Phase-Contrast MRI and CFD Modeling of Apparent 3He Gas Flow in Rat Pulmonary Airways

PubMed Central

Minard, Kevin R.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Carson, James P.; Corley, Richard A.

2012-01-01

Phase-contrast (PC) magnetic resonance imaging (MRI) with hyperpolarized 3He is potentially useful for developing and testing patient-specific models of pulmonary airflow. One challenge, however, is that PC-MRI provides apparent values of local 3He velocity that not only depend on actual airflow but also on gas diffusion. This not only blurs laminar flow patterns in narrow airways but also introduces anomalous airflow structure that reflects gas-wall interactions. Here, both effects are predicted in a live rat using computational fluid dynamics (CFD), and for the first time, simulated patterns of apparent 3He gas velocity are compared with in-vivo PC-MRI. Results show 1) that correlations (R2) between measured and simulated airflow patterns increase from 0.23 to 0.79 simply by accounting for apparent 3He transport, and 2) that remaining differences are mainly due to uncertain airway segmentation and partial volume effects stemming from relatively coarse MRI resolution. Higher-fidelity testing of pulmonary airflow predictions should therefore be possible with future imaging improvements. PMID:22771528

Phase-contrast MRI and CFD modeling of apparent 3He gas flow in rat pulmonary airways

NASA Astrophysics Data System (ADS)

Minard, Kevin R.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Carson, James P.; Corley, Richard A.

2012-08-01

Phase-contrast (PC) magnetic resonance imaging (MRI) with hyperpolarized 3He is potentially useful for developing and testing patient-specific models of pulmonary airflow. One challenge, however, is that PC-MRI provides apparent values of local 3He velocity that not only depend on actual airflow but also on gas diffusion. This not only blurs laminar flow patterns in narrow airways but also introduces anomalous airflow structure that reflects gas-wall interactions. Here, both effects are predicted in a live rat using computational fluid dynamics (CFD), and for the first time, simulated patterns of apparent 3He gas velocity are compared with in vivo PC-MRI. Results show (1) that correlations (R2) between measured and simulated airflow patterns increase from 0.23 to 0.79 simply by accounting for apparent 3He transport, and (2) that remaining differences are mainly due to uncertain airway segmentation and partial volume effects stemming from relatively coarse MRI resolution. Higher-fidelity testing of pulmonary airflow predictions should therefore be possible with future imaging improvements.

Physical interactions of hyperpolarized gas in the lung

NASA Astrophysics Data System (ADS)

Chen, Xiu-Hao Josette

1999-09-01

This thesis addresses key interactions of hyperpolarized (HP) gas within the biological environment of the lung using magnetic resonance imaging (MRI). The first excised lung image was obtained in 1994 by Albert et al ., indicating the relative youth of the HP gas MRI field. Thus, there are a multitude of parameters which need to be explored to optimize contrast mechanisms and pulse sequences for in vivo applications. To perform HP gas MRI, both the production of HP gas and development of appropriate MRI pulse sequences were necessary. The apparatus for gas polarization was transferred from Princeton University, then modified and optimized to provide larger quantities and higher polarizations. It was ultimately replaced by a prototype commercial apparatus. Existing MRI pulse sequences were changed to accommodate and exploit the unique situation of non-equilibrium polarized gas. Several physical parameters of the gas relating to structure and function in the lung were investigated. It was found that using a range of excitation powers, acquisition windows, and ventilatory cycle segments yielded dramatically different types of images in the guinea pig. Spatially localized lineshapes of HP 3He showed differentiated peaks (corresponding to frequency shifts) which represent gas in major airways (2 ppm) and alveoli (1-2 ppm). Quantitative maps of the diffusion coefficient (D) showed evidence of free diffusion in the trachea (average of 2.4 cm2/s for 3He and 0.68 cm2/s for 129Xe) and restricted diffusion combined with effects of gas mixtures in the distal pulmonary airspaces (average of 0.16 cm2/s for 3He and 0.021 cm2/s for 129Xe). Experimental measurements were verified with gas mixture and porous media theory for both 3He and 129Xe. The dephasing parameter, T*2 , was mapped showing sensitivity to changes in tidal volume and oxygen level. The T*2 values ranged from 9.2 to 15.9 ms in the intrapulmonary airspaces depending on the breathing paradigm. Experimental results were confirmed with porous media theory. Finally, the technique of D measurement was applied in a disease model. The histograms of D at end expiratory volume and 2 mL tidal volume held breath were shown to exhibit a significant shift in a healthy rat, but not in an elastase-induced (a model for emphysema) rat.

Hyperpolarized xenon-129 production and applications

NASA Astrophysics Data System (ADS)

Ruset, Iulian C.

Hyperpolarized 3He and 129Xe were initially developed and used in the nuclear physics community. Lately they are primarily used in Medical Resonance Imaging (MRI). Although first MRI polarized gas images were acquired using 129Xe, the research community has focused mostly on 3He, due to the well-known polarizing methods and higher polarization numbers achieved. The main purpose of this thesis is to present a novel design of a large-scale SEOP polarizer for producing large quantities of highly polarized 129Xe. High Rb-Xe spin-exchange rates through long-lived van de Waals molecules at low total pressure, implemented in a novel counterflow polarizer design, resulted in xenon polarization as high as 50% for 1.2 liters/hour, with a maximum of 64% for 0.3 l/h. We characterized and improved the polarization process by finding the optimum operating parameters of the polarizer. Two new methods to efficiently use high-power diode lasers are described: a new optical arrangement for a better beam shaping of fiber coupled lasers and the first external-cavity spectrum narrowing of a stack of laser diode arrays. A new accumulation technique for the hyperpolarized xenon was developed and full recovery of polarization after a freeze-thaw cycle was demonstrated for the first time. Two approaches for xenon delivery, frozen and gas states, were developed. Hyperpolarized xenon transportation to Brigham and Women's Hospital was successfully accomplished for collaborative research. First MRI images using hyperpolarized xenon acquired at BWH are presented. Final chapter is focused on describing a low field human MRI scanner using hyperpolarized 3He. We built a human scale imager with open access for orientational studies of the lung functionality. Horizontal and vertical human lung images were acquired as a first stage of this project.

Direct Measurement of Lung Motion Using Hyperpolarized Helium-3 MR Tagging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Jing; Miller, G. Wilson; Altes, Talissa A.

2007-07-01

Purpose: To measure lung motion between end-inhalation and end-exhalation using a hyperpolarized helium-3 (HP {sup 3}He) magnetic resonance (MR) tagging technique. Methods and Materials: Three healthy volunteers underwent MR tagging studies after inhalation of 1 L HP {sup 3}He gas diluted with nitrogen. Multiple-slice two-dimensional and volumetric three-dimensional MR tagged images of the lungs were obtained at end-inhalation and end-exhalation, and displacement vector maps were computed. Results: The grids of tag lines in the HP {sup 3}He MR images were well defined at end-inhalation and remained evident at end-exhalation. Displacement vector maps clearly demonstrated the regional lung motion and deformationmore » that occurred during exhalation. Discontinuity and differences in motion pattern between two adjacent lung lobes were readily resolved. Conclusions: Hyperpolarized helium-3 MR tagging technique can be used for direct in vivo measurement of respiratory lung motion on a regional basis. This technique may lend new insights into the regional pulmonary biomechanics and thus provide valuable information for the deformable registration of lung.« less

MR imaging of apparent 3He gas transport in narrow pipes and rodent airways

NASA Astrophysics Data System (ADS)

Minard, Kevin R.; Jacob, Richard E.; Laicher, Gernot; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

2008-10-01

High sensitivity makes hyperpolarized 3He an attractive signal source for visualizing gas flow with magnetic resonance (MR) imaging. Its rapid Brownian motion, however, can blur observed flow lamina and alter measured diffusion rates when excited nuclei traverse shear-induced velocity gradients during data acquisition. Here, both effects are described analytically, and predicted values for measured transport during laminar flow through a straight, 3.2-mm diameter pipe are validated using two-dimensional (2D) constant-time images of different binary gas mixtures. Results show explicitly how measured transport in narrow conduits is characterized by apparent values that depend on underlying gas dynamics and imaging time. In ventilated rats, this is found to obscure acquired airflow images. Nevertheless, flow splitting at airway branches is still evident and use of 3D vector flow mapping is shown to reveal surprising detail that highlights the correlation between gas dynamics and lung structure.

Rapid in vivo apparent diffusion coefficient mapping of hyperpolarized (13) C metabolites.

PubMed

Koelsch, Bertram L; Reed, Galen D; Keshari, Kayvan R; Chaumeil, Myriam M; Bok, Robert; Ronen, Sabrina M; Vigneron, Daniel B; Kurhanewicz, John; Larson, Peder E Z

2015-09-01

Hyperpolarized (13) C magnetic resonance allows for the study of real-time metabolism in vivo, including significant hyperpolarized (13) C lactate production in many tumors. Other studies have shown that aggressive and highly metastatic tumors rapidly transport lactate out of cells. Thus, the ability to not only measure the production of hyperpolarized (13) C lactate but also understand its compartmentalization using diffusion-weighted MR will provide unique information for improved tumor characterization. We used a bipolar, pulsed-gradient, double spin echo imaging sequence to rapidly generate diffusion-weighted images of hyperpolarized (13) C metabolites. Our methodology included a simultaneously acquired B1 map to improve apparent diffusion coefficient (ADC) accuracy and a diffusion-compensated variable flip angle scheme to improve ADC precision. We validated this sequence and methodology in hyperpolarized (13) C phantoms. Next, we generated ADC maps of several hyperpolarized (13) C metabolites in a normal rat, rat brain tumor, and prostate cancer mouse model using both preclinical and clinical trial-ready hardware. ADC maps of hyperpolarized (13) C metabolites provide information about the localization of these molecules in the tissue microenvironment. The methodology presented here allows for further studies to investigate ADC changes due to disease state that may provide unique information about cancer aggressiveness and metastatic potential. © 2014 Wiley Periodicals, Inc.

Nuclear spin imaging with hyperpolarized nuclei created by brute force method

NASA Astrophysics Data System (ADS)

Tanaka, Masayoshi; Kunimatsu, Takayuki; Fujiwara, Mamoru; Kohri, Hideki; Ohta, Takeshi; Utsuro, Masahiko; Yosoi, Masaru; Ono, Satoshi; Fukuda, Kohji; Takamatsu, Kunihiko; Ueda, Kunihiro; Didelez, Jean-P.; Prossati, Giorgio; de Waard, Arlette

2011-05-01

We have been developing a polarized HD target for particle physics at the SPring-8 under the leadership of the RCNP, Osaka University for the past 5 years. Nuclear polarizaton is created by means of the brute force method which uses a high magnetic field (~17 T) and a low temperature (~ 10 mK). As one of the promising applications of the brute force method to life sciences we started a new project, "NSI" (Nuclear Spin Imaging), where hyperpolarized nuclei are used for the MRI (Magnetic Resonance Imaging). The candidate nuclei with spin ½hslash are 3He, 13C, 15N, 19F, 29Si, and 31P, which are important elements for the composition of the biomolecules. Since the NMR signals from these isotopes are enhanced by orders of magnitudes, the spacial resolution in the imaging would be much more improved compared to the practical MRI used so far. Another advantage of hyperpolarized MRI is that the MRI is basically free from the radiation, while the problems of radiation exposure caused by the X-ray CT or PET (Positron Emission Tomography) cannot be neglected. In fact, the risk of cancer for Japanese due to the radiation exposure through these diagnoses is exceptionally high among the advanced countries. As the first step of the NSI project, we are developing a system to produce hyperpolarized 3He gas for the diagnosis of serious lung diseases, for example, COPD (Chronic Obstructive Pulmonary Disease). The system employs the same 3He/4He dilution refrigerator and superconducting solenoidal coil as those used for the polarized HD target with some modification allowing the 3He Pomeranchuk cooling and the following rapid melting of the polarized solid 3He to avoid the depolarization. In this report, the present and future steps of our project will be outlined with some latest experimental results.

Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

NASA Astrophysics Data System (ADS)

Koelsch, Bertram L.; Sriram, Renuka; Keshari, Kayvan R.; Leon Swisher, Christine; Van Criekinge, Mark; Sukumar, Subramaniam; Vigneron, Daniel B.; Wang, Zhen J.; Larson, Peder E. Z.; Kurhanewicz, John

2016-09-01

This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized 13C magnetic resonance spectroscopy. Using b-values of up to 15,000 s mm-2, a multi-exponential signal response was measured for hyperpolarized [1-13C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized 13C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized 13C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.

Signal-to-noise ratio, T2 , and T2* for hyperpolarized helium-3 MRI of the human lung at three magnetic field strengths.

PubMed

Komlosi, Peter; Altes, Talissa A; Qing, Kun; Mooney, Karen E; Miller, G Wilson; Mata, Jaime F; de Lange, Eduard E; Tobias, William A; Cates, Gordon D; Mugler, John P

2017-10-01

To evaluate T 2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 ( 3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T. Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T 2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose. As expected, T 2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant. Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T 2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Measurement of alveolar oxygen partial pressure in the rat lung using Carr-Purcell-Meiboom-Gill spin-spin relaxation times of hyperpolarized 3He and 129Xe at 74 mT.

PubMed

Kraayvanger, Ryan J; Bidinosti, Christopher P; Dominguez-Viqueira, William; Parra-Robles, Juan; Fox, Matthew; Lam, Wilfred W; Santyr, Giles E

2010-11-01

Regional measurement of alveolar oxygen partial pressure can be obtained from the relaxation rates of hyperpolarized noble gases, (3) He and (129) Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin-spin relaxation rate (R(2) ) of (3) He at low magnetic field strengths (<0.1 T) in vivo. R(2) measurements can be achieved efficiently using the Carr-Purcell-Meiboom-Gill pulse sequence. In this work, alveolar oxygen partial pressure measurements based on Carr-Purcell-Meiboom-Gill R(2) values of hyperpolarized (3) He and (129) Xe in vitro and in vivo in the rat lung at low magnetic field strength (74 mT) are presented. In vitro spin-spin relaxivity constants for (3) He and (129) Xe were determined to be (5.2 ± 0.6) × 10(-6) Pa(-1) sec(-1) and (7.3 ± 0.4) × 10(-6) Pa(-1) s(-1) compared with spin-lattice relaxivity constants of (4.0 ± 0.4) × 10(-6) Pa(-1) s(-1) and (4.3 ± 1.3) × 10(-6) Pa(-1) s(-1), respectively. In vivo experimental measurements of alveolar oxygen partial pressure using (3) He in whole rat lung show good agreement (r(2) = 0.973) with predictions based on lung volumes and ventilation parameters. For (129) Xe, multicomponent relaxation was observed with one component exhibiting an increase in R(2) with decreasing alveolar oxygen partial pressure. Copyright © 2010 Wiley-Liss, Inc.

Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR✩

PubMed Central

Koelsch, Bertram L.; Sriram, Renuka; Keshari, Kayvan R.; Swisher, Christine Leon; Van Criekinge, Mark; Sukumar, Subramaniam; Vigneron, Daniel B.; Wang, Zhen J.; Larson, Peder E.Z.; Kurhanewicz, John

2017-01-01

This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized 13C magnetic resonance spectroscopy. Using b-values of up to 15,000 s mm−2, a multi-exponential signal response was measured for hyperpolarized [1-13C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized 13C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized 13C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers. PMID:27434780

Dynamic MRI of Grid-Tagged Hyperpolarized Helium-3 for the Assessment of Lung Motion During Breathing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Jing; Sheng Ke; Benedict, Stanley H.

2009-09-01

Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. Results: Both temporal and spatial variations of pulmonary mechanics were observed inmore » normal subjects, including shear motion between different lobes of the same lung. Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.« less

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

PubMed Central

Kirby, Miranda; Ouriadov, Alexei; Svenningsen, Sarah; Owrangi, Amir; Wheatley, Andrew; Etemad‐Rezai, Roya; Santyr, Giles E.; McCormack, David G.; Parraga, Grace

2014-01-01

Abstract Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure. PMID:25347853

Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung cancer.

PubMed

Mathew, L; Castillo, R; Castillo, E; Yaremko, B; Rodrigues, G; Etemad-Rezai, R; Guerrero, T; Parraga, G

2012-07-01

Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver direct and regional measurements of lung function even in lung cancer patients in whom global lung function measurements are dominated by tumour burden. The purpose of this study was to directly compare quantitative measurements of gas distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation 1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using a semi-automated segmentation algorithm to generate percent-ventilated volume (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity volume. 4DCT pulmonary function maps were generated using deformable image registration of six expiratory phase images. The correspondence between identical tissue elements at inspiratory and expiratory phases was used to estimate regional gas distribution and PVV was quantified from these images. After accounting for differences in lung volumes between 3 He MRI (1.9±0.5L ipsilateral, 2.3±0.7 contralateral) and 4DCT (1.2±0.3L ipsilateral, 1.3±0.4L contralateral) during image acquisition, there was no statistically significant difference in PVV between 3 He MRI (72±11% ipsilateral, 79±12% contralateral) and 4DCT (74±3% ipsilateral, 75±4% contralateral). Our results indicate quantitative agreement in the regional distribution of inhaled gas in both static and dynamic imaging methods. PVV may be considered as a regional surrogate measurement of lung function or ventilation. © 2012 American Association of Physicists in Medicine.

Optical Pumping Spin Exchange 3He Gas Cells for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Kim, W.; Stepanyan, S. S.; Kim, A.; Jung, Y.; Woo, S.; Yurov, M.; Jang, J.

2009-08-01

We present a device for spin-exchange optical pumping system to produce large quantities of polarized noble gases for Magnetic Resonance Imaging (MRI). A method and design of apparatus for pumping the polarization of noble gases is described. The method and apparatus enable production, storage and usage of hyperpolarized noble gases for different purposes, including Magnetic Resonance Imaging of human and animal subjects. Magnetic imaging agents breathed into lungs can be observed by the radio waves of the MRI scanner and report back physical and functional information about lung's health and desease. The technique known as spin exchange optical pumping is used. Nuclear magnetic resonance is implemented to measure the polarization of hyperpolarized gas. The cells prepared and sealed under high vacuum after handling Alkali metals into the cell and filling with the 3He-N2 mixture. The cells could be refilled. The 3He reaches around 50% polarization in 5-15 hours.

Effects of superparamagnetic iron oxide nanoparticles on the longitudinal and transverse relaxation of hyperpolarized xenon gas

NASA Astrophysics Data System (ADS)

Burant, Alex; Antonacci, Michael; McCallister, Drew; Zhang, Le; Branca, Rosa Tamara

2018-06-01

SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) are often used in magnetic resonance imaging experiments to enhance Magnetic Resonance (MR) sensitivity and specificity. While the effect of SPIONs on the longitudinal and transverse relaxation time of 1H spins has been well characterized, their effect on highly diffusive spins, like those of hyperpolarized gases, has not. For spins diffusing in linear magnetic field gradients, the behavior of the magnetization is characterized by the relative size of three length scales: the diffusion length, the structural length, and the dephasing length. However, for spins diffusing in non-linear gradients, such as those generated by iron oxide nanoparticles, that is no longer the case, particularly if the diffusing spins experience the non-linearity of the gradient. To this end, 3D Monte Carlo simulations are used to simulate the signal decay and the resulting image contrast of hyperpolarized xenon gas near SPIONs. These simulations reveal that signal loss near SPIONs is dominated by transverse relaxation, with little contribution from T1 relaxation, while simulated image contrast and experiments show that diffusion provides no appreciable sensitivity enhancement to SPIONs.

Development of spatial-temporal ventilation heterogeneity and probability analysis tools for hyperpolarized 3He magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Choy, S.; Ahmed, H.; Wheatley, A.; McCormack, D. G.; Parraga, G.

2010-03-01

We developed image analysis tools to evaluate spatial and temporal 3He magnetic resonance imaging (MRI) ventilation in asthma and cystic fibrosis. We also developed temporal ventilation probability maps to provide a way to describe and quantify ventilation heterogeneity over time, as a way to test respiratory exacerbations or treatment predictions and to provide a discrete probability measurement of 3He ventilation defect persistence.

Perspectives of hyperpolarized noble gas MRI beyond 3He

PubMed Central

Lilburn, David M.L.; Pavlovskaya, Galina E.; Meersmann, Thomas

2013-01-01

Nuclear Magnetic Resonance (NMR) studies with hyperpolarized (hp) noble gases are at an exciting interface between physics, chemistry, materials science and biomedical sciences. This paper intends to provide a brief overview and outlook of magnetic resonance imaging (MRI) with hp noble gases other than hp 3He. A particular focus are the many intriguing experiments with 129Xe, some of which have already matured to useful MRI protocols, while others display high potential for future MRI applications. Quite naturally for MRI applications the major usage so far has been for biomedical research but perspectives for engineering and materials science studies are also provided. In addition, the prospects for surface sensitive contrast with hp 83Kr MRI is discussed. PMID:23290627

Two and three-dimensional segmentation of hyperpolarized 3He magnetic resonance imaging of pulmonary gas distribution

NASA Astrophysics Data System (ADS)

Heydarian, Mohammadreza; Kirby, Miranda; Wheatley, Andrew; Fenster, Aaron; Parraga, Grace

2012-03-01

A semi-automated method for generating hyperpolarized helium-3 (3He) measurements of individual slice (2D) or whole lung (3D) gas distribution was developed. 3He MRI functional images were segmented using two-dimensional (2D) and three-dimensional (3D) hierarchical K-means clustering of the 3He MRI signal and in addition a seeded region-growing algorithm was employed for segmentation of the 1H MRI thoracic cavity volume. 3He MRI pulmonary function measurements were generated following two-dimensional landmark-based non-rigid registration of the 3He and 1H pulmonary images. We applied this method to MRI of healthy subjects and subjects with chronic obstructive lung disease (COPD). The results of hierarchical K-means 2D and 3D segmentation were compared to an expert observer's manual segmentation results using linear regression, Pearson correlations and the Dice similarity coefficient. 2D hierarchical K-means segmentation of ventilation volume (VV) and ventilation defect volume (VDV) was strongly and significantly correlated with manual measurements (VV: r=0.98, p<.0001 VDV: r=0.97, p<.0001) and mean Dice coefficients were greater than 92% for all subjects. 3D hierarchical K-means segmentation of VV and VDV was also strongly and significantly correlated with manual measurements (VV: r=0.98, p<.0001 VDV: r=0.64, p<.0001) and the mean Dice coefficients were greater than 91% for all subjects. Both 2D and 3D semi-automated segmentation of 3He MRI gas distribution provides a way to generate novel pulmonary function measurements.

Hyperpolarized gas diffusion MRI for the study of atelectasis and acute respiratory distress syndrome.

PubMed

Cereda, Maurizio; Xin, Yi; Kadlecek, Stephen; Hamedani, Hooman; Rajaei, Jennia; Clapp, Justin; Rizi, Rahim R

2014-12-01

Considerable uncertainty remains about the best ventilator strategies for the mitigation of atelectasis and associated airspace stretch in patients with acute respiratory distress syndrome (ARDS). In addition to several immediate physiological effects, atelectasis increases the risk of ventilator-associated lung injury, which has been shown to significantly worsen ARDS outcomes. A number of lung imaging techniques have made substantial headway in clarifying the mechanisms of atelectasis. This paper reviews the contributions of computed tomography, positron emission tomography, and conventional MRI to understanding this phenomenon. In doing so, it also reveals several important shortcomings inherent to each of these approaches. Once these shortcomings have been made apparent, we describe how hyperpolarized (HP) gas MRI--a technique that is uniquely able to assess responses to mechanical ventilation and lung injury in peripheral airspaces--is poised to fill several of these knowledge gaps. The HP-MRI-derived apparent diffusion coefficient (ADC) quantifies the restriction of (3) He diffusion by peripheral airspaces, thereby obtaining pulmonary structural information at an extremely small scale. Lastly, this paper reports the results of a series of experiments that measured ADC in mechanically ventilated rats in order to investigate (i) the effect of atelectasis on ventilated airspaces, (ii) the relationship between positive end-expiratory pressure (PEEP), hysteresis, and the dimensions of peripheral airspaces, and (iii) the ability of PEEP and surfactant to reduce airspace dimensions after lung injury. An increase in ADC was found to be a marker of atelectasis-induced overdistension. With recruitment, higher airway pressures were shown to reduce stretch rather than worsen it. Moving forward, HP MRI has significant potential to shed further light on the atelectatic processes that occur during mechanical ventilation. Copyright © 2014 John Wiley & Sons, Ltd.

Hyperpolarized Gas Diffusion MRI for the Study of Atelectasis and Acute Respiratory Distress Syndrome

PubMed Central

Cereda, Maurizio; Xin, Yi; Kadlecek, Stephen; Hamedani, Hooman; Rajaei, Jennia; Clapp, Justin; Rizi, Rahim R.

2014-01-01

Considerable uncertainty remains about the best ventilator strategies for the mitigation of atelectasis and associated airspace stretch in patients with acute respiratory distress syndrome (ARDS). In addition to several immediate physiological effects, atelectasis increases the risk of ventilator-associated lung injury (VALI), which has been shown to significantly worsen ARDS outcomes. A number of lung imaging techniques have made substantial headway in clarifying the mechanisms of atelectasis. This paper reviews the contributions of CT, PET, and conventional MRI to understanding this phenomenon. In doing so, it also reveals several important shortcomings inherent to each of these approaches. Once these shortcomings have been made apparent, we describe how hyperpolarized gas magnetic resonance imaging (HP MRI)—a technique that is uniquely able to assess responses to mechanical ventilation and lung injury in peripheral airspaces—is poised to fill several of these knowledge gaps. The HP-MRI-derived apparent diffusion coefficient (ADC) quantifies the restriction of 3He diffusion by peripheral airspaces, thereby obtaining pulmonary structural information at an extremely small scale. Lastly, this paper reports the results of a series of experiments that measured ADC in mechanically ventilated rats in order to investigate (i) the effect of atelectasis on ventilated airspaces; (ii) the relationship between positive end-expiratory pressure (PEEP), hysteresis, and the dimensions of peripheral airspaces; and (iii) the ability of PEEP and surfactant to reduce airspace dimensions after lung injury. An increase in ADC was found to be a marker of atelectasis-induced overdistension. With recruitment, higher airway pressures were shown to reduce stretch rather than worsen it. Moving forward, HP MRI has significant potential to shed further light on the atelectatic processes that occur during mechanical ventilation. PMID:24920074

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

PubMed

Abdeen, Nishard; Cross, Albert; Cron, Gregory; White, Steven; Rand, Thomas; Miller, David; Santyr, Giles

2006-08-01

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases. Copyright 2006 Wiley-Liss, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, W.; Korea Basic Science Institute; Stepanyan, S. S.

We present a device for spin-exchange optical pumping system to produce large quantities of polarized noble gases for Magnetic Resonance Imaging (MRI). A method and design of apparatus for pumping the polarization of noble gases is described. The method and apparatus enable production, storage and usage of hyperpolarized noble gases for different purposes, including Magnetic Resonance Imaging of human and animal subjects. Magnetic imaging agents breathed into lungs can be observed by the radio waves of the MRI scanner and report back physical and functional information about lung's health and desease. The technique known as spin exchange optical pumping ismore » used. Nuclear magnetic resonance is implemented to measure the polarization of hyperpolarized gas. The cells prepared and sealed under high vacuum after handling Alkali metals into the cell and filling with the {sup 3}He-N{sub 2} mixture. The cells could be refilled. The {sup 3}He reaches around 50% polarization in 5-15 hours.« less

A 24-ch Phased-Array System for Hyperpolarized Helium Gas Parallel MRI to Evaluate Lung Functions.

PubMed

Lee, Ray; Johnson, Glyn; Stefanescu, Cornel; Trampel, Robert; McGuinness, Georgeann; Stoeckel, Bernd

2005-01-01

Hyperpolarized 3He gas MRI has a serious potential for assessing pulmonary functions. Due to the fact that the non-equilibrium of the gas results in a steady depletion of the signal level over the course of the excitations, the signal-tonoise ratio (SNR) can be independent of the number of the data acquisitions under certain circumstances. This provides a unique opportunity for parallel MRI for gaining both temporal and spatial resolution without reducing SNR. We have built a 24-channel receive / 2-channel transmit phased array system for 3He parallel imaging. Our in vivo experimental results proved that the significant temporal and spatial resolution can be gained at no cost to the SNR. With 3D data acquisition, eight fold (2x4) scan time reduction can be achieved without any aliasing in images. Additionally, a rigid analysis using the low impedance preamplifier for decoupling presented evidence of strong coupling.

3He Lung Morphometry Technique: Accuracy Analysis and Pulse Sequence Optimization

PubMed Central

Sukstanskii, A.L.; Conradi, M.S.; Yablonskiy, D.A.

2010-01-01

The 3He lung morphometry technique (Yablonskiy et al, JAP, 2009), based on MRI measurements of hyperpolarized gas diffusion in lung airspaces, provides unique information on the lung microstructure at the alveolar level. 3D tomographic images of standard morphological parameters (mean airspace chord length, lung parenchyma surface-to-volume ratio, and the number of alveoli per unit lung volume) can be created from a rather short (several seconds) MRI scan. These parameters are most commonly used to characterize lung morphometry but were not previously available from in vivo studies. A background of the 3He lung morphometry technique is based on a previously proposed model of lung acinar airways, treated as cylindrical passages of external radius R covered by alveolar sleeves of depth h, and on a theory of gas diffusion in these airways. The initial works approximated the acinar airways as very long cylinders, all with the same R and h. The present work aims at analyzing effects of realistic acinar airway structures, incorporating airway branching, physiological airway lengths, a physiological ratio of airway ducts and sacs, and distributions of R and h. By means of Monte Carlo computer simulations, we demonstrate that our technique allows rather accurate measurements of geometrical and morphological parameters of acinar airways. In particular, the accuracy of determining one of the most important physiological parameter of acinar airways – surface-to-volume ratio – does not exceed several percent. Second, we analyze the effect of the susceptibility induced inhomogeneous magnetic field on the parameter estimate and demonstrate that this effect is rather negligible at B0 ≤ 3T and becomes substantial only at higher B0 Third, we theoretically derive an optimal choice of MR pulse sequence parameters, which should be used to acquire a series of diffusion attenuated MR signals, allowing a substantial decrease in the acquisition time and improvement in accuracy of the results. It is demonstrated that the optimal choice represents three not equidistant b-values: b1 = 0, b2 ~ 2 s/cm2, b3 ~ 8 s/cm2. PMID:20937564

Longitudinal assessment of treatment effects on pulmonary ventilation using 1H/3He MRI multivariate templates

NASA Astrophysics Data System (ADS)

Tustison, Nicholas J.; Contrella, Benjamin; Altes, Talissa A.; Avants, Brian B.; de Lange, Eduard E.; Mugler, John P.

2013-03-01

The utitlity of pulmonary functional imaging techniques, such as hyperpolarized 3He MRI, has encouraged their inclusion in research studies for longitudinal assessment of disease progression and the study of treatment effects. We present methodology for performing voxelwise statistical analysis of ventilation maps derived from hyper­ polarized 3He MRI which incorporates multivariate template construction using simultaneous acquisition of IH and 3He images. Additional processing steps include intensity normalization, bias correction, 4-D longitudinal segmentation, and generation of expected ventilation maps prior to voxelwise regression analysis. Analysis is demonstrated on a cohort of eight individuals with diagnosed cystic fibrosis (CF) undergoing treatment imaged five times every two weeks with a prescribed treatment schedule.

Apparatus for preparing a solution of a hyperpolarized noble gas for NMR and MRI analysis

DOEpatents

Pines, Alexander [Berkeley, CA; Budinger, Thomas [Berkeley, CA; Navon, Gil [Ramat Gan, IL; Song, Yi-Qiao [Berkeley, CA; Appelt, Stephan [Waiblingen, DE; Bifone, Angelo [Rome, IT; Taylor, Rebecca [Berkeley, CA; Goodson, Boyd [Berkeley, CA; Seydoux, Roberto [Berkeley, CA; Room, Toomas [Albany, CA; Pietrass, Tanja [Socorro, NM

2008-06-10

The present invention relates generally to nuclear magnetic resonance (NMR) techniques for both spectroscopy and imaging. More particularly, the present invention relates to methods in which hyperpolarized noble gases (e.g., Xe and He) are used to enhance and improve NMR and MRI. Additionally, the hyperpolarized gas solutions of the invention are useful both in vitro and in vivo to study the dynamics or structure of a system. When used with biological systems, either in vivo or in vitro, it is within the scope of the invention to target the hyperpolarized gas and deliver it to specific regions within the system.

Enhancement of NMR and MRI in the presence of hyperpolarized noble gases

DOEpatents

Pines, Alexander; Budinger, Thomas; Navon, Gil; Song, Yi-Qiao; Appelt, Stephan; Bifone, Angelo; Taylor, Rebecca; Goodson, Boyd; Seydoux, Roberto; Room, Toomas; Pietrass, Tanja

2004-11-16

The present invention relates generally to nuclear magnetic resonance (NMR) techniques for both spectroscopy and imaging. More particularly, the present invention relates to methods in which hyperpolarized noble gases (e.g., Xe and He) are used to enhance and improve NMR and MRI. Additionally, the hyperpolarized gas solutions of the invention are useful both in vitro and in vivo to study the dynamics or structure of a system. When used with biological systems, either in vivo or in vitro, it is within the scope of the invention to target the hyperpolarized gas and deliver it to specific regions within the system.

Micro-imaging of the Mouse Lung via MRI

NASA Astrophysics Data System (ADS)

Wang, Wei

Quantitative measurement of lung microstructure is of great significance in assessment of pulmonary disease, particularly in the earliest stages. Conventional stereological assessment of ex-vivo fixed tissue specimens under the microscope has a long and successful tradition and is regarded as a gold standard, but the invasive nature limits its applications and the practicality of use in longitudinal studies. The technique for diffusion MRI-based 3He lung morphometry was previously developed and validated for human lungs, and was recently extended to ex-vivo mouse lungs. The technique yields accurate, quantitative information about the microstructure and geometry of acinar airways. In this dissertation, the 3He lung morphometry technique is for the first time successfully implemented for in-vivo studies of mice. It can generate spatially-resolved maps of parameters that reveal the microstructure of mouse lung. Results in healthy mice indicate excellent agreement between in-vivo morphometry via 3He MRI and microscopic morphometry after sacrifice. The implementation and validation of 3He morphometry in healthy mice open up new avenues for application of the technique as a precise, noninvasive, in-vivo biomarker of changes in lung microstructure, within various mouse models of lung disease. We have applied 3He morphometry to the Sendai mouse model of lung disease. Specifically, the Sendai-virus model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human COPD and asthma, but the effect on distal lung parenchyma had not been investigated. We imaged the time course and regional distribution of mouse lung microstructural changes in vivo after Sendai virus (SeV) infection with 1H and 3He diffusion MRI. 1H MR images detected the SeV-induced pulmonary inflammation in vivo and 3He lung morphometry showed modest increase in alveolar duct radius distal to airway inflammation, particularly in the lung periphery, indicating airspace enlargement after virus infection. Another important application of the imaging technique is the study of lung regeneration in a pneumonectomy (PNX) model. Partial resection of the lung by unilateral PNX is a robust model of compensatory lung growth. It is typically studied by postmortem morphometry in which longitudinal assessment in the same animal cannot be achieved. Here we successfully assess the microstructural changes and quantify the compensatory lung growth in vivo in the PNX mouse model via 1H and hyperpolarized 3He diffusion MRI. Our results show complete restoration in lung volume and total alveolar number with enlargement of alveolar size, which is consistent with prior histological studies conducted in different animals at various time points. This dissertation demonstrates that 3He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and can be applied to a variety of mouse pulmonary models. Particularly, it has great potential to become a valuable tool in understanding the time course and the mechanism of lung growth in individual animals and may provide insight into post-natal lung growth and lung regeneration.

