120 research outputs found
Emerging Techniques in Breast MRI
No full textAs indicated throughout this chapter, there is a constant effort to move to more sensitive, specific, and quantitative methods for characterizing breast tissue via magnetic resonance imaging (MRI). In the present chapter, we focus on six emerging techniques that seek to quantitatively interrogate the physiological and biochemical properties of the breast. At the physiological scale, we present an overview of ultrafast dynamic contrast-enhanced MRI and magnetic resonance elastography which provide remarkable insights into the vascular and mechanical properties of tissue, respectively. Moving to the biochemical scale, magnetization transfer, chemical exchange saturation transfer, and spectroscopy (both “conventional” and hyperpolarized) methods all provide unique, noninvasive, insights into tumor metabolism. Given the breadth and depth of information that can be obtained in a single MRI session, methods of data synthesis and interpretation must also be developed. Thus, we conclude the chapter with an introduction to two very different, though complementary, methods of data analysis: (1) radiomics and habitat imaging, and (2) mechanism-based mathematical modeling
Constructing the Reactions of the Socio-political Space to the Process of Making the Most Important State Decisions in the Context of the Public Governance Digital Transformation in Russia
No full textCan antimicrobial peptides scavenge around a cell in less than a second?
No full textAbstractAntimicrobial peptides, which play multiple host-defense roles, have garnered increased experimental focus because of their potential applications in the pharmaceutical and food production industries. While their mechanisms of action are richly debated, models that have been advanced share modes of peptide–lipid interactions that require peptide dynamics. Before the highly cooperative and specific events suggested in these models take place, peptides must undergo an important process of migration along the membrane surface and delivery from their site of binding on the membrane to the actual site of functional performance. This phenomenon, which contributes significantly to antimicrobial function, is poorly understood, largely due to a lack of experimental and computational tools needed to assess it. Here, we use 15N solid-state nuclear magnetic resonance to obtain molecular level data on the motions of piscidin's amphipathic helices on the surface of phospholipid bilayers. The studies presented here may help contribute to a better understanding of the speed at which the events that lead to antimicrobial response take place. Specifically, from the perspective of the kinetics of cellular processes, we discuss the possibility that piscidins and perhaps many other amphipathic antimicrobial peptides active on the membrane surface may represent a class of fast scavengers rather than static polypeptides attached to the water–lipid interface
Political and Legal Conceptions of Public Policy as Determinants of Constructing Interaction Between Government and Society in the Conditions of Digital Transformation of Governance in Russia
No full textEfficient 15N hyperpolarization of [15N3]metronidazole antibiotic via spin-relayed pulsed SABRE-SHEATH
No full textSignal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) is an NMR hyperpolarization technique that relies of the simultaneous exchange of parahydrogen and a to-be-hyperpolarized molecule on the metal center of a polarization-transfer catalyst in a microtesla magnetic field. Until recently, this method has been understood to perform hyperpolarization by establishing level anti-crossings between the nuclear spins of the parahydrogen derived hydrides (acting as a source of hyperpolarization) and those of the substrate. Recently, the application of highly non-intuitive pulse sequences (comprising pulses of microtesla DC fields) was predicted to hyperpolarize nuclear spins more efficiently than the canonical (static-field) SABRE-SHEATH approach. Here we show that by employing a basic “on-off” pulse sequence of rectangular microtesla pulses, it is possible to improve the hyperpolarization efficiency for SABRE-SHEATH of [15N3]metronidazole, an FDA-approved antibiotic (in non-enriched and non-hyperpolarized form) and potential hypoxia sensing molecule. Specifically, we demonstrate that 15N polarization of 18.5 % can be obtained in 80 s of parahydrogen bubbling parahydrogen through a solution containing 20 mM [15N3]metronidazole. In practice, (1.32 ± 0.14)-fold improvements in P15N was obtained with the pulsed method described here compared to static field technique variant. These results show that pulsed SABRE-SHEATH was successfully applied to 15N-labeled biologically relevant molecule. Moreover, we also demonstrate that although the pulsed SABRE-SHEATH sequence was designed for polarization transfer from parahydrogen derived hydrides to the metronidazole’s 15N catalyst-binding site, all three 15N sites of [15N3]metronidazole attained the hyperpolarized state. This spin-relayed polarization transfer becomes possible due to the 15N relay network established by their spin-spin J-couplings. The feasibility of the spin-relayed polarization transfer is demonstrated here for the first time for pulsed SABRE-SHEATH (as opposed to the static-field SABRE-SHEATH reported previously) and it paves the way to broad applicability of the technique
