Evaluation of STK17B as a cancer immunotherapy target utilizing highly potent and selective small molecule inhibitors.

Introduction: The serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy.

Methods: To assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library.

Metabolic imaging in living plants: A promising field for chemical exchange saturation transfer (CEST) MRI.

Magnetic resonance imaging (MRI) is a versatile technique in the biomedical field, but its application to the study of plant metabolism in vivo remains challenging because of magnetic susceptibility problems. In this study, we report the establishment of chemical exchange saturation transfer (CEST) for plant MRI. This method enables noninvasive access to the metabolism of sugars and amino acids in complex sink organs (seeds, fruits, taproots, and tubers) of major crops (maize, barley, pea, potato, sugar beet, and sugarcane).

Rotary excitation of non-sinusoidal pulsed magnetic fields: Towards non-invasive direct detection of cardiac conduction.

Purpose: There is a need for high resolution non-invasive imaging methods of physiologic magnetic fields. The purpose of this work is to develop a MRI detection approach for non-sinusoidal magnetic fields based on the rotary excitation (REX) mechanism which was previously successfully applied for the detection of oscillating magnetic fields in the sub-nT range.

Methods: The new detection concept was examined by means of Bloch simulations, evaluating the interaction effect of spin-locked magnetization and low-frequency pulsed magnetic fields.

Quantification of the rotating frame relaxation time T: Comparison of balanced spin-lock and continuous-wave Malcolm-Levitt preparations.

For the quantification of rotating frame relaxation times, the T relaxation pathway plays an essential role. Nevertheless, T imaging has been studied only to a small extent compared with T, and preparation techniques for T have so far been adapted from T methods. In this work, two different preparation concepts are compared specifically for the use of T mapping.

Enhancing quality and speed in database-free neural network reconstructions of undersampled MRI with SCAMPI.

Purpose: We present SCAMPI (Sparsity Constrained Application of deep Magnetic resonance Priors for Image reconstruction), an untrained deep Neural Network for MRI reconstruction without previous training on datasets. It expands the Deep Image Prior approach with a multidomain, sparsity-enforcing loss function to achieve higher image quality at a faster convergence speed than previously reported methods.

Methods: Two-dimensional MRI data from the FastMRI dataset with Cartesian undersampling in phase-encoding direction were reconstructed for different acceleration rates for single coil and multicoil data.

Seeing plants as never before.

Imaging has long supported our ability to understand the inner life of plants, their development, and response to a dynamic environment. While optical microscopy remains the core tool for imaging, a suite of novel technologies is now beginning to make a significant contribution to visualize plant metabolism. The purpose of this review was to provide the scientific community with an overview of current imaging methods, which rely variously on either nuclear magnetic resonance (NMR), mass spectrometry (MS) or infrared (IR) spectroscopy, and to present some examples of their application in order to illustrate their utility.

Non-destructive classification of unlabeled cells: Combining an automated benchtop magnetic resonance scanner and artificial intelligence.

In order to treat degenerative diseases, the importance of advanced therapy medicinal products has increased in recent years. The newly developed treatment strategies require a rethinking of the appropriate analytical methods. Current standards are missing the complete and sterile analysis of the product of interest to make the drug manufacturing effort worthwhile.

Iterative training of robust k-space interpolation networks for improved image reconstruction with limited scan specific training samples.

Purpose: To evaluate an iterative learning approach for enhanced performance of robust artificial-neural-networks for k-space interpolation (RAKI), when only a limited amount of training data (auto-calibration signals [ACS]) are available for accelerated standard 2D imaging.

Methods: In a first step, the RAKI model was tailored for the case of limited training data amount. In the iterative learning approach (termed iterative RAKI [iRAKI]), the tailored RAKI model is initially trained using original and augmented ACS obtained from a linear parallel imaging reconstruction.

Quantification correction for free-breathing myocardial T mapping in mice using a recursively derived description of a T* relaxation pathway.

Background: Fast and accurate T mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T relaxation pathway. In this study, we present an improved quantification method for T using a newly derived formalism of a T* relaxation pathway.

Quantitative monitoring of paramagnetic contrast agents and their allocation in plant tissues via DCE-MRI.

Background: Studying dynamic processes in living organisms with MRI is one of the most promising research areas. The use of paramagnetic compounds as contrast agents (CA), has proven key to such studies, but so far, the lack of appropriate techniques limits the application of CA-technologies in experimental plant biology. The presented proof-of-principle aims to support method and knowledge transfer from medical research to plant science.

2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis.

Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, = 5) and atherosclerotic apolipoprotein E-deficient (, = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI).

Fast myocardial T mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern.

Purpose: T dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T mapping sequence, which paves the way to cardiac T dispersion quantification within the limited measurement time of an in vivo study in small animals.

Multi-Perspective Anomaly Detection.

