MRI Visualization of Whole Brain Macro- and Microvascular Remodeling in a Rat Model of Ischemic Stroke: A Pilot Study

Using superparamagnetic iron oxide nanoparticles (SPION) as a single contrast agent, we investigated dual contrast cerebrovascular magnetic resonance imaging (MRI) for simultaneously monitoring macro- and microvasculature and their association with ischemic edema status (via apparent diffusion coefficient [ADC]) in transient middle cerebral artery occlusion (tMCAO) rat models. High-resolution T1-contrast based ultra-short echo time MR angiography (UTE-MRA) visualized size remodeling of pial arteries and veins whose mutual association with cortical ischemic edema status is rarely reported. ??R2?????R2*-MRI-derived vessel size index (VSI) and density indices (Q and MVD) mapped morphological changes of microvessels occurring in subcortical ischemic edema lesions. In cortical ischemic edema lesions, significantly dilated pial veins (p???=???0.0051) and thinned pial arteries (p???=???0.0096) of ipsilateral brains compared to those of contralateral brains were observed from UTE-MRAs. In subcortical regions, ischemic edema lesions had a significantly decreased Q and MVD values (p???<???0.001), as well as increased VSI values (p???<???0.001) than normal subcortical tissues in contralateral brains. This pilot study suggests that MR-based morphological vessel changes, including but not limited to venous blood vessels, are directly related to corresponding tissue edema status in ischemic stroke rat models

Fast Compartment Model Calibration using Annealed and Transformed Variational Inference

Compartment models are widely used in climate science, epidemiology, and physics, among other disciplines. An important example of a compartment model is susceptible-infected-recovered (SIR) model, which can describe disease dynamics. Bayesian inference for SIR models is challenging because likelihood evaluation requires solving expensive ordinary differential equations. Although variational inference (VI) can be a fast alternative to the traditional Bayes approaches, VI has limited applicability due to boundary issues and local optima problems. To address these challenges, we propose flexible VI methods based on deep generative models that do not require parametric assumptions on the variational distribution. We embed a surjective transformation in our framework to avoid posterior truncation at the boundary. We provide theoretical conditions that guarantee the success of the algorithm. Furthermore, our temperature annealing scheme can avoid being trapped in local optima through a series of intermediate posteriors. We apply our method to variants of SIR models, illustrating that the proposed method can provide fast and accurate inference compared to its competitors

The robustness of T2 value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI

Purpose: To evaluate the robustness of MR transverse relaxation times of trabecular bone from spin-echo and gradient-echo acquisitions at multiple spatial resolutions of 7 T. Methods: The effects of MRI resolutions to T-2 and T-2* trabecular bone were numerically evaluated by Monte Carlo simulations. T-2, T-2* and trabecular structural indices from multislice multi-echo and UTE acquisitions were measured in defatted human distal femoral condyles on a 7 T scanner. Reference structural indices were extracted from high-resolution microcomputed tomography images. For bovine knee trabecular samples with intact bone marrow, T-2 and T-2* were measured by degrading spatial resolutions on a 7 T system. Results: In the defatted trabecular experiment, both T-2 and T-2* values showed strong (vertical bar r vertical bar> 0.80) correlations with trabecular spacing and number, at a high spatial resolution of 125 mu m(3). The correlations for MR image-segmentation-olutions of 250 and 500 mu m(3). The correlations for T-2* rapidly dropped (vertical bar r vertical bar< 0.50) at a spatial resolution of 500 mu m(3), whereas those for T-2* remained consistently high (vertical bar r vertical bar> 0.85). In the bovine trabecular experiments with intact marrow, low- resolution (approximately 1 mm(3), 2 minutes) T-2 values did not shorten (vertical bar r vertical bar> 0.95 with respect to approximately 0.4mm(3), 11 minutes) and maintained consistent correlations (vertical bar r vertical bar > 0.70) with respect to trabecular spacing (turbo spin echo, 22.5 minutes). Conclusion: T-2 measurements of trabeculae at 7 T are robust with degrading spatial resolution and may be preferable in assessing trabecular spacing index with reduced scan time, when high-resolution 3D micro-MRI is difficult to obtain

