A computational model of rabbit geometry and ECG: Optimizing ventricular activation sequence and APD distribution

Computational modeling of electrophysiological properties of the rabbit heart is a commonly used way to enhance and/or complement findings from classic lab work on single cell or tissue levels. Yet, thus far, there was no possibility to extend the scope to include the resulting body surface potentials as a way of validation or to investigate the effect of certain pathologies. Based on CT imaging, we developed the first openly available computational geometrical model not only of the whole heart but also the complete torso of the rabbit. Additionally, we fabricated a 32-lead ECG-vest to record body surface potential signals of the aforementioned rabbit. Based on the developed geometrical model and the measured signals, we then optimized the activation sequence of the ventricles, recreating the functionality of the Purkinje network, and we investigated different apico-basal and transmural gradients in action potential duration. Optimization of the activation sequence resulted in an average root mean square error between measured and simulated signal of 0.074 mV/ms for all leads. The best-fit T-Wave, compared to measured data (0.038 mV/ms), resulted from incorporating an action potential duration gradient from base to apex with a respective shortening of 20 ms and a transmural gradient with a shortening of 15 ms from endocardium to epicardium. By making our model and measured data openly available, we hope to give other researchers the opportunity to verify their research, as well as to create the possibility to investigate the impact of electrophysiological alterations on body surface signals for translational research

Mechano‐electrical interactions and heterogeneities in wild‐type and drug‐induced long QT syndrome rabbits

Electromechanical reciprocity – comprising electro-mechanical (EMC) and mechano-electric coupling (MEC) – provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions – such as (drug-induced) acquired long QT syndrome (aLQTS) – might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS. To measure regional differences in EMC and MEC in vivo, we used tissue phase mapping cardiac MRI and a 24-lead ECG vest in healthy (control) and IKr-blocker E-4031-induced aLQTS rabbit hearts. MEC was studied in vivo by acutely increasing cardiac preload, and ex vivo by using voltage optical mapping (OM) in beating hearts at different preloads. In aLQTS, electrical repolarization (heart rate corrected RT-interval, RTn370) was prolonged compared to control (P < 0.0001) with increased spatial and temporal RT heterogeneity (P < 0.01). Changing electrical function (in aLQTS) resulted in significantly reduced diastolic mechanical function and prolonged contraction duration (EMC), causing increased apico-basal mechanical heterogeneity. Increased preload acutely prolonged RTn370 in both control and aLQTS hearts (MEC). This effect was more pronounced in aLQTS (P < 0.0001). Additionally, regional RT-dispersion increased in aLQTS. Motion-correction allowed us to determine APD-prolongation in beating aLQTS hearts, but limited motion correction accuracy upon preload-changes prevented a clear analysis of MEC ex vivo. Mechano-induced RT-prolongation and increased heterogeneity were more pronounced in aLQTS than in healthy hearts. Acute MEC effects may play an additional role in LQT-related arrhythmogenesis, warranting further mechanistic investigations

Segmental biventricular analysis of myocardial function using high temporal and spatial resolution tissue phase mapping.

OBJECTIVE Myocardial dysfunction of the right ventricle (RV) is an important indicator of RV diseases, e.g. RV infarction or pulmonary hypertension. Tissue phase mapping (TPM) has been widely used to determine function of the left ventricle (LV) by analyzing myocardial velocities. The analysis of RV motion is more complicated due to the different geometry and smaller wall thickness. The aim of this work was to adapt and optimize TPM to the demands of the RV. MATERIALS AND METHODS TPM measurements were acquired in 25 healthy volunteers using a velocity-encoded phase-contrast sequence and kt-accelerated parallel imaging in combination with optimized navigator strategy and blood saturation. Post processing was extended by a 10-segment RV model and a detailed biventricular analysis of myocardial velocities was performed. RESULTS High spatio-temporal resolution (1.0 × 1.0 × 6 mm3, 21.3 ms) and the optimized blood saturation enabled good delineation of the RV and its velocities. Global and segmental velocities, as well as time to peak velocities showed significant differences between the LV and RV. Furthermore, complex timing of the RV could be demonstrated by segmental time to peak analysis. CONCLUSION High spatio-temporal resolution TPM enables a detailed biventricular analysis of myocardial motion and might provide a reliable tool for description and detection of diseases affecting left and right ventricular function

UNFOLDed spiral SPiRIT TPM enables high spatio-temporal resolution analysis of cardiac function.