Anomaly detection is a critical problem in the manufacturing industry. In many applications, images of objects to be analyzed are captured from multiple perspectives which can be exploited to improve the robustness of anomaly detection. In this work, we build upon the deep support vector data description algorithm and address multi-perspective anomaly detection using three different fusion techniques, i.

Mattering and parental presence in systemic therapy using nonviolent resistance: The utilization of imaginary methods.

An empowered sense of "self" is crucial for emotional well-being and positive relationships. Certain family interaction patterns can disrupt the adult's sense of "mattering" to the child, eroding their perceived self-efficacy. Mattering can be understood as a felt sense of relational agency which is necessary for experiencing one's interactions as meaningful, effective, and self-determined.

Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch.

Purpose: Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements.

Evaluation of Plaque Characteristics and Inflammation Using Magnetic Resonance Imaging.

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth.

Serotonin transporter genotype modulates resting state and predator stress-induced amygdala perfusion in mice in a sex-dependent manner.

The serotonin transporter (5-HTT) is a key molecule of serotoninergic neurotransmission and target of many anxiolytics and antidepressants. In humans, 5-HTT gene variants resulting in lower expression levels are associated with behavioral traits of anxiety. Furthermore, functional magnetic resonance imaging (fMRI) studies reported increased cerebral blood flow (CBF) during resting state (RS) and amygdala hyperreactivity.

Balanced spin-lock preparation for B -insensitive and B -insensitive quantification of the rotating frame relaxation time T.

Purpose: Accurate and artifact-free T quantification is still a major challenge due to a susceptibility of the spin-locking module to B and/or B field inhomogeneities. In this study, we present a novel spin-lock preparation module (B-SL) that enables an almost full compensation of both types of inhomogeneities.

Methods: The new B-SL module contains a second 180° refocusing pulse to compensate each pulse in the preparation block by a corresponding pulse with opposite phase.

Fast self-navigated wall shear stress measurements in the murine aortic arch using radial 4D-phase contrast cardiovascular magnetic resonance at 17.6 T.

Purpose: 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice.

Alternatives to Carbon Dioxide-Taking Responsibility for Humanely Ending the Life of Animals.

Carbon dioxide (CO) is commonly used to kill rodents. However, a large body of research has now established that CO is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and Veterinary Office discussed the drawbacks and alternatives to CO in euthanasia protocols for laboratory animals.

Simultaneous T and T measurements using inversion recovery TrueFISP with principle component-based reconstruction, off-resonance correction, and multicomponent analysis.

Purpose: To improve the reconstruction quality for quantitative T and T measurements using the inversion recovery (IR) TrueFISP sequence and to demonstrate the potential for multicomponent analysis.

Methods: The iterative reconstruction method takes advantage of the high redundancy in the smooth exponential signals using principle component analysis (PCA). Multicomponent information is preserved and allows voxel-by-voxel computation of relaxation time spectra with an inverse Laplace transform.

Improved compressed sensing reconstruction for [Formula: see text]F magnetic resonance imaging.

Objective: In magnetic resonance imaging (MRI), compressed sensing (CS) enables the reconstruction of undersampled sparse data sets. Thus, partial acquisition of the underlying k-space data is sufficient, which significantly reduces measurement time. While F MRI data sets are spatially sparse, they often suffer from low SNR.

Towards quantitative perfusion MRI of the lung in COPD: The problem of short-term repeatability.

Purpose: 4D perfusion magnetic resonance imaging (MRI) with intravenous injection of contrast agent allows for a radiation-free assessment of regional lung function. It is therefore a valuable method to monitor response to treatment in patients with chronic obstructive pulmonary disease (COPD). This study was designed to evaluate its potential for monitoring short-term response to hyperoxia in COPD patients.

Real-time Triggered RAdial Single-Shot Inversion recovery for arrhythmia-insensitive myocardial T1 mapping: motion phantom validation and in vivo comparison.

Purpose: Cardiac T mapping has become an increasingly important imaging technique, contributing novel diagnostic options. However, currently utilized methods are often associated with accuracy problems because of heart rate variations and cardiac arrhythmia, limiting their value in clinical routine. This study aimed to introduce an improved arrhythmia-related robust T mapping sequence called RT-TRASSI (real-time Triggered RAdial Single-Shot Inversion recovery).

Positive chemical exchange contrast in MRI using Refocused Acquisition of Chemical Exchange Transferred Excitations (RACETE).

Purpose: A new chemical exchange MRI method is proposed which allows for direct detection of exchanging solute protons with concurrent water background suppression.

Methods: The proposed method, RACETE (Refocused Acquisition of Chemical Exchange Transferred Excitations), is based on a stimulated-echo-technique, where the first two excitation pulses are replaced by a train of N solute-selective excitation-transfer modules. This excitation cycle is then followed by a stimulated echo acquisition via selective refocusing of exchanged solute protons now present in the solvent pool.