Novel Imaging Contrast Methods for Hyperpolarized 13 C Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Reed, Galen Durant

Magnetic resonance imaging using hyperpolarized 13C-labeled small molecules has emerged as an extremely powerful tool for the in vivo monitoring of perfusion and metabolism. This work presents methods for improved imaging, parameter mapping, and image contrast generation for in vivo hyperpolarized 13C MRI. Angiography using hyperpolarized urea was greatly improved with a highly T2-weighted acquisition in combination with 15N labeling of the urea amide groups. This is due to the fact that the T2 of [13C]urea is strongly limited by the scalar coupling to the neighboring quadrupolar 14N. The long in vivo T2 values of [13C, 15N2]urea were utilized for sub-millimeter projection angiography using a contrast agent that could be safely injected in concentrations of 10-100 mM while still tolerated in patients with renal insufficiency. This study also presented the first method for in vivo T2 mapping of hyperpolarized 13C compounds. The in vivo T2 of urea was short in the blood and long within the kidneys. This persistent signal component was isolated to the renal filtrate, thus enabling for the first time direct detection of an imaging contrast agent undergoing glomerular filtration. While highly T2-weighted acquisitions select for molecules with short rotational correlation times, high diffusion weighting selects for those with the long translational correlation times. A specialized spin-echo EPI sequence was developed in order to generate highly diffusion-weighted hyperpolarized 13C images on a clinical MRI system operating within clinical peak- RF and gradient amplitude constraints. Low power adiabatic spin echo pulses were developed in order to generate a sufficiently large refocused bandwidth while maintaining low nominal power. This diffusion weighted acquisition gave enhanced tumor contrast-to-noise ratio when imaging [1-13C]lactate after infusion of [1-13C]pyruvate. Finally, the first in-man hyperpolarized 13C MRI clinical trial is discussed.

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

PubMed Central

Ebner, Lukas; Kammerman, Jeff; Driehuys, Bastiaan; Schiebler, Mark L.; Cadman, Robert V.; Fain, Sean B.

2016-01-01

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3 He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe MRI, and (4) propose clinical applications. PMID:27707585

The Fast and the Slow, the High and the Low - Investigations of Pb and He Diffusion in Accessory Minerals and Implications for Geochronology (Invited)

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.

2009-12-01

We have measured Pb diffusion in a range of accessory minerals over the past few decades, and have recently begun investigations of helium diffusion with a study of diffusion in apatite and zircon (Cherniak et al., 2009). In this work, we obtained the following Arrhenius relation for He diffusion in Durango fluorapatite: D = 2.10x10-6 exp( - 117 ± 6 kJ mol-1/RT) m2sec-1 In contrast to apatite, He diffusion in zircon exhibits marked anisotropy, with diffusion normal to c about two orders of magnitude slower than diffusion parallel to c. For He diffusion in zircon we determined these Arrhenius relations for diffusion normal and parallel to c: D⊥c = 2.3x10-7 exp(-146± 11 kJ mol-1/RT) 2sec-1 D∥c = 1.7x10-5 exp(-148± 17 kJ mol-1/RT)m2sec-1 As a continuation of these efforts, we have characterized diffusion of helium in natural monazite and titanite. Polished slabs of these minerals were implanted with 100 keV 3He at a dose of 5x1015 3He/cm2. Implanted monazite and titanite were annealed in Pt capsules in 1-atm furnaces for times ranging from 15 minutes to 6 weeks at temperatures from 252-600°C. 3He distributions in the minerals were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. For diffusion normal to (100) we obtain the following Arrhenius relation for He diffusion in monazite: D = 1.6x10-7 exp(-150 ± 11 kJ mol-1/RT) m2sec-1. Over the investigated temperature range, diffusivities are similar to those measured by Boyce et al. (2005), and fall between the values measured by Farley (2007) for diffusion in synthetic CePO4, NdPO4, SmPO4, and GdPO4. He diffusion in monazite is similar to He diffusion in zircon normal to c, and about 4 orders of magnitude slower than He diffusion in apatite (Cherniak et al., 2009). For diffusion in titanite, we obtain the Arrhenius relation: D = 8.7x10-7 exp(-143 ± 7 kJ mol-1/RT) m2sec-1. He diffusivities for titanites from two different localities are comparable, and similar to those measured in the outgassing experiments of Shuster et al. (2003). He diffusion in titanite is intermediate between He diffusion parallel and normal to c in zircon, and about 3 orders of magnitude slower than He diffusion in apatite (Cherniak et al., 2009). In this presentation, we will consider these findings in light of other determinations of He diffusion and Pb diffusion in various accessory phases, and discuss the implications of these diffusivities in interpreting thermal histories. Since He diffusion is many orders of magnitude faster than Pb diffusion, geologic conditions under which these species will be retained or lost span a broad and disparate range, with applications from surface processes to those deep in the crust. Boyce, J.W., Hodges, K.V., Olszewski, W.J., Jercinovic, M.J.(2005) G3, 6, Q12004; Cherniak, D.J., Watson, E.B., Thomas, J.B. (2009) Chem. Geol. (submitted); Farley, K.A. (2007) GCA 71, 4015-4024, Shuster, D.L., Farley, K.A., Sisterson, J.M., Burnett, D.S.(2003) EPSL 217, 19-32.

MRI of the lung gas-space at very low-field using hyperpolarized noble gases

NASA Technical Reports Server (NTRS)

Venkatesh, Arvind K.; Zhang, Adelaide X.; Mansour, Joey; Kubatina, Lyubov; Oh, Chang Hyun; Blasche, Gregory; Selim Unlu, M.; Balamore, Dilip; Jolesz, Ferenc A.; Goldberg, Bennett B.;

Pulmonary 3He Magnetic Resonance Imaging Biomarkers of Regional Airspace Enlargement in Alpha-1 Antitrypsin Deficiency.

PubMed

Lessard, Eric; Young, Heather M; Bhalla, Anurag; Pike, Damien; Sheikh, Khadija; McCormack, David G; Ouriadov, Alexei; Parraga, Grace

2017-11-01

Thoracic x-ray computed tomography (CT) and hyperpolarized 3 He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (L m ) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers. We enrolled patients with AATD (n = 8; 57 ± 7 years), ex-smokers with COPD (n = 8; 77 ± 6 years), and a control group of never-smokers (n = 5; 64 ± 2 years) who underwent thoracic CT, MRI, spirometry, plethysmography, the St. George's Respiratory Questionnaire, and the 6-minute walk test during a single 2-hour visit. MRI-derived ADC, L m , surface-to-volume ratio, and ventilation defect percent were generated for the apical, basal, and whole lung as was CT lung area ≤-950 Hounsfield units (RA 950 ), low attenuating clusters, and airway count. In patients with AATD, there was a significantly different MRI-derived ADC (P = .03), L m (P < .0001), and surface-to-volume ratio (P < .0001), but not diffusing capacity of carbon monoxide, residual volume or total lung capacity, or CT RA 950 (P > .05) compared to COPD ex-smokers with a significantly different St. George's Respiratory Questionnaire. In this proof-of-concept demonstration, we evaluated CT and MRI lung emphysema measurements and observed significantly worse MRI biomarkers of emphysema in patients with AATD compared to patients with COPD, although CT RA 950 and diffusing capacity of carbon monoxide were not significantly different, underscoring the sensitivity of MRI measurements of AATD emphysema. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Gating the glutamate gate of CLC-2 chloride channel by pore occupancy

PubMed Central

De Jesús-Pérez, José J.; Castro-Chong, Alejandra; Shieh, Ru-Chi; Hernández-Carballo, Carmen Y.; De Santiago-Castillo, José A.

2016-01-01

CLC-2 channels are dimeric double-barreled chloride channels that open in response to hyperpolarization. Hyperpolarization activates protopore gates that independently regulate the permeability of the pore in each subunit and the common gate that affects the permeability through both pores. CLC-2 channels lack classic transmembrane voltage–sensing domains; instead, their protopore gates (residing within the pore and each formed by the side chain of a glutamate residue) open under repulsion by permeant intracellular anions or protonation by extracellular H+. Here, we show that voltage-dependent gating of CLC-2: (a) is facilitated when permeant anions (Cl−, Br−, SCN−, and I−) are present in the cytosolic side; (b) happens with poorly permeant anions fluoride, glutamate, gluconate, and methanesulfonate present in the cytosolic side; (c) depends on pore occupancy by permeant and poorly permeant anions; (d) is strongly facilitated by multi-ion occupancy; (e) is absent under likely protonation conditions (pHe = 5.5 or 6.5) in cells dialyzed with acetate (an impermeant anion); and (f) was the same at intracellular pH 7.3 and 4.2; and (g) is observed in both whole-cell and inside-out patches exposed to increasing [Cl−]i under unlikely protonation conditions (pHe = 10). Thus, based on our results we propose that hyperpolarization activates CLC-2 mainly by driving intracellular anions into the channel pores, and that protonation by extracellular H+ plays a minor role in dislodging the glutamate gate. PMID:26666914

The effects of dual-domain mass transfer on the tritium-helium-3 dating method.

PubMed

Neumann, Rebecca B; Labolle, Eric M; Harvey, Charles F

2008-07-01

Diffusion of tritiated water (referred to as tritium) and helium-3 between mobile and immobile regions in aquifers (mass transfer) can affect tritium and helium-3 concentrations and hence tritium-helium-3 (3H/3He) ages that are used to estimate aquifer recharge and groundwater residence times. Tritium and helium-3 chromatographically separate during transport because their molecular diffusion coefficients differ. Simulations of tritium and helium-3 transport and diffusive mass transfer along stream tubes show that mass transfer can shift the 3H/3He age of the tritium and helium-3 concentration ([3H + 3He]) peak to dates much younger than the 1963 peak in atmospheric tritium. Furthermore, diffusive mass-transfer can cause the 3H/3He age to become younger downstream along a stream tube, even as the mean water-age must increase. Simulated patterns of [3H + 3He] versus 3H/3He age using a mass transfer model appear consistent with a variety of field data. These results suggest that diffusive mass transfer should be considered, especially when the [3H + 3He] peak is not well defined or appears younger than the atmospheric peak. 3H/3He data provide information about upstream mass-transfer processes that could be used to constrain mass-transfer models; however, uncritical acceptance of 3H/3He dates from aquifers with immobile regions could be misleading.

Helium-3 MR q-space imaging with radial acquisition and iterative highly constrained back-projection.

PubMed

O'Halloran, Rafael L; Holmes, James H; Wu, Yu-Chien; Alexander, Andrew; Fain, Sean B

2010-01-01

An undersampled diffusion-weighted stack-of-stars acquisition is combined with iterative highly constrained back-projection to perform hyperpolarized helium-3 MR q-space imaging with combined regional correction of radiofrequency- and T1-related signal loss in a single breath-held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole-lung coverage in a 13-sec breath-hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two-dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500-mL volume to the 1000-mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium-3 q-space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions. Copyright (c) 2009 Wiley-Liss, Inc.

Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

PubMed

Ouriadov, A; Farag, A; Kirby, M; McCormack, D G; Parraga, G; Santyr, G E

2015-12-01

Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity. © 2014 Wiley Periodicals, Inc.

An Update on 3He Correlation Function Research for the SNS nEDM collaboration

NASA Astrophysics Data System (ADS)

Reid, Austin; Golub, Robert; Dipert, Robert

2016-09-01

In the 65 years since Ramsey's null result for the neutron's permanent electric dipole moment (nEDM), techniques have become increasingly sensitive, establishing the present upper limit of 3 ×10-26 e .cm . This value was limited by an unexpected source of error: a freqency shift with linear dependence on the electric field colloquially called a false EDM. The next generation nEDM sensing apparatus being developed for the Spallation Neutron Source at Oak Ridge National Laboratory uses a 3He comagenetometer in a pure helium-II bath. The false EDM in 3He may be related to the 3He's position autocorrelation function, which in turn is accessible by a detailed study of T1 decay in hyperpolarized 3He. Existing measurements of this system were limited by temperature, noise, and 3He concentration. Dramatic improvements have been made on all three fronts by improving the thermal connection between the measurment cell and the dilution refrigerator, by adding additional shielding and a SQUID package, and by developing a MEOP 3He polarization system. Data collection is underway. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics, under Award Number DE-FG02-97ER41042.

Probing sub-alveolar length scales with hyperpolarized-gas diffusion NMR

NASA Astrophysics Data System (ADS)

Miller, Wilson; Carl, Michael; Mooney, Karen; Mugler, John; Cates, Gordon

2009-05-01

Diffusion MRI of the lung is a promising technique for detecting alterations of normal lung microstructure in diseases such as emphysema. The length scale being probed using this technique is related to the time scale over which the helium-3 or xenon-129 diffusion is observed. We have developed new MR pulse sequence methods for making diffusivity measurements at sub-millisecond diffusion times, allowing one to probe smaller length scales than previously possible in-vivo, and opening the possibility of making quantitative measurements of the ratio of surface area to volume (S/V) in the lung airspaces. The quantitative accuracy of simulated and experimental measurements in microstructure phantoms will be discussed, and preliminary in-vivo results will be presented.

Experimental investigation and numerical simulation of 3He gas diffusion in simple geometries: implications for analytical models of 3He MR lung morphometry.

PubMed

Parra-Robles, J; Ajraoui, S; Deppe, M H; Parnell, S R; Wild, J M

2010-06-01

Models of lung acinar geometry have been proposed to analytically describe the diffusion of (3)He in the lung (as measured with pulsed gradient spin echo (PGSE) methods) as a possible means of characterizing lung microstructure from measurement of the (3)He ADC. In this work, major limitations in these analytical models are highlighted in simple diffusion weighted experiments with (3)He in cylindrical models of known geometry. The findings are substantiated with numerical simulations based on the same geometry using finite difference representation of the Bloch-Torrey equation. The validity of the existing "cylinder model" is discussed in terms of the physical diffusion regimes experienced and the basic reliance of the cylinder model and other ADC-based approaches on a Gaussian diffusion behaviour is highlighted. The results presented here demonstrate that physical assumptions of the cylinder model are not valid for large diffusion gradient strengths (above approximately 15 mT/m), which are commonly used for (3)He ADC measurements in human lungs. (c) 2010 Elsevier Inc. All rights reserved.

Observation of cardiogenic flow oscillations in healthy subjects with hyperpolarized 3He MRI

PubMed Central

Collier, Guilhem J.; Marshall, Helen; Rao, Madhwesha; Stewart, Neil J.; Capener, David

2015-01-01

Recently, dynamic MRI of hyperpolarized 3He during inhalation revealed an alternation of the image intensity between left and right lungs with a cardiac origin (Sun Y, Butler JP, Ferrigno M, Albert MS, Loring SH. Respir Physiol Neurobiol 185: 468–471, 2013). This effect is investigated further using dynamic and phase-contrast flow MRI with inhaled 3He during slow inhalations (flow rate ∼100 ml/s) to elucidate airflow dynamics in the main lobes in six healthy subjects. The ventilation MR signal and gas inflow in the left lower lobe (LLL) of the lungs were found to oscillate clearly at the cardiac frequency in all subjects, whereas the MR signals in the other parts of the lungs had a similar oscillatory behavior but were smaller in magnitude and in anti-phase to the signal in the left lower lung. The airflow in the main bronchi showed periodic oscillations at the frequency of the cardiac cycle. In four of the subjects, backflows were observed for a short period of time of the cardiac cycle, demonstrating a pendelluft effect at the carina bifurcation between the left and right lungs. Additional 1H structural MR images of the lung volume and synchronized ECG recording revealed that maximum inspiratory flow rates in the LLL of the lungs occurred during systole when the corresponding left lung volume increased, whereas the opposite effect was observed during diastole, with gas flow redirected to the other parts of the lung. In conclusion, cardiogenic flow oscillations have a significant effect on regional gas flow and distribution within the lungs. PMID:26338461

WHAT MAKES A GOOD PEDIATRIC TRANSPLANT LUNG: INSIGHTS FROM IN VIVO LUNG MORPHOMETRY WITH HYPERPOLARIZED 3HE MRI (WHAT MAKES A GOOD PEDIATRIC TRANSPLANT LUNG)

PubMed Central

Fishman, Emily F.; Quirk, James D.; Sweet, Stuart C.; Woods, Jason C.; Gierada, David S.; Conradi, Mark S.; Siegel, Marilyn J.; Yablonskiy, Dmitriy A.

2016-01-01

Background Obtaining information on transplanted lung microstructure is an important part of the current care for monitoring transplant recipients. However, until now this information was only available from invasive lung biopsy. The objective of this study was to evaluate the use of an innovative non-invasive technique in vivo lung morphometry with hyperpolarized 3He MRI - to characterize lung microstructure in the pediatric lung transplant population. This technique yields quantitative measurements of acinar airways’ (alveolar ducts and sacs) parameters, such as acinar airways radii and alveolar depth. Methods Six pediatric lung transplant recipients with cystic fibrosis underwent in vivo lung morphometry MRI, pulmonary function testing, and quantitative CT. Results We found a strong correlation between lung lifespan and alveolar depth - patients with more shallow alveoli were likely to have a negative outcome sooner than those with larger alveolar depth. Combining morphometric results with CT we also determined mean alveolar wall thickness and found substantial increases in this parameter in some patients that negatively correlated with DLCO. Conclusion In vivo lung morphometry uniquely provides previously unavailable information on lung microstructure that may be predictive of a negative outcome and has a potential to aid in lung selection for transplantation. PMID:28120553

Helium Diffusion in Olivine

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.

2011-12-01

Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm experiments, indicating that the results reported here can be reasonably applied to modeling He transport in the upper mantle. The insensitivity of He diffusion to pressure over the investigated range of conditions suggests that compression of the mineral lattice is not sufficient to significantly influence migration of the relatively small helium atoms, which likely diffuse via crystal interstices. The He diffusivities in this work are generally consistent with results from the study of Futagami et al. (1993), who measured He diffusion in natural olivine by outgassing 4He implanted samples, and with the diffusivities measured by bulk-release of 4He and 3He by Shuster et al. (2003), but are about 2 orders of magnitude slower than the recent findings of Tolstikhin et al. (2010) and Blard et al. (2008) . An up-temperature extrapolation of our data also show reasonable agreement with the higher-temperature measurements of Hart (1984). Blard et al. (2008) GCA 72, 3788-3803; Futagami et al. (1993) GCA 57, 3177-3194; Hart (1984) EPSL 70, 297-302; Shuster et al.( 2003) EPSL 217, 19-32; Tolstikhin et al. (2010) GCA 74, 1436-1447

Bulk Nuclear Hyperpolarization of Inorganic Solids by Relay from the Surface.

PubMed

Björgvinsdóttir, Snædís; Walder, Brennan J; Pinon, Arthur C; Emsley, Lyndon

2018-06-14

NMR is a method of choice to determine structural and electronic features in inorganic materials, and has been widely used in the past, but its application is severely limited by its low relative sensitivity. We show how the bulk of proton-free inorganic solids can be hyperpolarized with a general strategy using impregnation dynamic nuclear polarization through homonuclear spin diffusion between low-γ nuclei. This is achieved either through direct hyperpolarization or with a pulse cooling cross-polarization method, transferring hyperpolarization from protons to heteronuclei at particle surfaces. We demonstrate a factor of 50 gain in overall sensitivity for the 119 Sn spectrum of powdered SnO 2 , corresponding to an acceleration of a factor >2500 in acquisition times. The method is also shown for 31 P spectra of GaP, 113 Cd spectra of CdTe, and 29 Si spectra of α-quartz.

Helium diffusion in carbonates

NASA Astrophysics Data System (ADS)

Amidon, W. H.; Cherniak, D. J.; Watson, E. B.; Hobbs, D.

2013-12-01

The abundance and large grain size of carbonate minerals make them a potentially attractive target for 4He thermochronology and 3He cosmogenic dating, although the diffusive properties of helium in carbonates remain poorly understood. This work characterizes helium diffusion in calcite and dolomite to better understand the crystal-chemical factors controlling He transport and retentivity. Slabs of cleaved natural calcite and dolomite, and polished sections of calcite cut parallel or normal to c, were implanted with 3He at 3 MeV with a dose of 5x1015/cm2. Implanted carbonates were heated in 1-atm furnaces, and 3He distributions following diffusion anneals were profiled with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. For 3He transport normal to cleavage surfaces in calcite, we obtain the following Arrhenius relation over the temperature range 78-300°C: Dcalcite = 9.0x10-9exp(-55 × 6 kJ mol-1/RT) m2sec-1. Diffusion in calcite exhibits marked anisotropy, with diffusion parallel to c about two orders of magnitude slower than diffusion normal to cleavage faces. He diffusivities for transport normal to the c-axis are similar in value to those normal to cleavage surfaces. Our findings are broadly consistent with helium diffusivities from step-heating measurements of calcite by Copeland et al. (2007); these bulk degassing data may reflect varying effects of diffusional anisotropy. Helium diffusion normal to cleavage surfaces in dolomite is significantly slower than diffusion in calcite, and has a much higher activation energy for diffusion. For dolomite, we obtain the following Arrhenius relation for He diffusion over the temperature range 150-400°C: Ddolomite = 9.0x10-8exp(-92 × 9 kJ mol-1/RT) m2sec-1. The role of crystallographic structure in influencing these differences among diffusivities was evaluated using the maximum aperture approach of Cherniak and Watson (2011), in which crystallographic structures are sectioned along possible diffusion directions and the maximum interstitial apertures in each 'slice' in the structure are identified. Preliminary results show that observed differences in diffusivities are consistent with the size of the smallest maximum aperture along each diffusion direction. In calcite, the smallest maximum apertures are ~0.92 and ~0.66 angstroms for cleavage-normal and c-axis parallel directions respectively. In dolomite, the smallest maximum aperture is ~0.78 angstroms for the cleavage normal direction. Work is in progress on characterizing helium diffusion for other orientations in dolomite, and in other carbonates, including aragonite and magnesite, and in implementing these diffusion findings in the interpretation and modeling of bulk volume diffusion in heterogeneous calcite crystals common in many geologic applications. Copeland et al. (2007) GCA 71, 4488-4511 Cherniak and Watson, (2011) Chem. Geo. 288, 149-161

Diffusion of Helium in the mantle: an explanation for MORB-OIB patterns of 3He/4He ratios

NASA Astrophysics Data System (ADS)

Morgan, W. J.; Morgan, J. P.

2011-12-01

OIBs have a wide range of 3He/4He ratios, MORBs have a much narrower range peaked at 3He/4He ≈ 8 Ra. In addition, the ratio of 3He/20Ne (both stable isotopes) is significantly higher in MORB than in OIB, likewise the ratio of 4He/21Ne (both daughter isotopes produced by U and Th decay) are similarly higher in MORB than OIB. (Stable 3He/36Ar and radiogenic 4He/40Ar have the same pattern as the He/Ne plots, only with more scatter.) [See Honda and Patterson, GCA 63, 1999.] We assume the rising mantle plumes are 'lumpy'; a mixture that includes lumps of primordial mantle (which will be rich in 3He, 20Ne, 22Ne, 36Ar, etc.) as well as lumps containing the EM1, EM2, HIMU components, all in a general matrix of relatively-barren, previously-melted 'harzburgite'. When the rising lumps (plums) melt, the He, Ne, Ar, and most of the other incompatible elements will go into the melts that are known as OIB. But not all of the lumps melt (near the edge, some don't rise shallow enough to pressure-release melt); those that don't melt go into the asthenosphere, flowing horizontally away from the rising column. At a spreading center, this asthenosphere contributes the 'plums' it has left but also some of the more barren matrix that the plums are embedded in becomes part of the melt because of the higher extents of partial melting that occur when making MORB. What is the effect of diffusion? If the helium, because of its small size, can diffuse a distance of 100 m or 1000 m in a billion-plus years (the 'age' of a lump) whereas neon or argon diffuse only decimeters or centimeters in this time because of their larger radii (i.e., not much more than non-noble incompatible elements like K, Rb, or U can diffuse), then the 3He and 4He (and H) can diffuse far out into the 'barren harzburgite' matrix. Thus when the lumps in a plume melt there will be a shortage of 3He and 4He relative to the 20Ne, 21Ne, or argon. With the extensive melting that occurs to make MORB, fluxing causes some of the barren matrix to contribute its 3He and 4He to the MORB melt which results in an excess of helium relative to neon and argon. This extraction of helium from the longtime-diffused-into barren matrix also can explain the uniformity of the 3/4 ratio in MORB as opposed to the variability of 3/4 in OIB where the individual lumps each contribute their own variable contents. What is lacking in this explanation are data on diffusion rates of the noble gases under deep mantle conditions. What experimental data exists suggest helium diffuses sufficiently fast, but published data only go up to ≈1300 °C, and at only uppermost mantle pressures. Can experiments in diamond anvils or calculations that include 'helium atoms' in molecular dynamics models give diffusion constants to test this hypothesis?

A new search for the permanent electric dipole moment of 129Xe at FRM-II

NASA Astrophysics Data System (ADS)

Sachdeva, N.; Chupp, T.; Degenkolb, S.; Fierlinger, P.; Kraegloh, E.; Kuchler, F.; Lins, T.; Meinel, J.; Niessen, B.; Stuiber, S.; Terrano, W. A.; Burghoff, M.; Fan, I.; Kilian, W.; Grüneberg, S.; Schnabel, A.; Seifert, F.; Stollfuss, D.; Trahms, L.; Voight, J.; Babcock, E.; Salhi, Z.; Huneau, J.; Singh, J.

2017-01-01

CP-violating sources in beyond-the-standard-model physics, necessary to explain baryon asymmetry, give rise to permanent electric dipole moments (EDMs). Precise EDM measurements of the neutron, electron, paramagnetic and diamagnetic atoms constrain CP-violating parameters. The previous limit for the 129Xe EDM is 6 ×10-27 e . cm (95 % CL). The HeXeEDM experiment at FRM-II (Munich Research Reactor) utilizes an ultralow magnetic field in a high-performance magnetically shielded room and 3He comagnetometer to improve the limit by up to three orders of magnitude. In the experiment, hyperpolarized 3He and 129Xe precession signals are detected with a SQUID magnetometer array in the presence of applied electric and magnetic fields. Recent progress will be presented. This work is supported US Department of Energy Grant No. DE FG02 04 ER41331.

Observation of cardiogenic flow oscillations in healthy subjects with hyperpolarized 3He MRI.

PubMed

Collier, Guilhem J; Marshall, Helen; Rao, Madhwesha; Stewart, Neil J; Capener, David; Wild, Jim M

2015-11-01

Recently, dynamic MRI of hyperpolarized (3)He during inhalation revealed an alternation of the image intensity between left and right lungs with a cardiac origin (Sun Y, Butler JP, Ferrigno M, Albert MS, Loring SH. Respir Physiol Neurobiol 185: 468-471, 2013). This effect is investigated further using dynamic and phase-contrast flow MRI with inhaled (3)He during slow inhalations (flow rate ∼100 ml/s) to elucidate airflow dynamics in the main lobes in six healthy subjects. The ventilation MR signal and gas inflow in the left lower lobe (LLL) of the lungs were found to oscillate clearly at the cardiac frequency in all subjects, whereas the MR signals in the other parts of the lungs had a similar oscillatory behavior but were smaller in magnitude and in anti-phase to the signal in the left lower lung. The airflow in the main bronchi showed periodic oscillations at the frequency of the cardiac cycle. In four of the subjects, backflows were observed for a short period of time of the cardiac cycle, demonstrating a pendelluft effect at the carina bifurcation between the left and right lungs. Additional (1)H structural MR images of the lung volume and synchronized ECG recording revealed that maximum inspiratory flow rates in the LLL of the lungs occurred during systole when the corresponding left lung volume increased, whereas the opposite effect was observed during diastole, with gas flow redirected to the other parts of the lung. In conclusion, cardiogenic flow oscillations have a significant effect on regional gas flow and distribution within the lungs. Copyright © 2015 the American Physiological Society.

Factors, fiction and endothelium-derived hyperpolarizing factor.

PubMed

Sandow, Shaun L

2004-09-01

1. The principal mediators of vascular tone are neural, endothelial and physical stimuli that result in the initiation of dilator and constrictor responses to facilitate the control of blood pressure. Two primary vasodilatory stimuli produced by the endothelium are nitric oxide (NO) and prostaglandins. An additional endothelium-dependent vasodilatory mechanism is characterized as the hyperpolarization-mediated relaxation that remains after the inhibition of the synthesis of NO and prostaglandins. This mechanism is due to the action of a so-called endothelium-derived hyperpolarizing factor (EDHF) and is dependent on either the release of diffusible factor(s) and/or to a direct contact-mediated mechanism. 2. Most evidence supports the concept that 'EDHF' activity is dependent on contact-mediated mechanisms. This involves the transfer of an endothelium-derived electrical current, as an endothelium-derived hyperpolarization (EDH), through direct heterocellular coupling of endothelial cells and smooth muscle cells via myoendothelial gap junctions (MEGJ). However, there is a lack of consensus with regard to the nature and mechanism of action of EDHF/EDH (EDH(F)), which has been shown to vary within and between vascular beds, as well as among species, strains, sex and during development, ageing and disease. 3. In addition to actual heterogeneity in EDH(F), further heterogeneity has resulted from the less-than-optimal design, analysis and interpretation of data in some key papers in the EDHF literature; with such views being perpetuated in the subsequent literature. 4. The focus of the present brief review is to examine what factors are proposed as EDH(F) and highlight the correlative structural and functional studies from our laboratory that demonstrate an integral role for MEGJ in the conduction of EDH, which account for the heterogeneity in EDH(F), while incorporating the reported diffusible mechanisms in the regulation of this activity. Furthermore, in addition to the reported heterogeneity in the nature and mechanism of action of EDH(F), the contribution of experimental design and technique to this heterogeneity will be examined.

Spin exchange optical pumping of neon and its applications

NASA Astrophysics Data System (ADS)

Ghosh, Rajat K.

Hyperpolarized noble gases are used in a variety of applications including medical diagnostic lung imaging, tests of fundamental symmetries, spin filters, atomic gyroscopes, and atomic magnetometers. Typically 3He is utilized because large 3He polarizations on the order of 80% can be achieved. This is accomplished by optically pumping an alkali vapour which polarizes a noble gas nucleus via spin exchange optical pumping. One hyperpolarized noble gas application of particular importance is the K-3He co-magnetometer. Here, the alkali atoms optically pump a diamagnetic noble gas. The magnetic holding field for the alkali and noble gas is reduced until both species are brought into hybrid magnetic resonance. The co-magnetometer exhibits many useful attributes which make it ideal for tests of fundamental physics, such as insensitivity to magnetic fields. The co-magnetometer would demonstrate increased sensitivity by replacing 3He with polarized 21Ne gas. Tests of CPT violation using co-magnetometers would be greatly improved if one utilizes polarized 21Ne gas. The sensitivity of the nuclear spin gyroscope is inversely proportional to the gyromagnetic ratio of the noble gas. Switching to neon would instigate an order of magnitude gain in sensitivity over 3He. In order to realize these applications the interaction parameters of 21Ne with alkali metals must be measured. The spin-exchange cross section sigmase, and magnetic field enhancement factor kappa0 are unknown, and have only been theoretically calculated. There are no quantitative predictions of the neon-neon quadrupolar relaxation rate Gammaquad. In this thesis I test the application of a K-3He co-magnetometer as a navigational gyroscope. I discuss the advantages of switching the buffer gas to 21Ne. I discuss the feasibility of utilizing polarized 21Ne for operation in a co-magnetometer, and construct a prototype 21Ne co-magnetometer. I investigate polarizing 21Ne with optical pumping via spin exchange collisions and measure the spin exchange rate coefficient of K and Rb with Ne to be 2.9 x 10-20cm 3/s and 0.81 x 10-19cm3/s. We measure the magnetic field enhancement factor kappa0 to be 30.8 +/- 2.7, and 35.7 +/- 3.7 for the K-Ne, and the Rb-Ne pair. We measure the quadrupolar relaxation coefficient to be 214 +/- 10 Amagat˙s. Furthermore the spin destruction cross section of Rb, and K with 21 Ne is measured to be 1.9 x 10-23cm2 and 1.1 x 10-23cm2.

TH-CD-202-09: Free-Breathing Proton MRI Functional Lung Avoidance Maps to Guide Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capaldi, D; Sheikh, K; Parraga, G

Purpose: Pulmonary functional MRI using inhaled gas contrast agents was previously investigated as a way to identify well-functioning lung in patients with NSCLC who are clinical candidates for radiotherapy. Hyperpolarized noble-gas ({sup 3}He and {sup 129}Xe) MRI has also been optimized to measure functional lung information, but for a number of reasons, the clinical translation of this approach to guide radiotherapy planning has been limited. As an alternative, free-breathing pulmonary 1H MRI using clinically available MRI systems and pulse sequences provides a non-contrast-enhanced method to generate both ventilation and perfusion maps. Free-breathing {sup 1}H MRI exploits non-rigid registration and Fouriermore » decomposition of MRI signal intensity differences (Bauman et al., MRM, 2009) that may be generated during normal tidal breathing. Here, our objective was to generate free-breathing {sup 1}H MRI ventilation and lung function avoidance maps in patients with NSCLC as a way to guide radiation therapy planning. Methods: Stage IIIA/IIIB NSCLC patients (n=8, 68±9yr) provided written informed consent to a randomized controlled clinical trial ( https://clinicaltrials.gov/ct2/show/NCT02002052 ) that aimed to compare outcomes related to image-guided versus conventional radiation therapy planning. Hyperpolarized {sup 3}He/{sup 129}Xe and dynamic free tidal-breathing {sup 1}H MRI were acquired as previously described (Capaldi et al., Acad Radiol, 2015). Non-rigid registration was performed using the modality-independent-neighbourhood-descriptor (MIND) deformable approach (Heinrich et al., Med Image Anal, 2012). Ventilation-defect-percent ({sup 3}He:VDP{sub He}, {sup 129}Xe:VDP{sub Xe}, Free-breathing-{sup 1}H:VDP{sub FB}) and the corresponding ventilation maps were compared using Pearson correlation coefficients (r) and the Dice similarity coefficient (DSC). Results: VDP{sub FB} was significantly related to VDP{sub He} (r=.71; p=.04) and VDP{sub Xe} (r=.80; p=.01) and there were also strong spatial relationships (DSC{sub He}/DSC{sub Xe}=89±3%/77±11%). Conclusion: In this proof of concept study in NSCLC patients, free-breathing {sup 1}H MRI ventilation defects were quantitatively and spatially related to inhaled-noble-gas MRI ventilation defects. Free-breathing {sup 1}H MRI measures lung function/ventilation that can be used to optimize radiotherapy planning in NSCLC patients.« less

The ellagitannin HeT induces electrolyte leakage, calcium influx and the accumulation of nitric oxide and hydrogen peroxide in strawberry.

