Jennifer Barry

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.

Quantitative magnetic resonance imaging can distinguish remodeling mechanisms after acute myocardial infarction based on the severity of ischemic insult

The type and extent of myocardial infarction encountered clinically is primarily determined by the severity of the initial ischemic insult. The purpose of the study was to differentiate longitudinal fluctuations in remodeling mechanisms in porcine myocardium following different ischemic insult durations. Animals (N = 8) were subjected to coronary balloon occlusion for either 90 or 45 min, followed by reperfusion. Imaging was performed on a 3 T MRI scanner between day‐2 and week‐6 postinfarction with edema quantified by T2, hemorrhage by T2*, vasodilatory function by blood‐oxygenation‐level‐dependent T2 alterations and infarction/microvascular obstruction by contrast‐enhanced imaging. The 90‐min model produced large transmural infarcts with hemorrhage and microvascular obstruction, while the 45 min produced small nontransmural and nonhemorrhagic infarction. In the 90‐min group, elevation of end‐diastolic‐volume, reduced cardiac function, persistence of edema, and prolonged vasodilatory dysfunction were all indicative of adverse remodeling; in contrast, the 45‐min group showed no signs of adverse remodeling. The 45‐ and 90‐min porcine models seem to be ideal for representing the low‐ and high‐risk patient groups, respectively, commonly encountered in the clinic. Such in vivo characterization will be a key in predicting functional recovery and may potentially allow evaluation of novel therapies targeted to alleviate ischemic injury and prevent microvascular obstruction/hemorrhage. Magn Reson Med, 70:1095–1105, 2013.

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.

Assessment of in vivo metabolism in failing hearts using hyperpolarised 13C magnetic resonance

Increasingly, abnormal metabolic substrate utilisation is considered a cause of heart failure (HF). Hyperpolarised 13C MR, a technique in which the fate of 13C-labelled metabolites can be followed in vivo using MR imaging or spectroscopy, has enabled non-invasive assessment of cardiac substrate utilisation.

Probing the cardiac malate–aspartate shuttle non‐invasively using hyperpolarized [1,2‐13C2]pyruvate

Previous studies have demonstrated that using hyperpolarized [2‐13C]pyruvate as a contrast agent can reveal 13C signals from metabolites associated with the tricarboxylic acid (TCA) cycle. However, the metabolites detectable from TCA cycle‐mediated oxidation of [2‐13C]pyruvate are the result of several metabolic steps. In the instance of the [5‐13C]glutamate signal, the amplitude can be modulated by changes to the rates of pyruvate dehydrogenase (PDH) flux, TCA cycle flux and metabolite pool size. Also key is the malate–aspartate shuttle, which facilitates the transport of cytosolic reducing equivalents into the mitochondria for oxidation via the malate–α‐ketoglutarate transporter, a process coupled to the exchange of cytosolic malate for mitochondrial α‐ketoglutarate. In this study, we investigated the mechanism driving the observed changes to hyperpolarized [2‐13C]pyruvate metabolism. Using hyperpolarized [1,2‐13C]pyruvate with magnetic resonance spectroscopy (MRS) in the porcine heart with different workloads, it was possible to probe 13C–glutamate labeling relative to rates of cytosolic metabolism, PDH flux and TCA cycle turnover in a single experiment non‐invasively. Via the [1‐13C]pyruvate label, we observed more than a five‐fold increase in the cytosolic conversion of pyruvate to [1‐13C]lactate and [1‐13C]alanine with higher workload. 13C–Bicarbonate production by PDH was increased by a factor of 2.2. Cardiac cine imaging measured a two‐fold increase in cardiac output, which is known to couple to TCA cycle turnover. Via the [2‐13C]pyruvate label, we observed that 13C–acetylcarnitine production increased 2.5‐fold in proportion to the 13C–bicarbonate signal, whereas the 13C–glutamate metabolic flux remained constant on adrenergic activation. Thus, the 13C–glutamate signal relative to the amount of 13C–labeled acetyl‐coenzyme A (acetyl‐CoA) entering the TCA cycle was decreased by 40%. The data strongly suggest that NADH (reduced form of nicotinamide adenine dinucleotide) shuttling from the cytosol to the mitochondria via the malate–aspartate shuttle is limited on adrenergic activation. Changes in [5‐13C]glutamate production from [2‐13C]pyruvate may play an important future role in non‐invasive myocardial assessment in patients with cardiovascular diseases, but careful interpretation of the results is required.

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.

Intrinsic MRI visualizes RF lesions within minutes after MR-guided ablation

Background MR visualization of RF lesions is an application of growing interest with the potential for translation to clinical ablation procedures. In particular, intrinsic-contrast MRI avoids the dynamic contrast produced in typical Gd-based MRI, and may differentiate the reversible and irreversible thermal injury thought to be caused by RF ablation. This distinction is important for assessing the permanence of ablation to eradicate the substrate of ventricular tachycardia in structural heart disease. In this study we investigate the potential of intrinsic-contrast MRI to visualize the features of thermal injury and evolution of RF lesions that may occur immediately after ablation.

Respiratory motion model based correction for improving the targeting accuracy of MRI-guided intracardiac electrophysiology procedures

Background Recently, there is an increased interest in using MRI to guide electrophysiology (EP) procedures as an alternative to X-ray fluoroscopy guidance, due to its excellent soft tissue contrast and lack of radiation. However, there exist tradeoffs between different MRI guidance schemes. Realtime 2D MR sequences are able to capture heart motion during an interventional setting, while sacrificing imaging quality, whereas high-resolution prior 3D roadmaps are static and do not reflect the respiratory motion of the heart. In this work, we explore the feasibility of deriving a motion model from these two complementary datasets, and evaluate its potential for improving the targeting accuracy of MRI-guided EP procedures.