Special Report on the Consensus QIBA Profile for Objective Analytical Validation of Non-calcified and High-risk Plaque and Other Biomarkers using Computed Tomography Angiography.

Rationale And Objectives: Evidence is building in support of the clinical utility of atherosclerotic plaque imaging by computed tomography angiography (CTA). There is increasing organized activity to embrace non-calcified plaque (NCP) as a formally defined biomarker for clinical trials, and high-risk plaque (HRP) for clinical care, as the most relevant measures for the field to advance and worthy of community efforts to validate. Yet the ability to assess the quantitative performance of any given specific solution to make these measurements or classifications is not available.

Structural modeling of hERG channel-drug interactions using Rosetta.

The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity.

Carotid Plaque-RADS: A Novel Stroke Risk Classification System.

Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features.

Objectives: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score.

A multiscale predictive digital twin for neurocardiac modulation.

Cardiac function is tightly regulated by the autonomic nervous system (ANS). Activation of the sympathetic nervous system increases cardiac output by increasing heart rate and stroke volume, while parasympathetic nerve stimulation instantly slows heart rate. Importantly, imbalance in autonomic control of the heart has been implicated in the development of arrhythmias and heart failure.

Revealing tumor microstructure with oscillating diffusion encoding MRI in pre-surgical and post-treatment glioma patients.

Purpose: We hypothesized that the time-dependent diffusivity at short diffusion times, as measured by oscillating gradient spin echo (OGSE) diffusion MRI, can characterize tissue microstructures in glioma patients.

Theory And Methods: Five adult patients with known diffuse glioma, including two pre-surgical and three with new enhancing lesions after treatment for high-grade glioma, were scanned in an ultra-high-performance gradient 3.0T MRI system.

Elucidation of a dynamic interplay between a beta-2 adrenergic receptor, its agonist, and stimulatory G protein.

G protein-coupled receptors (GPCRs) represent the largest group of membrane receptors for transmembrane signal transduction. Ligand-induced activation of GPCRs triggers G protein activation followed by various signaling cascades. Understanding the structural and energetic determinants of ligand binding to GPCRs and GPCRs to G proteins is crucial to the design of pharmacological treatments targeting specific conformations of these proteins to precisely control their signaling properties.

Structural modeling of the hERG potassium channel and associated drug interactions.

The voltage-gated potassium channel, K11.1, encoded by the human -Related Gene (hERG), is expressed in cardiac myocytes, where it is crucial for the membrane repolarization of the action potential. Gating of the hERG channel is characterized by rapid, voltage-dependent, C-type inactivation, which blocks ion conduction and is suggested to involve constriction of the selectivity filter.

MR Angiography Series: Neurovascular MR Angiography.

Neurovascular MR angiography (MRA) is an evolving imaging technique and is crucial for the workup of numerous neurologic disorders. While CT angiography (CTA) provides a more rapid imaging assessment, in select patients it can impart a small risk of contrast material-induced nephrotoxicity or radiation-associated cancers. In addition, MRA offers some advantages over CTA for neurovascular evaluation, including higher temporal resolution and the capability for vessel wall imaging.

MR Angiography Series: Fundamentals of Contrast-enhanced MR Angiography.

The Society for Magnetic Resonance Angiography (SMRA) is a group of researchers and clinicians who are passionate about the benefits of MR angiography (MRA) but understand its challenges. Their mission is to study MRA, continually improve and innovate for the benefit of patients, and most important, educate the medical community so they can take full advantage of the benefits of MRA and overcome its challenges. In support of that mission, the authors have created a series of self-learning modules on behalf of the SMRA to demystify MRA protocols and help the reader perform patient-friendly high-quality MRA on a routine basis in clinical practice.

Multinational Survey of Current Practice from Imaging to Treatment of Atherosclerotic Carotid Stenosis.

Background: In the last 20-30 years, there have been many advances in imaging and therapeutic strategies for symptomatic and asymptomatic individuals with carotid artery stenosis. Our aim was to examine contemporary multinational practice standards.

Methods: Departmental Review Board approval for this study was obtained, and 3 authors prepared the 44 multiple choice survey questions.

Prognostic Value of Intraplaque Neovascularization Detected by Carotid Contrast-Enhanced Ultrasound in Patients Undergoing Stress Echocardiography.

Background: Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events.

Computational Modeling of Carotid Bruits.

The sound generated by diseased carotid arteries was investigated through computational means using three-dimensional, idealized, stenosed carotid bifurcation models. Stenosis levels of 50% and 70% with axi-symmetric and asymmetric stenosis shapes were considered. The hemodynamic flow field was obtained by solving the incompressible, Navier-Stokes equations.