PubMed

Martos, Gustavo Gabriel; Mamaní, Alicia; Filippone, María Paula; Castagnaro, Atilio Pedro; Díaz Ricci, Juan Carlos

2018-02-01

HeT (1-0-galloyl-2,3; 4,6-bis-hexahydroxydiphenoyl-β-D-glucopyranose) is a penta-esterified ellagitannin obtained from strawberry leaves. Previous studies have shown that foliar application of HeT prior to inoculation with a virulent pathogen increases the resistance toward Colletotrichum acutatum in strawberry plants and to Xanthomonas citri subsp. citri in lemon plants. In this work we report that HeT induces an immediate leak of electrolytes, the hyperpolarization of the cellular membrane, a rapid Ca 2+ influx to the cytoplasm during the first few seconds, which in turn modulates the accumulation of nitric oxide 5 min after treatment. At longer times, a biphasic accumulation of H 2 O 2 with peaks at 2 and 5 h post treatment could be observed. In addition, HeT elicited the increase of alternative oxidase capacity during the first 12 h post treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Mis-estimation and bias of hyperpolarized apparent diffusion coefficient measurements due to slice profile effects.

PubMed

Gordon, Jeremy W; Milshteyn, Eugene; Marco-Rius, Irene; Ohliger, Michael; Vigneron, Daniel B; Larson, Peder E Z

2017-09-01

The purpose of this work was to explore the impact of slice profile effects on apparent diffusion coefficient (ADC) mapping of hyperpolarized (HP) substrates. Slice profile effects were simulated using a Gaussian radiofrequency (RF) pulse with a variety of flip angle schedules and b-value ordering schemes. A long T 1 water phantom was used to validate the simulation results, and ADC mapping of HP [ 13 C, 15 N 2 ]urea was performed on the murine liver to assess these effects in vivo. Slice profile effects result in excess signal after repeated RF pulses, causing bias in HP measurements. The largest error occurs for metabolites with small ADCs, resulting in up to 10-fold overestimation for metabolites that are in more-restricted environments. A mixed b-value scheme substantially reduces this bias, whereas scaling the slice-select gradient can mitigate it completely. In vivo, the liver ADC of hyperpolarized [ 13 C, 15 N 2 ]urea is nearly 70% lower (0.99 ± 0.22 vs 1.69 ± 0.21 × 10 -3 mm 2 /s) when slice-select gradient scaling is used. Slice profile effects can lead to bias in HP ADC measurements. A mixed b-value ordering scheme can reduce this bias compared to sequential b-value ordering. Slice-select gradient scaling can also correct for this deviation, minimizing bias and providing more-precise ADC measurements of HP substrates. Magn Reson Med 78:1087-1092, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

DOSY Analysis of Micromolar Analytes: Resolving Dilute Mixtures by SABRE Hyperpolarization.

PubMed

Reile, Indrek; Aspers, Ruud L E G; Tyburn, Jean-Max; Kempf, James G; Feiters, Martin C; Rutjes, Floris P J T; Tessari, Marco

2017-07-24

DOSY is an NMR spectroscopy technique that resolves resonances according to the analytes' diffusion coefficients. It has found use in correlating NMR signals and estimating the number of components in mixtures. Applications of DOSY in dilute mixtures are, however, held back by excessively long measurement times. We demonstrate herein, how the enhanced NMR sensitivity provided by SABRE hyperpolarization allows DOSY analysis of low-micromolar mixtures, thus reducing the concentration requirements by at least 100-fold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Origin of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion and vagus nerve.

PubMed Central

Ireland, S. J.

1987-01-01

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 X 10(-8)-3 X 10(-7) M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 X 10(-6) 1 X 10(-4) M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 X 10(-5) M), quipazine (1 X 10(-6) M) or MDL 72222 (1 X 10(-5) M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l-1. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 X 10(-3) M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 X 10(-7) - 3 X 10(-5)M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 X 10(-6)M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 X 10(-5)M) but were unaffected by spiperone (1 X 10(-7)M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not mediated through 5-HT3 receptors and is unlikely to be a consequence of depolarization. In contrast, on the rat vagus nerve, the post-5-HT hyperpolarization observed in the present study had the characteristics expected of depolarization-dependent activation of a sodium ion pump. PMID:3676601

Molecular dynamics simulations of the diffusion and coalescence of helium in tungsten

NASA Astrophysics Data System (ADS)

Zhou, Y. L.; Wang, J.; Hou, Q.; Deng, A. H.

2014-03-01

Molecular dynamics (MD) simulations are performed on the diffusion and coalescence of helium in tungsten. A new method for determining the effective capture radii (ECRs) and the dissociation energies of helium-related defects is proposed in this work. It is observed that the ECR of an interstitial helium atom trapping helium interstitials (denoted as He-Hen, n = 1-3) decreases with increasing temperature, except for He-He2 at T < 400 K. The traditional view that the ECR is approximately equal to the lattice constant, which has been widely used in kinetic Monte Carlo (KMC) and rate theory (RT) models, is only valid in some cases. However, the ECR between an interstitial helium atom and a substitutional helium atom (denoted as He-HeV) always approximates the third nearest-neighbor tetrahedral positions of the HeV. The diffusion coefficients Dn for helium clusters are also investigated. He2 migrates more quickly than a single He atom does at T < 400 K, whereas the diffusion path of He2 changes at higher temperatures. Another counterintuitive observation is that D5 > D3 > D4 at T < 500 K, which can be attributed to the disordered structure of He5. The Arrhenius relation describes the diffusion of Hen well in the temperature range from 300 K to 550 K, whereas the diffusion is not a standard thermally activated process at higher temperatures. Taken together, these results help elucidate the initial stage of helium bubble formation in tungsten as well as the requirements of long-term evolution methods such as KMC or RT models.

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PubMed

Wang, Chengbo; Mugler, John P; de Lange, Eduard E; Patrie, James T; Mata, Jaime F; Altes, Talissa A

2014-01-01

To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage. Copyright © 2013 Wiley Periodicals, Inc.

Diffusion of helium, hydrogen and deuterium in diamond: Experiment, theory and geochemical applications

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.; Meunier, V.; Kharche, N.

2018-07-01

Diffusivities of helium, deuterium and hydrogen have been characterized in diamond. Polished CVD diamond was implanted with either 3He, 2H, or 1H. Implanted samples were sealed under vacuum in silica glass capsules, and annealed in 1-atm furnaces. 3He, 2H and 1H distributions were measured with Nuclear Reaction Analysis. We obtain these Arrhenius relations: DHe = 4.00 × 10-15 exp(-138 ± 14 kJ mol-1/RT) m2 s-1. D2H = 1.02 × 10-4 exp(-262 ± 17 kJ mol-1/RT) m2 s-1. D1H = 2.60 × 10-4 exp(-267 ± 15 kJ mol-1/RT) m2 s-1. Diffusivities of 1H and 2H agree within experimental uncertainties, indicating little diffusive mass fractionation of hydrogen in diamond. To complement the experimental measurements, we performed calculations using a first-principles quantum mechanical description of diffusion in diamond within the Density Functional Theory (DFT). Differences in 1H and 2H diffusivities from calculations are found to be ∼4.5%, reflected in differences in the pre-exponential factor. This small difference in diffusivities, despite the large relative mass difference between these isotopes, is due to the fact that the atomistic process involved in the transition along the diffusion pathway is dictated by local changes to the diamond structures rather than to vibrations involving 1H/2H. This finding is consistent with the experimental results given experimental uncertainties. In contrast, calculations for helium diffusion in diamond indicate a difference of 15% between diffusivities of 3He and 4He. Calculations of diffusion distances for hydrogen using our data yield a distance of 50 μm in diamond in 300,000 years at 500 °C and ∼30 min at 1400 °C. Diffusion distances for He in diamond are shorter than for H at all temperatures above ∼350 °C, but differences increase dramatically with temperature because of the higher activation energy for H diffusion. For example, a 50 μm diffusion distance for He would be attained in ∼40 Myr at 500 °C and 400 yr at 1400 °C. For comparison, a 50 μm diffusion distance for N in diamond would require nearly 1 billion years at 1400 °C. The experimental data indicate that diamonds equilibrate with ambient H and He in the mantle on timescales brief relative to most geological processes and events. However, He diffusion in diamond is slower than in any other mineral measured to date, including other kimberlite-hosted minerals. Under some circumstances, diamond may provide information about mantle He not recoverable from other minerals. One possibility is diamonds entrained in kimberlites. Since the ascent of kimberlite from the mantle to near-surface is very rapid, entrained diamonds may retain most or all of the H and He acquired in mantle environments. Calculations using reasonable ascent rates and T-t paths indicate that He diffusive loss from kimberlite-hosted diamonds is negligible for grains of 1.0-0.2 mm radius, with fractional losses <0.15% for all ascent rates considered. If the host kimberlite magma is effectively quenched in the near-surface (or is erupted), diamonds should contain a faithful record of [He] and He isotopes from the mantle source region. Preservation of H in kimberlite-hosted diamonds is less clear-cut, with model outcomes depending critically upon rates of ascent and cooling.

Membrane hyperpolarization during human sperm capacitation

PubMed Central

López-González, I.; Torres-Rodríguez, P.; Sánchez-Carranza, O.; Solís-López, A.; Santi, C.M.; Darszon, A.; Treviño, C.L.

2014-01-01

Sperm capacitation is a complex and indispensable physiological process that spermatozoa must undergo in order to acquire fertilization capability. Spermatozoa from several mammalian species, including mice, exhibit a capacitation-associated plasma membrane hyperpolarization, which is necessary for the acrosome reaction to occur. Despite its importance, this hyperpolarization event has not been adequately examined in human sperm. In this report we used flow cytometry to show that a subpopulation of human sperm indeed undergo a plasma membrane hyperpolarization upon in vitro capacitation. This hyperpolarization correlated with two other well-characterized capacitation parameters, namely an increase in intracellular pH and Ca2+ concentration, measured also by flow cytometry. We found that sperm membrane hyperpolarization was completely abolished in the presence of a high external K+ concentration (60 mM), indicating the participation of K+ channels. In order to identify, which of the potential K+ channels were involved in this hyperpolarization, we used different K+ channel inhibitors including charybdotoxin, slotoxin and iberiotoxin (which target Slo1) and clofilium (a more specific blocker for Slo3). All these K+ channel antagonists inhibited membrane hyperpolarization to a similar extent, suggesting that both members of the Slo family may potentially participate. Two very recent papers recorded K+ currents in human sperm electrophysiologically, with some contradictory results. In the present work, we show through immunoblotting that Slo3 channels are present in the human sperm membrane. In addition, we found that human Slo3 channels expressed in CHO cells were sensitive to clofilium (50 μM). Considered altogether, our data indicate that Slo1 and Slo3 could share the preponderant role in the capacitation-associated hyperpolarization of human sperm in contrast to what has been previously reported for mouse sperm, where Slo3 channels are the main contributors to the hyperpolarization event. PMID:24737063

Microinjections into the pedunculopontine tegmentum: effects of the GABAA antagonist, bicuculline, on sleep, PGO waves and behavior.

PubMed

Sanford, L D; Hunt, W K; Ross, R J; Morrison, A R; Pack, A I

1998-07-01

Neurons in the peribrachial region (PB) at the pontine border are implicated in the generation of ponto-geniculo-occipital (PGO) waves, which appear spontaneously during rapid eye movement sleep (REM) and in association with alerting behaviors during waking, as well as in the regulation of REM itself. It has been hypothesized that PGO-related bursting in a subpopulation of these neurons results from low threshold spikes triggered by phasic hyperpolarizations or by excitatory inputs reaching a steadily hyperpolarized neuron. The hyperpolarization necessary for triggering the low threshold spikes may come from local GABA neurons or from GABAergic input into PB. To test the hypothesis that antagonizing GABA would alter PGO wave generation and/or behavioral state, we microinfused, in cats, the GABAA antagonist, bicuculline, locally into PB and monitored behavior, behavioral state and PGO waves recorded in the lateral geniculate bodies. Bicuculline produced no significant alteration in PGO wave activity. In 3 cats, bicuculline produced behaviors ranging from spontaneous orienting and startle (4 cats) to flight behaviors (2 cats) and aggressiveness (2 cats), an effect probably due to diffusion into the central gray region. Thus, the results do not support a GABAA-ergic role in PB in the generation of PGO waves.

3He Diffusion MRI of the Lung

PubMed Central

Conradi, Mark S.; Yablonskiy, Dmitriy A.; Woods, Jason C.; Gierada, David S.; Jacob, Richard E.; Chang, Yulin V.; Choong, Cliff K.; Sukstanskii, Alex L.; Tanoli, Tariq; Lefrak, Stephen S.; Cooper, Joel D.

2007-01-01

Rationale and Objectives MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. Results We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. Methods Techniques for purging and imaging excised lungs are discussed. PMID:16253852

Diffuse gas emissions at the Ukinrek Maars, Alaska: Implications for magmatic degassing and volcanic monitoring

USGS Publications Warehouse

Evans, William C.; Bergfeld, D.; McGimsey, R.G.; Hunt, A.G.

2009-01-01

Diffuse CO2 efflux near the Ukinrek Maars, two small volcanic craters that formed in 1977 in a remote part of the Alaska Peninsula, was investigated using accumulation chamber measurements. High CO2 efflux, in many places exceeding 1000 g m-2 d-1, was found in conspicuous zones of plant damage or kill that cover 30,000-50,000 m2 in area. Total diffuse CO2 emission was estimated at 21-44 t d-1. Gas vents 3-km away at The Gas Rocks produce 0.5 t d-1 of CO2 that probably derives from the Ukinrek Maars basalt based on similar ??13C values (???-6???), 3He/4He ratios (5.9-7.2 RA), and CO2/3He ratios (1-2 ?? 109) in the two areas. A lower 3He/4He ratio (2.7 RA) and much higher CO2/3He ratio (9 ?? 1010) in gas from the nearest arc-front volcanic center (Mount Peulik/Ugashik) provide a useful comparison. The large diffuse CO2 emission at Ukinrek has important implications for magmatic degassing, subsurface gas transport, and local toxicity hazards. Gas-water-rock interactions play a major role in the location, magnitude and chemistry of the emissions.

Gradient-induced Longitudinal Relaxation of Hyperpolarized Noble Gases in the Fringe Fields of Superconducting Magnets Used for Magnetic Resonance

PubMed Central

Zheng, Wangzhi; Cleveland, Zackary I.; Möller, Harald E.; Driehuys, Bastiaan

2010-01-01

When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of 3He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum 3He relaxation rate of 3.83 × 10−3 s−1 (T1 = 4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T1 would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T1 of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius. PMID:21134771

Gradient-induced longitudinal relaxation of hyperpolarized noble gases in the fringe fields of superconducting magnets used for magnetic resonance.

PubMed

Zheng, Wangzhi; Cleveland, Zackary I; Möller, Harald E; Driehuys, Bastiaan

2011-02-01

When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of (3)He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum (3)He relaxation rate of 3.83×10(-3) s(-1) (T(1)=4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T(1) would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T(1) of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient-induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius. Copyright © 2010 Elsevier Inc. All rights reserved.

A validation of the 3H/3He method for determining groundwater recharge

NASA Astrophysics Data System (ADS)

Solomon, D. K.; Schiff, S. L.; Poreda, R. J.; Clarke, W. B.

1993-09-01

Tritium and He isotopes have been measured at a site where groundwater flow is nearly vertical for a travel time of 100 years and where recharge rates are spatially variable. Because the mid-1960s 3H peak (arising from aboveground testing of thermonuclear devices) is well-defined, the vertical groundwater velocity is known with unusual accuracy at this site. Utilizing 3H and its stable daughter 3He to determine groundwater ages, we compute a recharge rate of 0.16 m/yr, which agrees to within about 5% of the value based on the depth of the 3H peak (measured both in 1986 and 1991) and two-dimensional modeling in an area of high recharge. Zero 3H/3He age occurs at a depth that is approximately equal to the average depth of the annual low water table, even though the capillary fringe extends to land surface during most of the year at the study site. In an area of low recharge (0.05 m/yr) where the 3H peak (and hence the vertical velocity) is also well-defined, the 3H/3He results could not be used to compute recharge because samples were not collected sufficiently far above the 3H peak; however, modeling indicates that the 3H/3He age gradient near the water table is an accurate measure of vertical velocities in the low-recharge area. Because 3H and 3He have different diffusion coefficients, and because the amount of mechanical mixing is different in the area of high recharge than in the low-recharge area, we have separated the dispersive effects of mechanical mixing from molecular diffusion. We estimate a longitudinal dispersivity of 0.07 m and effective diffusion coefficients for 3H (3HHO) and 3He of 2.4×10-5 and 1.3×10-4 m2/day, respectively. Although the 3H/3He age gradient is an excellent indicator of vertical groundwater velocities above the mid-1960s 3H peak, dispersive mixing and diffusive loss of 3He perturb the age gradient near and below the 3H peak.

Cannabinoid CB1 receptor and endothelium-dependent hyperpolarization in guinea-pig carotid, rat mesenteric and porcine coronary arteries

PubMed Central

Chataigneau, T; Félétou, M; Thollon, C; Villeneuve, N; Vilaine, J- P; Duhault, J; Vanhoutte, P M

1998-01-01

The purpose of these experiments was to determine whether or not the endothelium-dependent hyperpolarizations of the vascular smooth muscle cells (observed in the presence of inhibitors of nitric oxide synthase and cyclo-oxygenase) can be attributed to the production of an endogenous cannabinoid.Membrane potential was recorded in the guinea-pig carotid, rat mesenteric and porcine coronary arteries by intracellular microelectrodes.In the rat mesenteric artery, the cannabinoid receptor antagonist, SR 141716 (1 μM), did not modify either the resting membrane potential of smooth muscle cells or the endothelium-dependent hyperpolarization induced by acetylcholine (1 μM) (17.3±1.8 mV, n=4 and 17.8±2.6 mV, n=4, in control and presence of SR 141716, respectively). Anandamide (30 μM) induced a hyperpolarization of the smooth muscle cells (12.6±1.4 mV, n=13 and 2.0±3.0 mV, n=6 in vessels with and without endothelium, respectively) which could not be repeated in the same tissue, whereas acetylcholine was still able to hyperpolarize the preparation. The hyperpolarization induced by anandamide was not significantly influenced by SR 141716 (1 μM). HU-210 (30 μM), a synthetic CB1 receptor agonist, and palmitoylethanolamide (30 μM), a CB2 receptor agonist, did not influence the membrane potential of the vascular smooth muscle cells.In the rat mesenteric artery, the endothelium-dependent hyperpolarization induced by acetylcholine (1 μM) (19.0±1.7 mV, n=6) was not altered by glibenclamide (1 μM; 17.7±2.3 mV, n=3). However, the combination of charybdotoxin (0.1 μM) plus apamin (0.5 μM) abolished the acetylcholine-induced hyperpolarization and under these conditions, acetylcholine evoked a depolarization (7.7±2.7 mV, n=3). The hyperpolarization induced by anandamide (30 μM) (12.6±1.4 mV, n=13) was significantly inhibited by glibenclamide (4.0±0.4 mV, n=4) but not significantly affected by the combination of charybdotoxin plus apamin (17.3±2.3 mV, n=4).In the guinea-pig carotid artery, acetylcholine (1 μM) evoked endothelium-dependent hyperpolarization (18.8±0.7 mV, n=15). SR 141716 (10 nM to 10 μM), caused a direct, concentration-dependent hyperpolarization (up to 10 mV at 10 μM) and a significant inhibition of the acetylcholine-induced hyperpolarization. Anandamide (0.1 to 3 μM) did not influence the membrane potential. At a concentration of 30 μM, the cannabinoid agonist induced a non-reproducible hyperpolarization (5.6±1.3 mV, n=10) with a slow onset. SR 141716 (1 μM) did not affect the hyperpolarization induced by 30 μM anandamide (5.3±1.5 mV, n=3).In the porcine coronary artery, anandamide up to 30 μM did not hyperpolarize or relax the smooth muscle cells. The endothelium-dependent hyperpolarization and relaxation induced by bradykinin were not influenced by SR 141716 (1 μM).These results indicate that the endothelium-dependent hyperpolarizations, observed in the guinea-pig carotid, rat mesenteric and porcine coronary arteries, are not related to the activation of cannabinoid CB1 receptors. PMID:9535027

Investigation of Lung Structure-Function Relationships Using Hyperpolarized Noble Gases

NASA Astrophysics Data System (ADS)

Thomen, Robert P.

Magnetic Resonance Imaging (MRI) is an application of the nuclear magnetic resonance (NMR) phenomenon to non-invasively generate 3D tomographic images. MRI is an emerging modality for the lung, but it suffers from low sensitivity due to inherent low tissue density and short T(*/2) . Hyperpolarization is a process by which the nuclear contribution to NMR signal is greatly enhanced to more than 100,000 times that of samples in thermal equilibrium. The noble gases 3He and 129Xe are most often hyperpolarized by transfer of light angular momentum through the electron of a vaporized alkali metal to the noble gas nucleus (called Spin Exchange Optical Pumping). The enhancement in NMR signal is so great that the gas itself can be imaged via MRI, and because noble gases are chemically inert, they can be safely inhaled by a subject, and the gas distribution within the interior of the lung can be imaged. The mechanics of respiration is an elegant physical process by which air is is brought into the distal airspaces of the lungs for oxygen/carbon dioxide gas exchange with blood. Therefore proper description of lung function is intricately related to its physical structure , and the basic mechanical operation of healthy lungs -- from pressure driven airflow, to alveolar airspace gas kinetics, to gas exchange by blood/gas concentration gradients, to elastic contraction of parenchymal tissue -- is a process decidedly governed by the laws of physics. This dissertation will describe experiments investigating the relationship of lung structure and function using hyperpolarized (HP) noble gas MRI. In particular HP gases will be applied to the study of several pulmonary diseases each of which demonstrates unique structure-function abnormalities: asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Successful implementation of an HP gas acquisition protocol for pulmonary studies is an involved and stratified undertaking which requires a solid theoretical foundation in NMR and hyperpolarization theory, construction of dedicated hardware, development of dedicated software, and appropriate image analysis techniques for all acquired data. The author has been actively involved in each of these and has dedicated specific chapters of this dissertation to their description. First, a brief description of lung structure-function investigations and pulmonary imaging will be given (chapter 1). Brief discussions of basic NMR, MRI, and hyperpolarization theory will be given (chapters 2 and 3) followed by their particular methods of implementation in this work (chapters 4 and 5). Analysis of acquired HP gas images will be discussed (chapter 6), and the investigational procedures and results for each lung disease examined will be detailed (chapter 7). Finally, a quick digression on the strengths and limitations of HP gas MRI will be provided (chapter 8).

Experimental evidence of age-related adaptive changes in human acinar airways

PubMed Central

Quirk, James D.; Sukstanskii, Alexander L.; Woods, Jason C.; Lutey, Barbara A.; Conradi, Mark S.; Gierada, David S.; Yusen, Roger D.; Castro, Mario

2015-01-01

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized 3He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized 3He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

Spin Diffusion Coefficient of A1-PHASE of Superfluid 3He at Low Temperatures

NASA Astrophysics Data System (ADS)

Afzali, R.; Pashaee, F.

The spin diffusion coefficient tensor of the A1-phase of superfluid 3He at low temperatures and melting pressure is calculated using the Boltzmann equation approach and Pfitzner procedure. Then considering Bogoliubov-normal interaction, we show that the total spin diffusion is proportional to 1/T2, the spin diffusion coefficient of superfluid component D\\uparrowxzxz is proportional to T-2, and the spin diffusion coefficient of super-fluid component D\\uparrowxxxx (=D\\uarrowxyxy) is independent of temperature. Furthermore, it is seen that superfluid components play an important role in spin diffusion of the A1-phase.

Fast Xe-129 relaxation in solid xenon near its melting point: Cross-over from Raman scattering of phonons to vacancy diffusion.

NASA Astrophysics Data System (ADS)

Kuzma, N. N.; Patton, B.; Raman, K.; Happer, W.

2002-03-01

NMR measurements of longitudinal relaxation times T1 in pure solid xenon were carried out using both natural-abundance and isotopically-enriched samples of hyperpolarized ^129Xe. At temperatures below 120 K and fields above 500 Gauss, the relaxation rate 1/T1 is field- and abundance-independent, consistent with the model of ^129Xe spin-flip Raman scattering of phonons(R. J. Fitzgerald et al.), Phys. Rev. B 59, 8795 (1999).. Above 120 K, vacancies invade the xenon lattice(P. R. Granfors et al.) Phys. Rev. B 24, 4753 (1981)., and a dramatic cross-over to the nuclear dipole-dipole relaxation due to the diffusion of vacancies is observed. As a result, the measured relaxation times of xenon near its melting point strongly depend on field and somewhat on ^129Xe abundance, and can be as short as several seconds, leading to potential difficulties in cryogenic applications of hyperpolarized ^129Xe. The data are analyzed using the theory of nuclear relaxation due to spin diffusion in cubic crystals(C. A. Sholl, J. Phys. C 21), 319 (1988)., and some estimates of the vacancy density and jump rates are discussed.

Developing a new, passive diffusion sampling array to detect helium anomalies associated with volcanic unrest

USGS Publications Warehouse

Dame, Brittany E; Solomon, D Kip; Evans, William C.; Ingebritsen, Steven E.

2015-01-01

Helium (He) concentration and 3 He/ 4 He anomalies in soil gas and spring water are potentially powerful tools for investigating hydrothermal circulation associated with volca- nism and could perhaps serve as part of a hazards warning system. However, in operational practice, He and other gases are often sampled only after volcanic unrest is detected by other means. A new passive diffusion sampler suite, intended to be collected after the onset of unrest, has been developed and tested as a relatively low-cost method of determining He- isotope composition pre- and post-unrest. The samplers, each with a distinct equilibration time, passively record He concen- tration and isotope ratio in springs and soil gas. Once collected and analyzed, the He concentrations in the samplers are used to deconvolve the time history of the He concentration and the 3 He/ 4 He ratio at the collection site. The current suite consisting of three samplers is sufficient to deconvolve both the magnitude and the timing of a step change in in situ con- centration if the suite is collected within 100 h of the change. The effects of temperature and prolonged deployment on the suite ’ s capability of recording He anomalies have also been evaluated. The suite has captured a significant 3 He/ 4 He soil gas anomaly at Horseshoe Lake near Mammoth Lakes, California. The passive diffusion sampler suite appears to be an accurate and affordable alternative for determining He anomalies associated with volcanic unrest.

Ultrafast NMR diffusion measurements exploiting chirp spin echoes.

PubMed

Ahola, Susanna; Mankinen, Otto; Telkki, Ville-Veikko

2017-04-01

Standard diffusion NMR measurements require the repetition of the experiment multiple times with varying gradient strength or diffusion delay. This makes the experiment time-consuming and restricts the use of hyperpolarized substances to boost sensitivity. We propose a novel single-scan diffusion experiment, which is based on spatial encoding of two-dimensional data, employing the spin-echoes created by two successive adiabatic frequency-swept chirp π pulses. The experiment is called ultrafast pulsed-field-gradient spin-echo (UF-PGSE). We present a rigorous derivation of the echo amplitude in the UF-PGSE experiment, justifying the theoretical basis of the method. The theory reveals also that the standard analysis of experimental data leads to a diffusion coefficient value overestimated by a few per cent. Although the overestimation is of the order of experimental error and thus insignificant in many practical applications, we propose that it can be compensated by a bipolar gradient version of the experiment, UF-BP-PGSE, or by corresponding stimulated-echo experiment, UF-BP-pulsed-field-gradient stimulated-echo. The latter also removes the effect of uniform background gradients. The experiments offer significant prospects for monitoring fast processes in real time as well as for increasing the sensitivity of experiments by several orders of magnitude by nuclear spin hyperpolarization. Furthermore, they can be applied as basic blocks in various ultrafast multidimensional Laplace NMR experiments. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Monitoring tumor response of prostate cancer to radiation therapy by multi-parametric 1H and hyperpolarized 13C magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Zhang, Vickie Yi

Radiation therapy is one of the most common curative therapies for patients with localized prostate cancer, but despite excellent success rates, a significant number of patients suffer post- treatment cancer recurrence. The accurate characterization of early tumor response remains a major challenge for the clinical management of these patients. Multi-parametric MRI/1H MR spectroscopy imaging (MRSI) has been shown to increase the diagnostic performance in evaluating the effectiveness of radiation therapy. 1H MRSI can detect altered metabolic profiles in cancerous tissue. In this project, the concentrations of prostate metabolites from snap-frozen biopsies of recurrent cancer after failed radiation therapy were correlated with histopathological findings to identify quantitative biomarkers that predict for residual aggressive versus indolent cancer. The total choline to creatine ratio was significantly higher in recurrent aggressive versus indolent cancer, suggesting that use of a higher threshold tCho/Cr ratio in future in vivo 1H MRSI studies could improve the selection and therapeutic planning for patients after failed radiation therapy. Varying radiation doses may cause a diverse effect on prostate cancer micro-environment and metabolism, which could hold the key to improving treatment protocols for individual patients. The recent development and clinical translation of hyperpolarized 13C MRI have provided the ability to monitor both changes in the tumor micro-environment and its metabolism using a multi-probe approach, [1-13C]pyruvate and 13C urea, combined with 1H Multi-parametric MRI. In this thesis, hyperpolarized 13C MRI, 1H dynamic contrast enhancement, and diffusion weighted imaging were used to identify early radiation dose response in a transgenic prostate cancer model. Hyperpolarized pyruvate to lactate metabolism significantly decreased in a dose dependent fashion by 1 day after radiation therapy, prior to any changes observed using 1H DCE and diffusion weighted imaging. Hyperpolarized 13C urea and 1H DCE both show increase in perfusion/permeability by 4 days post-radiation. In tumor region treated with high dose radiation, ADC values significantly increased post-radiation, suggesting a decrease in cellular density. These dose dependent changes can be used as markers of early tumor response to the impact of increasing doses of radiation therapy. In addition, a spectral-spatial pulse sequence was developed for the 14T to dynamically observe kinetic information in a transgenic prostate cancer model before and after radiation therapy. A novel modeling approach was proposed to parameterize perfusion in the kinetic modeling of pyruvate to lactate conversion for better characterization of pyruvate metabolism. Unlike single time point HP 13C urea imaging, quantitative pharmacokinetic parameters such as blood flow and extracellular extravascular volume fraction can be extracted from dynamic acquisitions. Blood flow measured by hyperpolarized 13C urea was highly correlated with Ktrans measured by 1H DCE, suggesting hyperpolarized urea might be able to provide similar information as 1H DCE. The results of this thesis show that Multi-parametric MRI, including functional MRI, 1H MRSI, and hyperpolarized 13C, holds great potential for evaluating early tumor response to radiation therapy of prostate cancer. The findings of this thesis will be useful in designing future studies for using combined Multi-parametric 1H and hyperpolarized 13C MRI to improve planning and assessing radiation therapy in individual prostate cancer patients.

Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarization in the guinea-pig carotid artery

PubMed Central

Chataigneau, Thierry; Félétou, Michel; Duhault, Jacques; Vanhoutte, Paul M

1998-01-01

Using intracellular microelectrodes, we investigated the effects of 17-octadecynoic acid (17-ODYA) on the endothelium-dependent hyperpolarization induced by acetylcholine in the guinea-pig isolated internal carotid artery with endothelium. In the presence of Nω-nitro-L-arginine (L-NOARG, 100 μM) and indomethacin (5 μM) to inhibit nitric oxide synthase and cyclo-oxygenase, acetylcholine (1 μM) evoked an endothelium-dependent hyperpolarization which averaged −16.4 mV starting from a resting membrane potential of −56.8 mV. There was a negative correlation between the amplitude of the hyperpolarization and the absolute values of the resting membrane potential. The acetylcholine-induced endothelium-dependent hyperpolarization was not altered by charybdotoxin (0.1 μM) or iberiotoxin (30 nM). It was partially but significantly reduced by apamin (0.5 μM) to −12.8±1.2 mV (n=10) or the combination of apamin plus iberiotoxin (−14.3±3.4 mV, n=4). However, the combination of charybdotoxin and apamin abolished the hyperpolarization and under these conditions, acetylcholine evoked a depolarization (+7.1±3.7 mV, n=8). 17-ODYA (10 μM) produced a significant hyperpolarization of the resting membrane potential which averaged −59.6 mV and a partial but significant inhibition of the acetylcholine-induced endothelium-dependent hyperpolarization (−10.9 mV). Apamin did not modify the effects of 17-ODYA but in the presence of charybdotoxin or iberiotoxin, 17-ODYA no longer influenced the resting membrane potential or the acetylcholine-induced hyperpolarization. When compared to solvent (ethanol, 1% v/v), epoxyeicosatrienoic acids (EpETrEs) (5,6-, 8,9-, 11,12- and 14,15-EpETrE, 3 μM) did not affect the cell membrane potential and did not relax the guinea-pig isolated internal carotid artery. These results indicate that, in the guinea-pig internal carotid artery, the involvement of metabolites of arachidonic acid through the cytochrome P450 pathway in endothelium-dependent hyperpolarization is unlikely. Furthermore, the hyperpolarization mediated by the endothelium-derived hyperpolarizing factor (EDHF) is probably not due to the opening of BKCa channels. PMID:9504399

Application unit for the administration of contrast gases for pulmonary magnetic resonance imaging: optimization of ventilation distribution for (3) He-MRI.

PubMed

Güldner, M; Becker, St; Wolf, U; Düber, C; Friesenecker, A; Gast, K K; Heil, W; Hoffmann, C; Karpuk, S; Otten, E W; Rivoire, J; Salhi, Z; Scholz, A; Schreiber, L M; Terekhov, M

2015-09-01

MRI of lung airspaces using gases with MR-active nuclei ((3) He, (129) Xe, and (19) F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a (3) He bolus. A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-(3) He MRI. The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging. The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements. © 2014 Wiley Periodicals, Inc.

Restricted diffusion in a model acinar labyrinth by NMR: Theoretical and numerical results

NASA Astrophysics Data System (ADS)

Grebenkov, D. S.; Guillot, G.; Sapoval, B.

2007-01-01

A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results

NASA Astrophysics Data System (ADS)

Patz, Samuel; Muradyan, Iga; Hrovat, Mirko I.; Dabaghyan, Mikayel; Washko, George R.; Hatabu, Hiroto; Butler, James P.

2011-01-01

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time τ, three critical determinants of the lung's primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90° radio-frequency pulses applied to the dissolved phase, rather than traditional 180° pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and τ in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ~320 to 80 cm-1 both h~13 μm and τ~1.5 s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and τ were normal. The two COPD subjects had SA/Vgas values ~25% that of normals, quantifying septal surface loss in emphysema; h and τ were normal. These are the first noninvasive, non-radiation-based, quantitative measurements of h and τ in patients with pulmonary disease.

Stability chart of small mixed 4He-3He clusters

NASA Astrophysics Data System (ADS)

Guardiola, R.; Navarro, J.

2003-11-01

A stability chart of mixed 4He and 3He clusters has been obtained by means of the diffusion Monte Carlo method, using both the Aziz HFD-B and the Tang-Toennies-Yiu atom-atom interaction. The investigated clusters contain up to eight 4He atoms and up to 20 3He atoms. One single 4He binds 20 3He atoms, and two 4He bind 1, 2, 8, and more than 14 3He atoms. All clusters with three or more 4He atoms are bound, although the combinations 4He33He9,10,11 and 4He34He9 are metastable. Clusters with 2, 8, and 20 3He atoms are particularly stable and define magic 3He numbers.

Vertical Gradients in Regional Alveolar Oxygen Tension in Supine Human Lung Imaged by Hyperpolarized 3He MRI

PubMed Central

Hamedani, Hooman; Shaghaghi, Hoora; Kadlecek, Stephen J.; Xin, Yi; Han, Biao; Siddiqui, Sarmad; Rajaei, Jennia; Ishii, Masaru; Rossman, Milton; Rizi, Rahim R.