Parahydrogen Induced Polarization of 1-<sup>13</sup>C‑Phospholactate‑<i>d</i><sub>2</sub> for Biomedical Imaging with >30,000,000-fold NMR Signal Enhancement in Water
No full textThe synthetic protocol for preparation
of 1-<sup>13</sup>C-phosphoenolpyruvate-<i>d</i><sub>2</sub>, precursor for parahydrogen-induced polarization
(PHIP) of 1-<sup>13</sup>C-phospholactate-<i>d</i><sub>2</sub>, is reported. <sup>13</sup>C nuclear spin polarization of 1-<sup>13</sup>C-phospholactate-<i>d</i><sub>2</sub> was increased
by >30,000,000-fold (5.75 mT) in water. The reported <sup>13</sup>C polarization level approaching unity (>15.6%), long lifetime
of <sup>13</sup>C hyperpolarized 1-<sup>13</sup>C-phospholactate-<i>d</i><sub>2</sub> (58 ± 4 s versus 36 ± 2 s for nondeuterated
form at 47.5 mT), and large production quantities (52 μmoles
in 3 mL) in aqueous medium make this compound useful as a potential
contrast agent for the molecular imaging of metabolism and other applications
Limits of Spatial Resolution of Phase Encoding Dimensions in MRI of Metals
No full textLimits of Spatial Resolution of Phase Encoding Dimensions
in MRI of Metal
Parahydrogen-Induced Polarization with a Rh-Based Monodentate Ligand in Water
No full textReported here is a water-soluble Rh(I)-based catalyst
for performing
parahydrogen-induced polarization (PHIP). The [Rh(I)(norbornadiene)(THP)<sub>2</sub>]<sup>+</sup>[BF<sub>4</sub>]<sup>−</sup> catalyst
utilizes the monodentate phosphine ligand tris(hydroxymethyl)phosphine
(THP). The monodentate PHIP catalyst is less susceptible to oxygenation
by air and the THP ligand is significantly less expensive than bidentate
water-soluble PHIP ligands. In situ PHIP detection with this monodentate
Rh(I)-based catalyst in water yielded 12% <sup>13</sup>C polarization
for the parahydrogen addition product, 2-hydroxyethyl 1-<sup>13</sup>C-propionate-d<sub>2,3,3</sub> (HEP), with a <sup>13</sup>C <i>T</i><sub>1</sub> relaxation of 108 s at 0.0475 T. PHIP polarization
yields were high, reflecting efficient hydrogenation even under conditions
of high content of the oxidized phosphine form of the THP ligand
Spin–Lattice Relaxation of Hyperpolarized Metronidazole in Signal Amplification by Reversible Exchange in Micro-Tesla Fields
No full textSimultaneous
reversible chemical exchange of para-hydrogen and
to-be-hyperpolarized substrate on metal centers enables
spontaneous transfer of spin order from para-hydrogen
singlet to nuclear spins of the substrate. When performed at a sub-micro-tesla
magnetic field, this technique of NMR signal amplification by reversible
exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH).
SABRE-SHEATH has been shown to hyperpolarize nitrogen-15 sites of
a wide range of biologically interesting molecules to a high polarization
level (P > 20%) in 1 min. Here, we report on a
systematic
study of 1H, 13C, and 15N spin–lattice
relaxation (T1) of metronidazole-13C2-15N2 in the SABRE-SHEATH
hyperpolarization process. In the micro-tesla range, we find that
all 1H, 13C, and 15N spins studied
share approximately the same T1 values
(ca. 4 s under the conditions studied) because of mixing of their
Zeeman levels, which is consistent with the model of relayed SABRE-SHEATH
effect. These T1 values are significantly
lower than those at a higher magnetic field (i.e. the Earth’s
magnetic field and above), which exceed 3 min in some cases. Moreover,
these relatively short T1 values observed
below 1 μT limit the polarization build-up process of SABRE-SHEATH,
thereby limiting the maximum attainable 15N polarization.
The relatively short T1 values observed
below 1 μT are primarily caused by intermolecular interactions
with quadrupolar iridium centers or dihydride protons of the employed
polarization transfer catalyst, whereas intramolecular spin–spin
interactions with 14N quadrupolar centers have a significantly
smaller contribution. The presented experimental results and their
analysis will be beneficial for more rational design of SABRE-SHEATH
(i) polarization transfer catalysts and (ii) hyperpolarized molecular
probes in the context of biomedical imaging and other applications
Inside Cover: Toward Hyperpolarized <sup>19</sup> F Molecular Imaging via Reversible Exchange with Parahydrogen (ChemPhysChem 15/2017)
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