The rodent heart is frequently used to study human cardiovascular disease (CVD). Although advanced cardiovascular ultrasound imaging methods are available for human clinical practice, application of these techniques to small animals remains limited due to the temporal and spatial-resolution demands. Here, an ultrasound vector-flow workflow is demonstrated that enables visualization and quantification of the complex hemodynamics within the mouse heart. Wild type (WT) and fibroblast growth factor homologous factor 2 (FHF2)-deficient mice (Fhf2 KO/Y ), which present with hyperthermia-induced ECG abnormalities highly reminiscent of Brugada syndrome, were used as a mouse model of human CVD. An 18-MHz linear array was used to acquire high-speed (30 kHz), plane-wave data of the left ventricle (LV) while increasing core body temperature up to 41.5 °C. Hexplex (i.e., six output) processing of the raw data sets produced the output of vector-flow estimates (magnitude and phase); B-mode and color-Doppler images; Doppler spectrograms; and local time histories of vorticity and pericardium motion. Fhf2 WT/Y mice had repeatable beat-to-beat cardiac function, including vortex formation during diastole, at all temperatures. In contrast, Fhf2 KO/Y mice displayed dyssynchronous contractile motion that disrupted normal inflow vortex formation and impaired LV filling as temperature rose. PF 429242 purchase The hexplex processing approach demonstrates the ability to visualize and quantify the interplay between hemodynamic and mechanical function in a mouse model of human CVD.We designed a dedicated multi-detector multi-pinhole brain SPECT scanner to generate images of higher quality compared to general-purpose systems. The system, AdaptiSPECT-C, is intended to adapt its sensitivity-resolution trade-off by varying its aperture configurations allowing both high-sensitivity dynamic and high-spatial-resolution static imaging. The current system design consists of 23 detector heads arranged in a truncated spherical geometry. In this work, we investigated the axial and angular sampling capability of the current stationary system design. Two data acquisition schemes using limited rotation of the gantry and two others using axial translation of the imaging bed were also evaluated concerning their impact on image quality through improved sampling. Increasing both angular and axial sampling in the current prototype system resulted in quantitative improvements in image quality metrics and qualitative appearance of the images as determined in studies with specifically selected phantoms. Visual improvements for the brain phantoms with clinical distributions were less pronounced but presented quantitative improvements in the fidelity (normalized root-mean-square error (NRMSE)) and striatal specific binding ratio (SBR) for a dopamine transporter (DAT) distribution, and in NRMSE and activity recovery for a brain perfusion distribution. More pronounced improvements with increased sampling were seen in contrast recovery coefficient, bias, and coefficient of variation for a lesion in the brain perfusion distribution. The negligible impact of the most cranial ring of detectors on axial sampling, but its significant impact on sensitivity and angular sampling in the cranial portion of the imaging volume-of-interest were also determined.We present an evolution-strategy based approach to solve the magnitude least squares (MLS) design problem of low flip-angle slice-selective parallel transmit RF pulses for ultra-high field MRI using SAR and peak-RF-constraints. A combined transmit k-space trajectory and RF pulse weight optimization is proposed in two algorithmic steps. The first step is a coarse grid search to find an initial solution that fulfills all constraints for the subsequent multistage optimization. This avoids convergence to the next nearest local minimum. The second step attempts to refine the results using multiple evolution strategies. We compare the performance of our approach with the non-convex optimization methods described in the literature. The proposed algorithm converges for phantom and in vivo data and only requires an initial estimate of the range of suitable regularization parameters. It demonstrates improved excitation homogeneity compared to published spoke-design methods and allows optimization for homogeneity with a subsequent reduction in the SAR burden. Moreover, excitation homogeneity and the SAR burden can be balanced against each other, enabling a further reduction in SAR at the cost of minor relaxations in excitation homogeneity. This feature makes the algorithm a good candidate for SAR limited sequences in ultra-high field imaging. The algorithm is validated using phantom and in vivo measurements obtained with a 16-channel transmit array at 9.4T.Given impressive abilities of GANs in generating highly realistic images, they are also being used in novel ways in applications in the life sciences, raising an interesting question in scientific or biomedical studies. Consider the setting where we are restricted to only using the samples from a trained GAN for downstream group difference analysis, will we obtain similar conclusions? In this work, we explore if ?generated? data, i.e., sampled from such GANs can be used for performing statistical group difference tests in cases versus controls studies, common across many scientific disciplines. We provide a detailed analysis describing regimes where this may be feasible. We complement the technical results with an empirical study focused on the analysis of cortical thickness on brain mesh surfaces in an Alzheimer?s disease dataset. To exploit the geometric nature of the data, we use simple ideas from spectral graph theory to show how adjustments to existing GANs can yield improvements. To our knowledge, our work offers the first analysis assessing whether the Null distribution in ?healthy versus diseased subjects? type statistical testing using data generated from the GANs coincides with the one obtained from the same analysis with real cortical thickness data.Bempedoic acid, a new therapeutic for treatment of hypercholesterolemia, inhibits hepatic ATP-citrate lyase in the cholesterol synthesis pathway after its conjugation with coenzyme A. Sensitive and selective methods were required to study the pharmacokinetic behavior of bempedoic acid and its active 8-keto metabolite in clinical studies. A mixed mode anion exchange extraction on 96-well plates was developed to favor high, selective recoveries of these dicarboxylic acids from urine or plasma. Adsorptive losses in urine led to inaccurate measurements unless samples were acidified and diluted with isopropanol prior to any specimen transfers. Tandem mass spectrometry with negative ion electrospray ionization permitted lower limits of measurement of 20 and 10 ng/mL for the drug and metabolite in either matrix. The methods were validated to current regulatory standards and have been the basis for pharmacokinetic measurements in 26 clinical studies involving over 15,000 samples.