2015-01-01

Purpose To evaluate whether regional alveolar oxygen tension (PAO2) vertical gradients imaged with hyperpolarized 3He can identify smoking-induced pulmonary alterations. To compare these gradients with common clinical measurements including pulmonary function tests, the six minute walk test, and the St. George’s Respiratory Questionnaire. Materials and Methods 8 healthy nonsmokers, 12 asymptomatic smokers, and 7 symptomatic subjects with chronic obstructive pulmonary disease (COPD) underwent two sets of back-to-back PAO2 imaging acquisitions in supine position with two opposite directions (top to bottom and bottom to top), followed by clinically standard pulmonary tests. The whole-lung mean, standard deviation (DPAO2) and vertical gradients of PAO2 along the slices were extracted, and the results were compared with clinically derived metrics. Statistical tests were performed to analyze the differences between cohorts. Results The anterior-posterior vertical gradients and DPAO2 effectively differentiated all three cohorts (p<0.05). The average vertical gradient PAO2 in healthy subjects was −1.03 ± 0.51 Torr/cm toward lower values in the posterior/dependent regions. The directional gradient was absent in smokers (0.36 ± 1.22 Torr/cm) and was in the opposite direction in COPD subjects (2.18 ± 1.54 Torr/cm). The vertical gradients correlated with Smoking History (p=0.004); BMI (p=0.037), PFT metrics (FEV1, p=0.025; and %RV/TLC, p=0.033) and with distance walked in six minutes (p=0.009). Discussion Regional PAO2 data indicate that cigarette smoke induces physiological alterations that are not being detected by the most widely used physiologic tests. PMID:25395184

Experiment E89-044 of quasi-elastic diffusion 3He(e,e'p) at Jefferson Laboratory: Analyze cross sections of the two body breakup in parallel kinematics; Experience E89-044 de diffusion quasi-elastique 3he(e,e'p) au Jefferson Laboratory : analyse des sections efficaces de desintegration a deux corps en cinematique parallele (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penel-Nottaris, Emilie

2004-07-01

The Jefferson Lab Hall A experiment has measured the 3He(e,e'p) reaction cross sections. The separation of the longitudinal and transverse response functions for the two-body breakup reaction in parallel kinematics allows to study the bound proton electromagnetic properties in the 3He nucleus and the involved nuclear mechanisms beyond impulse approximation. Preliminary cross sections show some disagreement with theoretical predictions for the forward angles kinematics around 0 MeV/c missing momenta, and sensitivity to final state interactions and 3He wave functions for missing momenta of 300 MeV/c.

3D He-3 diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, Rick E.; Minard, Kevin R.; Laicher, Gernot J.

2008-08-21

In this work, we validate 3He magnetic resonance imaging as a non-invasive morphometric tool to assess emphysematous disease state on a local level. Emphysema was induced intratracheally in rats with 25U/100g body weight of porcine pancreatic elastase dissolved in 200 μL saline. Rats were then paired with saline-dosed controls. Nine three-dimensional 3He diffusion-weighted images were acquired at one-, two-, or three-weeks post-dose, after which the lungs were harvested and prepared for histological analysis. Recently introduced indices sensitive to the heterogeneity of the airspace size distribution were calculated. These indices, D1 and D2, were derived from the moments of the meanmore » equivalent airway diameters. Averaged over the entire lung, it is shown that the 3He diffusivity (Dave) and anisotropy (Dan) both correlate with histology (R = 0.85, p < 0.0001 and R = 0.88, p < 0.0001, respectively). By matching small (0.046 cm2) regions in 3He images with corresponding regions in histological slices, Dave and Dan each correlate significantly with both D1 and D2 (R = 0.93, p < 0.0001). It is concluded that 3He MRI is a viable non-invasive morphometric tool for localized in vivo emphysema assessment.« less

The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion.

PubMed

Konig, Stéphane; Béguet, Anne; Bader, Charles R; Bernheim, Laurent

2006-08-01

In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K+ channel (Kir2.1) activation, allows the generation of an intracellular Ca2+ signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2. Blocking hyperpolarization inhibits myoblast differentiation. The link between hyperpolarization-induced Ca2+ signals and the four main regulatory pathways involved in myoblast differentiation was the object of this study. Of the calcineurin, p38-MAPK, PI3K and CaMK pathways, only the calcineurin pathway was inhibited when Kir2.1-linked hyperpolarization was blocked. The CaMK pathway, although Ca2+ dependent, is unaffected by changes in membrane potential or block of Kir2.1 channels. Concerning the p38-MAPK and PI3K pathways, their activity is present already in proliferating myoblasts and they are unaffected by hyperpolarization or Kir2.1 channel block. We conclude that the Kir2.1-induced hyperpolarization triggers human myoblast differentiation via the activation of the calcineurin pathway, which, in turn, induces expression/activity of myogenin and MEF2.

Noninvasive in Vivo MRI Assessment of Prostate Cancer Using Hyperpolarized 15N Choline

DTIC Science & Technology

2017-01-01

for hyperpolarized 15N NMR and MRI, and (iii) to evaluate the efficacy of using hyperpolarized 15N choline as in vivo biomarker for prostate cancer...accomplished. GOAL 3. to evaluate the efficacy of using hyperpolarized 15N choline as in vivo biomarker for prostate cancer. For this Goal, the...science and technology? We currently have no metric to evaluate that the results of this project has any significant impact on public awareness or

4-D segmentation and normalization of 3He MR images for intrasubject assessment of ventilated lung volumes

NASA Astrophysics Data System (ADS)

Contrella, Benjamin; Tustison, Nicholas J.; Altes, Talissa A.; Avants, Brian B.; Mugler, John P., III; de Lange, Eduard E.

2012-03-01

Although 3He MRI permits compelling visualization of the pulmonary air spaces, quantitation of absolute ventilation is difficult due to confounds such as field inhomogeneity and relative intensity differences between image acquisition; the latter complicating longitudinal investigations of ventilation variation with respiratory alterations. To address these potential difficulties, we present a 4-D segmentation and normalization approach for intra-subject quantitative analysis of lung hyperpolarized 3He MRI. After normalization, which combines bias correction and relative intensity scaling between longitudinal data, partitioning of the lung volume time series is performed by iterating between modeling of the combined intensity histogram as a Gaussian mixture model and modulating the spatial heterogeneity tissue class assignments through Markov random field modeling. Evaluation of the algorithm was retrospectively applied to a cohort of 10 asthmatics between 19-25 years old in which spirometry and 3He MR ventilation images were acquired both before and after respiratory exacerbation by a bronchoconstricting agent (methacholine). Acquisition was repeated under the same conditions from 7 to 467 days (mean +/- standard deviation: 185 +/- 37.2) later. Several techniques were evaluated for matching intensities between the pre and post-methacholine images with the 95th percentile value histogram matching demonstrating superior correlations with spirometry measures. Subsequent analysis evaluated segmentation parameters for assessing ventilation change in this cohort. Current findings also support previous research that areas of poor ventilation in response to bronchoconstriction are relatively consistent over time.

Compressed Sensing for Resolution Enhancement of Hyperpolarized 13C Flyback 3D-MRSI

PubMed Central

Hu, Simon; Lustig, Michael; Chen, Albert P.; Crane, Jason; Kerr, Adam; Kelley, Douglas A.C.; Hurd, Ralph; Kurhanewicz, John; Nelson, Sarah J.; Pauly, John M.; Vigneron, Daniel B.

2008-01-01

High polarization of nuclear spins in liquid state through dynamic nuclear polarization has enabled the direct monitoring of 13C metabolites in vivo at very high signal to noise, allowing for rapid assessment of tissue metabolism. The abundant SNR afforded by this hyperpolarization technique makes high resolution 13C 3D-MRSI feasible. However, the number of phase encodes that can be fit into the short acquisition time for hyperpolarized imaging limits spatial coverage and resolution. To take advantage of the high SNR available from hyperpolarization, we have applied compressed sensing to achieve a factor of 2 enhancement in spatial resolution without increasing acquisition time or decreasing coverage. In this paper, the design and testing of compressed sensing suited for a flyback 13C 3D-MRSI sequence are presented. The key to this design was the undersampling of spectral k-space using a novel blipped scheme, thus taking advantage of the considerable sparsity in typical hyperpolarized 13C spectra. Phantom tests validated the accuracy of the compressed sensing approach and initial mouse experiments demonstrated in vivo feasibility. PMID:18367420

Probing alanine transaminase catalysis with hyperpolarized 13CD3-pyruvate

NASA Astrophysics Data System (ADS)

Barb, A. W.; Hekmatyar, S. K.; Glushka, J. N.; Prestegard, J. H.

2013-03-01

Hyperpolarized metabolites offer a tremendous sensitivity advantage (>104 fold) when measuring flux and enzyme activity in living tissues by magnetic resonance methods. These sensitivity gains can also be applied to mechanistic studies that impose time and metabolite concentration limitations. Here we explore the use of hyperpolarization by dissolution dynamic nuclear polarization (DNP) in mechanistic studies of alanine transaminase (ALT), a well-established biomarker of liver disease and cancer that converts pyruvate to alanine using glutamate as a nitrogen donor. A specific deuterated, 13C-enriched analog of pyruvic acid, 13C3D3-pyruvic acid, is demonstrated to have advantages in terms of detection by both direct 13C observation and indirect observation through methyl protons introduced by ALT-catalyzed H-D exchange. Exchange on injecting hyperpolarized 13C3D3-pyruvate into ALT dissolved in buffered 1H2O, combined with an experimental approach to measure proton incorporation, provided information on mechanistic details of transaminase action on a 1.5 s timescale. ALT introduced, on average, 0.8 new protons into the methyl group of the alanine produced, indicating the presence of an off-pathway enamine intermediate. The opportunities for exploiting mechanism-dependent molecular signatures as well as indirect detection of hyperpolarized 13C3-pyruvate and products in imaging applications are discussed.

Helium measurements of pore fluids obtained from the San Andreas Fault Observatory at Depth (SAFOD, USA) drill cores

NASA Astrophysics Data System (ADS)

Ali, S.; Stute, M.; Torgersen, T.; Winckler, G.; Kennedy, B. M.

2011-02-01

4He accumulated in fluids is a well established geochemical tracer used to study crustal fluid dynamics. Direct fluid samples are not always collectable; therefore, a method to extract rare gases from matrix fluids of whole rocks by diffusion has been adapted. Helium was measured on matrix fluids extracted from sandstones and mudstones recovered during the San Andreas Fault Observatory at Depth (SAFOD) drilling in California, USA. Samples were typically collected as subcores or from drillcore fragments. Helium concentration and isotope ratios were measured 4-6 times on each sample, and indicate a bulk 4He diffusion coefficient of 3.5 ± 1.3 × 10-8 cm2 s-1 at 21°C, compared to previously published diffusion coefficients of 1.2 × 10-18 cm2 s-1 (21°C) to 3.0 × 10-15 cm2 s-1 (150°C) in the sands and clays. Correcting the diffusion coefficient of 4Hewater for matrix porosity (˜3%) and tortuosity (˜6-13) produces effective diffusion coefficients of 1 × 10-8 cm2 s-1 (21°C) and 1 × 10-7 (120°C), effectively isolating pore fluid 4He from the 4He contained in the rock matrix. Model calculations indicate that <6% of helium initially dissolved in pore fluids was lost during the sampling process. Complete and quantitative extraction of the pore fluids provide minimum in situ porosity values for sandstones 2.8 ± 0.4% (SD, n = 4) and mudstones 3.1 ± 0.8% (SD, n = 4).

(U-Th)/He dating and He diffusion in calcite from veins and breccia

NASA Astrophysics Data System (ADS)

Gautheron, C.; Cros, A.; Pagel, M.; Berthet, P.; Tassan-Got, L.; Douville, E.; Pinna-Jamme, R.; Sarda, P.

2013-12-01

Knowledge of He retention in crystalline calcite is mandatory to estimate the possibility of (U-Th)/He dating of calcite. To this aim, fault-filling calcite crystals from the Eocene/Oligocene Gondrecourt graben, Paris Basin, Eastern France, have been sampled, based on their relatively old, Eocene-Oligocene, precipitation age and cold thermal history (<40°C since precipitation). The samples were sorted into three main tectonic and morphological groups, including successively (1) micro-fracture calcites, (2) breccia and associated geodic calcites, and (3) vein and associated geodic calcites. (U-Th)/He dating of 63 calcite fragments yields ages dispersed from 0.2×0.02 to 35.8×2.7 Ma, as well as two older dates of 117×10 and 205×28 Ma (1s). These He ages correlate to grain chemistry, such as to Sr and ΣREE concentrations or (La/Yb)N ratios, and these correlations probably reflect the evolution of parent fluid. Only the oldest He ages are in agreement with the He-retentive character of calcite as determined by Copeland et al. (2007), and these ages were obtained for the most recently precipitated crystals. To better understand the large He-age scatter and why calcites precipitated earlier show younger ages, He diffusion experiments have been conducted on 10 Gondrecourt calcite fragments from 3 samples with He ages of 0.2 to 6 Ma. In addition, a crystallographic investigation by X-Ray Diffraction (XRD) performed on similar samples reveals that the crystal structure evolves with increasing temperature, showing with micro-cracks and cleavage opening. These XRD results indicate that, in fault-filling calcite, He retention is controlled by multiple diffusion domains (MDD, Lovera et al., 1991) with various sizes, and therefore, evolves through time with strong consequences on (U-Th)/He age. We thus interpret the Gondrecourt calcite (U-Th)/He age scatter of older samples as a consequence of cleavage opening due to a succession of calcite crystallization phases related to the deformation history. Finally, we propose that the crystallization age of a calcite crystal with a known thermal history can nevertheless be retrieved by the (U-Th)/He method provided the He diffusion pattern can be measured by careful step-heating degassing analysis. Copeland, P., Watson, E.B., Urizar, S.C., Patterson, D., Lapen, T.J., 2007. Alpha thermochronology of carbonates. Geochim. Cosmochim. Acta, 71: 4488-4511. Cros, A. Gautheron, C., Pagel, M., Berthet, P., Tassan-Got, L., Douville, E., Pinna-Jamme, R., Sarda, P., submitted GCA, He behavior in calcite filling viewed by (U-Th)/He dating, He diffusion and crystallographic studies. Lovera, O.M., Richter, F.M., Harrison, T.M., 1991. Diffusion domains determined by 39Ar released during step heating. Journal of Geophysical Research, 96: 2057-2069.

Achieving 1% NMR polarization in water in less than 1 min using SABRE

NASA Astrophysics Data System (ADS)

Zeng, Haifeng; Xu, Jiadi; McMahon, Michael T.; Lohman, Joost A. B.; van Zijl, Peter C. M.

2014-09-01

The development of biocompatible hyperpolarized media is a crucial step towards application of hyperpolarization in vivo. This article describes the achievement of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the parahydrogen induced polarization technique based on signal amplification by reversible exchange (SABRE). Polarization was achieved in less than 1 min.

Interrogating the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2015-12-01

Apatite (U-Th)/He thermochronology is commonly used to study landscape evolution and potential links between climate, erosion and tectonics. The technique relies on a quantitative understanding of (i) helium diffusion kinetics in apatite, (ii) an evolving 4He concentration, (iii) accumulating damage to the crystal lattice caused by radioactive decay[1], and (iv) the thermal annealing of such damage[2],[3], which are each functions of both time and temperature. Uncertainty in existing models of helium diffusion kinetics has resulted in conflicting conclusions, especially in settings involving burial heating through geologic time. The effects of alpha recoil damage annealing are currently assumed to follow the kinetics of fission track annealing (e.g., reference [3]), although this assumption is difficult to fully validate. Here, we present results of modeling exercises and a suite of experiments designed to interrogate the effects of damage annealing on He diffusivity in apatite that are independent of empirical calibrations of fission track annealing. We use the existing experimental results for Durango apatite[2] to develop and calibrate a new function that predicts the effects of annealing temperature and duration on measured diffusivity. We also present a suite of experiments conducted on apatite from Sierra Nevada, CA granite to establish whether apatites with different chemical compositions have the same behavior as Durango apatite. Crystals were heated under vacuum to temperatures between 250 and 500°C for 1, 10, or 100 hours. The samples were then irradiated with ~220 MeV protons to produce spallogenic 3He, the diffusant then used in step-heating diffusion experiments. We compare the results of these experiments and model calibrations to existing models. Citations: [1]Shuster, D., Flowers R., and Farley K., (2006), EPSL 249(3-4), 148-161; [2]Shuster, D. and Farley, K., (2009), GCA 73 (1), 6183-6196; [3]Flowers, R., Ketcham, R., Shuster, D. and Farley, K., (2009), GCA 73, 2347-2365.

Diffuse degassing He/CO2 ratio before and during the 2011-12 El Hierro submarine eruption, Canary Islands

NASA Astrophysics Data System (ADS)

Padrón, Eleazar; Hernández, Pedro A.; Melián, Gladys V.; Barrancos, José; Padilla, Germán; Pérez, Nemesio M.; Dionis, Samara; Rodríguez, Fátima; Asensio-Ramos, María; Calvo, David

2015-04-01

El Hierro Island (278 km2) is the youngest and the SW-most of the Canary Islands. On July 16, 2011, a seismic-volcanic crisis started with the occurrence of more than 11,900 seismic events and significant deformation along the island, culminating with the eruption onset in October 12. Since at El Hierro Islands there are not any surface geothermal manifestation (fumaroles, etc), we have focused our studies on soil degassing surveys. Between July 2011 to March 2012, seventeen diffuse CO2 and He emissions soil gas surveys were undertaken at El Hierro volcanic system (600 observation sites) with the aim to investigate the relationship between their temporal variations and the volcanic activity (Padrón et al., 2013; Melián et al., 2014). Based on the diffuse He/CO2 emission ratio, a sharp increase before the eruption onset was observed, reaching the maximum value on September 26 (6.8×10-5), sixteen days before the occurrence of the eruption. This increase coincided with an increase in seismic energy release during the volcanic unrest and occurred together with an increase on the 3He/4He isotopic ratio in groundwaters from a well in El Hierro Island (Padrón et al., 2013; from 2-3 RA to 7.2 RA where RA = 3He/4He ratio in air), one month prior to the eruption onset. Early degassing of new gas-rich magma batch at depth could explain the observed increase on the He/CO2 ratio, causing a preferential partitioning of CO2 in the gas phase with respect to the He, due to the lower solubility of CO2 than that of He in basaltic magmas. During the eruptive period (October 2011-March 2012) the prevalence of a magmatic CO2-dominated component is evident, as indicated by the generally lower He/CO2 ratios and high 3He/4He values (Padrón et al., 2013). The onset of the submarine eruption might have produced a sudden release of volcanic gases, and consequently, a decrease in the volcanic gas pressure of the magma bodies moving beneath the island, reflected by a drastic decrease in the diffuse helium emissions measured after the eruption onset. Therefore, this study shows that higher diffuse He/CO2 emission ratios preceded the 2011-2012 El Hierro submarine eruption, clearly show the critical role that both gas species can play in the prediction of major volcanic events and demonstrates the importance of performing soil He and CO2 surveys as a useful geochemical monitoring tool in active volcanic regions. Padrón et al. (2013) Geology 41(5), 539-542; Melián et al. (2014) JGR, 119: 6976-6991, doi:10.1002/2014JB011013

The influence of artificial radiation damage and thermal annealing on helium diffusion kinetics in apatite

NASA Astrophysics Data System (ADS)

Shuster, David L.; Farley, Kenneth A.

2009-01-01

Recent work [Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249(3-4), 148-161] revealing a correlation between radiogenic 4He concentration and He diffusivity in natural apatites suggests that helium migration is retarded by radiation-induced damage to the crystal structure. If so, the He diffusion kinetics of an apatite is an evolving function of time and the effective uranium concentration in a cooling sample, a fact which must be considered when interpreting apatite (U-Th)/He ages. Here we report the results of experiments designed to investigate and quantify this phenomenon by determining He diffusivities in apatites after systematically adding or removing radiation damage. Radiation damage was added to a suite of synthetic and natural apatites by exposure to between 1 and 100 h of neutron irradiation in a nuclear reactor. The samples were then irradiated with a 220 MeV proton beam and the resulting spallogenic 3He used as a diffusant in step-heating diffusion experiments. In every sample, irradiation increased the activation energy ( E a) and the frequency factor ( D o/ a2) of diffusion and yielded a higher He closure temperature ( T c) than the starting material. For example, 100 h in the reactor caused the He closure temperature to increase by as much as 36 °C. For a given neutron fluence the magnitude of increase in closure temperature scales negatively with the initial closure temperature. This is consistent with a logarithmic response in which the neutron damage is additive to the initial damage present. In detail, the irradiations introduce correlated increases in E a and ln( D o/a 2) that lie on the same array as found in natural apatites. This strongly suggests that neutron-induced damage mimics the damage produced by U and Th decay in natural apatites. To investigate the potential consequences of annealing of radiation damage, samples of Durango apatite were heated in vacuum to temperatures up to 550 °C for between 1 and 350 h. After this treatment the samples were step-heated using the remaining natural 4He as the diffusant. At temperatures above 290 °C a systematic change in T c was observed, with values becoming lower with increasing temperature and time. For example, reduction of T c from the starting value of 71 to ˜52 °C occurred in 1 h at 375 °C or 10 h at 330 °C. The observed variations in T c are strongly correlated with the fission track length reduction predicted from the initial holding time and temperature. Furthermore, like the neutron irradiated apatites, these samples plot on the same E a - ln( D o/ a2) array as natural samples, suggesting that damage annealing is simply undoing the consequences of damage accumulation in terms of He diffusivity. Taken together these data provide unequivocal evidence that at these levels, radiation damage acts to retard He diffusion in apatite, and that thermal annealing reverses the process. The data provide support for the previously described radiation damage trapping kinetic model of Shuster et al. (2006) and can be used to define a model which fully accommodates damage production and annealing.

Regional alveolar partial pressure of oxygen measurement with parallel accelerated hyperpolarized gas MRI.

PubMed

Kadlecek, Stephen; Hamedani, Hooman; Xu, Yinan; Emami, Kiarash; Xin, Yi; Ishii, Masaru; Rizi, Rahim

2013-10-01

Alveolar oxygen tension (Pao2) is sensitive to the interplay between local ventilation, perfusion, and alveolar-capillary membrane permeability, and thus reflects physiologic heterogeneity of healthy and diseased lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging (MRI)-based Pao2 mapping techniques have been reported, and considerable effort has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging scheme, using parallel accelerated MRI, which significantly reduces measurement error. The proposed Pao2 mapping scheme was computer-simulated and was tested on both phantoms and five human subjects. Where possible, correspondence between actual local oxygen concentration and derived values was assessed for both bias (deviation from the true mean) and imaging artifact (deviation from the true spatial distribution). Phantom experiments demonstrated a significantly reduced coefficient of variation using the accelerated scheme. Simulation results support this observation and predict that correspondence between the true spatial distribution and the derived map is always superior using the accelerated scheme, although the improvement becomes less significant as the signal-to-noise ratio increases. Paired measurements in the human subjects, comparing accelerated and fully sampled schemes, show a reduced Pao2 distribution width for 41 of 46 slices. In contrast to proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise penalty; its use in Pao2 measurement is therefore always beneficial. Comparison of multiple schemes shows that the benefit arises from a longer time-base during which oxygen-induced depolarization modifies the signal strength. Demonstration of the accelerated technique in human studies shows the feasibility of the method and suggests that measurement error is reduced here as well, particularly at low signal-to-noise levels. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

The Effect of He3 Diffusion on the Pulsational Spectra of DBV Models

NASA Astrophysics Data System (ADS)

Montgomery, M. H.; Winget, D. E.

Isotopic separation is inevitable in white dwarf stars if our understanding of diffusion is correct. This can have many important, and largely unexplored, astrophysical consequences. Asteroseismology gives an opportunity to investigate this possibility. We first examine the relevant timescales for diffusion in these objects, and compare them to the evolutionary timescales in the context of the DBV white dwarfs. We then explore the consequences which He3 separation has on the pulsational spectra of DBV models. Since GD 358 is the best-studied member of this class of variables, we pay particular attention to the way this could affect previous fits.

Hyperpolarized ketone body metabolism in the rat heart.

PubMed

Miller, Jack J; Ball, Daniel R; Lau, Angus Z; Tyler, Damian J

2018-06-01

The aim of this work was to investigate the use of 13 C-labelled acetoacetate and β-hydroxybutyrate as novel hyperpolarized substrates in the study of cardiac metabolism. [1- 13 C]Acetoacetate was synthesized by catalysed hydrolysis, and both it and [1- 13 C]β-hydroxybutyrate were hyperpolarized by dissolution dynamic nuclear polarization (DNP). Their metabolism was studied in isolated, perfused rat hearts. Hyperpolarized [1- 13 C]acetoacetate metabolism was also studied in the in vivo rat heart in the fed and fasted states. Hyperpolarization of [1- 13 C]acetoacetate and [1- 13 C]β-hydroxybutyrate provided liquid state polarizations of 8 ± 2% and 3 ± 1%, respectively. The hyperpolarized T 1 values for the two substrates were 28 ± 3 s (acetoacetate) and 20 ± 1 s (β-hydroxybutyrate). Multiple downstream metabolites were observed within the perfused heart, including acetylcarnitine, citrate and glutamate. In the in vivo heart, an increase in acetylcarnitine production from acetoacetate was observed in the fed state, as well as a potential reduction in glutamate. In this work, methods for the generation of hyperpolarized [1- 13 C]acetoacetate and [1- 13 C]β-hydroxybutyrate were investigated, and their metabolism was assessed in both isolated, perfused rat hearts and in the in vivo rat heart. These preliminary investigations show that DNP can be used as an effective in vivo probe of ketone body metabolism in the heart. © 2018 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Achieving 1% NMR polarization in water in less than 1min using SABRE.

PubMed

Zeng, Haifeng; Xu, Jiadi; McMahon, Michael T; Lohman, Joost A B; van Zijl, Peter C M

2014-09-01

The development of biocompatible hyperpolarized media is a crucial step towards application of hyperpolarization in vivo. This article describes the achievement of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the parahydrogen induced polarization technique based on signal amplification by reversible exchange (SABRE). Polarization was achieved in less than 1 min. Copyright © 2014 Elsevier Inc. All rights reserved.

Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery

PubMed Central

Jiang, Zhi-Gen; Nuttall, Alfred L; Zhao, Hui; Dai, Chun-Fu; Guan, Bing-Cai; Si, Jun-Qiang; Yang, Yu-Qin

2005-01-01

The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than −60 mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by Nω-nitro-l-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba2+ (100 μm) and ouabain (1 μm) each attenuated ACh-hyperpolarization by ∼ 30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba2+ and 18β-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K+ (10 mm) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49: 1. Ba2+ blocked the K+-induced hyperpolarization by ∼ 85% in both cell types, whereas ouabain inhibited K+-hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18β-Glycyrrhetinic acid blocked the high K+-hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca2+-activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K+ channels (Kir) and Na+–K+ pump current by elevated interstitial K+ released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of Kir and pump current activation is at 8 : 1 or less. PMID:15731195

Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery.

PubMed

Jiang, Zhi-Gen; Nuttall, Alfred L; Zhao, Hui; Dai, Chun-Fu; Guan, Bing-Cai; Si, Jun-Qiang; Yang, Yu-Qin

2005-04-15

The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than -60 mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by N(omega)-nitro-L-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba(2)(+) (100 microm) and ouabain (1 microm) each attenuated ACh-hyperpolarization by approximately 30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba(2)(+) and 18beta-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K(+) (10 mm) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49 : 1. Ba(2)(+) blocked the K(+)-induced hyperpolarization by approximately 85% in both cell types, whereas ouabain inhibited K(+)-hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18beta-Glycyrrhetinic acid blocked the high K(+)-hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca(2)(+)-activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K(+) channels (K(ir)) and Na(+)-K(+) pump current by elevated interstitial K(+) released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of K(ir) and pump current activation is at 8 : 1 or less.

Regional Ventilation Changes in the Lung: Treatment Response Mapping by Using Hyperpolarized Gas MR Imaging as a Quantitative Biomarker.

PubMed

Horn, Felix C; Marshall, Helen; Collier, Guilhem J; Kay, Richard; Siddiqui, Salman; Brightling, Christopher E; Parra-Robles, Juan; Wild, Jim M

2017-09-01

Purpose To assess the magnitude of regional response to respiratory therapeutic agents in the lungs by using treatment response mapping (TRM) with hyperpolarized gas magnetic resonance (MR) imaging. TRM was used to quantify regional physiologic response in adults with asthma who underwent a bronchodilator challenge. Materials and Methods This study was approved by the national research ethics committee and was performed with informed consent. Imaging was performed in 20 adult patients with asthma by using hyperpolarized helium 3 ( 3 He) ventilation MR imaging. Two sets of baseline images were acquired before inhalation of a bronchodilating agent (salbutamol 400 μg), and one set was acquired after. All images were registered for voxelwise comparison. Regional treatment response, ΔR(r), was calculated as the difference in regional gas distribution (R[r] = ratio of inhaled gas to total volume of a voxel when normalized for lung inflation volume) before and after intervention. A voxelwise activation threshold from the variability of the baseline images was applied to ΔR(r) maps. The summed global treatment response map (ΔR net ) was then used as a global lung index for comparison with metrics of bronchodilator response measured by using spirometry and the global imaging metric percentage ventilated volume (%VV). Results ΔR net showed significant correlation (P < .01) with changes in forced expiratory volume in 1 second (r = 0.70), forced vital capacity (r = 0.84), and %VV (r = 0.56). A significant (P < .01) positive treatment effect was detected with all metrics; however, ΔR net showed a lower intersubject coefficient of variation (64%) than all of the other tests (coefficient of variation, ≥99%). Conclusion TRM provides regional quantitative information on changes in inhaled gas ventilation in response to therapy. This method could be used as a sensitive regional outcome metric for novel respiratory interventions. © RSNA, 2017 Online supplemental material is available for this article.

Oxygen-weighted Hyperpolarized 3He MR Imaging: A Short-term Reproducibility Study in Human Subjects

PubMed Central

Ishii, Masaru; Hamedani, Hooman; Clapp, Justin T.; Kadlecek, Stephen J.; Xin, Yi; Gefter, Warren B.; Rossman, Milton D.

2015-01-01

Purpose To determine whether hyperpolarized helium 3 magnetic resonance (MR) imaging to measure alveolar partial pressure of oxygen (Pao2) shows sufficient test-retest repeatability and between-cohort differences to be used as a reliable technique for detection of alterations in gas exchange in asymptomatic smokers. Materials and Methods The protocol was approved by the local institutional review board and was HIPAA compliant. Informed consent was obtained from all subjects. Two sets of MR images were obtained 10 minutes apart in 25 subjects: 10 nonsmokers (five men, five women; mean ± standard deviation age, 50 years ± 6) and 15 smokers (seven women, eight men; mean age, 50 years ± 8). A mixed-effects model was developed to identify the regional repeatability of Pao2 measurements as an intraclass correlation coefficient. Ten smokers were matched with the 10 nonsmokers on the basis of signal-to-noise ratio (SNR). Three separate models were generated: one for nonsmokers, one for the SNR-matched smokers, and one for the five remaining smokers, who were imaged with a significantly higher SNR. Results Short-term back-to-back regional reproducibility was assessed by using intraclass correlation coefficients, which were 0.67 and 0.65 for SNR case-matched nonsmokers and smokers, respectively. Repeatability was a strong function of SNR; a 50% increase in SNR in the remaining smokers improved the intraclass correlation coefficient to 0.82. Although repeatability was not significantly different between the SNR-matched cohorts (P = .44), the smoker group showed higher spatial and temporal variability in Pao2. Conclusion The short-term test-retest repeatability of hyperpolarized gas MR imaging of regional Pao2 was good. Asymptomatic smokers exhibited greater spatial and temporal variability in Pao2 than did the nonsmokers, which suggests that this parameter allows detection of small functional alterations associated with smoking. © RSNA, 2015 Online supplemental material is available for this article. PMID:26110668

­­­Experimental Quantifications of Radiation Damage Annealing and Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Shuster, D. L.

2017-12-01

(U-Th)/He thermochronology in apatite requires a quantitative description of He diffusivity as a function of temperature and through geologic time. Although variability in diffusion kinetics across a range of natural apatite samples has revealed that higher concentrations of alpha-recoil radiation damage correlates with lower He diffusivity (i.e., at a given temperature, [1]), only one published study has experimentally quantified the effects of annealing for a single apatite specimen (Durango apatite, [2]). Although these effects have been incorporated into now widely applied numerical models, underlying assumptions in these models—in particular, that He diffusivity in all apatite crystals responds with the same rate of damage annealing—have been called into question, and further evaluation is warranted (e.g., [3], [4]). Here, we will describe a suite of experiments conducted on apatite from a single hand sample of granite from Sierra Nevada, CA as well as Durango apatite, to establish whether these two apatites with different chemical compositions and thermal pasts exhibit the same response to annealing conditions. Crystals from both samples were heated under vacuum to temperatures between 220 and 500 °C for 1, 10, 100 or 1000 hours. The samples were then irradiated with 220 MeV protons to produce spallation 3He, the diffusant used in subsequent step-heating degassing experiments. Our preliminary results indicate different minima in closure temperatures of 55 oC and 65 oC for the Durango and Sierra apatite, respectively, when exposed to sufficiently high temperatures (>350 oC) for durations > 1 hour, yet similar transitions from low diffusivities at T <200 oC (and higher activation energy, Ea) to higher diffusivity (lower Ea) across a range of experimental annealing temperatures and durations. We will interpret these results with a new model framework for describing the effects of annealing on diffusivity, and will discuss potential implications of our experimental results, the required assumptions in our analyses, and potential limitations of such empirical quantifications. References: [1] Shuster, D. et al. (2006), EPSL 294, 148-161; [2] Shuster, D., Farley, K. (2009), GCA 73 (1), 6183-6196; [3] Gautheron, C. et al. (2013), Chem. Geol. 351, 257-267; [4] Fox, M., Shuster, D. (2014), EPSL 397, 174-183.

Helium diffusion parameters of hematite from a single-diffusion-domain crystal

NASA Astrophysics Data System (ADS)

Farley, K. A.

2018-06-01

This contribution reports new parameters for helium diffusion in hematite useful for interpretation of cosmogenic 3He and radiogenic 4He chronometry. Fragments of a coarse, euhedral single crystal of hematite from Minas Gerais, Brazil were subjected to bulk step-heating helium diffusion experiments after proton irradiation to make a uniform distribution of 3He. Aliquots of three different grain sizes ranging from ∼300 to ∼700 μm in equivalent-sphere radius yielded helium diffusion activation energies Ea ∼ 170 kJ/mol, very similar to previous estimates for Ea in hematite. Uniquely in this specimen, diffusivity varies with the dimensions of the analyzed fragments in precisely the fashion expected if the diffusion domain corresponds to the physical grain. This contrasts with previous studies that concluded that the analyzed hematites consist of polycrystalline aggregates in which helium migration is governed by the size distribution of the constituent crystallites. These new data permit a direct estimate of the helium diffusivity at infinite temperature for hematite of ln(Do) = -0.66 ± 0.35 in cm2/s. The major implication of the new diffusion parameters is that hematite is very retentive of helium even at very small crystal sizes. For example, a 20 nm radius hematite crystal, at the smallest end of the size range so far described in dated polycrystalline hematite specimens, will retain more than 99% of its ingrown He over 1 Myr at 30 °C, and more than 90% over 100 Myr. Under most conditions, hematite is close to quantitatively helium-retentive on the Earth's surface, simplifying radiogenic and cosmogenic helium dating of this phase. In a system cooling at 10 °C/Myr, the 20 nm hematite crystal has a He closure temperature of ∼70 °C, similar to a typical ∼100 μm apatite crystal. Helium is likely held tightly in hematite owing to its dense hexagonal closest packing structure and absence of migration-enhancing channels. The isostructural minerals corundum and ilmenite are likely to be similarly helium retentive.