Design of a slider-crank leg mechanism for mobile hopping robotic platforms

Legged locomotion has been widely researched due to its effectiveness in overcoming uneven terrains. Due to previous efforts there has been much progress in achieving dynamic gait stability and as the next step, mimicking the high speed and efficiency observed in animals has become a research interest. The main barrier in developing such a robotic platform is the limitation in the power efficiency of the actuator: the use of pneumatic actuators produce sufficient power but are heavy and big; electronic motors can be compact but are disadvantageous in producing sudden impact from stall which is required for high speed legged locomotion. As a new attempt in this paper we suggest a new leg design for a mobile robot which uses the slider-crank mechanism to convert the continuous motor rotation into piston motion which is used to impact the ground. We believe this new mechanism will have advantage over conventional leg mechanism designs using electronic motors since it uses the continuous motion of the motor instead of sudden rotation movements from stall state which is not ideal to draw out maximum working condition from an electronic motor. In order to control impact timing from the periodic motion of the piston a mechanical passive clutch trigger mechanism was developed. Dynamic analysis was performed to determine the optimal position for the mechanical switch position of the clutch trigger mechanism, and the results were verified through simulation and experiment. Development of a legged locomotion with two degrees of freedom, slider-crank mechanism for impact and additional actuation for swing motion, is proposed for future work

Simulation of microvascular signal changes used on a gadolinium-chelated contrast agent at 3 T MRI in the presence of amyloid-beta plaques

It is important to understand microvascular alterations in the brain of Alzheimer disease (AD) patients which usually has amyloid-beta plaques in an imaging voxel, causing a phase dispersion in an MRI signal. The objective of this study was to simulate the changes of transverse relaxation rates and microvascular indexes with and without the presence of amyloid-beta plaques in an imaging voxel with using a clinically available contrast agent. The Monte Carlo simulations with the finite perturber method were used to calculate microvascular indices of mean vessel diameter (mVD), vessel size index (VSI), mean vessel density (Q), blood volume fraction (BVf), and microvessel-weighted imaging (MvWI) with and without the presence of amyloid-beta plaques in an imaging voxel. The simulation was performed with the conditions of three different magnetic field strengths (1.5 T, 3 T and 7 T), several different echo times for gradient-echo (15, 40, and 60 ms) and spin-echo (20, 80, and 100 ms) images, and two different contrast agents (gadolinium (Gd)-chelated and superparamagnetic iron oxide nanoparticles (SPION)-based contrast agents). The changes of relaxation rates and microvascular indexes were evaluated with increasing the microvascular vessel sizes and with increasing the amyloid plaque loads. In the microvascular structures without amyloid plaques, Delta R2* and Delta R2 increased as the B-0 field became stronger, the susceptibility difference of the contrast agent became larger, and the echo time was increased. Both mVD and VSI increased with increasing microvessel sizes, but Q decreased with increasing microvessel sizes. In the microvascular structures with amyloid plaques, Delta R2* and Delta R2 were not varied with increasing the vessel radius, but higher in the 3.81% concentration of amyloid plaque than 1.83% of that. BVf and MvWI were increased with increasing the plaque load. The BVf and MvWI indices were sensitive to evaluate the integrity of the microvascular in the AD brain since those values were increased with increasing the plaque load. Therefore, it is worthwhile to evaluate microvascular structure changes in the AD human brain using 3 T MRI with a Gd contrast agent

Exploring chemical space for lead identification by propagating on chemical similarity network