A detailed TPM analysis of cardiac function necessitates high spatio-temporal resolution which leads to prolonged scan durations. These scan times are typically too long for data acquisition within a single breath hold. Respiratory navigator-gating can compensate breathing-related motion, but causes an additional increase in measurement time and images with residual motion artifacts. The aim of this study was to combine UNFOLD with variable density spiral SPiRIT TPM to achieve an additional scan time reduction by a factor of 2 and an effective undersampling factor of 6. UNFOLDed SPiRIT TPM demonstrates good results and enables scan times within very short breath holding

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

AIMS Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD. METHODS AND RESULTS We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E', invasive LV end-diastolic pressure, and N-terminal pro-brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD- (total number 41). DD+ showed enlarged LA with LA end-diastolic volume/height performing best to identify DD+ with a cut-off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD-: -14.5 ± 6.5%/s vs. DD+: -10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD-: -4.2 ± 1.6%/s vs. DD+: -3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD-: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD-: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD-: -3.6 ± 0.7 ms vs. DD+: -2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD-: -5.0 ± 1.8 ms vs. DD+: -3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD-: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD-. CONCLUSIONS Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD

In vitro study to simulate the intracardiac magnetohydrodynamic effect

PURPOSE Blood flow causes induced voltages via the magnetohydrodynamic (MHD) effect distorting electrograms (EGMs) made during magnetic resonance imaging. To investigate the MHD effect in this context MHD voltages occurring inside the human heart were simulated in an in vitro model system inside a 1.5 T MR system. METHODS The model was developed to produce MHD signals similar to those produced by intracardiac flow and to acquire them using standard clinical equipment. Additionally, a new approach to estimate MHD distortions on intracardiac electrograms is proposed based on the analytical calculation of the MHD signal from MR phase contrast data. RESULTS The recorded MHD signals were similar in magnitude to intracardiac signals that would be measured by an electrogram of the left ventricle. The dependency of MHD signals on magnetic field strength and electrode separation was well reflected by an analytical model. MHD signals reconstructed from MR flow data were in excellent agreement with the MHD signal measured by clinical equipment. CONCLUSION The in vitro model allows investigation of MHD effects on intracardiac electrograms. A phase contrast MR scan was successfully applied to characterize and estimate the MHD distortion on intracardiac signals allowing correction of these effects. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc

Preclinical 4D-flow magnetic resonance phase contrast imaging of the murine aortic arch

<div><p>Purpose</p><p>Cardiovascular diseases remain the number one death cause worldwide. Preclinical 4D flow phase contrast magnetic resonance imaging can provide substantial insights in the analysis of aortic pathophysiologies in various animal models. These insights may allow a better understanding of pathophysiologies, therapy monitoring, and can possibly be translated to humans. This study provides a framework to acquire the velocity field within the aortic arch. It analyses important flow values at different locations within the aortic arch. Imaging parameters with high temporal and spatial resolution are provided, that still allow combining this time-consuming method with other necessary imaging-protocols.</p><p>Methods</p><p>A new setup was established where a prospectively gated 4D phase contrast sequence is combined with a highly sensitive cryogenic coil on a preclinical magnetic resonance scanner. The sequence was redesigned to maintain a close to steady state condition of the longitudinal magnetization and hence to overcome steady state artifacts. Imaging parameters were optimized to provide high spatial and temporal resolution. Pathline visualizations were generated from the acquired velocity data in order to display complex flow patterns.</p><p>Results</p><p>Our setup allows data acquisition with at least two times the rate than that of previous publications based on Cartesian encoding, at an improved image quality. The “steady state” sequence reduces observed artifacts and provides uniform image intensity over the heart cycle. This made possible quantification of blood speed and wall shear stress (WSS) within the aorta and its branches. The highest velocities were observed in the ascending aorta with 137.5 ± 8 cm/s. Peak velocity values in the Brachiocephalic trunk were 57 ± 12 cm/s. Quantification showed that the peak flow occurs around 20 ms post R-wave in the ascending aorta. The highest mean axial wall shear stress was observed in the analysis plane between the left common carotid artery (LCCA) and the left subclavian artery. A stable image quality allows visualizing complex flow patterns by means of streamlines and for the first time, to the best of our knowledge, pathline visualizations from 4D flow MRI in mice.</p><p>Conclusion</p><p>The described setup allows analyzing pathophysiologies in mouse models of cardiovascular diseases in the aorta and its branches with better image quality and higher spatial and temporal resolution than previous Cartesian publications. Pathlines provide an advanced analysis of complex flow patterns in the murine aorta. An imaging protocol is provided that offers the possibility to acquire the aortic arch at sufficiently high resolution in less than one hour. This allows the combination of the flow assessment with other multifunctional imaging protocols.</p></div