Temperature-Ramped 129Xe Spin-Exchange Optical Pumping

PubMed Central

2015-01-01

We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode 129Xe hyperpolarizer utilizing three key temperature regimes: (i) “hot”—where the 129Xe hyperpolarization rate is maximal, (ii) “warm”—where the 129Xe hyperpolarization approaches unity, and (iii) “cool”—where hyperpolarized 129Xe gas is transferred into a Tedlar bag with low Rb content (<5 ng per ∼1 L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hyperpolarized 129Xe gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant γSEOP of 62.5 ± 3.7 × 10–3 min–1 vs 29.9 ± 1.2 × 10–3 min–1) while achieving nearly the same maximum %PXe value (88.0 ± 0.8% vs 90.1% ± 0.8%, for a 500 Torr (67 kPa) Xe cell loading—corresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of ∼3.1 × 105 and ∼2.32 × 108 at the relevant fields for clinical imaging and HP 129Xe production of 3 T and 4 mT, respectively); moreover, the intercycle “dead” time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of 129Xe hyperpolarization or the experimental stability for automation—making this approach beneficial for improving the overall 129Xe production rate in clinical settings. PMID:25008290

A first-principles and experimental study of helium diffusion in periclase MgO

NASA Astrophysics Data System (ADS)

Song, Zhewen; Wu, Henry; Shu, Shipeng; Krawczynski, Mike; Van Orman, James; Cherniak, Daniele J.; Bruce Watson, E.; Mukhopadhyay, Sujoy; Morgan, Dane

2018-02-01

The distribution of He isotopes is used to trace heterogeneities in the Earth's mantle, and is particularly useful for constraining the length scale of heterogeneity due to the generally rapid diffusivity of helium. However, such an analysis is challenging because He diffusivities are largely unknown in lower mantle phases, which can influence the He profiles in regions that cycle through the lower mantle. With this motivation, we have used first-principles simulations based on density functional theory to study He diffusion in MgO, an important lower mantle phase. We first studied the case of interstitial helium diffusion in perfect MgO and found a migration barrier of 0.73 eV at zero pressure. Then we used the kinetic Monte Carlo method to study the case of substitutional He diffusion in MgO, where we assumed that He diffuses on the cation sublattice through cation vacancies. We also performed experiments on He diffusion at atmospheric pressure using ion implantation and nuclear reaction analysis in both as-received and Ga-doped samples. A comparison between the experimental and simulation results are shown. This work provides a foundation for further studies at high-pressure.

Investigation of a new model of dipolar-coupled nuclear spin relaxation and applications of dynamic nuclear polarization

NASA Astrophysics Data System (ADS)

Sorte, Eric G.

This work presents the results of various investigations using various techniques of hyperpolarizing the nuclei of atoms. Hyperpolarization implies magnetic order in excess of the thermal order obtained naturally as described by Curie's law. The main portion of this work presents the results of a detailed experimental exploration of predictions arising from a new model of transverse nuclear spin relaxation in quantum systems, based on possible manifestations of microscopic chaos in quantum systems. Experiments have been carried out on a number of hyperpolarized xenon samples, each differing in its relative percentage of xenon isotopes in order to vary the homonuclear and heteronuclear dipole couplings in the spin system. The experiments were performed under a variety of conditions in an attempt to observe the behaviors predicted by the model. Additionally, much more extensive measurements were made on a number of samples of solid CaF2 in both single crystal and powder forms. These samples, although thermally polarized, were observed with superior signal to noise ratios than even the hyperpolarized xenon solids, allowing for more precise measurements for comparison to the theory. This work thus contains the first experimental evidence for the majority of the model's predictions. Additionally, this work contains the first precise measurements of the frequency-shift enhancement parameters for 129Xe and krypton in the presence of spin-polarized Rb. The determination of these important numbers will be useful to many groups who utilize spin-exchange optical pumping in their labs. This work built on the prior knowledge of a precise number for the frequency-shift enhancement parameter of 3He in Rb vapor. Finally, I detail work using NMR to detect nuclear-spin polarization enhancement in silicon phosphorus by a novel, photo-induced hyperpolarization technique developed by the Boehme research group at the University of Utah. Significant nuclear polarization enhancements were observed by the Boehme group due to electron-photon interactions in semiconductor soilds; these enhancements were observed by their effects on the ambient electrons and measured with electron spin resonance techniques. The work described here details experiments to observe the enhanced nuclear polarization by directly measuring the intensity increase in an NMR measurement. I will conclude this dissertation with a brief appendix giving a summary of one additional project involving the use of high pressure fluorinated gas NMR to measure the internal topology and characteristics of energy-rich oil shales.

(U-Th)/He ages of phosphates from Zagami and ALHA77005 Martian meteorites: Implications to shock temperatures

NASA Astrophysics Data System (ADS)

Min, Kyoungwon; Farah, Annette E.; Lee, Seung Ryeol; Lee, Jong Ik

2017-01-01

Shock conditions of Martian meteorites provide crucial information about ejection dynamics and original features of the Martian rocks. To better constrain equilibrium shock temperatures (Tequi-shock) of Martian meteorites, we investigated (U-Th)/He systematics of moderately-shocked (Zagami) and intensively shocked (ALHA77005) Martian meteorites. Multiple phosphate aggregates from Zagami and ALHA77005 yielded overall (U-Th)/He ages 92.2 ± 4.4 Ma (2σ) and 8.4 ± 1.2 Ma, respectively. These ages correspond to fractional losses of 0.49 ± 0.03 (Zagami) and 0.97 ± 0.01 (ALHA77005), assuming that the ejection-related shock event at ∼3 Ma is solely responsible for diffusive helium loss since crystallization. For He diffusion modeling, the diffusion domain radius is estimated based on detailed examination of fracture patterns in phosphates using a scanning electron microscope. For Zagami, the diffusion domain radius is estimated to be ∼2-9 μm, which is generally consistent with calculations from isothermal heating experiments (1-4 μm). For ALHA77005, the diffusion domain radius of ∼4-20 μm is estimated. Using the newly constrained (U-Th)/He data, diffusion domain radii, and other previously estimated parameters, the conductive cooling models yield Tequi-shock estimates of 360-410 °C and 460-560 °C for Zagami and ALHA77005, respectively. According to the sensitivity test, the estimated Tequi-shock values are relatively robust to input parameters. The Tequi-shock estimates for Zagami are more robust than those for ALHA77005, primarily because Zagami yielded intermediate fHe value (0.49) compared to ALHA77005 (0.97). For less intensively shocked Zagami, the He diffusion-based Tequi-shock estimates (this study) are significantly higher than expected from previously reported Tpost-shock values. For intensively shocked ALHA77005, the two independent approaches yielded generally consistent results. Using two other examples of previously studied Martian meteorites (ALHA84001 and Los Angeles), we compared Tequi-shock and Tpost-shock estimates. For intensively shocked meteorites (ALHA77005, Los Angeles), the He diffusion-based approach yield slightly higher or consistent Tequi-shock with estimations from Tpost-shock, and the discrepancy between the two methods increases as the intensity of shock increases. The reason for the discrepancy between the two methods, particularly for less-intensively shocked meteorites (Zagami, ALHA84001), remains to be resolved, but we prefer the He diffusion-based approach because its Tequi-shock estimates are relatively robust to input parameters.

Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed

PubMed Central

Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M.; Murillo, Ma Divina; Gálvez, José A.; Díaz-de-Villegas, María D.; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

2017-01-01

Opening of intermediate-conductance calcium-activated potassium channels (KCa3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KCa3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KCa3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KCa currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KCa3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KCa3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KCa3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KCa3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. PMID:26821335

Nuclear spin hyperpolarization of the solvent using signal amplification by reversible exchange (SABRE).

PubMed

Moreno, Karlos X; Nasr, Khaled; Milne, Mark; Sherry, A Dean; Goux, Warren J

2015-08-01

Here we report the polarization of the solvent OH protons by SABRE using standard iridium-based catalysts under slightly acidic conditions. Solvent polarization was observed in the presence of a variety of structurally similar N-donor substrates while no solvent enhancement was observed in the absence of substrate or para-hydrogen (p-H2). Solvent polarization was sensitive to the polarizing field and catalyst:substrate ratio in a manner similar to that of substrate protons. SABRE experiments with pyridine-d5 suggest a mechanism where hyperpolarization is transferred from the free substrate to the solvent by chemical exchange while measured hyperpolarization decay times suggest a complimentary mechanism which occurs by direct coordination of the solvent to the catalytic complex. We found the solvent hyperpolarization to decay nearly 3 times more slowly than its characteristic spin-lattice relaxation time suggesting that the hyperpolarized state of the solvent may be sufficiently long lived (∼20s) to hyperpolarize biomolecules having exchangeable protons. This route may offer future opportunities for SABRE to impact metabolic imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Nuclear spin hyperpolarization of the solvent using signal amplification by reversible exchange (SABRE)

NASA Astrophysics Data System (ADS)

Moreno, Karlos X.; Nasr, Khaled; Milne, Mark; Sherry, A. Dean; Goux, Warren J.

2015-08-01

Here we report the polarization of the solvent OH protons by SABRE using standard iridium-based catalysts under slightly acidic conditions. Solvent polarization was observed in the presence of a variety of structurally similar N-donor substrates while no solvent enhancement was observed in the absence of substrate or para-hydrogen (p-H2). Solvent polarization was sensitive to the polarizing field and catalyst:substrate ratio in a manner similar to that of substrate protons. SABRE experiments with pyridine-d5 suggest a mechanism where hyperpolarization is transferred from the free substrate to the solvent by chemical exchange while measured hyperpolarization decay times suggest a complimentary mechanism which occurs by direct coordination of the solvent to the catalytic complex. We found the solvent hyperpolarization to decay nearly 3 times more slowly than its characteristic spin-lattice relaxation time suggesting that the hyperpolarized state of the solvent may be sufficiently long lived (∼20 s) to hyperpolarize biomolecules having exchangeable protons. This route may offer future opportunities for SABRE to impact metabolic imaging.

Insight into He diffusion in apatite by ion beam experiments and quantum calculations: implication for the (U-Th)/He thermochronometer

NASA Astrophysics Data System (ADS)

Gautheron, C.; Mbongo-Djimbi, D.; Gerin, C.; Roques, J.; Bachelet, C.; Oliviero, E.; Tassan-Got, L.

2015-12-01

The apatite (U-Th)/He (AHe) system has rapidly become a very popular thermochronometer, however, interpretation of AHe age depends on a precise knowledge of He diffusion. Several studies suggest that He retention is function of the amount of damage that is controlled by U-Th concentration, grain chemistry and thermal history. Still, the models are not well constrained and do not fully explain the mechanism of He retention. In order to have a deeper insight into this issue, a multidisciplinary study on apatite combining physical methods such as multi-scale theoretical diffusion calculations based on Density Functional Theory (DFT) with diffusion experiments by ion beam Elastic Recoil Diffusion Analysis (ERDA) were performed. Quantum calculations permit to quantify He diffusivity base level for damage-free crystal and to estimate the additional energy cost to extract He atoms trapped in point defects (i.e. vacancies). On the other hand ion beam ERDA experiments allow to measure He diffusivity in artificially damaged crystals. We show that damage-free apatite crystals are characterized by low retention behavior and closure temperature of ~35°C for pure F-apatite to higher value for Cl rich apatite (up to 12°C higher), for typical grain size and cooling rate (Mbongo-Djimbi et al., 2015). Our computed closure temperature is slightly lower than previously reported experimental values (~50°C). Using ERDA and DFT modeling of damage, we show how He diffusivity is influenced by damage. Finally, we are able to propose a new modeling of He diffusion incorporating mechanisms not included in classical damage models, and taking into account the level of damage and apatite chemistry. We show that it could affect significantly AHe age interpretation. Mbongo-Djimbi D. et al. 2015. Apatite composition effect on (U-Th)/He thermochronometer: an atomistic point of view. Geohimica Cosmochim. Acta.

Plate Tectonic Cycling and Whole Mantle Convection Modulate Earth's 3He/22Ne Ratio

NASA Astrophysics Data System (ADS)

Dygert, N. J.; Jackson, C.; Hesse, M. A.; Tremblay, M. M.; Shuster, D. L.; Gu, J.

2016-12-01

3He and 22Ne are not produced in the mantle or fractionated by partial melting, and neither isotope is recycled back into the mantle by subduction of oceanic basalt or sediment. Thus, it is a surprise that large 3He/22Ne variations exist within the mantle and that the mantle has a net elevated 3He/22Ne ratio compared to volatile-rich planetary precursor materials. Depleted subcontinental lithospheric mantle and mid-ocean ridge basalt (MORB) mantle have distinctly higher 3He/22Ne compared to ocean island basalt (OIB) sources ( 4-12.5 vs. 2.5-4.5, respectively) [1,2]. The low 3He/22Ne of OIBs approaches chondritic ( 1) and solar nebula values ( 1.5). The high 3He/22Ne of the MORB mantle is not similar to solar sources or any known family of meteorites, requiring a mechanism for fractionating He from Ne in the mantle and suggesting isolation of distinct mantle reservoirs throughout geologic time. We model the formation of a MORB source with elevated and variable 3He/22Ne though diffusive exchange between dunite channel-hosted basaltic liquids and harzburgite wallrock beneath mid-ocean ridges. Over timescales relevant to mantle upwelling beneath spreading centers, He may diffuse tens to hundreds of meters into wallrock while Ne is relatively immobile, producing a regassed, depleted mantle lithosphere with elevated 3He/22Ne. Subduction of high 3He/22Ne mantle would generate a MORB source with high 3He/22Ne. Regassed, high 3He/22Ne mantle lithosphere has He concentrations 2-3 orders of magnitude lower than undegassed mantle. To preserve the large volumes of high 3He/22Ne mantle required by the MORB source, mixing between subducted and undegassed mantle reservoirs must have been limited throughout geologic time. Using the new 3He/22Ne constraints, we ran a model similar to [3] to quantify mantle mixing timescales, finding they are on the order of Gyr assuming physically reasonable seafloor spreading rates, and that Earth's convecting mantle has lost >99% of its primordial volatile elements. Most significantly, mantle convection is not and cannot have been layered for most of geologic time. [1] Graham (2002), RiMG 74, 247-317. [2] Jalowitzki et al. (2016), EPSL 450, 263-273. [3] Gonnermann & Mukhopadhyay (2009), Nature, 560-563.

Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca2+ channels

PubMed Central

Bartoletti, Theodore M.; Jackman, Skyler L.; Babai, Norbert; Mercer, Aaron J.; Kramer, Richard H.

2011-01-01

Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca2+ channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca2+ channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca2+ currents (ICa) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca2+ channel number and single-channel current amplitude were calculated by mean-variance analysis of ICa. Two different comparisons—one comparing average numbers of release events to average ICa amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone ICa—suggested that fewer than three Ca2+ channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca2+ channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca2+ dependence of release, Ca2+ channel number, and Ca2+ channel properties. The model replicated observations when a barrier was added to slow Ca2+ diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca2+ buffers did not affect release efficiency. The tight clustering of Ca2+ channels, along with a high-Ca2+ affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca2+ influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light. PMID:21880934

Release from the cone ribbon synapse under bright light conditions can be controlled by the opening of only a few Ca(2+) channels.

PubMed

Bartoletti, Theodore M; Jackman, Skyler L; Babai, Norbert; Mercer, Aaron J; Kramer, Richard H; Thoreson, Wallace B

2011-12-01

Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca(2+) channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca(2+) channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca(2+) currents (I(Ca)) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca(2+) channel number and single-channel current amplitude were calculated by mean-variance analysis of I(Ca). Two different comparisons-one comparing average numbers of release events to average I(Ca) amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone I(Ca)-suggested that fewer than three Ca(2+) channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca(2+) channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca(2+) dependence of release, Ca(2+) channel number, and Ca(2+) channel properties. The model replicated observations when a barrier was added to slow Ca(2+) diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca(2+) buffers did not affect release efficiency. The tight clustering of Ca(2+) channels, along with a high-Ca(2+) affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca(2+) influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light.

Renal MR angiography and perfusion in the pig using hyperpolarized water.

PubMed

Wigh Lipsø, Kasper; Hansen, Esben Søvsø Szocska; Tougaard, Rasmus Stilling; Laustsen, Christoffer; Ardenkjaer-Larsen, Jan Henrik

2017-09-01

To study hyperpolarized water as an angiography and perfusion tracer in a large animal model. Protons dissolved in deuterium oxide (D 2 O) were hyperpolarized in a SPINlab dissolution dynamic nuclear polarization (dDNP) polarizer and subsequently investigated in vivo in a pig model at 3 Tesla (T). Approximately 15 mL of hyperpolarized water was injected in the renal artery by hand over 4-5 s. A liquid state polarization of 5.3 ± 0.9% of 3.8 M protons in 15 mL of deuterium oxide was achieved with a T 1 of 24 ± 1 s. This allowed injection through an arterial catheter into the renal artery and subsequently high-contrast imaging of the entire kidney parenchyma over several seconds. The dynamic images allow quantification of tissue perfusion, with a mean cortical perfusion of 504 ± 123 mL/100 mL/min. Hyperpolarized water MR imaging was successfully demonstrated as a renal angiography and perfusion method. Quantitative perfusion maps of the kidney were obtained in agreement with literature and control experiments with gadolinium contrast. Magn Reson Med 78:1131-1135, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Constraining Galactic cosmic-ray parameters with Z ≤ 2 nuclei

NASA Astrophysics Data System (ADS)

Coste, B.; Derome, L.; Maurin, D.; Putze, A.

2012-03-01

Context. The secondary-to-primary B/C ratio is widely used for studying Galactic cosmic-ray propagation processes. The 2H/4He and 3He/4He ratios probe a different Z/A regime, which provides a test for the "universality" of propagation. Aims: We revisit the constraints on diffusion-model parameters set by the quartet (1H, 2H, 3He, 4He), using the most recent data as well as updated formulae for the inelastic and production cross-sections. Methods: Our analysis relies on the USINE propagation package and a Markov Chain Monte Carlo technique to estimate the probability density functions of the parameters. Simulated data were also used to validate analysis strategies. Results: The fragmentation of CNO cosmic rays (resp. NeMgSiFe) on the interstellar medium during their propagation contributes to 20% (resp. 20%) of the 2H and 15% (resp. 10%) of the 3He flux at high energy. The C to Fe elements are also responsible for up to 10% of the 4He flux measured at 1 GeV/n. The analysis of 3He/4He (and to a lesser extent 2H/4He) data shows that the transport parameters are consistent with those from the B/C analysis: the diffusion model with δ ~ 0.7 (diffusion slope), Vc ~ 20 km s-1 (galactic wind), Va ~ 40 km s-1 (reacceleration) is favoured, but the combination δ ~ 0.2, Vc ~ 0, and Va ~ 80 km s-1 is a close second. The confidence intervals on the parameters show that the constraints set by the quartet data can compete with those derived from the B/C data. These constraints are tighter when adding the 3He (or 2H) flux measurements, and the tightest when the He flux is added as well. For the latter, the analysis of simulated and real data shows an increased sensitivity to biases. Using the secondary-to-primary ratio along with a loose prior on the source parameters is recommended to obtain the most robust constraints on the transport parameters. Conclusions: Light nuclei should be systematically considered in the analysis of transport parameters. They provide independent constraints that can compete with those obtained from the B/C analysis.

Modeling 3H-3He Gas-Liquid Phase Transport for Interpretation of Groundwater Age

NASA Astrophysics Data System (ADS)

Carle, S. F.; Esser, B.; Moran, J. E.

2009-12-01

California’s Groundwater Ambient Monitoring and Assessment (GAMA) Program has measured many hundreds of tritium (3H) and helium-3 (3He) concentrations in well water samples to derive estimates of groundwater age at production and monitoring wells in California basins. However, a 3H-3He age differs from an ideal groundwater age tracer in several respects: (1) the radioactive decay of 3H results in the accumulation of 3He being first-order with respect to 3H activity (versus a zero-order age-mass accumulation process for an ideal tracer), (2) surface concentrations of 3H as measured in precipitation over the last several decades have not been uniform, and (3) the 3H-3He “clock” begins at the water table and not at the ground surface where 3H source measurements are made. To better understand how these non-idealities affect interpretation of 3H-3He apparent groundwater age, we are modeling coupled gas-liquid phase flow and 3H-3He transport including processes of radiogenic decay, phase equilibrium, and molecular diffusion for water, air, 3H, and 3He components continuously through the vadose zone and saturated zone. Assessment of coupled liquid-gas phase processes enables consideration of 3H-3He residence time and dispersion within the vadose zone, including partitioning of tritiogenic 3He to the gas phase and subsequent diffusion into the atmosphere. The coupled gas-liquid phase modeling framework provides direct means to compare apparent 3H-3He age to ideal mean or advective groundwater ages for the same groundwater flow conditions. Examples are given for common groundwater flow systems involving areal recharge, discharge to streams or long-screened wells, and aquifer system heterogeneity. The Groundwater Ambient Monitoring and Assessment program is sponsored by the California State Water Resources Control Board and carried out in cooperation with the U.S. Geological Survey. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

Age-related peculiarities of contractile activity of rat myocardium during blockade of hyperpolarization-activated currents.

PubMed

Zefirov, T L; Gibina, A E; Sergejeva, A M; Ziyatdinova, N I; Zefirov, A L

2007-09-01

Contractile activity of atrial and ventricular myocardial strips isolated from rats of various age was examined under conditions of blockade of non-selective hyperpolarization-activated cation currents. Addition of ZD7288, a blocker of non-selective hyperpolarization-activated cation currents, to the perfusion solution increased the contraction force of atrial and ventricular strips in 1-, 8-, and 20-week rats, but produced an opposite effect on contractile activity of atrial and ventricular strips in 3-week rats.

Potential and tension changes induced by sodium removal in dog Purkinje fibres: role of an electrogenic sodium-calcium exchange.

PubMed Central

Croaboeuf, E; Gautier, P; Giuraudou, P

1981-01-01

1. Isolated dog Purkinje fibres were bathed in K-free media or in the presence of ouabain 10(-4) M in order to depress the electrogenic sodium pump activity. Membrane potential and mechanical tension were recorded in the presence of normal external sodium concentration and during lowering or removal of external Na. 2. Lowering or removal of external Na (Na being replaced by choline, Tris, sucrose or Li) induced a hyperpolarization and a contracture which reached a maximum after 1 or 2 min and then decreased progressively. Using Tris, Em increased from -40 +/- 3 to -72 +/- 10 mV (n = 39). The Na-free contracture and hyperpolarization did not occur in the absence of Na pump depression. 3. Tetrodotoxin (1.2 x 10(-5)M), Mn (4 mM), verapamil (1-4 x 10(-5) M) tetraethylammonium (5 mM), 4-aminopyridine (5 mM) and Cs (20 mM, in the presence of ouabain) did not alter the Na-free contracture and hyperpolarization. On the other hand Mn (20 mM), acid media (external pH less than 6.0) and low temperatures depressed or suppressed both the hyperpolarization and contracture. Lanthanum (0.4 mM) did not suppress the hyperpolarization and the contracture. On the contrary the Na-free contracture was generally increased in the presence of La. 4. Caffeine (10 mM) induced strong contractures with no changes in Em, thus demonstrating the possibility for the Purkinje fibers of developing contractures without concomitant hyperpolarizations. 5. It can be concluded that the Na-free contracture and hyperpolarization are not due to changes in passive conductances but are related to the functioning of an electrogenic Na-Ca exchange mechanism which carries inwardly 1 Ca and outwardly 3 or more Na. Images Fig. 1 PMID:7264984

Vascular Reactivity Profile of Novel KCa 3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed.

PubMed

Oliván-Viguera, Aida; Valero, Marta Sofía; Pinilla, Estéfano; Amor, Sara; García-Villalón, Ángel Luis; Coleman, Nichole; Laría, Celia; Calvín-Tienza, Víctor; García-Otín, Ángel-Luis; Fernández-Fernández, José M; Murillo, M Divina; Gálvez, José A; Díaz-de-Villegas, María D; Badorrey, Ramón; Simonsen, Ulf; Rivera, Luis; Wulff, Heike; Köhler, Ralf

2016-08-01

Opening of intermediate-conductance calcium-activated potassium channels (KC a 3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KC a 3.1-selective positive-gating modulators, SKA-111 and SKA-121, to (1) evoke porcine endothelial cell KC a 3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KC a currents evoked by bradykinin (BK) were potentiated ≈7-fold by either SKA-111 or SKA-121 (both at 1 μM) and were blocked by a KC a 3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinin-induced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by ≈2-fold. Potentiation of the BK response was prevented by KC a 3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KC a 3.1 channels improves BK-induced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KC a 3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.

PubMed

Timm, Kerstin N; Hartl, Johannes; Keller, Markus A; Hu, De-En; Kettunen, Mikko I; Rodrigues, Tiago B; Ralser, Markus; Brindle, Kevin M

2015-12-01

A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells. © 2014 Wiley Periodicals, Inc.

Pipe and grain boundary diffusion of He in UO 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galvin, C. O.T.; Cooper, M. W. D.; Fossati, P. C. M.

Molecular dynamics simulations have been conducted to study the effects of dislocations and grain boundaries on He diffusion inmore » $$\\text{U}{{\\text{O}}_{2}}$$ . Calculations were carried out for the {100}, {110} and {111} $$\\langle 1\\,1\\,0\\rangle $$ edge dislocations, the screw $$\\langle 1\\,1\\,0\\rangle $$ dislocation and Σ5, Σ13, Σ19 and Σ25 tilt grain boundaries. He diffusivity as a function of distance from the dislocation core and grain boundaries was investigated for the temperature range 2300–3000 K. An enhancement in diffusivity was predicted within 20 Å of the dislocations or grain boundaries. Further investigation showed that He diffusion in the edge dislocations follows anisotropic behaviour along the dislocation core, suggesting that pipe diffusion occurs. Here, an Arrhenius plot of He diffusivity against the inverse of temperature was also presented and the activation energy calculated for each structure, as a function of distance from the dislocation or grain boundary.« less

Pipe and grain boundary diffusion of He in UO 2

DOE PAGES

Galvin, C. O.T.; Cooper, M. W. D.; Fossati, P. C. M.; ...

2016-10-12

Molecular dynamics simulations have been conducted to study the effects of dislocations and grain boundaries on He diffusion inmore » $$\\text{U}{{\\text{O}}_{2}}$$ . Calculations were carried out for the {100}, {110} and {111} $$\\langle 1\\,1\\,0\\rangle $$ edge dislocations, the screw $$\\langle 1\\,1\\,0\\rangle $$ dislocation and Σ5, Σ13, Σ19 and Σ25 tilt grain boundaries. He diffusivity as a function of distance from the dislocation core and grain boundaries was investigated for the temperature range 2300–3000 K. An enhancement in diffusivity was predicted within 20 Å of the dislocations or grain boundaries. Further investigation showed that He diffusion in the edge dislocations follows anisotropic behaviour along the dislocation core, suggesting that pipe diffusion occurs. Here, an Arrhenius plot of He diffusivity against the inverse of temperature was also presented and the activation energy calculated for each structure, as a function of distance from the dislocation or grain boundary.« less

Molecular dynamics computer simulation of permeation in solids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.

1997-12-31

In this work the authors simulate permeation of gases and cations in solid models using molecular mechanics and a dual control volume grand canonical molecular dynamics technique. The molecular sieving nature of microporous zeolites are discussed and compared with that for amorphous silica made by sol-gel methods. One mesoporous and one microporous membrane model are tested with Lennard-Jones gases corresponding to He, H{sub 2}, Ar and CH{sub 4}. The mesoporous membrane model clearly follows a Knudsen diffusion mechanism, while the microporous model having a hard-sphere cutoff pore diameter of {approximately}3.4 {angstrom} demonstrates molecular sieving of the methane ({sigma} = 3.8more » {angstrom}) but anomalous behavior for Ar ({sigma} = 3.4 {angstrom}). Preliminary results of Ca{sup +} diffusion in calcite and He/H{sub 2} diffusion in polyisobutylene are also presented.« less

Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro.

PubMed

Van den Hooff, P; Galvan, M

1992-08-01

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.

3D hyperpolarized C-13 EPI with calibrationless parallel imaging

NASA Astrophysics Data System (ADS)

Gordon, Jeremy W.; Hansen, Rie B.; Shin, Peter J.; Feng, Yesu; Vigneron, Daniel B.; Larson, Peder E. Z.

2018-04-01

With the translation of metabolic MRI with hyperpolarized 13C agents into the clinic, imaging approaches will require large volumetric FOVs to support clinical applications. Parallel imaging techniques will be crucial to increasing volumetric scan coverage while minimizing RF requirements and temporal resolution. Calibrationless parallel imaging approaches are well-suited for this application because they eliminate the need to acquire coil profile maps or auto-calibration data. In this work, we explored the utility of a calibrationless parallel imaging method (SAKE) and corresponding sampling strategies to accelerate and undersample hyperpolarized 13C data using 3D blipped EPI acquisitions and multichannel receive coils, and demonstrated its application in a human study of [1-13C]pyruvate metabolism.

A hybrid multibreath wash-in wash-out lung function quantification scheme in human subjects using hyperpolarized 3 He MRI for simultaneous assessment of specific ventilation, alveolar oxygen tension, oxygen uptake, and air trapping.

PubMed

Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Siddiqui, Sarmad; Gatens, Heather; Naji, Joseph; Ishii, Masaru; Cereda, Maurizio; Rossman, Milton; Rizi, Rahim

2017-08-01

To present a method for simultaneous acquisition of alveolar oxygen tension (P A O 2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the P A O 2 and SV maps to produce a map of oxygen uptake (R). An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, P A O 2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. The overall whole lung ADC, SV, P A O 2 , and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm 2 /s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm 2 /s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm 2 /s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, P A O 2 , and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med 78:611-624, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Radiogenic helium in shallow groundwater within a clay till, southwestern Ontario

USGS Publications Warehouse

Sheldon, Amy L.; Solomon, D. Kip; Poreda, Robert J.; Hunt, Andrew

2003-01-01

Profiles of 4He in pore water were measured in clay aquitards in SW Ontario. The 4He distributions are consistent with groundwater velocities that are <6 mm yr−1, and thus diffusion is the dominant transport mechanism for 4He. Modeling indicates that the effective diffusion coefficient for 4He is 6.3 ± 1.6 × 10−6 cm2 s−1. Furthermore, the profiles are consistent with the internal release of 4He from aquitard sediments at a rate of 0.03–0.13 μcc(STP) kg−1 yr−1. These rates are also consistent with laboratory release experiments and, on average, are 600 times greater than the production of 4He from U/Th decay. Modeling and the ratio of 21Ne to 4He within the sediments indicate that although the aquitards were deposited about 13 kA BP, the sediments released >70% of initial 4He for 50 to 60 kA prior to incorporation into the till.

Preservation of extraterrestrial 3He in 480-Ma-old marine limestones.

PubMed

Patterson, D B; Farley, K A; Schmitz, B

1998-11-01

We have measured the helium abundance and isotopic composition of a suite of Lower Ordovician marine limestones and associated fossil meteorites from Kinnekulle, Sweden. Limestone 3He/4He ratios as high as 11.5 times the atmospheric value in fused samples and up to 23 times atmospheric in a single step-heat fraction indicate the presence of extraterrestrial helium, and demonstrate that at least a fraction of the extraterrestrial 3He carried by interplanetary dust particles must be retained against diffusive and diagenetic losses for up to 480 Ma. The carrier phase has not been identified but is not magnetic. Extrapolation of high-temperature 3He diffusivities in these sediments is consistent with strong retention of extraterrestrial 3He under ambient Earth-surface conditions. Combination of the observed helium concentrations with sedimentation rates estimated from conodont biostratigraphy suggest that the flux of extraterrestrial 3He in the Early Ordovician was about 0.5 x 10(-12) cm3 STP cm-2 ka-1, ignoring potential post-deposition helium loss. This value is indistinguishable from the average 3He flux estimated for the Cenozoic Era. In contrast, previous studies of fossil meteorites, Ir abundances, and Os isotopic ratios in the limestone suggest that the total accretion rate of extraterrestrial material during the studied interval was at least an order of magnitude higher than the Cenozoic average. This disparity may reflect significant post-depositional loss of 3He from IDPs within these old limestones; if so, the match between the Ordovician flux and the Cenozoic average would be fortuitous. Alternatively, the size distribution of infalling objects during the Early Ordovician may have been enriched only in extraterrestrial material too large to retain 3He during atmospheric entry heating (> approximately 30 micrometers). The fossil meteorites themselves also preserve extraterrestrial helium. Meteorite 3He concentrations of 2 to 9 x 10(-12) cm3 STP g-1 are several orders of magnitude lower than found in most modern meteorites, suggesting very substantial helium loss (probably >99.9%) from these chemically altered objects. The Meteorites carry 3He concentrations only a factor of a few higher than the host limestones. The meteorites themselves cannot be the source of the extraterrestrial 3He observed in the limestones.

Catecholamines release mediators in the opossum oesophageal circular smooth muscle.

PubMed Central

Daniel, E E; Jager, L P; Jury, J

1987-01-01

1. Effects of catecholamines applied exogenously to the circular smooth muscle layer of the body of the oesophagus of the opossum (Didelphis marsupialis) were studied, simultaneously measuring changes in the membrane potential, the membrane conductance and the contractility of the muscle, using the double sucrose-gap technique. 2. Superfusion of the smooth muscle with Krebs solution at 27 degrees C containing dopamine (10(-6)-10(-4) M) dose-dependently caused a hyperpolarization of the smooth muscle cells and an increased membrane resistance followed after gradual repolarization by oscillations of the membrane potential, often accompanied by muscle action potentials. During the hyperpolarization, the tendency for the membrane potential to sag during prolonged application of hyperpolarizing currents was reduced and the 'off' depolarization following such currents was increased. This muscle did not develop active tension prior to treatment; it therefore did not relax during the hyperpolarizations, but contracted following the depolarized phase of oscillations. 3. The non-adrenergic, non-cholinergic nerve-mediated inhibitory junction potential (i.j.p.) showed a small reduction in amplitude during superfusion with dopamine, explicable as a result of the drug-induced hyperpolarization. The 'off' response following the i.j.p., decreased transiently when the membrane potential was hyperpolarized to its maximum value. Then it increased to values larger than control as the membrane repolarized. Vasoactive intestinal polypeptide (VIP, 10(-6) M) produced a similar response but hyperpolarizations were smaller. 4. Of the tested catecholamines, isoprenaline, phenylephrine, butylated hydroxytoluene-920 (BHT-920) and clonidine were ineffective whereas the potency order for other catecholamines was dopamine greater than noradrenaline greater than or equal to adrenaline greater than DOPA. The catecholamine-induced responses were not affected by alpha- or beta-adrenoreceptor antagonists given alone or in combination. Of the dopamine receptor antagonists tested domperidone was without effect, whereas haloperidol reduced and bulbocapnine blocked the response. The findings suggested that a receptor resembling DA1-type peripheral receptor mediated the effects of dopamine on opossum oesophagus. 5. The catecholamine-induced responses and those to VIP disappeared completely in Cl-(-)free medium (isethionate replacement). 6. Conditioning depolarization of the smooth muscle cells decreased but hyperpolarization increased the amplitude of the hyperpolarization (up to 20 mV). With larger hyperpolarizations the responses decreased and disappeared at around 50 mV hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3625558

Fast Dynamic 3D MRSI with Compressed Sensing and Multiband Excitation Pulses for Hyperpolarized 13C Studies

PubMed Central

Larson, Peder E. Z.; Hu, Simon; Lustig, Michael; Kerr, Adam B.; Nelson, Sarah J.; Kurhanewicz, John; Pauly, John M.; Vigneron, Daniel B.

