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Purpose: Cardiomyocyte organization and performance underlie cardiac function, but the in vivo mobility of these cells during contraction and filling remains difficult to probe. Herein, a novel trigger delay (TD) scout sequence was used to acquire high in-plane resolution (1.6 mm) Spin-Echo (SE) cardiac diffusion tensor imaging (cDTI) at three distinct cardiac phases. The objective was to characterize cardiomyocyte organization and mobility throughout the cardiac cycle in healthy volunteers. Materials and methods: Nine healthy volunteers were imaged with cDTI at three distinct cardiac phases (early systole, late systole, and diastasis). The sequence used a free-breathing Spin-Echo (SE) cDTI protocol (b-values = 350s/mm2, twelve diffusion encoding directions, eight repetitions) to acquire high-resolution images (1.6x1.6x8mm3) at 3T in ~7 minutes/cardiac phase. Helix Angle (HA), Helix Angle Range (HAR), E2 angle (E2A), Transverse Angle (TA), Mean Diffusivity (MD), diffusion tensor eigenvalues (λ1-2-3), and Fractional Anisotropy (FA) in the left ventricle (LV) were characterized. Results: Images from the patient-specific TD scout sequence demonstrated that SE cDTI acquisition was possible at early systole, late systole, and diastasis in 78%, 100% and 67% of the cases, respectively. At the mid-ventricular level, mobility (reported as median [IQR]) was observed in HAR between early systole and late systole (76.9 [72.6, 80.5]° vs 96.6 [85.9, 100.3]°, p<0.001). E2A also changed significantly between early systole, late systole, and diastasis (27.7 [20.8, 35.1]° vs 45.2 [42.1, 49]° vs 20.7 [16.6, 26.4]°, p<0.001). Conclusion: We demonstrate that it is possible to probe cardiomyocyte mobility using multi-phase and high resolution cDTI. In healthy volunteers, aggregate cardiomyocytes re-orient themselves more longitudinally during contraction, while cardiomyocyte sheetlets tilt radially during wall thickening. These observations provide new insights into the three-dimensional mobility of myocardial microstructure during systolic contraction. [ABSTRACT FROM AUTHOR]

Purpose: Real-time magnetic resonance imaging (MRI) is a promising alternative to X-ray fluoroscopy for guiding cardiovascular catheterization procedures. Major challenges, however, include the lack of guidewires that are compatible with the MRI environment, not susceptible to radiofrequency-induced heating, and reliably visualized. Preclinical evaluation of new guidewire designs has been conducted at 1.5T. Here we further evaluate the safety (device heating), device visualization, and procedural feasibility of 3T MRI-guided cardiovascular catheterization using a novel MRI-visible glass-fiber epoxy-based guidewire in phantoms and porcine models. Methods: To evaluate device safety, guidewire tip heating (GTH) was measured in phantom experiments with different combinations of catheters and guidewires. In vivo cardiovascular catheterization procedures were performed in both healthy (N = 5) and infarcted (N = 5) porcine models under real-time 3T MRI guidance using a glass-fiber epoxy-based guidewire. The times for each procedural step were recorded separately. Guidewire visualization was assessed by measuring the dimensions of the guidewire-induced signal void and contrast-to-noise ratio (CNR) between the guidewire tip signal void and the blood signal in real-time gradient-echo MRI (specific absorption rate [SAR] = 0.04 W/kg). Results: In the phantom experiments, GTH did not exceed 0.35°C when using the real-time gradient-echo sequence (SAR = 0.04 W/kg), demonstrating the safety of the glass-fiber epoxy-based guidewire at 3T. The catheter was successfully placed in the left ventricle (LV) under real-time MRI for all five healthy subjects and three out of five infarcted subjects. Signal void dimensions and CNR values showed consistent visualization of the glass-fiber epoxy-based guidewire in real-time MRI. The average time (minutes:seconds) for the catheterization procedure in all subjects was 4:32, although the procedure time varied depending on the subject's specific anatomy (standard deviation = 4:41). Conclusions: Real-time 3T MRI-guided cardiovascular catheterization using a new MRI-visible glass-fiber epoxy-based guidewire is feasible in terms of visualization and guidewire navigation, and safe in terms of radiofrequency-induced guidewire tip heating. [ABSTRACT FROM AUTHOR]

Heart failure is a leading cause of death, yet its underlying electrophysiological (EP) mechanisms are not well understood. In this study, we use a multiscale approach to analyze a model of heart failure and connect its results to features of the electrocardiogram (ECG). The heart failure model is derived by modifying a previously validated electrophysiology model for a healthy rabbit heart. Specifically, in accordance with the heart failure literature, we modified the cell EP by changing both membrane currents and calcium handling. At the tissue level, we modeled the increased gap junction lateralization and lower conduction velocity due to downregulation of Connexin 43. At the biventricular level, we reduced the apex-to-base and transmural gradients of action potential duration (APD). The failing cell model was first validated by reproducing the longer action potential, slower and lower calcium transient, and earlier alternans characteristic of heart failure EP. Subsequently, we compared the electrical wave propagation in one dimensional cables of healthy and failing cells. The validated cell model was then used to simulate the EP of heart failure in an anatomically accurate biventricular rabbit model. As pacing cycle length decreases, both the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing. Moreover, T-wave alternans is significantly more pronounced in the failing heart. At rapid pacing, APD maps show areas of conduction block in the failing heart. Finally, accelerated pacing initiated wave reentry and breakup in the failing heart. Further, the onset of VF was not observed with an upregulation of SERCA, a potential drug therapy, using the same protocol. The changes introduced at the cell and tissue level have increased the failing heart’s susceptibility to dynamic instabilities and arrhythmias under rapid pacing. However, the observed increase in arrhythmogenic potential is not due to a steepening of the restitution curve (not present in our model), but rather to a novel blocking mechanism. [ABSTRACT FROM AUTHOR]

We describe a sequence of methods to produce a partial differential equation model of the electrical activation of the ventricles. In our framework, we incorporate the anatomy and cardiac microstructure obtained from magnetic resonance imaging and diffusion tensor imaging of a New Zealand White rabbit, the Purkinje structure and the Purkinje-muscle junctions, and an electrophysiologically accurate model of the ventricular myocytes and tissue, which includes transmural and apex-to-base gradients of action potential characteristics. We solve the electrophysiology governing equations using the finite element method and compute both a 6-lead precordial electrocardiogram (ECG) and the activation wavefronts over time. We are particularly concerned with the validation of the various methods used in our model and, in this regard, propose a series of validation criteria that we consider essential. These include producing a physiologically accurate ECG, a correct ventricular activation sequence, and the inducibility of ventricular fibrillation. Among other components, we conclude that a Purkinje geometry with a high density of Purkinje muscle junctions covering the right and left ventricular endocardial surfaces as well as transmural and apex-to-base gradients in action potential characteristics are necessary to produce ECGs and time activation plots that agree with physiological observations. [ABSTRACT FROM AUTHOR]