Congenital Long-QT Syndrome (LQTS) is a genetic dis- order affecting the repolarization of the heart. The most prevalent subtypes of LQTS are LQT1-3. In this work, we aim to evaluate the differences in the T-waves of simu- lated LQT1-3 in order to identify markers in the ECG that might help to classify patients solely based on ECG mea- surements. For LQT1, mutation S277L was used to char- acterize IKs and mutation S818L in IKr for LQT2. Volt- age clamp data were used to parametrize the ion channel equations of the ten Tusscher and Panfilov model of hu- man ventricular electrophysiology. LQT3 was integrated using an existing mutant INa model. The monodomain model was used in a transmural and apico-basal heteroge- neous model of the ventricles to calculate ventricular exci- tation propagation. The forward calculation on a torso model was performed to determine body surface ECGs. Compared to the physiological case with a QT-time of 375 ms, this interval was prolonged in all LQTS (LQT1 423 ms; LQT2 394 ms; LQT3 405 ms). The T-wave ampli- tude was changed (Einthoven lead II: LQT1 108%; LQT2 91%; LQT3 103%). Also, the width of the T-wave was en- larged (full width at half maximum: LQT1 111%; LQT2 125%; LQT3 109%). At the current state of modeling and data analysis, the three LQTS have not been distinguish- able solely by ECG data.
OBJECT: Most functional magnetic resonance imaging (fMRI) experiments use gradient-echo echo planar imaging (GE EPI) to detect the blood oxygenation level-dependent (BOLD) effect. This technique may fail in the presence of anatomy-related susceptibility-induced field gradients in the human head. In this work, we present a novel 3D compensation method in combination with a template-based correction that can be optimized over particular regions of interest to recover susceptibility-induced signal loss without acquisition time penalty. MATERIALS AND METHODS: Based on an evaluation of B(0) field maps of eight subjects, slice-dependent gradient compensation moments are derived for maximal BOLD sensitivity in two compromised regions: the orbitofrontal cortex and the amygdala areas. A modified EPI sequence uses these additional gradient moments in all three imaging directions. The method is compared to non-compensated, template-based and subject-specific correction gradients and also in a breath-holding experiment. RESULTS: The slice-dependent gradient compensation method significantly improves signal intensity/BOLD sensitivity by about 35/43% in the orbitofrontal cortex and by 17/30% in the amygdala areas compared to a conventional acquisition. Template-based correction and subject-specific correction perform equally well. The BOLD sensitivity in the breath hold experiment is effectively increased in compensated regions. CONCLUSION: The new method addresses the problem of susceptibility-induced signal loss, without compromising temporal resolution. It can be used for event-related functional experiments without requiring additional subject-specific calibration or calculation time.
Generally, models of cardiac electrophysiology describe physiologic conditions in detail. However, other conditions, such as drug interactions or mutations of ion channels are of interest for research. Therefore, the simulated ion currents have to be fitted to measured voltage or patch clamp data. In this work, three different methods for the model parametrization were compared: one based on Powells algorithm implemented in a modular C++ framework and two optimization techniques realized in Matlab. The latter two approaches differed in solving the ordinary differential equations describing the channel gating. They can either be approximated numerically or solved analytically, since the transmembrane voltage is a piecewise constant function during the applied clamp protocol. All three methods were compared regarding computing time and quality of the fit using least squares. The modular C++ framework was slower than the numerical Matlab method, which took longer than the analytical one. The quality of the fit was similar for almost all analyzed methods. Therefore, the analytical method grants a fast and reliable solution for the calibration of ion current models for applications with constant membrane voltage, as e.g. in case of voltage or patch clamp data.