2010-01-01

Hyperpolarized 13C MRSI can detect not only the uptake of the pre-polarized molecule but also its metabolic products in vivo, thus providing a powerful new method to study cellular metabolism. Imaging the dynamic perfusion and conversion of these metabolites provides additional tissue information but requires methods for efficient hyperpolarization usage and rapid acquisitions. In this work, we have developed a time-resolved 3D MRSI method for acquiring hyperpolarized 13C data by combining compressed sensing methods for acceleration and multiband excitation pulses to efficiently use the magnetization. This method achieved a 2 sec temporal resolution with full volumetric coverage of a mouse, and metabolites were observed for up to 60 sec following injection of hyperpolarized [1-13C]-pyruvate. The compressed sensing acquisition used random phase encode gradient blips to create a novel random undersampling pattern tailored to dynamic MRSI with sampling incoherency in four (time, frequency and two spatial) dimensions. The reconstruction was also tailored to dynamic MRSI by applying a temporal wavelet sparsifying transform in order to exploit the inherent temporal sparsity. Customized multiband excitation pulses were designed with a lower flip angle for the [1-13C]-pyruvate substrate given its higher concentration than its metabolic products ([1-13C]-lactate and [1-13C]-alanine), thus using less hyperpolarization per excitation. This approach has enabled the monitoring of perfusion and uptake of the pyruvate, and the conversion dynamics to lactate and alanine throughout a volume with high spatial and temporal resolution. PMID:20939089

Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange

PubMed Central

2015-01-01

Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene)] for signal amplification by reversible exchange (SABRE) was monitored by in situ hyperpolarized proton NMR at 9.4 T. During the catalyst-activation process, the COD moiety undergoes hydrogenation that leads to its complete removal from the Ir complex. A transient hydride intermediate of the catalyst is observed via its hyperpolarized signatures, which could not be detected using conventional nonhyperpolarized solution NMR. SABRE enhancement of the pyridine substrate can be fully rendered only after removal of the COD moiety; failure to properly activate the catalyst in the presence of sufficient substrate can lead to irreversible deactivation consistent with oligomerization of the catalyst molecules. Following catalyst activation, results from selective RF-saturation studies support the hypothesis that substrate polarization at high field arises from nuclear cross-relaxation with hyperpolarized 1H spins of the hydride/orthohydrogen spin bath. Importantly, the chemical changes that accompanied the catalyst’s full activation were also found to endow the catalyst with water solubility, here used to demonstrate SABRE hyperpolarization of nicotinamide in water without the need for any organic cosolvent—paving the way to various biomedical applications of SABRE hyperpolarization methods. PMID:25372972

Towards hyperpolarized 13C-succinate imaging of brain cancer

PubMed Central

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2009-01-01

We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADE-NA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood–brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. PMID:17303454

Towards hyperpolarized 13C-succinate imaging of brain cancer

NASA Astrophysics Data System (ADS)

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2007-05-01

We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

Single-Grain (U-Th)/He Ages of Phosphates from St. Severin Chondrite

NASA Astrophysics Data System (ADS)

Min, K. K.; Reiners, P. W.; Shuster, D. L.

2010-12-01

Thermal evolution of chondrites provides valuable information on the heat budget, internal structure and dimensions of their parent bodies once existed before disruption. St. Severin LL6 ordinary chondrite is known to have experienced relatively slow cooling compared to H chondrites. The timings of primary cooling and subsequent thermal metamorphism were constrained by U/Pb (4.55 Ga), Sm/Nd (4.55 Ga), Rb/Sr (4.51 Ga) and K/Ar (4.4 Ga) systems. However, cooling history after the thermal metamorphism in a low temperature range (<200 °C) is poorly understood. In order to constrain the low-T thermal history of this meteorite, we performed (1) single-grain (U-Th)/He dating for five chlorapatite and fourteen merrillite aggregates from St. Severin, (2) examination of textural and chemical features of the phosphate aggregates using a scanning electron microscope (SEM), and (3) proton-irradiation followed by 4He and 3He diffusion experiments for single grains of chlorapatite and merrillite from Guarena meteorite, for general characterization of He diffusivity in these major U-Th reservoirs in meteorites. The α-recoil-uncorrected ages from St. Severin are distributed in a wide range of 333 ± 6 Ma and 4620 ± 1307 Ma. The probability density plot of these data shows a typical younging-skewed age distribution with a prominent peak at ~ 4.3 Ga. The weighted mean of the nine oldest samples is 4.284 ± 0.130 Ga, which is consistent with the peak of the probability plot. The linear dimensions of the phosphates are generally in the range of ~50 µm to 200 µm. The α recoil correction factor (FT) based on the morphology of the phosphate yields improbably old ages (>4.6 Ga), suggesting that within the sample aggregates, significant amounts of the α particles ejected from phosphates were implanted into the adjacent phases and therefore that this correction may not be appropriate in this case. The minimum FT value of 0.95 is calculated based on the peak (U-Th)/He age and 40Ar/39Ar data which provide the upper limit of the α-recoil-corrected (U-Th)/He ages. From these data, we conclude that the St. Severin cooled through the closure temperatures of chlorapatite and merrillite during ~4.3 - 4.4 Ga. The radiogenic 4He and proton-induced 3He diffusion experiments yield two well-defined linear trends in Arrhenius plot for chlorapatite (r = 43 µm) and merrillite (r = 59 µm) grains. The linear regression of 3He data for chlorapatite yields Ea = 128.1 ± 2.4 kJ/mol, and ln(Do/a2) = 11.6 ± 0.5 ln(s-1) which are generally consistent with the terrestrial Durango apatite and meteoritic Acapulco apatite. Linear regression to the merrillite data corresponds to Ea = 135.1 ± 2.5 kJ/mol, and ln(Do/a2) = 5.73 ± 0.37 ln(s-1). The new data indicate that diffusive retentivity of He within merrillite is significantly higher than that of chlorapatite, which has implications for quantitative interpretation of He ages measured in meteoritic phosphates.

Measuring radial profiles of nuclear burn in ICF implosions at OMEGA and the NIF using proton emission imaging

NASA Astrophysics Data System (ADS)

Seguin, F. H.; Rinderknecht, H. G.; Rosenberg, M.; Zylstra, A.; Frenje, J.; Li, C. K.; Petrasso, R.; Marshall, F. J.; Sangster, T. C.; Hoffman, N. M.; Amendt, P. A.; Bellei, C.; Le Pape, S.; Wilks, S. C.

2014-10-01

Fusion reactions in ICF implosions of D3He-filled capsules produce 14.7-MeV D3He protons and 3-MeV DD protons. Measurements of the spatial distributions of the D3He and DD reactions are studied with a penumbral imaging system that utilizes a CR-39-based imaging detector to simultaneously record separate penumbral images of the two types of protons. Measured burn profiles are useful for studying implosion physics and provide a critical test for benchmarking simulations. Recent implosions at OMEGA of CD capsules containing 3He gas fill and SiO2 capsules containing low-pressure D3He gas were expected to have hollow D3He burn profiles (in the 3He-filled capsule, due to fuel-shell mix), but penumbral imaging showed that the reactions were centrally peaked due to enhanced ion diffusion. The imaging technique is to be implemented soon on the NIF. This work was supported in part by NLUF, DOE, and LLE.

On the 3He anomaly in hot subdwarf B stars

NASA Astrophysics Data System (ADS)

Schneider, David; Irrgang, Andreas; Heber, Ulrich; Nieva, Maria F.; Przybilla, Norbert

2017-12-01

Decades ago, 3He isotope enrichment in helium-weak B-type main-sequence, in blue horizontal branch and in hot subdwarf B (sdB) stars, i.e., helium-core burning stars of the extreme horizontal branch, were discovered. Diffusion processes in the atmosphere of these stars lead to the observed abundance anomalies. Quantitative spectral analyses of high-resolution spectra to derive photospheric isotopic helium abundance ratios for known 3He sdBs have not been performed yet. We present preliminary results of high-resolution and high S/N spectra to determine the 3He and 4He abundances of nine known 3He sdBs. We used a hybrid local/non-local thermodynamic equilibrium (LTE/NLTE) approach for B-type stars investigating multiple He i lines, including λ4922 Å and λ6678 Å, which show the strongest isotopic shifts in the optical spectral range.We also report the discovery of four new 3He sdBs from the ESO Supernova Progenitor survey. Most of the 3He sdBs cluster in a narrow temperature strip between ˜ 26000 K and ˜ 30000 K and have almost no atmospheric 4He at all. Interestingly, three 3He sdBs show evidence for vertical helium stratification.

Retention and diffusion of H, He, O, C impurities in Be

NASA Astrophysics Data System (ADS)

Zhang, Pengbo; Zhao, Jijun; Wen, Bin

2012-04-01

We report the energetics and diffusion behavior of H, He, O, and C impurities in beryllium as fusion materials from first-principles calculations. Among the six interstitial sites in Be, the basal tetrahedral one is most stable for H, He, O, while C prefers to occupy an octahedral site. Solution of O impurity in Be is an exothermic process with solution energy of -2.37 eV, whereas solution of H, C and He is an endothermic process (solution energy: 1.55 eV, 2.46 eV, and 5.70 eV, respectively). Overall speaking, these impurities prefer to diffuse along longer paths. The H and O impurities share the same out-of-plane diffusion path via basal tetrahedral sites, while the He and C impurities in Be mainly diffuse via basal tetrahedral and octahedral sites along the (0 0 1) plane. Diffusion of He in Be is easiest with a lowest barrier of 0.14 eV; whereas H diffusion in Be is also rather fast with migration energies of 0.4 eV. On the contrary, diffusion of C and O impurities is more difficult because of strong bonding with lattice atoms and high energy barriers of 0.42 and 1.63 eV, respectively. Our theoretical results provide the fundamental parameters for understanding the impurity aggregation and bubble formation in early stage of irradiation damage.

Volcanic soil gas 4He/CO2 ratio: a useful geochemical tool for eruption forecasting

NASA Astrophysics Data System (ADS)

Asensio-Ramos, M.; Perez, N. M.; Padron, E.; Melián, G.; Hernandez Perez, P. A.; Padilla, G.; Barrancos, J.; Rodríguez, F.; Sumino, H.; Calvo, D.

2016-12-01

Magmatic gases that percolate through volcano's porous flanks in a non-visible (diffuse) way disturb the chemical composition of soil gases at the surface environment of the volcano, generating enrichments of CO2, He and other gases. Two of the gases which have attracted attention in soil degassing studies are He and CO2 because both species have similar low solubility in silicate melts. However, once they are exsolved from the melts, their movement through the crust towards the surface is very different: CO2, which is a reactive gas, is affected by the occurrence of interfering processes, while interaction of He during its ascent is minimum. Their geochemical differences yield higher relative He/CO2 ratios in the fumarole gases than is actually present in the magma, but it decreases when the magma reservoir reaches enough pressure to generate incipient fracture systems approaching the eruption. In this work, we present quasi daily estimations of diffusive He through the whole surface of El Hierro, the youngest island of the Canarian archipelago, considering He emission data reported in the literature (Padrón et al., 2013. Geology, 41, 539-542), using the same procedure as for diffuse CO2 emission time series (Melián et al., 2014. J. Geophys. Res., 119, 6976-6991). After the occurrence of more than 11,000 seismic events, a shallow submarine eruption about 2 km off the south coast in the southernmost part of El Hierro, started in October 12, 2011 and lasted for 5 month. The herein presented methodology enables the calculation of the diffuse He/CO2 emission ratio of the entire island during the volcanic unrest. Two different emission peaks for both He and CO2, with approximately the same delay between them ( 23 days), were observed. The combination of both time series resulted in a drastic increase in the He/CO2 emission ratio of the island (up to 1.1×10-3) two weeks before the eruption onset. Additionally, a second significant He/CO2 emission peak (up to 5.5×10-4) was observed between 3 and 4 November, some days before the highest lava emission period. The detailed time series of He/CO2 emission ratio during El Hierro 2011-2012 submarine eruption presented here demonstrate the importance of its continuous monitoring in active volcanic regions, mainly in areas without visible manifestations of volcanic fluid discharges.

Effect of membrane hyperpolarization induced by a K+ channel opener on histamine-induced Ca2+ mobilization in rabbit arterial smooth muscle.

PubMed

Watanabe, Y; Suzuki, A; Suzuki, H; Itoh, T

1996-03-01

1. The role of membrane hyperpolarization on agonist-induced contraction was investigated in intact and alpha-toxin-skinned smooth muscles of rabbit mesenteric artery by use of the ATP-sensitive K+ channel opener, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2- dimethyl-2H-1-benzopyran-3-ol (Y-26763), and either histamine (Hist) or noradrenaline (NA). 2. Hist (3 microM) and NA (10 microM) both produced a phasic, followed by a tonic increase in intracellular Ca2+ concentration ([Ca2+]i) and force. Y-26763 (10 microM) potently inhibited the NA-induced phasic and tonic increase in [Ca2+]i and force. In contrast, Y-26763 attenuated the Hist-induced phasic increase in [Ca2+]i and force but had almost no effect on the tonic response. However, ryanodine-treatment of muscles in order to inhibit the function of intracellular Ca2+ storage sites altered the action of Y-26763 which now attenuated the Hist-induced tonic increase in [Ca2+]i and force in a concentration-dependent manner (at concentrations > 1 microM). Glibenclamide (10 microM) attenuated the inhibitory action of Y-26763. 3. Hist (3 microM) depolarized the smooth muscle cells to the same extent as NA (10 microM). In the absence of either agonist, Y-26763 (over 30 nM) hyperpolarized the membrane and glibenclamide inhibited this hyperpolarization. Y-26763 (10 microM) almost abolished the NA-induced membrane depolarization, but only slightly attenuated the Hist-induced membrane depolarization in which the delta (delta) value (the difference before and after application of Hist) was not modified by any concentration of Y-26763. In ryanodine-treated smooth muscle cells, Y-26763 hyperpolarized the membrane and potently inhibited the membrane depolarization induced by Hist. 4. In ryanodine-treated muscle, Y-26763 had no measurable effect on the Hist-induced [Ca2+]i-force relationship. Y-26763 also had no apparent effect on the myofilament Ca(2+)-sensitivity in the presence of Hist in alpha-toxin-skinned smooth muscles. 5. It is concluded that the membrane hyperpolarization induced by Y-26763 may not be enough to inhibit the Hist-activated Ca2+ influx. It is also suggested that Hist prevents the membrane hyperpolarization induced by Y-26763, activating an unknown mechanism which is thought to depend on the function of intracellular Ca2+ storage sites.

A rare case of short stature: Say Meyer syndrome.

PubMed

Karthik, T S; Prasad, N Rajendra; Rani, P Radha; Maheshwari, Rushikesh; Reddy, P Amaresh; Chakradhar, B V S; Menon, Bindu

2013-10-01

Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. We are reporting a case of Say Meyer syndrome presented to our hospital for short stature and developmental delay at age 3½ years. A 3½-year-old boy presented to our hospital for decreased growth velocity from the age of 1 year. History revealed the boy had a birth weight of 2.3 kg, had an episode of seizures in the neonatal period. He was born to non-consanguineous marriage. He had global developmental delay and there was a lack of bowel and bladder control. History did not reveal any hearing or visual impairment. No history of any chronic systemic illnesses. Magnetic resonance imaging (MRI) brain revealed mild diffuse frontotemporal atrophy with multiple irregular gliotic areas in bilateral frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres. Diffuse thinning of corpus callosum. Diffuse periventricular hyper intensity on T2W and fluid attenuated inversion recovery sequences. Say Meyer syndrome is rare X linked condition characterized by developmental delay, short stature and metopic suture synostosis. Characteristic MRI brain findings include diffuse frontotemporal atrophy with multiple gliotic areas in frontal lobes. Diffuse white matter volume loss in bilateral cerebral hemispheres.

Studies of multi-ion-fluid yield anomaly in shock-driven implosions

NASA Astrophysics Data System (ADS)

Rinderknecht, H. G.; Rosenberg, M. J.; Li, C. K.; Zylstra, A. B.; Sio, H.; Gatu Johnson, M.; Frenje, J. A.; Séguin, F. H.; Petrasso, R. D.; Amendt, P. A.; Bellei, C.; Wilks, S. C.; Zimmerman, G.; Hoffman, N. M.; Kagan, G.; Molvig, K.; Glebov, V. Yu.; Stoeckl, C.; Marshall, F. J.; Seka, W.; Delettrez, J. A.; Sangster, T. C.; Betti, R.; Goncharov, V. N.; Meyerhofer, D. D.

2014-10-01

A. NIKROO, GA - Anomalously reduced yields relative to hydrodynamically calculated values have been observed for mixtures of D:3He compared to pure D2 gas-filled implosions in a series of shock-driven implosions at OMEGA. An extensive suite of measurements including temporal and spatial measurements of both the DD- and D3He-fusion reactions were obtained to identify the origin and physics behind this anomalous yield reduction. Measured spectral linewidths of fusion products suggest that the D ions are not thermalized to 3He during the burn, contributing to the reduced yield. The hypothesis that ion-species separation due to diffusive processes contributes to the observed yield reduction is explored using hydrodynamic simulations incorporating ion diffusion. Recent observations by Rosenberg et al. of a yield reduction with increased ion-ion mean free path do not explain the observed anomalous yield trend. Future work that will directly probe species separation with high-precision relative fusion reaction rate measurements between DD-neutrons and D3He-protons using the DualPTD instrument is discussed. This work was supported in part by the U.S. DOE, NLUF, LLE, and LLNL.

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized 13 C,15 N-Urea.

PubMed

Bertelsen, Lotte B; Nielsen, Per M; Qi, Haiyun; Nørlinger, Thomas S; Zhang, Xiaolu; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2017-04-01

In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient. Hyperpolarized three-dimensional balanced steady state 13 C MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group. A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription. MRI and hyperpolarized [ 13 C, 15 N]urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77:1650-1655, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Crucial importance of the endothelial K+ channel SK3 and connexin40 in arteriolar dilations during skeletal muscle contraction.

PubMed

Milkau, Malte; Köhler, Ralf; de Wit, Cor

2010-09-01

Skeletal muscle activity requires substantial increases in blood flow, and the underlying vasodilation involves endothelial activity, but the contribution of the endothelium-dependent hyperpolarizing factor (EDHF) is only poorly defined. In EDHF signaling, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels SK3 and IK1 is a key step and also initiates gap junction-dependent conducted dilations. We assessed the role of SK3, IK1, and connexin40 (Cx40) in muscular contraction-induced dilations in the microcirculation in vivo. Hitherto, arterioles were observed in the electrically stimulated cremaster skeletal muscle of anesthetized mice lacking SK3, IK1, or Cx40 using intravital microscopy. Genetic deficiency of SK3, but not of IK1, strongly attenuated dilations to muscular contraction. Similarly, pharmacologic blockade of SK3 by the specific blocker UCL1684 impaired such dilations in wild-type and IK1-deficient mice. In contrast, IK1 was required for acetylcholine-induced dilations. Genetic deficiency of Cx40 also attenuated dilations induced by muscular contraction but not by acetylcholine. These data support the concept that endothelial hyperpolarization through activation of SK3 contributes to exercise hyperemia and the hyperpolarization ascends the vascular tree through gap junctions formed by Cx40 to orchestrate dilation. The differential impact of SK3- and IK1-deficiency on dilations to distinct stimuli suggests stimulus-dependent activation of these endothelial channels.

Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

DTIC Science & Technology

2014-10-01

as a biomarker of tumor aggressiveness in a MR compatible 3D cell and tissue culture bioreactor ” to be presented at the ISMRM Workshop on Magnetic... Cell Carcinoma, Hyperpolarized 13C MR, Sub-renal capsule, patient derived tissue slice cultures , bioreactor 3. OVERALL PROJECT SUMMARY: Aim...grade from high grade RCCs using human TSCs cultured in a bioreactor . Aim 2:Identify HP 13C metabolic markers that discriminate low grade from

Involvement of a Na+/HCO-3 cotransporter in mouse sperm capacitation.

PubMed

Demarco, Ignacio A; Espinosa, Felipe; Edwards, Jennifer; Sosnik, Julian; De La Vega-Beltran, Jose Luis; Hockensmith, Joel W; Kopf, Gregory S; Darszon, Alberto; Visconti, Pablo E

2003-02-28

Mammalian sperm are incapable of fertilizing eggs immediately after ejaculation; they acquire fertilization capacity after residing in the female tract for a finite period of time. The physiological changes sperm undergo in the female reproductive tract that render sperm able to fertilize constitute the phenomenon of "sperm capacitation." We have demonstrated that capacitation is associated with an increase in the tyrosine phosphorylation of a subset of proteins and that these events are regulated by an HCO(3)(-)/cAMP-dependent pathway involving protein kinase A. Capacitation is also accompanied by hyperpolarization of the sperm plasma membrane. Here we present evidence that, in addition to its role in the regulation of adenylyl cyclase, HCO(3)(-) has a role in the regulation of plasma membrane potential in mouse sperm. Addition of HCO(3)(-) but not Cl(-) induces a hyperpolarizing current in mouse sperm plasma membranes. This HCO(3)(-)-dependent hyperpolarization was not observed when Na(+) was replaced by the non-permeant cation choline(+). Replacement of Na(+) by choline(+) also inhibited the capacitation-associated increase in protein tyrosine phosphorylation as well as the zona pellucida-induced acrosome reaction. The lack of an increase in protein tyrosine phosphorylation was overcome by the presence of cAMP agonists in the incubation medium. The lack of a hyperpolarizing HCO(3)(-) current and the inhibition of the capacitation-dependent increase in protein tyrosine phosphorylation in the absence of Na(+) suggest that a Na(+)/HCO(3)(-) cotransporter is present in mouse sperm and is coupled to events regulating capacitation.

Radiation damage-He diffusivity models applied to deep-time thermochronology: Zircon and titanite (U-Th)/He datasets from cratonic settings

NASA Astrophysics Data System (ADS)

Guenthner, W.; DeLucia, M. S.; Marshak, S.; Reiners, P. W.; Drake, H.; Thomson, S.; Ault, A. K.; Tillberg, M.

2017-12-01

Advances in understanding the effects of radiation damage on He diffusion in uranium-bearing accessory minerals have shown the utility of damage-diffusivity models for interpreting datasets from geologic settings with long-term, low-temperature thermal histories. Craton interiors preserve a billion-year record of long-term, long-wavelength vertical motions of the lithosphere. Prior thermochronologic work in these settings has focused on radiation damage models used in conjunction with apatite (U-Th)/He dates to constrain Phanerozoic thermal histories. Owing to the more complex damage-diffusivity relationship in zircon, the zircon (U-Th)/He system yields both higher and, in some cases, lower temperature sensitivities than the apatite system, and this greater range in turn allows researchers to access deeper time (i.e., Proterozoic) segments of craton time-temperature histories. Here, we show two examples of this approach by focusing on zircon (U-Th)/He datasets from 1.8 Ga granitoids of the Fennoscandian Shield in southeastern Sweden, and 1.4 Ga granites and rhyolites of the Ozark Plateau in southeastern Missouri. In the Ozark dataset, the zircon (U-Th)/He data, combined with a damage-diffusivity model, predict negative correlations between date and effective uranium (eU) concentration (a measurement proportional to radiation damage) from thermal histories that include an episode of Proterozoic cooling (interpreted as exhumation) following reheating (interpreted as burial) to temperature of 260°C at 850-680 Ma. In the Fennoscandian Shield, a similar damage model-based approach yields time-temperature constraints with burial to 217°C between 944 Ma and 851 Ma, followed by exhumation from 850 to 500 Ma, and burial to 154°C between 366 Ma and 224 Ma. Our Fennoscandian Shield samples also include titanite (U-Th)/He dates that span a wide range (945-160 Ma) and are negatively correlated with eU concentration, analogous to our zircon He dataset. These results support the initial findings of Baughman et al. (2017, Tectonics), and suggest that further research into the radiation damage effect on He diffusion in titanite could yield a comprehensive damage-diffusivity model for the titanite (U-Th)/He thermochronometer.

Helium Diffusion in Natural Xenotime

NASA Astrophysics Data System (ADS)

Anderson, A. J.; Hodges, K. V.; Van Soest, M. C.; Hanchar, J. M.

2017-12-01

Xenotime (nominally YPO4) occurs as an accessory mineral in felsic igneous rocks, pegmatites, and gneisses, often incorporating weight percent levels of U, Th, and REEs. Although commonly used for precise U-Pb geochronology, xenotime is seldom used for (U-Th)/He thermochronometry despite the fact that its high radionuclide content allows for the rapid accumulation of radiogenic He that could potentially allow for the precise dating of very young cooling events in active geologic settings. Xenotime's likely high concentrations of radiogenic 4He also make it a promising candidate for laser microprobe (U-Th)/He dating. Unfortunately, limited data are currently available for He diffusion in xenotime, and previous experimental studies of natural and synthetic xenotime have led to discrepant results (1). Published estimates of the (U-Th)/He closure temperature for xenotime based on these experiments range from 60˚C to 300˚C. In this contribution, we report new results for incremental step heating `bulk' 4He diffusion experiments on a fragment of a natural xenotime crystal from the Torghar district of the Khyber Agency in the Federally Administered Tribal Areas of Pakistan. Laser ablation 238U/206Pb dating of this crystal yields a crystallization age of 28.82 ± 0.13 Ma. The results of our He diffusion experiments- which display excellent linearity on an Arrhenius plot assuming a spherical geometry - indicate kinetic parameters of E 133 kJ/mol and ln(D0/a2) 10.9 s-1. Our results imply a preliminary (U-Th)/He closure temperature of 80˚C for xenotime crystals with a diffusion dimension of 220 μm. This closure temperature is much lower than that previously estimated for natural xenotime (1), and it is possible, perhaps likely, that He diffusion in natural xenotime crystals display a strong compositional dependency (1). Nevertheless, our experimental data suggest that near-end member (YPO4) xenotime has an intrinsic helium diffusivity consistent with a closure temperature comparable to that of the apatite (U-Th)/He thermochronometer. As a consequence, xenotime He chronometry may serve as a higher-precision alternative to apatite He chronometry for revealing low temperature cooling histories of rocks in which it crystallized. References: 1) Farley, 2007, Geochimica et Cosmochimica Acta, v. 71.

A helium-based model for the effects of radiation damage annealing on helium diffusion kinetics in apatite

NASA Astrophysics Data System (ADS)

Willett, Chelsea D.; Fox, Matthew; Shuster, David L.

2017-11-01

Widely used to study surface processes and the development of topography through geologic time, (U-Th)/He thermochronometry in apatite depends on a quantitative description of the kinetics of 4He diffusion across a range of temperatures, timescales, and geologic scenarios. Empirical observations demonstrate that He diffusivity in apatite is not solely a function of temperature, but also depends on damage to the crystal structure from radioactive decay processes. Commonly-used models accounting for the influence of thermal annealing of radiation damage on He diffusivity assume the net effects evolve in proportion to the rate of fission track annealing, although the majority of radiation damage results from α-recoil. While existing models adequately quantify the net effects of damage annealing in many geologic scenarios, experimental work suggests different annealing rates for the two damage types. Here, we introduce an alpha-damage annealing model (ADAM) that is independent of fission track annealing kinetics, and directly quantifies the influence of thermal annealing on He diffusivity in apatite. We present an empirical fit to diffusion kinetics data and incorporate this fit into a model that tracks the competing effects of radiation damage accumulation and annealing on He diffusivity in apatite through geologic time. Using time-temperature paths to illustrate differences between models, we highlight the influence of damage annealing on data interpretation. In certain, but not all, geologic scenarios, the interpretation of low-temperature thermochronometric data can be strongly influenced by which model of radiation damage annealing is assumed. In particular, geologic scenarios involving 1-2 km of sedimentary burial are especially sensitive to the assumed rate of annealing and its influence on He diffusivity. In cases such as basement rocks in Grand Canyon and the Canadian Shield, (U-Th)/He ages predicted from the ADAM can differ by hundreds of Ma from those predicted by other models for a given thermal path involving extended residence between ∼40-80 °C.

A 3He-129Xe co-magnetometer probed by a Rb magnetometer with Ramsey-pulse technique

NASA Astrophysics Data System (ADS)

Sheng, Dong; Kabcenell, Aaron; Romalis, Michael

2013-05-01

We report the recent progress in development of a new kind of co-magnetometer, benifiting from both the long spin coherence time of a noble gas and a highly sensitive alkali metal magnetometer. Due to the Fermi-contact interaction between alkali metal electron spin and noble gas nuclear spin the effective magnetization of the noble gas is enhanced by a factor of 6 to 600, allowing near quantum-limited detection of nuclear spins. Collisions between polarized alkali atoms and noble gas also introduce a large shift to the nuclear spin precession frequency. We reduce this effect by using Ramsey pulse techniques to measure the noble gas spin precession frequency ``in the dark'' by turning off the pumping laser between Ramsey pulses. A furthur reduction of the back-hyperpolarization from the noble gas can be achieved by controlling the cell temperature on short time scale. We showed that a 3He-129Xe Ramsey co-magnetometer is effective in cancelling fluctuations of external magnetic fields and gradients and developed cells with sufficient 129Xe T2 time without surface coatings. The new co-magnetometer has potential applications for many precision measurements, such as searches for spin-gravity couplings, electric dipole moments, and nuclear spin gyroscopes. Supported by DARPA.

Effects of K(+) channel openers on spontaneous action potentials in detrusor smooth muscle of the guinea-pig urinary bladder.

PubMed

Takagi, Hiroaki; Hashitani, Hikaru

2016-10-15

The modulation of spontaneous excitability in detrusor smooth muscle (DSM) upon the pharmacological activation of different populations of K(+) channels was investigated. Effects of distinct K(+) channel openers on spontaneous action potentials in DSM of the guinea-pig bladder were examined using intracellular microelectrode techniques. NS1619 (10μM), a large conductance Ca(2+)-activated K(+) (BK) channel opener, transiently increased action potential frequency and then prevented their generation without hyperpolarizing the membrane in a manner sensitive to iberiotoxin (IbTX, 100nM). A higher concentration of NS1619 (30μM) hyperpolarized the membrane and abolished action potential firing. NS309 (10μM) and SKA31 (100μM), small conductance Ca(2+)-activated K(+) (SK) channel openers, dramatically increased the duration of the after-hyperpolarization and then abolished action potential firing in an apamin (100nM)-sensitive manner. Flupirtine (10μM), a Kv7 channel opener, inhibited action potential firing without hyperpolarizing the membrane in a manner sensitive to XE991 (10μM), a Kv7 channel blocker. BRL37344 (10μM), a β3-adrenceptor agonist, or rolipram (10nM), a phosphodiesterase 4 inhibitor, also inhibited action potential firing. A higher concentration of rolipram (100nM) hyperpolarized the DSM and abolished the action potentials. IbTX (100nM) prevented the rolipram-induced blockade of action potentials but not the hyperpolarization. BK and Kv7 channels appear to predominantly contribute to the stabilization of DSM excitability. Spare SK channels could be pharmacologically activated to suppress DSM excitability. BK channels appear to be involved in the cyclic AMP-induced inhibition of action potentials but not the membrane hyperpolarization. Copyright © 2016 Elsevier B.V. All rights reserved.

Preferential inhibition of Ih in rat trigeminal ganglion neurons by an organic blocker.

PubMed

Janigro, D; Martenson, M E; Baumann, T K

1997-11-15

The potency and specificity of a novel organic Ih current blocker DK-AH 268 (DK, Boehringer) was studied in cultured rat trigeminal ganglion neurons using whole-cell patch-clamp recording techniques. In neurons current-clamped at the resting potential, the application of 10 microM DK caused a slight hyperpolarization of the membrane potential and a small increase in the threshold for action potential discharge without any major change in the shape of the action potential. In voltage-clamped neurons, DK caused a reduction of a hyperpolarization-activated current. Current subtraction protocols revealed that the time-dependent, hyperpolarization-activated currents blocked by 10 microM DK or external Cs+ (3 mM) had virtually identical activation properties, suggesting that DK and Cs+ caused blockade of the same current, namely Ih. The block of Ih by DK was dose-dependent. At the intermediate and higher concentrations of DK (10 and 100 microM) a decrease in specificity was observed so that time-independent, inwardly rectifying and noninactivating, voltage-gated outward potassium currents were also reduced by DK but to a much lesser extent than the time-dependent, hyperpolarization-activated currents. Blockade of the time-dependent, hyperpolarization-activated currents by DK appeared to be use-dependent since it required hyperpolarization for the effect to take place. Relief of DK block was also aided by membrane hyperpolarization. Since both the time-dependent current blocked by DK and the Cs+-sensitive time-dependent current behaved as Ih, we conclude that 10 microM DK can preferentially reduce Ih without a major effect on other potassium currents. Thus, DK may be a useful agent in the investigation of the function of Ih in neurons.

Helium diffusion in apatite assessed by ERDA and implications for (U-Th)/He dating

NASA Astrophysics Data System (ADS)

Stuebner, K.; Jonckheere, R.; Ratschbacher, L.

2006-12-01

The strength of a low-temperature geochronometer, like (U-Th)/He(apatite), lies in the low activation energy of He-diffusion, which makes the system sensitive to temperatures <100°C. A thorough understanding of the diffusion kinetics of He in apatite is crucial for the interpretation of (U-Th)/He ages. Diffusion parameters derived from high temperature step heating experiments and reported in the literature span a broad range: E_a=30-40 kcal/mol (1σ-error ~2 kcal/mol); ln(D0/a2)=8-26 s^-^1 or ln(D0)=8- 130 cm2/s and with the standard experimental setup it is not possible to determine the grain size independent parameter D0. We employ a new approach using Elastic Recoil Detection Analysis (ERDA) to characterise He diffusion at low temperatures. ERDA allows to measure element-concentration profiles across the upper 2 μm of 1x1cm plane surface samples. Implantation of high-dose (5E+15 ions cm2), low- energy Helium ions (50-250 keV) in polished thin sections of a large Durango apatite crystal produces narrow, near-Gaussian distribution of Helium at a depth <1 μm beneath the crystal surface. Diffusion results in normally distributed concentration-profiles across the initial layer. The He-profile is approximated by a Gaussian curve with variance σ2 = 2 D t = D0 exp(-E_a/RT) t. Dt increases exponentially with T and linearly with t, so that knowledge of the t-T conditions of a set of samples allows to calculate the diffusion parameters from the fitted Gauss-distributions. With this approach Helium diffusion is observed on a sub-μm scale, which allows not only a precise determination of E_a and D0, but also circumvents assumptions that are necessary for the step-heating approach (spherical diffusion geometry, dimension of the diffusion domain) and is independent of grain size or shape. It facilitates investigation of the dependence of diffusion on the crystallographic direction, on the anion composition (OH, F, Cl) of apatite and on the degree of radiogenic lattice damage.

