To shift or to rotate? Comparison of acquisition strategies for multi-slice super-resolution magnetic resonance imaging.

Multi-slice (MS) super-resolution reconstruction (SRR) methods have been proposed to improve the trade-off between resolution, signal-to-noise ratio and scan time in magnetic resonance imaging. MS-SRR consists in the estimation of an isotropic high-resolution image from a series of anisotropic MS images with a low through-plane resolution, where the anisotropic low-resolution images can be acquired according to different acquisition schemes. However, it is yet unclear how these schemes compare in terms of statistical performance criteria, especially for regularized MS-SRR. In this work, the estimation performance of two commonly adopted MS-SRR acquisition schemes based on shifted and rotated MS images respectively are evaluated in a Bayesian framework. The maximum a posteriori estimator, which introduces regularization by incorporating prior knowledge in a statistically well-defined way, is put forward as the estimator of choice and its accuracy, precision, and Bayesian mean squared error (BMSE) are used as performance criteria. Analytic calculations as well as Monte Carlo simulation experiments show that the rotated scheme outperforms the shifted scheme in terms of precision, accuracy, and BMSE. Furthermore, the superior performance of the rotated scheme is confirmed in real data experiments and in retrospective simulation experiments with and without inter-image motion. Results show that the rotated scheme allows regularized MS-SRR with a higher accuracy and precision than the shifted scheme, besides being more resilient to motion.

Model-based super-resolution reconstruction with joint motion estimation for improved quantitative MRI parameter mapping.

Quantitative Magnetic Resonance (MR) imaging provides reproducible measurements of biophysical parameters, and has become an essential tool in clinical MR studies. Unfortunately, 3D isotropic high resolution (HR) parameter mapping is hardly feasible in clinical practice due to prohibitively long acquisition times. Moreover, accurate and precise estimation of quantitative parameters is complicated by inevitable subject motion, the risk of which increases with scanning time. In this paper, we present a model-based super-resolution reconstruction (SRR) method that jointly estimates HR quantitative parameter maps and inter-image motion parameters from a set of 2D multi-slice contrast-weighted images with a low through-plane resolution. The method uses a Bayesian approach, which allows to optimally exploit prior knowledge of the tissue and noise statistics. To demonstrate its potential, the proposed SRR method is evaluated for a T1 and T2 quantitative mapping protocol. Furthermore, the method's performance in terms of precision, accuracy, and spatial resolution is evaluated using simulated as well as real brain imaging experiments. Results show that our proposed fully flexible, quantitative SRR framework with integrated motion estimation outperforms state-of-the-art SRR methods for quantitative MRI.

Acetylcholine Reduces IKr and Prolongs Action Potentials in Human Ventricular Cardiomyocytes.

Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K+ current (IKr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on IKr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in IKr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of IKr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in IKr.

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.