Motivation: Lead identification is a fundamental step to prioritize candidate compounds for downstream drug discovery process. Machine learning (ML) and deep learning (DL) approaches are widely used to identify lead compounds using both chemical property and experimental information. However, ML or DL methods rarely consider compound similarity information directly since ML and DL models use abstract representation of molecules for model construction. Alternatively, data mining approaches are also used to explore chemical space with drug candidates by screening undesirable compounds. A major challenge for data mining approaches is to develop efficient data mining methods that search large chemical space for desirable lead compounds with low false positive rate. Results: In this work, we developed a network propagation (NP) based data mining method for lead identification that performs search on an ensemble of chemical similarity networks. We compiled 14 fingerprint-based similarity networks. Given a target protein of interest, we use a deep learning-based drug target interaction model to narrow down compound candidates and then we use network propagation to prioritize drug candidates that are highly correlated with drug activity score such as IC50. In an extensive experiment with BindingDB, we showed that our approach successfully discovered intentionally unlabeled compounds for given targets. To further demonstrate the prediction power of our approach, we identified 24 candidate leads for CLK1. Two out of five synthesizable candidates were experimentally validated in binding assays. In conclusion, our framework can be very useful for lead identification from very large compound databases such as ZINC

Paramagnetic Carbon Nanosheets with Random Hole???defects and Oxygenated Functional Groups

Ordered graphitic carbon nanosheets (GCNs) were, for the first time, synthesized by the direct condensation of multifunctional phenylacetyl building blocks (monomers) in the presence of phosphorous pentoxide. The GCNs had highly ordered structures with random hole???defects and oxygenated functional groups, showing paramagnetism. The results of combined structural and magnetic analyses indicate that the hole???defects and functional groups are associated with the appearance and stabilization of unpaired spins. DFT calculations further suggest that the emergence of stabilized spin moments near the edge???groups necessitates the presence of functionalized carbon atoms around the hole???defects. That is, both hole???defects and oxygenated functional groups are essential ingredients for the generation and stabilization of spins in GCNs

Facile Preparation of Zwitterion-Stabilized Superparamagnetic Iron Oxide Nanoparticles (ZSPIONs) as an MR Contrast Agent for in Vivo Applications

We describe a simple method for synthesizing superparamagnetic nanoparticles (SPIONs) as small, stable contrast agents for magnetic resonance imaging (MRI) based on sulfobetaine zwitterionic ligands. SPIONs synthesized by thermal decomposition were coated with zwitterions to impart water dispersibility and high in vivo stability through the nanoemulsion method. Zwitterion surfactant coating layers are formed easily on oleic acid-stabilized SPIONs via hydrophobic and van der Waals interactions. Our zwitterion-coated SPIONs (ZSPIONs) had ultrathin (∼5 nm) coating layers with mean sizes of 12.0 ± 2.5 nm, as measured by dynamic light scattering (DLS). Upon incubation in 1 M NaCl and 10% FBS, the ZSPIONs showed high colloidal stabilities without precipitating, as monitored by DLS. The T2 relaxivity coefficient of the ZSPIONs, obtained by measuring the relaxation rate on the basis of the iron concentration, was 261 mM^–1s^–1. This value was much higher than that of the commercial T2 contrast agent because of the ultrathin coating layer. Furthermore, we confirmed that ZSPIONs can be used as MR contrast agents for in vivo applications such as tumor imaging and lymph node mapping

Mapping of Microvascular Architecture in the Brain of an Alzheimer???s Disease Mouse Model using MR

Increasing evidence suggests that alterations in cerebral microvasculature play a critical role in the pathogenesis of Alzheimer's disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture of AD transgenic (Tg) mice and compare it with that of non-Tg mice using brain microvascular indices obtained by MRI. Seven non-Tg mice and 10 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after the injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculating Delta R2* and Delta R2, the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density, mean vessel-weighted image (MvWI) and blood volume fraction (BVf) were mapped. Voxel-based analyses and region of interest (ROI)-based analyses were performed to compare the indices of the non-Tg and Tg groups. Voxel comparisons showed that BVf, mVD, VSI and MvWI were greater in the Tg group than in the non-Tg group. Additionally, the ROI-based analysis showed that Delta R2*, BVf, mVD, MvWI and VSI increased in several brain regions of the Tg group compared with those in the non-Tg group. VSI and mVD increased in Tg mice; these findings indicated microvascular disruption in the brain that could be related to damage to the neurovascular unit in AD caused by cerebral amyloid angiopathy