Ultra-sensitive atomic magnetometer for studying magnetization fields produced by hyperpolarized helium-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zou, Sheng; Zhang, Hong; Fang, Jian-cheng, E-mail: fangjiancheng@buaa.edu.cn

2016-04-14

An ingenious approach to acquire the absolute magnetization fields produced by polarized atoms has been presented in this paper. The method was based on detection of spin precession signal of the hyperpolarized helium-3 with ultra-sensitive atomic magnetometer of potassium by referring to time-domain analysis. At first, dynamic responses of the mixed spin ensembles in the presence of variant external magnetic fields have been analyzed by referring to the Bloch equation. Subsequently, the relevant equipment was established to achieve the functions of hyperpolarizing helium-3 and detecting the precession of spin-polarized noble gas. By analyzing the transient response of the magnetometer inmore » time domain, we obtained the relevant damping ratio and natural frequency. When the value of damping ratio reached the maximum value of 0.0917, the combined atomic magnetometer was in equilibrium. We draw a conclusion from the steady response: the magnetization fields of the polarized electrons and the hyperpolarized nuclei were corresponding 16.12 nT and 90.74 nT. Under this situation, the nuclear magnetization field could offset disturbing magnetic fields perpendicular to the orientation of the electronic polarization, and it preserved the electronic spin staying in a stable axis. Therefore, the combined magnetometer was particularly attractive for inertial measurements.« less

Variable helium diffusion characteristics in fluorite

NASA Astrophysics Data System (ADS)

Wolff, R.; Dunkl, I.; Kempe, U.; Stockli, D.; Wiedenbeck, M.; von Eynatten, H.

2016-09-01

Precise analysis of the diffusion characteristics of helium in fluorite is crucial for establishing the new fluorite (U-Th-Sm)/He thermochronometer (FHe), which potentially provides a powerful tool for dating ore deposits unsuitable for the application of conventional geochronometers. Incremental helium outgassing experiments performed on fluorites derived from a spectrum of geological environments suggest a thermally activated volume diffusion mechanism. The diffusion behaviour is highly variable and the parameters range between log D0/a2 = 0.30 ± 0.27-7.27 ± 0.46 s-1 and Ea = 96 ± 3.5-182 ± 3.8 kJ/mol. Despite the fact that the CaF2 content of natural fluorites in most cases exceeds 99 weight percent, the closure temperature (Tc) of the fluorite (U-Th-Sm)/He thermochronometer as calculated from these diffusion parameters varies between 46 ± 14 °C and 169 ± 9 °C, considering a 125 μm fragment size. Here we establish that minor substitutions of calcium by rare earth elements and yttrium (REE + Y) and related charge compensation by sodium, fluorine, oxygen and/or vacancies in the fluorite crystal lattice have a significant impact on the diffusivity of helium in the mineral. With increasing REE + Y concentrations F vacancies are reduced and key diffusion pathways are narrowed. Consequently, a higher closure temperature is to be expected. An empirical case study confirms this variability: two fluorite samples from the same deposit (Horni Krupka, Czech Republic) with ca. 170 °C and ca. 43 °C Tc yield highly different (U-Th-Sm)/He ages of 290 ± 10 Ma and 79 ± 10 Ma, respectively. Accordingly, the fluorite sample with the high Tc could have quantitatively retained helium since the formation of the fluorite-bearing ores in the Permian, despite subsequent Mesozoic burial and associated regional hydrothermal heating. In contrast, the fluorite with the low Tc yields a Late Cretaceous age close to the apatite fission track (AFT) and apatite (U-Th)/He ages (AHe) from the same locality. Remarkably, thermal modelling of FHe yields comparable results to the well-established modelling based on AFT and AHe.

Primordial Noble Gases from Earth's Core

NASA Astrophysics Data System (ADS)

Wang, K.; Lu, X.; Brodholt, J. P.

2016-12-01

Recent partitioning experiment suggests helium is more compatible in iron melt than in molten silicates at high pressures (> 10 GPa) (1), thus provide the possibility of the core as being the primordial noble gases warehouse that is responsible for the high primordial/radiogenic noble gas isotopic ratios observed in plume-related basalts. However, the possible transportation mechanism of the noble gases from the core to the overlying mantle is still ambiguous, understanding how this process would affect the noble gas isotopic characteristics of the mantle is critical to validate this core reservoir model. As diffusion is a dominant mass transport process that plays an important role in chemical exchange at the core-mantle boundary (CMB), we have determined the diffusion coefficients of helium, neon and argon in major lower mantle minerals, i.e. periclase (MgO), bridgemanite (MgSiO3-Pv) and post-perovskite (MgSiO3-PPv), by first-principles calculation based on density functional theory (DFT). As expected, the diffusion rate of helium is the fastest at the CMB, which is in the range of 3 × 10-10 to 1 × 10-8 m2/s. The neon diffusion is slightly slower, from 5 × 10-10 to 5 × 10-9 m2/s. Argon diffuses slowest at the rate from 1 × 10-10 to 2 × 10-10 m2/s. We have further simulated the evolution of noble gas isotopic ratios in the mantle near the CMB. Considering its close relationship with the mantle plumes and very likely to be the direct source of "hot-spot" basalts, we took a close investigation on the large low-shear-velocity provinces (LLSVPs). Under reasonable assumptions based on our diffusion parameters, the modelling results indicate that LLSVP is capable of generating all the noble gas isotope signals, e.g., 3He/4He = 55 Ra, 3He/22Ne = 3.1, 3He/36Ar = 0.82, 40Ar/36Ar = 9500, that are in good agreement with the observed values in "hot-spot" basalts (2). Therefore, this core-reservior hypothesis is a self-consistent model that can fits in multiple noble gas isotopic constrains. (1) Bouhifd, M.A., Jephcoat, A.P., Heber, V.S., Kelley, S.P., 2013. Helium in Earth's early core. Nat. Geosci. 6, 982-986. (2) Mukhopadhyay, S., 2012. Early differentiation and volatile accretion recorded in deep-mantle neon and xenon. Nature 486, 101-124.

Hyperpolarized 13 C,15 N2 -Urea MRI for assessment of the urea gradient in the porcine kidney.

PubMed

Hansen, Esben S S; Stewart, Neil J; Wild, Jim M; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2016-12-01

A decline in cortico-medullary osmolality gradient of the kidney may serve as an early indicator of pathological disruption of the tubular reabsorption process. The purpose of this study was to investigate the feasibility of hyperpolarized 13 C, 15 N 2 -urea MRI as a biomarker of renal function in healthy porcine kidneys resembling the human physiology. Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a 13 C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized 13 C, 15 N 2 -urea via a femoral vein catheter. Images were acquired at different time points after urea injection, and following treatment with furosemide. A gradient in cortico-medullary urea was observed with an intramedullary accumulation 75 s after injection of hyperpolarized 13 C, 15 N 2 -urea, whereas images acquired at earlier time points postinjection were dominated by cortical perfusion. Furosemide treatment resulted in an increased urea accumulation in the cortical space, leading to a reduction of the medullary-to-cortical signal ratio of 49%. This study demonstrates that hyperpolarized 13 C, 15 N 2 -urea MRI is capable of identifying the intrarenal accumulation of urea and can differentiate acute renal functional states in multipapillary kidneys, highlighting the potential for human translation. Magn Reson Med 76:1895-1899, 2016. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Interatomic potentials for HeAr, HeKr, and HeXe from multiproperty fits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Danielson, L.J.; Keil, M.

1988-01-15

Crossed molecular beam measurements of differential cross sections (DCS) are reported for elastic scattering of He by Ar, Kr, and Xe at high resolution. Interatomic potentials are determined by simultaneously fitting the DCS's, as well as mixture viscosity and interaction second virial data. Bias due to systematic and potential model errors are examined and are used to estimate the accuracy of the potential energy curves obtained. Attractive well depths are 2.59, 2.67, and 2.64 meV +- 3% for HeAr, HeKr, and HeXe, respectively, agreeing with the best available HeAr potential and a previously proposed HeKr potential, but significantly deeper thanmore » previously reported potentials for HeXe. The HeXe attractive well is also considerably broader than previously reported. Attractive minimum positions are 3.48, 3.70, and 4.00 A ( +- 0.03 A) for HeAr, HeKr, and HeXe, respectively. Including the accurate diffusion data of Dunlop and co-workers (Physica A 95, 561 (1979)) and the absolute integral cross sections of Pirani and Vecchiocattivi (J. Chem. Phys. 66, 372 (1977) and revisions thereto) verify the error bounds for all three potentials.« less

Laser depth profiling studies of helium diffusion in Durango fluorapatite

NASA Astrophysics Data System (ADS)

van Soest, Matthijs C.; Monteleone, Brian D.; Hodges, Kip V.; Boyce, Jeremy W.

2011-05-01

Ultraviolet lasers coupled with sensitive mass spectrometers provide a useful way to measure laboratory-induced noble gas diffusion profiles in minerals, thus enabling the calculation of diffusion parameters. We illustrate this laser ablation depth profiling (LADP) technique for a previously well-studied mineral-isotopic system: 4He in Durango fluorapatite. LADP studies were conducted on oriented, polished slabs from a single crystal that were heated under vacuum to a variety of temperatures between 300 and 450 °C for variable times. The resolved 4He profiles exhibited error-function loss as predicted by previous bulk 4He diffusion studies. All of the slabs, regardless of crystallographic orientation, yielded modeled diffusivities that are statistically co-linear on an Arrhenius diagram, suggesting no diffusional anisotropy of 4He in this material. The data indicate an activation energy of 142.2 ± 5.0 (2 σ) kJ/mol and diffusivity at infinite temperature - reported as ln( D0) - of -4.71 ± 0.94 (2 σ) m 2/s. These values imply a bulk closure temperature for 4He in Durango fluorapatite of 74 °C for a 50 μm radius grain, infinite cylinder geometry, and a cooling rate of 10 °C/Myr.

Para-hydrogen induced polarization of amino acids, peptides and deuterium-hydrogen gas.

PubMed

Glöggler, Stefan; Müller, Rafael; Colell, Johannes; Emondts, Meike; Dabrowski, Martin; Blümich, Bernhard; Appelt, Stephan

2011-08-14

Signal Amplification by Reversible-Exchange (SABRE) is a method of hyperpolarizing substrates by polarization transfer from para-hydrogen without hydrogenation. Here, we demonstrate that this method can be applied to hyperpolarize small amounts of all proteinogenic amino acids and some chosen peptides down to the nanomole regime and can be detected in a single scan in low-magnetic fields down to 0.25 mT (10 kHz proton frequency). An outstanding feature is that depending on the chemical state of the used catalyst and the investigated amino acid or peptide, hyperpolarized hydrogen-deuterium gas is formed, which was detected with (1)H and (2)H NMR spectroscopy at low magnetic fields of B(0) = 3.9 mT (166 kHz proton frequency) and 3.2 mT (20 kHz deuterium frequency).

Coupling between diffusion and orientation of pentacene molecules on an organic surface.

PubMed

Rotter, Paul; Lechner, Barbara A J; Morherr, Antonia; Chisnall, David M; Ward, David J; Jardine, Andrew P; Ellis, John; Allison, William; Eckhardt, Bruno; Witte, Gregor

2016-04-01

The realization of efficient organic electronic devices requires the controlled preparation of molecular thin films and heterostructures. As top-down structuring methods such as lithography cannot be applied to van der Waals bound materials, surface diffusion becomes a structure-determining factor that requires microscopic understanding. Scanning probe techniques provide atomic resolution, but are limited to observations of slow movements, and therefore constrained to low temperatures. In contrast, the helium-3 spin-echo (HeSE) technique achieves spatial and time resolution on the nm and ps scale, respectively, thus enabling measurements at elevated temperatures. Here we use HeSE to unveil the intricate motion of pentacene admolecules diffusing on a chemisorbed monolayer of pentacene on Cu(110) that serves as a stable, well-ordered organic model surface. We find that pentacene moves along rails parallel and perpendicular to the surface molecules. The experimental data are explained by admolecule rotation that enables a switching between diffusion directions, which extends our molecular level understanding of diffusion in complex organic systems.

15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH

PubMed Central

2016-01-01

NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% 15N-polarization (Theis, T.; et al. J. Am. Chem. Soc.2015, 137, 1404). Hyperpolarization on 15N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on 15N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable 15N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient 15N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T1), and reversible oxygen quenching are studied on a test system of 15N-pyridine in methanol-d4. Moreover, we demonstrate the first proof-of-principle 13C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first 15N images (2 × 2 mm2 resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T1 relaxation times suitable for biomedical imaging and spectroscopy. PMID:25960823

15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH.

PubMed

Truong, Milton L; Theis, Thomas; Coffey, Aaron M; Shchepin, Roman V; Waddell, Kevin W; Shi, Fan; Goodson, Boyd M; Warren, Warren S; Chekmenev, Eduard Y

2015-04-23

NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10% 15 N-polarization (Theis, T.; et al. J. Am. Chem. Soc. 2015 , 137 , 1404). Hyperpolarization on 15 N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on 15 N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable 15 N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient 15 N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time ( T 1 ), and reversible oxygen quenching are studied on a test system of 15 N-pyridine in methanol- d 4 . Moreover, we demonstrate the first proof-of-principle 13 C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first 15 N images (2 × 2 mm 2 resolution). Importantly, this method enables hyperpolarization of molecular sites with NMR T 1 relaxation times suitable for biomedical imaging and spectroscopy.

He diffusion in zircon: Observations from (U-Th)/He age suites and 4He diffusion experiments and implications for radiation damage and anisotropic effects

NASA Astrophysics Data System (ADS)

Guenthner, W. R.; Reiners, P. W.

2009-12-01

Despite widespread use of zircon (U-Th)/He thermochronometry in many geologic applications, our understanding of the kinetics of He diffusion in this system is rudimentary. Previous studies have shown that both radiation damage and crystallographic anisotropy may strongly influence diffusion kinetics and ages. We present observations of zircon He ages from multiple single-grain analyses from both detrital and bedrock suites from a wide variety of locations, showing relationships consistent with effects arising from the interaction of radiation damage and anisotropy. Individual zircons in each suite have experienced the same post-depositional or exhumational t-T history but grains appear to have experienced differential He loss that is correlated with effective uranium (eU) content, a proxy for the relative extent of radiation damage within each suite. Several suites of zircons heated to partial resetting upon burial or that have experienced slow cooling show positive correlations between age and eU. Examples of partially reset detrital samples include Cretaceous Sevier foreland basin sandstones buried to ~6-8 km depth, with ages ranging from 88-309 Ma across an eU range of 215-1453 ppm, and Apennines and Olympics greywackes heated to >~120 °C, showing similar trends. Some slowly-cooled bedrock samples also show positive age-eU correlations, suggesting increasing closure temperature with higher extents of radiation damage. Conversely, zircons from cratonal bedrock samples with high levels of radiation damage—measured as accumulated alpha dosage (in this case >~10^18 α/g)—generally show negative age-eU correlations. We interpret these contrasting age-eU relationships as a manifestation of the interaction of radiation damage and anisotropic diffusion: at low damage, He diffusivity is relatively high and preferentially through c-axis-parallel channels. As suggested by Farley (2007), however, with increasing damage, channels are progressively blocked and He diffusivity decreases. Eventually, a crystal reaches a threshold level (>~10^18 α/g ) wherein radiation damage is so extensive that damage zones become interconnected and He diffusivity increases once again. In order to evaluate these assertions, we conducted a series of step-heating experiments on several pairs of zircon slabs. Individual slabs were crystallographically oriented either orthogonal or parallel to the c-axis and each pair possessed varying degrees of radiation damage. Results from these experiments provide new closure temperature estimates, explain age-eU correlations within a data set, and allow us to construct diffusion models that more accurately describe the t-T history of a given sample.

Effect on Membrane Potential and Electrical Activity of Adding Sodium to Sodium-Depleted Cardiac Purkinje Fibers

PubMed Central

Wiggins, Jay R.; Cranefield, Paul F.

1974-01-01

Canine cardiac Purkinje fibers exposed to Na-free solutions containing 128 mM TEA and 16 mM Ca show resting potentials in the range -50 to -90 mV; if the concentration of Na in the perfusate is raised from 0 to 4 to 24 mM, hyperpolarization follows. If the initial resting potential is low, the hyperpolarization tends to be greater; the average increase in the presence of 8 mM Na is 14 mV. Such hyperpolarization is not induced by adding Na to K-free solutions, is not seen in cooled fibers, or in fibers exposed to 10-3 M ouabain, nor is it induced by adding Li and thus may result from electrogenic sodium extrusion. Fibers exposed to Na-free solutions are often spontaneously active; if they are quiescent they often show repetitive activity during depolarizing pulses. Such spontaneous or repetitive activity is suppressed by the addition of Na. This suppression may or may not be related to the hyperpolarization. PMID:4418558

Degassing of 3H/3He, CFCs and SF6 by denitrification: measurements and two-phase transport simulations.

PubMed

Visser, Ate; Schaap, Joris D; Broers, Hans Peter; Bierkens, Marc F P

2009-01-26

The production of N2 gas by denitrification may lead to the appearance of a gas phase below the water table prohibiting the conservative transport of tracer gases required for groundwater dating. We used a two-phase flow and transport model (STOMP) to study the reliability of 3H/3He, CFCs and SF6 as groundwater age tracers under agricultural land where denitrification causes degassing. We were able to reproduce the amount of degassing (R2=69%), as well as the 3H (R2=79%) and 3He (R2=76%) concentrations observed in a 3H/3He data set using simple 2D models. We found that the TDG correction of the 3H/3He age overestimated the control 3He/3He age by 2.1 years, due to the accumulation of 3He in the gas phase. The total uncertainty of degassed 3H/3He ages of 6 years (+/-2 sigma) is due to the correction of degassed 3He using the TDG method, but also due to the travel time in the unsaturated zone and the diffusion of bomb peak 3He. CFCs appear to be subject to significant degradation in anoxic groundwater and SF6 is highly susceptible to degassing. We conclude that 3H/3He is the most reliable method to date degassed groundwater and that two-phase flow models such as STOMP are useful tools to assist in the interpretation of degassed groundwater age tracer data.

Helium diffusion experiments on synthetic apatite crystals and single-grain fragments: can we retrieve the He diffusion profiles?

NASA Astrophysics Data System (ADS)

Kasanzu, C.; Beucher, R.; Brown, R. W.; Persano, C.; Stuart, F.

2011-12-01

Apatite (U-Th)/he thermochronometry is one of the most widely used methods of quantifying thermal histories of rocks within the vicinity of the surface. Theoretical and practical development carried out during the last decade, among which was the release of affordable LASERs, have led to standard practice of analyzing single grain rather than multigrain aliquots. The standard theoretical basis for interpreting these ages assumes that the technique is used on full grains. However, the natural weak cleavage of apatite leads to fragmentation of these individual prismatic crystals during the rock crushing and mineral separation process. Apatites are most often broken along a weak cleavage perpendicular to the c-axis. It is therefore common practice to analyze fragments of whole grains, not complete crystals. It is also well known that dating often leads to single ages being more dispersed than expected whatever the efforts to avoid perturbations on the He system. Using a theoretical numerical model and considering both axial and radial diffusion, we demonstrate thata largepart (most?) of the dispersion is due to analyses of single apatite fragments. This effect is larger for older grains which have exprienced a slow cooling history and have well rounded diffusive profiles. Ages are a strongfunction of the fragment size (length specifically), we show that ages from apatite fragments with 1 prismatic termination (1T) can be used to retrieve the helium diffusion profile, provided a sufficient number of single fragment analyses are carried out. The shape of the helium diffusion profile provides a strong constraint on the style of the thermal history and so we propose to use single crystal fragment analyses to extract a mean diffusion profile, and deduce the thermal history of the sample. In order to test these ideas, we performed a set of experiments with natural samples and semi-synthetic grains of apatite. Synthetic grains are obtained by drilling cores of various length/width ratios within standard Durango crystals while natural grains are separated from a deep borehole in south-Africa (BK1) and from the Australian craton. Several experiences are presented: 1) (U-Th)/He dating of about 100 1T single-fragment aliquots of different shape ratio from the BK1 borehole; 2) (U-Th)/He dating of 20 2T single-fragment aliquot from an Australian sample previously dated following standard procedure. 3) (U-Th)/He dating of synthetic fragmentsfrom synthetic grains previously degassed by a known percentageusing a thermo-regulated furnace. The results of the experiments lead to important new insight into the natural dispersion of (U-Th)/He single-grain ages. They show that far from being problematic, highly dispersed data may indeed contain first-order information on the thermal history of rocks. We discuss all the details of the standard (U-Th)/He approach such as the effects of temporally variable diffusivity (e.g. radiation damage models), zonation of U and Th and arbitrary grain size variations.

Do twisted laser beams evoke nuclear hyperpolarization?

PubMed

Schmidt, A B; Andrews, D L; Rohrbach, A; Gohn-Kreuz, C; Shatokhin, V N; Kiselev, V G; Hennig, J; von Elverfeldt, D; Hövener, J-B

2016-07-01

The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low-field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5nm and various topological charges. We acquired (1)H and (19)F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be able to induce electronic (e.g. in rubidium) and subsequent nuclear hyperpolarization. Compared to the plane wave, the additional transitions caused by a twisted wave are of the order of 10(-3) less. This suggests that the twist of the laser is unlikely to be responsible for the hyperpolarization of nuclear spins, unless a new mechanism of momentum transfer is identified. Copyright © 2016 Elsevier Inc. All rights reserved.

Single-shot diffusion measurement in laser-polarized Gas

NASA Technical Reports Server (NTRS)

Peled, S.; Tseng, C. H.; Sodickson, A. A.; Mair, R. W.; Walsworth, R. L.; Cory, D. G.

1999-01-01

A single-shot pulsed gradient stimulated echo sequence is introduced to address the challenges of diffusion measurements of laser polarized 3He and 129Xe gas. Laser polarization enhances the NMR sensitivity of these noble gases by >10(3), but creates an unstable, nonthermal polarization that is not readily renewable. A new method is presented which permits parallel acquisition of the several measurements required to determine a diffusive attenuation curve. The NMR characterization of a sample's diffusion behavior can be accomplished in a single measurement, using only a single polarization step. As a demonstration, the diffusion coefficient of a sample of laser-polarized 129Xe gas is measured via this method. Copyright 1999 Academic Press.

In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

PubMed Central

Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Nouls, John C.; Freeman, Matthew S.; Qi, Yi; Driehuys, Bastiaan

2012-01-01

Background Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal. Methods and Principal Findings Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions Extracorporeal infusion of HP 129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe. PMID:22363613

Bumetanide hyperpolarizes Madin-Darby canine kidney cells and enhances cellular gentamicin uptake via elevating cytosolic Ca2+ thus facilitating intermediate conductance Ca2+-activated potassium channels

PubMed Central

Wang, Tian; Yang, Yu-qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S.; Jiang, Zhi-Gen

2012-01-01

Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby Canine kidney (MDCK) cells. We found that bumetanide and furosemide concentration-dependently enhanced cytoplasmic GTTR fluorescence by ~60%. This enhancement was suppressed by La3+, a non-selective cation channel (NSCC) blocker, and by K+ channel blockers Ba2+ and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl− channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (Vr) ~−80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba2+ or clotrimazole, and absent in elevated [Ca2+]i, but not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca2+. Ba2+ and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current Vr near −85 mV, and reduced GTTR uptake by ~20%. La3+ alone hyperpolarized the cells by ~−14 mV, reduced the I/V slope with a net current Vr near −10 mV, and inhibited GTTR uptake by ~50%. In the presence of La3+, bumetanide caused negligible potential or I/V change. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating the intracellular Ca2+ and thus a facilitation of the intermediate conductance Ca2+-activated K+ channels. PMID:23109177

Bumetanide hyperpolarizes madin-darby canine kidney cells and enhances cellular gentamicin uptake by elevating cytosolic Ca(2+) thus facilitating intermediate conductance Ca(2+)--activated potassium channels.

PubMed

Wang, Tian; Yang, Yu-Qin; Karasawa, Takatoshi; Wang, Qi; Phillips, Amanda; Guan, Bing-Cai; Ma, Ke-Tao; Jiang, Meiyan; Xie, Ding-Hua; Steyger, Peter S; Jiang, Zhi-Gen

2013-04-01

Loop diuretics such as bumetanide and furosemide enhance aminoglycoside ototoxicity when co-administered to patients and animal models. The underlying mechanism(s) is poorly understood. We investigated the effect of these diuretics on cellular uptake of aminoglycosides, using Texas Red-tagged gentamicin (GTTR), and intracellular/whole-cell recordings of Madin-Darby canine kidney (MDCK) cells. We found that bumetanide and furosemide dose-dependently enhanced cytoplasmic GTTR fluorescence by ~60 %. This enhancement was suppressed by La(3+), a non-selective cation channel (NSCC) blocker, and by K(+) channel blockers Ba(2+) and clotrimazole, but not by tetraethylammonium (TEA), 4-aminopyridine (4-AP) or glipizide, nor by Cl(-) channel blockers diphenylamine-2-carboxylic acid (DPC), niflumic acid (NFA), and CFTRinh-172. Bumetanide and furosemide hyperpolarized MDCK cells by ~14 mV, increased whole-cell I/V slope conductance; the bumetanide-induced net current I/V showed a reversal potential (V r) ~-80 mV. Bumetanide-induced hyperpolarization and I/V change was suppressed by Ba(2+) or clotrimazole, and absent in elevated [Ca(2+)]i, but was not affected by apamin, 4-AP, TEA, glipizide, DPC, NFA, or CFTRinh-172. Bumetanide and furosemide stimulated a surge of Fluo-4-indicated cytosolic Ca(2+). Ba(2+) and clotrimazole alone depolarized cells by ~18 mV and reduced I/V slope with a net current V r near -85 mV, and reduced GTTR uptake by ~20 %. La(3+) alone hyperpolarized the cells by ~-14 mV, reduced the I/V slope with a net current V r near -10 mV, and inhibited GTTR uptake by ~50 %. In the presence of La(3+), bumetanide-caused negligible change in potential or I/V. We conclude that NSCCs constitute a major cell entry pathway for cationic aminoglycosides; bumetanide enhances aminoglycoside uptake by hyperpolarizing cells that increases the cation influx driving force; and bumetanide-induced hyperpolarization is caused by elevating intracellular Ca(2+) and thus facilitating activation of the intermediate conductance Ca(2+)-activated K(+) channels.

Assessment of Remote Sensing Technologies for Location of Hydrogen and Helium Leaks

NASA Technical Reports Server (NTRS)

Sellar, R. Glenn; Sohn, Yongho; Mathur, Varun; Reardon, Peter

2001-01-01

In Phase 1 of this project, a hierarchy of techniques for H2 and He leak location was developed. A total of twelve specific remote sensing techniques were evaluated; the results are summarized. A basic diffusion model was also developed to predict the concentration and distribution of H2 or He resulting from a leak. The objectives of Phase 2 of the project consisted of the following four tasks: Advance Rayleigh Doppler technique from TRL 1 to TRL 2; Plan to advance Rayleigh Doppler technique from TRL 2 to TRL 3; Advance researchers and resources for further advancement; Extend diffusion model.

Nuclear magnetic resonance diffusion pore imaging: Experimental phase detection by double diffusion encoding

NASA Astrophysics Data System (ADS)

Demberg, Kerstin; Laun, Frederik Bernd; Windschuh, Johannes; Umathum, Reiner; Bachert, Peter; Kuder, Tristan Anselm

2017-02-01

Diffusion pore imaging is an extension of diffusion-weighted nuclear magnetic resonance imaging enabling the direct measurement of the shape of arbitrarily formed, closed pores by probing diffusion restrictions using the motion of spin-bearing particles. Examples of such pores comprise cells in biological tissue or oil containing cavities in porous rocks. All pores contained in the measurement volume contribute to one reconstructed image, which reduces the problem of vanishing signal at increasing resolution present in conventional magnetic resonance imaging. It has been previously experimentally demonstrated that pore imaging using a combination of a long and a narrow magnetic field gradient pulse is feasible. In this work, an experimental verification is presented showing that pores can be imaged using short gradient pulses only. Experiments were carried out using hyperpolarized xenon gas in well-defined pores. The phase required for pore image reconstruction was retrieved from double diffusion encoded (DDE) measurements, while the magnitude could either be obtained from DDE signals or classical diffusion measurements with single encoding. The occurring image artifacts caused by restrictions of the gradient system, insufficient diffusion time, and by the phase reconstruction approach were investigated. Employing short gradient pulses only is advantageous compared to the initial long-narrow approach due to a more flexible sequence design when omitting the long gradient and due to faster convergence to the diffusion long-time limit, which may enable application to larger pores.

Evaluation of Heterogeneous Metabolic Profile in an Orthotopic Human Glioblastoma Xenograft Model Using Compressed Sensing Hyperpolarized 3D 13C Magnetic Resonance Spectroscopic Imaging

PubMed Central

Park, Ilwoo; Hu, Simon; Bok, Robert; Ozawa, Tomoko; Ito, Motokazu; Mukherjee, Joydeep; Phillips, Joanna J.; James, C. David; Pieper, Russell O.; Ronen, Sabrina M.; Vigneron, Daniel B.; Nelson, Sarah J.

2013-01-01

High resolution compressed sensing hyperpolarized 13C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in 13C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D 13C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-13C]-pyruvate using a 3T scanner. The 13C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing 13C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct 13C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of 13C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue. PMID:22851374

Evaluation of heterogeneous metabolic profile in an orthotopic human glioblastoma xenograft model using compressed sensing hyperpolarized 3D 13C magnetic resonance spectroscopic imaging.

PubMed

Park, Ilwoo; Hu, Simon; Bok, Robert; Ozawa, Tomoko; Ito, Motokazu; Mukherjee, Joydeep; Phillips, Joanna J; James, C David; Pieper, Russell O; Ronen, Sabrina M; Vigneron, Daniel B; Nelson, Sarah J

2013-07-01

High resolution compressed sensing hyperpolarized (13)C magnetic resonance spectroscopic imaging was applied in orthotopic human glioblastoma xenografts for quantitative assessment of spatial variations in (13)C metabolic profiles and comparison with histopathology. A new compressed sensing sampling design with a factor of 3.72 acceleration was implemented to enable a factor of 4 increase in spatial resolution. Compressed sensing 3D (13)C magnetic resonance spectroscopic imaging data were acquired from a phantom and 10 tumor-bearing rats following injection of hyperpolarized [1-(13)C]-pyruvate using a 3T scanner. The (13)C metabolic profiles were compared with hematoxylin and eosin staining and carbonic anhydrase 9 staining. The high-resolution compressed sensing (13)C magnetic resonance spectroscopic imaging data enabled the differentiation of distinct (13)C metabolite patterns within abnormal tissues with high specificity in similar scan times compared to the fully sampled method. The results from pathology confirmed the different characteristics of (13)C metabolic profiles between viable, non-necrotic, nonhypoxic tumor, and necrotic, hypoxic tissue. Copyright © 2012 Wiley Periodicals, Inc.

Silicon Nanoparticles as Hyperpolarized Magnetic Resonance Imaging Agents

PubMed Central

Aptekar, Jacob W.; Cassidy, Maja C.; Johnson, Alexander C.; Barton, Robert A.; Lee, Menyoung; Ogier, Alexander C.; Vo, Chinh; Anahtar, Melis N.; Ren, Yin; Bhatia, Sangeeta N.; Ramanathan, Chandrasekhar; Cory, David G.; Hill, Alison L.; Mair, Ross W.; Rosen, Matthew S.; Walsworth, Ronald L.

2014-01-01

Magnetic resonance imaging of hyperpolarized nuclei provides high image contrast with little or no background signal. To date, in-vivo applications of pre-hyperpolarized materials have been limited by relatively short nuclear spin relaxation times. Here, we investigate silicon nanoparticles as a new type of hyperpolarized magnetic resonance imaging agent. Nuclear spin relaxation times for a variety of Si nanoparticles are found to be remarkably long, ranging from many minutes to hours at room temperature, allowing hyperpolarized nanoparticles to be transported, administered, and imaged on practical time scales. Additionally, we demonstrate that Si nanoparticles can be surface functionalized using techniques common to other biologically targeted nanoparticle systems. These results suggest that Si nanoparticles can be used as a targetable, hyperpolarized magnetic resonance imaging agent with a large range of potential applications. PMID:19950973

Ab Initio Values of the Thermophysical Properties of Helium as Standards

PubMed Central

Hurly, John J.; Moldover, Michael R.

2000-01-01

Recent quantum mechanical calculations of the interaction energy of pairs of helium atoms are accurate and some include reliable estimates of their uncertainty. We combined these ab initio results with earlier published results to obtain a helium-helium interatomic potential that includes relativistic retardation effects over all ranges of interaction. From this potential, we calculated the thermophysical properties of helium, i.e., the second virial coefficients, the dilute-gas viscosities, and the dilute-gas thermal conductivities of 3He, 4He, and their equimolar mixture from 1 K to 104 K. We also calculated the diffusion and thermal diffusion coefficients of mixtures of 3He and 4He. For the pure fluids, the uncertainties of the calculated values are dominated by the uncertainties of the potential; for the mixtures, the uncertainties of the transport properties also include contributions from approximations in the transport theory. In all cases, the uncertainties are smaller than the corresponding experimental uncertainties; therefore, we recommend the ab initio results be used as standards for calibrating instruments relying on these thermophysical properties. We present the calculated thermophysical properties in easy-to-use tabular form. PMID:27551630

Noninvasive quantification of alveolar morphometry in elderly never- and ex-smokers

PubMed Central

Paulin, Gregory A; Ouriadov, Alexei; Lessard, Eric; Sheikh, Khadija; McCormack, David G; Parraga, Grace

2015-01-01

Diffusion-weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized 3He MRI estimates of the alveolar dimensions in 38 healthy elderly never-smokers (73 ± 6 years, 15 males) and 21 elderly ex-smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex-smoker and never-smoker subgroups were significantly different for FEV1/FVC (P = 0.0001) and DLCO (P = 0.009); while ex-smokers with emphysema reported significantly diminished FEV1/FVC (P = 0.02) and a trend toward lower DLCO (P = 0.05) than ex-smokers without emphysema. MRI apparent diffusion coefficients (ADC) and CT measurements of emphysema (relative area–CT density histogram, RA950) were significantly different (P = 0.001 and P = 0.007) for never-smoker and ex-smoker subgroups. In never-smokers, the MRI estimate of mean linear intercept (260 ± 27 μm) was significantly elevated as compared to the results previously reported in younger never-smokers (210 ± 30 μm), and trended smaller than in the age-matched ex-smokers (320 ± 72 μm, P = 0.06) evaluated here. Never-smokers also reported significantly smaller internal (220 ± 24 μm, P = 0.01) acinar radius but greater alveolar sheath thickness (120 ± 4 μm, P < 0.0001) than ex-smokers. Never-smokers were also significantly different than ex-smokers without emphysema for alveolar sheath thickness but not ADC, while ex-smokers with emphysema reported significantly different ADC but not alveolar sheath thickness compared to ex-smokers without CT evidence of emphysema. Differences in alveolar measurements in never- and ex-smokers demonstrate the sensitivity of MRI measurements to the different effects of smoking and aging on acinar morphometry. PMID:26462748

Pressure relaxation and diffusion of vacancies in rapidly grown helium crystals

NASA Astrophysics Data System (ADS)

Birchenko, A. P.; Mikhin, N. P.; Rudavskii, E. Ya.; Smirnov, S. N.; Fysun, Ya. Yu.

