates of action potential duration) were found by subtracting activation times from repolarization times. Overall, we observed that ARI values in the BZ have recovered from the acute stage and were close to values in healthy tissue. In general we observed a weak negative correlation between the activation times and ARI values, also not a significant variation (p < 0.5) between mean ARI values in the BZ area and those in the healthy areas.

Progress on Customization of Predictive MRI-Based Macroscopic Models from Experimental Data

MR image-based computer heart models are powerful non-invasive tools that can help us predict the transmural electrical propagation of abnormal depolarization-repolarization waves in the presence of infarct scars i.e., collagenous fibrosis, a major cause of sudden death; however, an important step is the customization of these models from electrophysiology studies EP . In this work, we used MR-EP data obtained in a pre-clinical animal model i.e., three healthy and two infarcted swine hearts and customized a simple mono-domain model i.e., the Aliev-Panfilov model. Specifically, we estimated the mathematical parameters corresponding to: a the repolarization phase from in vivo activation-recovery intervals, ARIs recorded in vivo with a CARTO system, and b the anisotropy ratio from fluorescence microscopic imaging of connexin 43, Cx43. Our measurements showed that in the ischemic peri-infarct areas the ARIs intervals were shorter by ~ 14% compared to those in normal tissue, and that there was a significant reduction > 50% in the Cx43 density which tunes the cell-to-cell coupling and tissue bulk conductivity with respect to both longitudinal and transverse directions of the myocyte. In addition, we included comparisons between virtual in silico simulations of activation maps obtained with different parameters used as input to a 3D MR-based biventricular model. Our preliminary results demonstrated the feasibility of using generic parameters to customize such MR-based models; however, further quantitative studies are needed. Finally, we discussed the overall advantages and limitations of our simplified approach, along with future directions.

A pre-clinical framework to characterize peri-infarct remodelling using in vivo t 1 maps and CARTO data

The purpose of this work was to use in vivo MR imaging and electro-anatomical maps to characterize dense scars and border zone, BZ (a mixture of collagen and viable fibers). To better understand how these measures might probe potentially arrhythmogenic substrates, we developed a preclinical swine model of chronic infarction and integrated in vivo MRI and electrophysiology (EP) data in five swine at 5-6 weeks post-infarction. Specifically, we first aligned and registered T1-maps (from MR studies) and bipolar voltage maps (from CARTO-EP studies) using Vurtigo, an open source software. We then performed a quantitative analysis based on circumferential segments defined in the short-axis of MR images. Our results demonstrated a negative linear relation between bipolar voltage maps and T1 maps within the first two mm of the endocardial surface. The results of our novel approach suggest that T1-maps combined with limited EP measurements can be used to evaluate the biophysical properties of healing myocardium post-infarction, and to distinguish between the infarct categories (i.e., dense scar vs. BZ) with remodelled electrical characteristics.