MR imaging of vulnerable carotid plaque.

Current risk stratification for stroke is still based upon percentage of carotid stenosis, despite this measure providing minimal patient-specific information on the actual risk of stroke for both symptomatic individuals without significant carotid artery stenosis as well as asymptomatic carotid stenosis patients. A continuously growing body of literature suggests that the identification and quantification of certain carotid plaque characteristics, including lipid-rich necrotic core (LRNC), thin/ruptured fibrous cap (FC), and intraplaque hemorrhage (IPH), provide a superior means of predicting future stroke. These characteristics are identifiable via magnetic resonance imaging (MRI), with most features detectable using commercially available coils and sequences utilized in routine clinical practice in as little as 4 minutes.

Author Correction: Combined spatiotemporal and frequency-dependent shear wave elastography enables detection of vulnerable carotid plaques as validated by MRI.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Computational Pipeline to Predict Cardiotoxicity: From the Atom to the Rhythm.

Rationale: Drug-induced proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhythmia. But QT interval is too sensitive a marker and not selective, resulting in many useful drugs eliminated in drug discovery.

Objective: To predict the impact of a drug from the drug chemistry on the cardiac rhythm.

Oscillating diffusion-encoding with a high gradient-amplitude and high slew-rate head-only gradient for human brain imaging.

Purpose: We investigate the importance of high gradient-amplitude and high slew-rate on oscillating gradient spin echo (OGSE) diffusion imaging for human brain imaging and evaluate human brain imaging with OGSE on the MAGNUS head-gradient insert (200 mT/m amplitude and 500 T/m/s slew rate).

Methods: Simulations with cosine-modulated and trapezoidal-cosine OGSE at various gradient amplitudes and slew rates were performed. Six healthy subjects were imaged with the MAGNUS gradient at 3T with OGSE at frequencies up to 100 Hz and b = 450 s/mm .

Selectivity filter modalities and rapid inactivation of the hERG1 channel.

The human -related gene (hERG1) channel conducts small outward K currents that are critical for cardiomyocyte membrane repolarization. The gain-of-function mutation N629D at the outer mouth of the selectivity filter (SF) disrupts inactivation and K-selective transport in hERG1, leading to arrhythmogenic phenotypes associated with long-QT syndrome. Here, we combined computational electrophysiology with Markov state model analysis to investigate how SF-level gating modalities control selective cation transport in wild-type (WT) and mutant (N629D) hERG1 variants.

Combined spatiotemporal and frequency-dependent shear wave elastography enables detection of vulnerable carotid plaques as validated by MRI.

Fatal cerebrovascular events are often caused by rupture of atherosclerotic plaques. However, rupture-prone plaques are often distinguished by their internal composition rather than degree of luminal narrowing, and conventional imaging techniques might thus fail to detect such culprit lesions. In this feasibility study, we investigate the potential of ultrasound shear wave elastography (SWE) to detect vulnerable carotid plaques, evaluating group velocity and frequency-dependent phase velocities as novel biomarkers for plaque vulnerability.

Highly efficient head-only magnetic field insert gradient coil for achieving simultaneous high gradient amplitude and slew rate at 3.0T (MAGNUS) for brain microstructure imaging.

Purpose: To develop a highly efficient magnetic field gradient coil for head imaging that achieves 200 mT/m and 500 T/m/s on each axis using a standard 1 MVA gradient driver in clinical whole-body 3.0T MR magnet.

Methods: A 42-cm inner diameter head-gradient used the available 89- to 91-cm warm bore space in a whole-body 3.

A demonstration of modularity, reuse, reproducibility, portability and scalability for modeling and simulation of cardiac electrophysiology using Kepler Workflows.

Multi-scale computational modeling is a major branch of computational biology as evidenced by the US federal interagency Multi-Scale Modeling Consortium and major international projects. It invariably involves specific and detailed sequences of data analysis and simulation, often with multiple tools and datasets, and the community recognizes improved modularity, reuse, reproducibility, portability and scalability as critical unmet needs in this area. Scientific workflows are a well-recognized strategy for addressing these needs in scientific computing.

Structural basis for antiarrhythmic drug interactions with the human cardiac sodium channel.

The human voltage-gated sodium channel, hNa1.5, is responsible for the rapid upstroke of the cardiac action potential and is target for antiarrhythmic therapy. Despite the clinical relevance of hNa1.

Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation.

Ion channels are implicated in many essential physiological events such as electrical signal propagation and cellular communication. The advent of K and Na ion channel structure determination has facilitated numerous investigations of molecular determinants of their behaviour. At the same time, rapid development of computer hardware and molecular simulation methodologies has made computational studies of large biological molecules in all-atom representation tractable.

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.

Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit.