Samuel O. Oduneye

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.

Distribution of abnormal potentials in chronic myocardial infarction using a real time magnetic resonance guided electrophysiology system

BackgroundIdentification of viable slow conduction zones manifested by abnormal local potentials is integral to catheter ablation of ventricular tachycardia (VT) sites. The relationship between contrast patterns in cardiovascular magnetic resonance (CMR) and local electrical mapping is not well characterized. The purpose of this study was to identify regions of isolated, late and fractionated diastolic potentials in sinus rhythm and controlled-paced rhythm in post-infarct animals relative to regions detected by late gadolinium enhancement CMR (LGE-CMR).MethodsUsing a real-time MR-guided electrophysiology system, electrogram (EGM) recordings were used to generate endocardial electroanatomical maps in 6 animals. LGE-CMR was also performed and tissue classification (dense infarct, gray zone and healthy myocardium) was then correlated to locations of abnormal potentials.ResultsFor abnormal potentials in sinus rhythm, relative occurrence was equivalent 24%, 27% and 22% in dense scar, gray zone and healthy tissue respectively (p = NS); in paced rhythm, the relative occurrence of abnormal potentials was found to be different with 30%, 42% and 21% in dense scar, gray zone and healthy myocardium respectively (p = 0.001). For location of potentials, in the paced case, the relative frequency of abnormal EGMs was 19.9%, 65.4% and 14.7% in the entry, central pathway and exit respectively (p = 0.05), putative regions being defined by activation times.ConclusionsOur data suggests that gray zone quantified by LGE-CMR exhibits abnormal potentials more frequently than in healthy tissue or dense infarct when right ventricular apex pacing is used.

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.

In vivo contact EP data and ex vivo MR-based computer models: registration and model-dependent errors

Sudden cardiac death is a major cause of death in industrialized world; in particular, patients with prior infarction can develop lethal arrhythmia. Our aim is to understand the transmural propagation of electrical wave and to accurately predict activation times under different stimulation conditions (sinus rhythm and paced) using MRI-based computer models of normal or structurally diseased hearts. Parameterization of such models is a prerequisite step prior integration into clinical platforms. In this work, we first evaluated the errors associated with the registration process between contact EP data and MRI-based models, using in vivo CARTO maps recorded in three swine hearts (two healthy and one infarcted) and the corresponding heart meshes obtained from high-resolution ex vivo diffusion weighted DW-MRI (voxel size < 1mm3). We used the open-source software Vurtigo to align, register and project the CARTO depolarization maps (from LV-endocardium and epicardium) onto the MR-derived meshes, with an acceptable registration error of < 5mm in all maps. We then compared simulation results obtained with the macroscopic monodomain formalism (i.e., the two-variable Aliev-Panfilov model), the simple Eikonal model, and the complex bidomain model (TNNP model) under different stimulation conditions. We found small errors between the measured and the predicted activation times, as well as between the depolarization times using these three models (e.g., with a mean error of 3.4 ms between the A-P and TNNP model), suggesting that simple mathematical formalisms might be a good choice for integration of fast, predictive models into clinical platforms.

Novel Framework to Integrate Real-Time MR-Guided EP Data with T1 Mapping-Based Computational Heart Models

Real-time MRI-guided electrophysiology (EP) interventions hold the potential to replace conventional X-ray guided procedures aimed to eliminate potentially lethal scar-related arrhythmia. Furthermore, although cardiac MR can provide excellent structural information (i.e., anatomy and scar), these catheter-based procedures have limited electrical information due to sparse electrical maps recorded from endocardial surfaces. In this paper, we propose a novel framework to augment such sparse electrical maps with 3D transmural electrical wave propagation obtained non-invasively using computer modelling. First, we performed real-time MR-guided EP studies using a preclinical pig model (i.e., in 1 healthy and 2 chronically infarcted animals). Specifically, the MR scans employed 2D T1-mapping (1 × 1 × 5 mm spatial resolution) based on a multi-contrast late enhancement method. For the EP studies we used an MR-compatible system (Imricor). Second, the stacks of resulting segmented images were used to build 3D heart models with various zones (i.e., healthy, scar and gray zone). Lastly, the 3D heart models were coupled with simple monodomain reaction-diffusion equations (e.g. eikonal and Aliev-Panfilov). Our simulations showed that these mathematical formalisms are advantageous due to fast computations, allowing us to predict the electrical wave propagation through dense LV meshes (e.g. >100 K elements, element size ~1.5 mm) in <3 min on a consumer computer. Overall, preliminary results demonstrated that the 3D MCLE-based models predicted close activation times and patterns compared to our measured EP maps, while also providing 3D transmural information and a precise location of the infarction. Future work will focus on calibrating directly (in near real-time) T1-based personalized heart models from electrical maps obtained during real-time MR-guided EP mapping procedures.

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).

In Vivo Parametric T1 Maps Correlate with Structural and Molecular Characteristics of Focal Fibrosis

The purpose of this work was to use noninvasive in vivo MRI to characterize the substrate (i.e., known as gray zone, GZ) of ventricular arrhythmia, a major cause of sudden death. Our aim was to use a preclinical model of chronic infarction to study the structural and molecular characteristics of infarcted areas. For this, we related parametric T1 maps with the density of collagen and gap junctions (Cx43 proteins) in patchy fibrosis in n = 6 swine with chronic infarction. Specifically, in vivo T1 relaxation maps were calculated from 2D multi-contrast late enhancement (MCLE) MR images obtained at 1 × 1 × 5 mm resolution. Quantitative analysis and regression analysis demonstrated that the comparison between GZ and scar extent in MCLE to the corresponding areas identified in histology, yielded very good correlations in both cases (i.e., goodness of fit: R2 = 0.89 for GZ, and 0.92 for dense scar, respectively). Furthermore, the gap junction Cx43 density was significantly reduced (i.e., by > 50%) in the ischemic GZ areas determined from MCLE. These novel results suggest that in vivo 2D parametric T1 maps can be used to evaluate the biophysical properties of healing myocardium post-infarction, and to distinguish between the infarct categories (i.e., scar vs. GZ) with re-modelled structural and electrical characteristics.

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.