We present a review outlining the basic mechanism, background, recent technical developments, and clinical applications of aqueous dielectric padding in the field of MRI. Originally meant to be a ...temporary solution, it has gained traction as an effective method for correcting B1+ inhomogeneities due to the unique properties of the calcium titanate and barium titanate perovskites used. Aqueous dielectric pads have used a variety of high‐permittivity materials over the years to improve the quality of MRI acquisitions at 1.5 and 3 T and more recently for 7 T neuroimaging applications. The technical development and assessment of these pads have been advanced by an increased use of mathematical modeling and electromagnetic simulations. These tools have allowed for a more complete understanding of the physical interactions between dielectric pads and the RF coil, making testing and safety assessments more accurate. The ease of use and effectiveness that dielectric pads offer have allowed them to become more commonplace in tackling imaging challenges in more clinically focused environments. More recently, they have seen usage not only in anatomical imaging methods but also in specialized metabolic imaging sequences such as GluCEST and NOEMTR. New colossally high‐permittivity materials have been proposed; however, practical utilization has been a continued challenge due to unfavorable frequency dependences as well as safety limitations. A new class of metasurfaces has been under development to address the shortcomings of conventional dielectric padding while also providing increased performance in enhancing MRI images.
In MRI, B1+ field inhomogeneities can result in signal loss, leading to image degradation, especially in ultrahigh‐field imaging applications. For several years dielectric pads have been a novel solution that aid in correcting these artifacts and improve acquired MR data. In this review, we describe recent technical developments and clinical applications of aqueous dielectric padding in the field of MRI.
...the American Taxpayer Relief Act of 2012 (12) gave providers the option of satisfying the requirements of the Physician Quality Reporting System (PQRS) (13) by participating in qualifying ...registries.\n Physio-Control Inc., ZOLL Inc.), 2012-2015; PIlow * Hypothermia Duration After Resuscitation Trial (HART) Pilot Study (Submitted to NHLBI, CR Bard Medical Division Inc., Cincinnati Sub-Zero Inc., EMCOOLS AG, Gaymar/Stryker Inc. ZOLL Circulation Inc.; 2013-2015low * Mild hypothermia for resuscitated out-of-hospital cardiac arrest patients (R01-HL089554-01), 2007-2013; Co-I Randomized Trial of Hemofiltration After Resuscitation from Cardiac Arrest (NHLBI R21 HL093641-01A1), 2009-2011; PI Resuscitation Outcomes Consortium (National Institutes of Health U01 HL077863-05), 2004-2010; Co-PIdagger Sotera Wireless, San Diego, California Velocity Pilot Study of Ultrafast Hypothermia in Patients with ST-elevation Myocardial Infarction (Velomedix Inc.), 2012-2014; PI (waived personal compensation) Washington Study of Ultrasound in Resuscitation (Philips Healthcare Inc.), 2013-2014; PIlow * Medic One Foundationlow * Novel method of tracking location of monitor/defibrillators in time and spacelow * None Randal J. Thomas Content AHA GWTG Steering Committee None None None None None None Martha Radford Content NCDR Management Board None None None None None None Debra Ness Content: National Partnership for Women and Families None None None None None None Frederic Resnic Content: NCDR Science and Quality Oversight Committee St. Jude Medical None None None FDAdagger National Institutes of Healthdagger None * This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant.
Purpose
Nuclear Overhauser effect (NOE) is based on dipolar cross‐relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on ...determining the reproducibility of NOE magnetization transfer ratio (NOEMTR) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T).
Methods
We optimized the B1+$$ {\mathrm{B}}_1^{+} $$ amplitude and length of the saturation pulse by acquiring NOE images with different B1+$$ {\mathrm{B}}_1^{+} $$ values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and B1+$$ {\mathrm{B}}_1^{+} $$ inhomogeneities. To isolate the individual contributions from z‐spectra, we have fit the NOE z‐spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast.
Results
We found that a saturation amplitude of 0.72 μT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were ∼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%–4.2%, and rNOE range was 2.9%–10.5%.
Conclusion
This work has demonstrated an excellent reproducibility of both inter‐ and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.
VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies ...provide support for the idea that VX-787 occupies the 7-methyl GTP (m(7)GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection.
With nicotine dependence being a significant healthcare issue worldwide there is a growing interest in developing novel therapies and diagnostic aids to assist in treating nicotine addiction. ...Glutamate (Glu) plays an important role in cognitive function regulation in a wide range of conditions including traumatic brain injury, aging, and addiction. Chemical exchange saturation transfer (CEST) imaging via ultra-high field MRI can image the exchange of certain saturated labile protons with the surrounding bulk water pool, making the technique a novel tool to investigate glutamate in the context of addiction. The aim of this work was to apply glutamate weighted CEST (GluCEST) imaging to study the dorsal anterior cingulate cortex (dACC) in a small population of smokers and non-smokers to determine its effectiveness as a biomarker of nicotine use.
2D GluCEST images were acquired on 20 healthy participants: 10 smokers (ages 29-50) and 10 non-smokers (ages 25-69), using a 7T MRI system. T1-weighted images were used to segment the GluCEST images into white and gray matter tissue and further into seven gray matter regions. Wilcoxon rank-sum tests were performed, comparing mean GluCEST contrast between smokers and non-smokers across brain regions.
GluCEST levels were similar between smokers and non-smokers; however, there was a moderate negative age dependence (R2 = 0.531) in smokers within the cingulate gyrus.
Feasibility of GluCEST imaging was demonstrated for in vivo investigation of smokers and non-smokers to assess glutamate contrast differences as a potential biomarker with a moderate negative age correlation in the cingulate gyrus suggesting reward network involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the ...cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay ( Wagaman P. C. ; Leong M. A. ; Simmen K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105−114 ) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.
ABSTRACT The Murchison Widefield Array (MWA) has collected hundreds of hours of Epoch of Reionization (EoR) data and now faces the challenge of overcoming foreground and systematic contamination to ...reduce the data to a cosmological measurement. We introduce several novel analysis techniques, such as cable reflection calibration, hyper-resolution gridding kernels, diffuse foreground model subtraction, and quality control methods. Each change to the analysis pipeline is tested against a two-dimensional power spectrum figure of merit to demonstrate improvement. We incorporate the new techniques into a deep integration of 32 hours of MWA data. This data set is used to place a systematic-limited upper limit on the cosmological power spectrum of mK2 at k = 0.27 h Mpc−1 and z = 7.1, consistent with other published limits, and a modest improvement (factor of 1.4) over previous MWA results. From this deep analysis, we have identified a list of improvements to be made to our EoR data analysis strategies. These improvements will be implemented in the future and detailed in upcoming publications.
A
bstract
We present measurements of the branching fractions for the decays
B
→
Kμ
+
μ
−
and
B
→
Ke
+
e
−
, and their ratio (
R
K
), using a data sample of 711 fb
−
1
that contains 772 × 10
6
B
B
¯
...events. The data were collected at the ϒ(4
S
) resonance with the Belle detector at the KEKB asymmetric-energy
e
+
e
−
collider. The ratio
R
K
is measured in five bins of dilepton invariant-mass-squared (
q
2
):
q
2
∈ (0
.
1
,
4
.
0)
,
(4
.
00
,
8
.
12)
,
(1
.
0
,
6
.
0), (10
.
2
,
12
.
8) and (
>
14
.
18) GeV
2
/c
4
, along with the whole
q
2
region. The
R
K
value for
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
is
1.03
−
0.24
+
0.28
± 0
.
01. The first and second uncertainties listed are statistical and systematic, respectively. All results for
R
K
are consistent with Standard Model predictions. We also measure
CP
-averaged isospin asymmetries in the same
q
2
bins. The results are consistent with a null asymmetry, with the largest difference of 2.6 standard deviations occurring for the
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
bin in the mode with muon final states. The measured differential branching fractions,
d
ℬ
/dq
2
, are consistent with theoretical predictions for charged
B
decays, while the corresponding values are below the expectations for neutral
B
decays. We have also searched for lepton-flavor-violating
B
→
Kμ
±
e
∓
decays and set 90% confidence-level upper limits on the branching fraction in the range of 10
−
8
for
B
+
→
K
+
μ
±
e
∓
, and
B
0
→
K
0
μ
±
e
∓
modes.
ABSTRACT Detection of the cosmological neutral hydrogen signal from the Epoch of Reionization (EoR) and estimation of its basic physical parameters are principal scientific aims of many current ...low-frequency radio telescopes. Here we describe the Cosmological H i Power Spectrum Estimator (CHIPS), an algorithm developed and implemented with data from the Murchison Widefield Array, to compute the two-dimensional and spherically-averaged power spectrum of brightness temperature fluctuations. The principal motivations for CHIPS are the application of realistic instrumental and foreground models to form the optimal estimator, thereby maximizing the likelihood of unbiased signal estimation, and allowing a full covariant understanding of the outputs. CHIPS employs an inverse-covariance weighting of the data through the maximum likelihood estimator, thereby allowing use of the full parameter space for signal estimation ("foreground suppression"). We describe the motivation for the algorithm, implementation, application to real and simulated data, and early outputs. Upon application to a set of 3 hr of data, we set a 2 upper limit on the EoR dimensionless power at Mpc−1 of mK2 in the redshift range z = 6.2-6.6, consistent with previous estimates.
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