2018-04-01

An experimental study of the features of pressure relaxation in rapidly grown crystals of a diluted solid solution 3He-4He, at temperatures above 1.3 K, was performed. A cylindrical cell with capacitive pressure sensors at the ends was used for measurements. It was found that, when the helium crystals were grown at cooling rates ≳4 mK/s, the difference in pressure ΔP registered by the sensors at 1.3 K reached 2.4 bars. The ΔP value decreased with subsequent stepwise increase in temperature, but reached zero only after thorough annealing at the premelting temperatures. The kinetics of pressure changes at the sample ends at different temperatures was recorded. The results obtained were interpreted within the framework of the structural relaxation model based on the monovacancy diffusion mechanism. The proposed model made it possible to explain the dependence of ΔP on the time and temperature recorded in the experiment, as well as to determine the activation energy of the structural relaxation process and the diffusion coefficient of vacancies. The details of the vacancy model are described in the Appendix.

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Plasma barodiffusion in inertial-confinement-fusion implosions: application to observed yield anomalies in thermonuclear fuel mixtures.

PubMed

Amendt, Peter; Landen, O L; Robey, H F; Li, C K; Petrasso, R D

2010-09-10

The observation of large, self-generated electric fields (≥10(9)  V/m) in imploding capsules using proton radiography has been reported [C. K. Li, Phys. Rev. Lett. 100, 225001 (2008)]. A model of pressure gradient-driven diffusion in a plasma with self-generated electric fields is developed and applied to reported neutron yield deficits for equimolar D3He [J. R. Rygg, Phys. Plasmas 13, 052702 (2006)] and (DT)3He [H. W. Herrmann, Phys. Plasmas 16, 056312 (2009)] fuel mixtures and Ar-doped deuterium fuels [J. D. Lindl, Phys. Plasmas 11, 339 (2004)]. The observed anomalies are explained as a mild loss of deuterium nuclei near capsule center arising from shock-driven diffusion in the high-field limit.

Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors.

PubMed

Gallagher, Ferdia A; Sladen, Helen; Kettunen, Mikko I; Serrao, Eva M; Rodrigues, Tiago B; Wright, Alan; Gill, Andrew B; McGuire, Sarah; Booth, Thomas C; Boren, Joan; McIntyre, Alan; Miller, Jodi L; Lee, Shen-Han; Honess, Davina; Day, Sam E; Hu, De-En; Howat, William J; Harris, Adrian L; Brindle, Kevin M

2015-10-01

Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolarized (13)C label between bicarbonate (H(13)CO3(-)) and carbon dioxide ((13)CO2), following injection of hyperpolarized H(13)CO3(-), using (13)C-magnetic resonance spectroscopy ((13)C-MRS) magnetization transfer measurements. (31)P-MRS measurements of the chemical shift of the pH probe, 3-aminopropylphosphonate, and (13)C-MRS measurements of the H(13)CO3(-)/(13)CO2 peak intensity ratio showed that CAIX overexpression lowered extracellular pH in these tumors. However, the (13)C measurements overestimated pH due to incomplete equilibration of the hyperpolarized (13)C label between the H(13)CO3(-) and (13)CO2 pools. Paradoxically, tumors overexpressing CAIX showed lower enzyme activity using magnetization transfer measurements, which can be explained by the more acidic extracellular pH in these tumors and the decreased activity of the enzyme at low pH. This explanation was confirmed by administration of bicarbonate in the drinking water, which elevated tumor extracellular pH and restored enzyme activity to control levels. These results suggest that CAIX expression is increased in hypoxia to compensate for the decrease in its activity produced by a low extracellular pH and supports the hypothesis that a major function of CAIX is to lower the extracellular pH. ©2015 American Association for Cancer Research.

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced non-persistent radicals

PubMed Central

Bastiaansen, Jessica A. M.; Yoshihara, Hikari A. I.; Capozzi, Andrea; Schwitter, Juerg; Gruetter, Rolf; Merritt, Matthew E.; Comment, Arnaud

2018-01-01

Purpose To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13C-labeled substrate mixture prepared using photo-induced non-persistent radicals. Methods Droplets of mixed [1-13C]pyruvic and [1-13C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet (UV) light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization (DNP) in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo. Results UV-irradiation created non-persistent radicals in a mixture containing 13C-labeled pyruvic and butyric acids and enabled the hyperpolarization of both substrates by DNP. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to UV irradiation. In the rat heart, the in vivo13C signals from lactate, alanine, bicarbonate and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Conclusion Co-polarization of two 13C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13C-substrates may simplify the translation to clinical use because no filtration is required prior to injection. PMID:29411415

Substance P and bradykinin activate different types of KCa currents to hyperpolarize cultured porcine coronary artery endothelial cells

PubMed Central

Frieden, M; Sollini, M; Bény, J-L

1999-01-01

Substance P and bradykinin, endothelium-dependent vasodilators of pig coronary artery, trigger in endothelial cells a rise in cytosolic Ca2+ concentration ([Ca2+]i) and membrane hyperpolarization. The aim of the present study was to determine the type of Ca2+-dependent K+ (KCa) currents underlying the endothelial cell hyperpolarization. The substance P-induced increase in [Ca2+]i was 30 % smaller than that induced by bradykinin, although the two peptides triggered a membrane hyperpolarization of the same amplitude. The two agonists evoked a large outward K+ current of the same conductance at maximal stimulation. Agonists applied together produced the same maximal current amplitude as either one applied alone. Iberiotoxin (50 nM) reduced by about 40 % the K+ current activated by bradykinin without modifying the substance P response. Conversely, apamin (1 μm) inhibited the substance P-induced K+ current by about 65 %, without affecting the bradykinin response. Similar results were obtained on peptide-induced membrane hyperpolarization. Bradykinin-induced, but not substance P-induced, endothelium-dependent relaxation resistant to NG-nitro-L-arginine and indomethacin was partly inhibited by 3 μm 17-octadecynoic acid (17-ODYA), an inhibitor of cytochrome P450 epoxygenase. Similarly, the bradykinin-induced K+ current was reduced by 17-ODYA. Our results show that responses to substance P and bradykinin result in a hyperpolarization due to activation of different KCa currents. A current consistent with the activation of large conductance (BKCa) channels was activated only by bradykinin, whereas a current consistent with the activation of small conductance (SKCa) channels was stimulated only by substance P. The observation that a similar electrical response is produced by different pools of channels implies distinct intracellular pathways leading to KCa current activation. PMID:10457055

Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.

PubMed

Cain, Stuart M; Tyson, John R; Jones, Karen L; Snutch, Terrance P

2015-06-01

Burst-firing in distinct subsets of thalamic relay (TR) neurons is thought to be a key requirement for the propagation of absence seizures. However, in the well-regarded Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model as yet there has been no link described between burst-firing in TR neurons and spike-and-wave discharges (SWDs). GAERS ventrobasal (VB) neurons are a specific subset of TR neurons that do not normally display burst-firing during absence seizures in the GAERS model, and here, we assessed the underlying relationship of VB burst-firing with Ih and T-type calcium currents between GAERS and non-epileptic control (NEC) animals. In response to 200-ms hyperpolarizing current injections, adult epileptic but not pre-epileptic GAERS VB neurons displayed suppressed burst-firing compared to NEC. In response to longer duration 1,000-ms hyperpolarizing current injections, both pre-epileptic and epileptic GAERS VB neurons required significantly more hyperpolarizing current injection to burst-fire than those of NEC animals. The current density of the Hyperpolarization and Cyclic Nucleotide-activated (HCN) current (Ih) was found to be increased in GAERS VB neurons, and the blockade of Ih relieved the suppressed burst-firing in both pre-epileptic P15-P20 and adult animals. In support, levels of HCN-1 and HCN-3 isoform channel proteins were increased in GAERS VB thalamic tissue. T-type calcium channel whole-cell currents were found to be decreased in P7-P9 GAERS VB neurons, and also noted was a decrease in CaV3.1 mRNA and protein levels in adults. Z944, a potent T-type calcium channel blocker with anti-epileptic properties, completely abolished hyperpolarization-induced VB burst-firing in both NEC and GAERS VB neurons.

Efficient production of hyperpolarized bicarbonate by chemical reaction on a DNP precursor to measure pH.

PubMed

Ghosh, Rajat K; Kadlecek, Stephen J; Pourfathi, Mehrdad; Rizi, Rahim R

2015-11-01

To produce hyperpolarized bicarbonate indirectly via chemical reaction from a hyperpolarized precursor and utilize it for the simultaneous regional measurement of metabolism and pH. Alpha keto carboxylic acids are first hyperpolarized by dissolution dynamic nuclear polarization (DNP). These precursor molecules are rapidly reacted with hydrogen peroxide (H2O2) to decarboxylate the species, resulting in new target molecules. Unreacted H2O2 is removed from the system by reaction with sulfite. Interrogation of the ratio of dissolved carbon dioxide (CO2) to bicarbonate can be used to determine pH. Conversion of hyperpolarized alpha keto acids to bicarbonate and CO2 results in a minimal loss of the spin order. The reaction can be conducted to completion within seconds and preserves the nuclear spin polarization. Through a rapid chemical reaction, we can conserve the nuclear spin order of a DNP precursor to generate multiple hyperpolarized bioprobes otherwise unamenable to polarization. This indirect technique for the production of hyperpolarized agents can be applied to different precursor compounds to generate additional novel probes. © 2014 Wiley Periodicals, Inc.

Conodont (U Th)/He thermochronology: Initial results, potential, and problems

NASA Astrophysics Data System (ADS)

Peppe, Daniel J.; Reiners, Peter W.

2007-06-01

We performed He diffusion experiments and (U-Th)/He age determinations on conodonts from a variety of locations to explore the potential of conodont (U-Th)/He thermochronology to constrain thermal and exhumation histories of some sedimentary-rock dominated terrains. Based on two diffusion experiments and age results from some specimens, He diffusion in conodont elements appears to be similar to that in Durango apatite fragments of similar size, and closure temperatures are approximately 60-70 °C (for cooling rates of ˜ 10 °C/m.y.). (U-Th)/He ages of conodonts from some locations yield reproducible ages consistent with regional thermal history constraints and, in at least two cases, require a closure temperature lower than ˜ 80 °C. Other samples however, yield irreproducible ages, and in one case yield ages much younger than expected based on regional geologic considerations. These irreproducible samples show inverse correlations between parent nuclides and age consistent with late-stage open-system U-Th behavior.

Ground-Water Temperature, Noble Gas, and Carbon Isotope Data from the Espanola Basin, New Mexico

USGS Publications Warehouse

Manning, Andrew H.

2009-01-01

Ground-water samples were collected from 56 locations throughout the Espanola Basin and analyzed for general chemistry (major ions and trace elements), carbon isotopes (delta 13C and 14C activity) in dissolved inorganic carbon, noble gases (He, Ne, Ar, Kr, Xe, and 3He/4He ratio), and tritium. Temperature profiles were measured at six locations in the southeastern part of the basin. Temperature profiles suggest that ground water generally becomes warmer with distance from the mountains and that most ground-water flow occurs at depths 50 years old, consistent with the 14C ages. Terrigenic He (Heterr) concentrations in ground water are high (log Delta Heterr of 2 to 5) throughout much of the basin. High Heterr concentrations are probably caused by in situ production in the Tesuque Formation from locally high concentrations of U-bearing minerals (Northeast zone only), or by upward diffusive/advective transport of crustal- and mantle-sourced He possibly enhanced by basement piercing faults, or by both. The 3He/4He ratio of Heterr (Rterr) is commonly high (Rterr/Ra of 0.3-2.0, where Ra is the 3He/4He ratio in air) suggesting that Espanola Basin ground water commonly contains mantle-sourced He. The 3He/4He ratio of Heterr is generally the highest in the western and southern parts of the basin, closest to the western border fault system and the Quaternary to Miocene volcanics of the Jemez Mountains and Cerros del Rio.

Blockade of hyperpolarizing currents produces a dose-dependent effect on heart rate.

PubMed

Ziyatdinova, N I; Giniatullin, R A; Svyatova, N V; Zefirov, T L

2001-03-01

Intravenous injection of ZD 7288, a new specific hyperpolarizing current blocker, dose-dependently reduces heart rate in adult rats. The autonomic nervous system modulates changes in heart rate caused by hyperpolarizing currents.

Rapid Catalyst Capture Enables Metal-Free para-Hydrogen-Based Hyperpolarized Contrast Agents.

PubMed

Barskiy, Danila A; Ke, Lucia A; Li, Xingyang; Stevenson, Vincent; Widarman, Nevin; Zhang, Hao; Truxal, Ashley; Pines, Alexander

2018-05-10

Hyperpolarization techniques based on the use of para-hydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of para-hydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals, and their administration in vivo should be avoided. Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 s) Ir-based catalyst capture by metal scavenging agents can produce pure para-hydrogen-based hyperpolarized contrast agents, as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.

Generalizing, Extending, and Maximizing Nitrogen-15 Hyperpolarization Induced by Parahydrogen in Reversible Exchange

PubMed Central

2017-01-01

Signal Amplification by Reversible Exchange (SABRE) is a fast and convenient NMR hyperpolarization method that uses cheap and readily available para-hydrogen as a hyperpolarization source. SABRE can hyperpolarize protons and heteronuclei. Here we focus on the heteronuclear variant introduced as SABRE-SHEATH (SABRE in SHield Enables Alignment Transfer to Heteronuclei) and nitrogen-15 targets in particular. We show that 15N-SABRE works more efficiently and on a wider range of substrates than 1H-SABRE, greatly generalizing the SABRE approach. In addition, we show that nitrogen-15 offers significantly extended T1 times of up to 12 minutes. Long T1 times enable higher hyperpolarization levels but also hold the promise of hyperpolarized molecular imaging for several tens of minutes. Detailed characterization and optimization are presented, leading to nitrogen-15 polarization levels in excess of 10% on several compounds. PMID:28392884

Nickel suppresses the PACAP-induced increase in guinea pig cardiac neuron excitability

PubMed Central

Tompkins, John D.; Merriam, Laura A.; Girard, Beatrice M.; May, Victor

2015-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent intercellular signaling molecule involved in multiple homeostatic functions. PACAP/PAC1 receptor signaling increases excitability of neurons within the guinea pig cardiac ganglia, making them a unique system to establish mechanisms underlying PACAP modulation of neuronal function. Calcium influx is required for the PACAP-increased cardiac neuron excitability, although the pathway is unknown. This study tested whether PACAP enhancement of calcium influx through either T-type or R-type channels contributed to the modulation of excitability. Real-time quantitative polymerase chain reaction analyses indicated transcripts for Cav3.1, Cav3.2, and Cav3.3 T-type isoforms and R-type Cav2.3 in cardiac neurons. These neurons often exhibit a hyperpolarization-induced rebound depolarization that remains when cesium is present to block hyperpolarization-activated nonselective cationic currents (Ih). The T-type calcium channel inhibitors, nickel (Ni2+) or mibefradil, suppressed the rebound depolarization, and treatment with both drugs hyperpolarized cardiac neurons by 2–4 mV. Together, these results are consistent with the presence of functional T-type channels, potentially along with R-type channels, in these cardiac neurons. Fifty micromolar Ni2+, a concentration that suppresses currents in both T-type and R-type channels, blunted the PACAP-initiated increase in excitability. Ni2+ also blunted PACAP enhancement of the hyperpolarization-induced rebound depolarization and reversed the PACAP-mediated increase in excitability, after being initiated, in a subset of cells. Lastly, low voltage-activated currents, measured under perforated patch whole cell recording conditions and potentially flowing through T-type or R-type channels, were enhanced by PACAP. Together, our results suggest that a PACAP-enhanced, Ni2+-sensitive current contributes to PACAP-induced modulation of neuronal excitability. PMID:25810261

Lung morphometry using hyperpolarized 129 Xe multi-b diffusion MRI with compressed sensing in healthy subjects and patients with COPD.

PubMed

Zhang, Huiting; Xie, Junshuai; Xiao, Sa; Zhao, Xiuchao; Zhang, Ming; Shi, Lei; Wang, Ke; Wu, Guangyao; Sun, Xianping; Ye, Chaohui; Zhou, Xin

2018-05-04

To demonstrate the feasibility of compressed sensing (CS) to accelerate the acquisition of hyperpolarized (HP) 129 Xe multi-b diffusion MRI for quantitative assessments of lung microstructural morphometry. Six healthy subjects and six chronic obstructive pulmonary disease (COPD) subjects underwent HP 129 Xe multi-b diffusion MRI (b = 0, 10, 20, 30, and 40 s/cm 2 ). First, a fully sampled (FS) acquisition of HP 129 Xe multi-b diffusion MRI was conducted in one healthy subject. The acquired FS dataset was retrospectively undersampled in the phase encoding direction, and an optimal twofold undersampled pattern was then obtained by minimizing mean absolute error (MAE) between retrospective CS (rCS) and FS MR images. Next, the FS and CS acquisitions during separate breath holds were performed on five healthy subjects (including the above one). Additionally, the FS and CS synchronous acquisitions during a single breath hold were performed on the sixth healthy subject and one COPD subject. However, only CS acquisitions were conducted in the rest of the five COPD subjects. Finally, all the acquired FS, rCS and CS MR images were used to obtain morphometric parameters, including acinar duct radius (R), acinar lumen radius (r), alveolar sleeve depth (h), mean linear intercept (L m ), and surface-to-volume ratio (SVR). The Wilcoxon signed-rank test and the Bland-Altman plot were employed to assess the fidelity of the CS reconstruction. Moreover, the t-test was used to demonstrate the effectiveness of the multi-b diffusion MRI with CS in clinical applications. The retrospective results demonstrated that there was no statistically significant difference between rCS and FS measurements using the Wilcoxon signed-rank test (P > 0.05). Good agreement between measurements obtained with the CS and FS acquisitions during separate breath holds was demonstrated in Bland-Altman plots of slice differences. Specifically, the mean biases of the R, r, h, L m , and SVR between the CS and FS acquisitions were 1.0%, 2.6%, -0.03%, 1.5%, and -5.5%, respectively. Good agreement between measurements with the CS and FS acquisitions was also observed during the single breath-hold experiments. Furthermore, there were significant differences between the morphometric parameters for the healthy and COPD subjects (P < 0.05). Our study has shown that HP 129 Xe multi-b diffusion MRI with CS could be beneficial in lung microstructural assessments by acquiring less data while maintaining the consistent results with the FS acquisitions. © 2018 American Association of Physicists in Medicine.

Kinetic analysis of hyperpolarized data with minimum a priori knowledge: Hybrid maximum entropy and nonlinear least squares method (MEM/NLS).

PubMed

Mariotti, Erika; Veronese, Mattia; Dunn, Joel T; Southworth, Richard; Eykyn, Thomas R

2015-06-01

To assess the feasibility of using a hybrid Maximum-Entropy/Nonlinear Least Squares (MEM/NLS) method for analyzing the kinetics of hyperpolarized dynamic data with minimum a priori knowledge. A continuous distribution of rates obtained through the Laplace inversion of the data is used as a constraint on the NLS fitting to derive a discrete spectrum of rates. Performance of the MEM/NLS algorithm was assessed through Monte Carlo simulations and validated by fitting the longitudinal relaxation time curves of hyperpolarized [1-(13) C] pyruvate acquired at 9.4 Tesla and at three different flip angles. The method was further used to assess the kinetics of hyperpolarized pyruvate-lactate exchange acquired in vitro in whole blood and to re-analyze the previously published in vitro reaction of hyperpolarized (15) N choline with choline kinase. The MEM/NLS method was found to be adequate for the kinetic characterization of hyperpolarized in vitro time-series. Additional insights were obtained from experimental data in blood as well as from previously published (15) N choline experimental data. The proposed method informs on the compartmental model that best approximate the biological system observed using hyperpolarized (13) C MR especially when the metabolic pathway assessed is complex or a new hyperpolarized probe is used. © 2014 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.

Ion Thermal Decoupling and Species Separation in Shock-Driven Implosions

DOE PAGES

Rinderknecht, Hans G.; Rosenberg, M. J.; Li, C. K.; ...

2015-01-14

Here, anomalous reduction of the fusion yields by 50% and anomalous scaling of the burn-averaged ion temperatures with the ion-species fraction has been observed for the first time in D 3He-filled shock-driven inertial confinement fusion implosions. Two ion kinetic mechanisms are used to explain the anomalous observations: thermal decoupling of the D and 3He populations and diffusive species separation. The observed insensitivity of ion temperature to a varying deuterium fraction is shown to be a signature of ion thermal decoupling in shock-heated plasmas. The burn-averaged deuterium fraction calculated from the experimental data demonstrates a reduction in the average core deuteriummore » density, as predicted by simulations that use a diffusion model. Accounting for each of these effects in simulations reproduces the observed yield trends.« less

Intergalactic Helium Absorption toward High-Redshift Quasars

NASA Technical Reports Server (NTRS)

Giroux, Mark L.; Fardal, Mark A.; Shull, J. Michael

1995-01-01

The recent Hubble Space Telescope (HST) observations of the z(q) = 3.286 quasar Q0302-003 (Jakobsen et at. 1994) and the z(q) = 3.185 quasar Q1935-67 by Tytler (1995) show absorption edges at the redshifted wavelength of He II 304 A. A key goal is to distinguish between contributions from discrete Ly-alpha forest clouds and a smoothly distributed intergalactic medium (IGM). We model the contributions from each of these sources of He II absorption, including the distribution of line Doppler widths and column densities, the 'He II proximity effect' from the quasar, and a self-consistent derivation of the He II opacity of the universe as a function of the spectrum of ionizing sources, with the assumption that both the clouds and the IGM are photoionized. The He II edge can be fully accounted for by He II line blanketing for reasonable distributions of line widths and column densities in the Ly-alpha forest, provided that the ionizing sources have spectral index alpha(s) greater than 1.5, and any He II proximity effect is neglected. Even with some contribution from a diffuse IGM, it is difficult to account for the edge observed by Jakobsen et al. (1994) with a 'hard' source spectrum (alpha(s) less than 1.3). The proximity effect modifies the relative contributions of the clouds and IGM to tau(He II) near the quasar (z approx. less than z(q)) and markedly increases the amount of He II absorption required. This implies, for example, that to account for the He II edge with line blanketing alone, the minimum spectral index alpha(s) must be increased from 1.5 to 1.9. We demonstrate the need for higher resolution observations that characterize the change in transmission as z approaches z(q) and resolve line-free gaps in the continuum. We set limits on the density of the diffuse IGM and suggest that the IGM and Ly-alpha clouds are likely to be a significant repository for dark baryons.

Dynamics and Solubility of He and CO 2 in Brine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Tuan Anh; Tenney, Craig M.

2016-09-01

Molecular dynamics simulation was implemented using LAMMPS simulation package (1) to study the diffusivity of He 3 and CO 2 in NaCl aqueous solution. To simulate at infinite dilute gas concentration, we placed one He 3 or CO 2 molecule in an initial simulation box of 24x24x33Å 3 containing 512 water molecules and a certain number of NaCl molecules depending on the concentration. Initial configuration was set up by placing water, NaCl, and gas molecules into different regions in the simulation box. Calculating diffusion coefficient for one He or CO 2 molecule consistently yields poor results. To overcome this, formore » each simulation at specific conditions (i.e., temperature, pressure, and NaCl concentration), we conducted 50 simulations initiated from 50 different configurations. These configurations are obtained by performing the simulation starting from the initial configuration mentioned above in the NVE ensemble (i.e., constant number of particles, volume, and energy). for 100,000 time steps and collecting one configuration every 2,000 times step. The output temperature of this simulation is about 500K. The collected configurations were then equilibrated for 2ns in the NPT ensemble (i.e., constant number of particles, pressure, and temperature) followed by 9ns simulations in the NVT ensemble (i.e., constant number of particles, volume, and temperature). The time step is 1fs for all simulations.« less

Computational (DFT) and Experimental (EXAFS) Study of the Interaction of [Ir(IMes)(H)2 (L)3 ] with Substrates and Co-substrates Relevant for SABRE in Dilute Systems.

PubMed

van Weerdenburg, Bram J A; Engwerda, Anthonius H J; Eshuis, Nan; Longo, Alessandro; Banerjee, Dipanjan; Tessari, Marco; Guerra, Célia Fonseca; Rutjes, Floris P J T; Bickelhaupt, F Matthias; Feiters, Martin C

2015-07-13

Signal amplification by reversible exchange (SABRE) is an emerging hyperpolarization method in NMR spectroscopy, in which hyperpolarization is transferred through the scalar coupling network of para-hydrogen derived hydrides in a metal complex to a reversibly bound substrate. Substrates can even be hyperpolarized at concentrations below that of the metal complex by addition of a suitable co-substrate. Here we investigate the catalytic system used for trace detection in NMR spectroscopy with [Ir(IMes)(H)2 (L)3 ](+) (IMes=1,3-dimesitylimidazol-2-ylidene) as catalyst, pyridine as a substrate and 1-methyl-1,2,3-triazole as co-substrate in great detail. With density functional theory (DFT), validated by extended X-ray absorption fine structure (EXAFS) experiments, we provide explanations for the relative abundance of the observed metal complexes, as well as their contribution to SABRE. We have established that the interaction between iridium and ligands cis to IMes is weaker than that with the trans ligand, and that in mixed complexes with pyridine and triazole, the latter preferentially takes up the trans position. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In Situ and Ex Situ Low-Field NMR Spectroscopy and MRI Endowed by SABRE Hyperpolarization**

PubMed Central

Barskiy, Danila A.; Kovtunov, Kirill V.; Koptyug, Igor V.; He, Ping; Groome, Kirsten A.; Best, Quinn A.; Shi, Fan; Goodson, Boyd M.; Shchepin, Roman V.; Truong, Milton L.; Coffey, Aaron M.; Waddell, Kevin W.; Chekmenev, Eduard Y.

2015-01-01

By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 105-fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high-resolution low-field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real-time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low-field (milli-Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen-enhanced NMR and MRI, which are free from the limitations of high-field magnetic resonance (including susceptibility-induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields. PMID:25367202

Signal-to-noise ratio comparison of encoding methods for hyperpolarized noble gas MRI

NASA Technical Reports Server (NTRS)

Zhao, L.; Venkatesh, A. K.; Albert, M. S.; Panych, L. P.

2001-01-01

Some non-Fourier encoding methods such as wavelet and direct encoding use spatially localized bases. The spatial localization feature of these methods enables optimized encoding for improved spatial and temporal resolution during dynamically adaptive MR imaging. These spatially localized bases, however, have inherently reduced image signal-to-noise ratio compared with Fourier or Hadamad encoding for proton imaging. Hyperpolarized noble gases, on the other hand, have quite different MR properties compared to proton, primarily the nonrenewability of the signal. It could be expected, therefore, that the characteristics of image SNR with respect to encoding method will also be very different from hyperpolarized noble gas MRI compared to proton MRI. In this article, hyperpolarized noble gas image SNRs of different encoding methods are compared theoretically using a matrix description of the encoding process. It is shown that image SNR for hyperpolarized noble gas imaging is maximized for any orthonormal encoding method. Methods are then proposed for designing RF pulses to achieve normalized encoding profiles using Fourier, Hadamard, wavelet, and direct encoding methods for hyperpolarized noble gases. Theoretical results are confirmed with hyperpolarized noble gas MRI experiments. Copyright 2001 Academic Press.

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

Endothelium-dependent Hyperpolarization-mediated Vasodilatation Compensates Nitric Oxide-mediated Endothelial Dysfunction during Ischemia in Diabetes-induced Canine Coronary Collateral Microcirculation in Vivo.

PubMed

Yada, Toyotaka; Shimokawa, Hiroaki; Tachibana, Hiroyuki

2018-04-17

It has been previously demonstrated that endothelial caveolin-1 plays crucial roles to produce an endothelium-derived hyperpolarizing factor in mouse mesenteric arteries. We examined whether this mechanism is involved in the endothelium-derived hyperpolarizing-mediated responses to compensate reduced NO-mediated responses in diabetes mellitus during coronary occlusion in dogs in vivo. Canine subepicardial collateral coronary small arteries (≥100 μm) and arterioles (<100 μm) were observed by an intravital microscope. Experiments were performed during occlusion of the left anterior descending coronary artery (90 min) under the following conditions (n=6 each); (i) control, (ii) diabetes mellitus, and (iii) diabetes mellitus+L-NMMA+K C a channel blockade. Vascular and myocardial levels of caveolin-1, eNOS and caspase-3 were measured by ELISA. Caveolin-1 levels in the ischemic area were greater in coronary microvessels than in conduit arteries in the control group. NO-mediated coronary vasodilatations of small arteries to bradykinin did not increase in diabetes mellitus associated with decreased eNOS phosphorylation at Ser1177 compared with baseline of controls, and were restored by compensation of endothelium-derived hyperpolarizing, and were suppressed by K C a channel blockade. NO-mediated vasodilatations of small coronary arteries during coronary occlusion are impaired in diabetes mellitus and are compensated by endothelium-derived hyperpolarizing of arterioles in dogs in vivo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Microtesla SABRE enables 10% nitrogen-15 nuclear spin polarization.

PubMed

Theis, Thomas; Truong, Milton L; Coffey, Aaron M; Shchepin, Roman V; Waddell, Kevin W; Shi, Fan; Goodson, Boyd M; Warren, Warren S; Chekmenev, Eduard Y

2015-02-04

Parahydrogen is demonstrated to efficiently transfer its nuclear spin hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B(3) amide) by conducting "signal amplification by reversible exchange" (SABRE) at microtesla fields within a magnetic shield. Following transfer of the sample from the magnetic shield chamber to a conventional NMR spectrometer, the (15)N NMR signals for these molecules are enhanced by ∼30,000- and ∼20,000-fold at 9.4 T, corresponding to ∼10% and ∼7% nuclear spin polarization, respectively. This method, dubbed "SABRE in shield enables alignment transfer to heteronuclei" or "SABRE-SHEATH", promises to be a simple, cost-effective way to hyperpolarize heteronuclei. It may be particularly useful for in vivo applications because of longer hyperpolarization lifetimes, lack of background signal, and facile chemical-shift discrimination of different species.

Microtesla SABRE Enables 10% Nitrogen-15 Nuclear Spin Polarization

PubMed Central

2016-01-01

Parahydrogen is demonstrated to efficiently transfer its nuclear spin hyperpolarization to nitrogen-15 in pyridine and nicotinamide (vitamin B3 amide) by conducting “signal amplification by reversible exchange” (SABRE) at microtesla fields within a magnetic shield. Following transfer of the sample from the magnetic shield chamber to a conventional NMR spectrometer, the 15N NMR signals for these molecules are enhanced by ∼30,000- and ∼20,000-fold at 9.4 T, corresponding to ∼10% and ∼7% nuclear spin polarization, respectively. This method, dubbed “SABRE in shield enables alignment transfer to heteronuclei” or “SABRE-SHEATH”, promises to be a simple, cost-effective way to hyperpolarize heteronuclei. It may be particularly useful for in vivo applications because of longer hyperpolarization lifetimes, lack of background signal, and facile chemical-shift discrimination of different species. PMID:25583142

Helium isotopes in ferromanganese crusts from the central Pacific Ocean

USGS Publications Warehouse

Basu, S.; Stuart, F.M.; Klemm, V.; Korschinek, G.; Knie, K.; Hein, J.R.

2006-01-01

Helium isotopes have been measured in samples of two ferromanganese crusts (VA13/2 and CD29-2) from the central Pacific Ocean. With the exception of the deepest part of crust CD29-2 the data can be explained by a mixture of implanted solar- and galactic cosmic ray-produced (GCR) He, in extraterrestrial grains, and radiogenic He in wind-borne continental dust grains. 4He concentrations are invariant and require retention of less than 12% of the in situ He produced since crust formation. Loss has occurred by recoil and diffusion. High 4He in CD29-2 samples older than 42 Ma are correlated with phosphatization and can be explained by retention of up to 12% of the in situ-produced 4He. 3He/4He of VA13/2 samples varies from 18.5 to 1852 Ra due almost entirely to variation in the extraterrestrial He contribution. The highest 3He/4He is comparable to the highest values measured in interplanetary dust particles (IDPs) and micrometeorites (MMs). Helium concentrations are orders of magnitude lower than in oceanic sediments reflecting the low trapping efficiency for in-falling terrestrial and extraterrestrial grains of Fe-Mn crusts. The extraterrestrial 3He concentration of the crusts rules out whole, undegassed 4–40 μm diameter IDPs as the host. Instead it requires that the extraterrestrial He inventory is carried by numerous particles with significantly lower He concentrations, and occasional high concentration GCR-He-bearing particles.

Design of a 15N Molecular Unit to Achieve Long Retention of Hyperpolarized Spin State

NASA Astrophysics Data System (ADS)

Nonaka, Hiroshi; Hirano, Masashi; Imakura, Yuki; Takakusagi, Yoichi; Ichikawa, Kazuhiro; Sando, Shinsuke

2017-01-01

Nuclear hyperpolarization is a phenomenon that can be used to improve the sensitivity of magnetic resonance molecular sensors. However, such sensors typically suffer from short hyperpolarization lifetime. Herein we report that [15N, D14]trimethylphenylammonium (TMPA) has a remarkably long spin-lattice relaxation time (1128 s, 14.1 T, 30 °C, D2O) on its 15N nuclei and achieves a long retention of the hyperpolarized state. [15N, D14]TMPA-based hyperpolarized sensor for carboxylesterase allowed the highly sensitive analysis of enzymatic reaction by 15N NMR for over 40 min in phophate-buffered saline (H2O, pH 7.4, 37 °C).

Hyperpolarized NMR: d-DNP, PHIP, and SABRE.

PubMed

Kovtunov, Kirill Viktorovich; Pokochueva, Ekaterina; Salnikov, Oleg; Cousin, Samuel; Kurzbach, Dennis; Vuichoud, Basile; Jannin, Sami; Chekmenev, Eduard; Goodson, Boyd; Barskiy, Danila; Koptyug, Igor

2018-05-23

NMR signals intensities can be enhanced by several orders of magnitude via utilization of techniques for hyperpolarization of different molecules, and it allows one to overcome the main sensitivity challenge of modern NMR/MRI techniques. Hyperpolarized fluids can be successfully used in different applications of material science and biomedicine. This focus review covers the fundamentals of the preparation of hyperpolarized liquids and gases via dissolution dynamic nuclear polarization (d-DNP) and parahydrogen-based techniques such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP) in both heterogeneous and homogeneous processes. The different novel aspects of hyperpolarized fluids formation and utilization along with the possibility of NMR signal enhancement observation are described. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization

NASA Astrophysics Data System (ADS)

Theis, Thomas; Truong, Milton; Coffey, Aaron M.; Chekmenev, Eduard Y.; Warren, Warren S.

2014-11-01

Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate "Low-Irradiation Generation of High Tesla-SABRE" (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules.

Nerve-mediated descending inhibition in the proximal colon of the rabbit.

PubMed

Julé, Y

1980-12-01

1. Descending inhibition in the rabbit proximal colon, evoked by distension, was studied in vivo by recording extracellularly electrical activity from pressure electrodes placed on the serosa. 2. Distention produced, blow the level of the balloon, a brief hyperpolarization of smooth muscle fibres which could be recorded up to 20 cm from the point of distension. 3. This hyperpolarization like that produced by vagal stimulation (inhibitory junction potentials) persisted in the presence of sympathetic blocking agents and atropine, and was produced by non-adrenergic non-cholinergic intramural neurones. 4. In the presence of vagally evoked excitatory junction potentials (e.j.p.s), distension produced a transient inhibition of e.j.p.s, in addition to the hyperpolarization of smooth muscle. 5. The inhibition of these e.j.p.s persisted in the presence of sympathetic blocking agents, but in contrast to the hyperpolarization of smooth muscle produced by distension alone, was modulated by drugs interfering with 5-HT synthesis, re-uptake and activity. 6. The results indicate that descending inhibition in the rabbit proximal colon was produced by two distinct neuronal non-adrenergic inhibitory mechanisms exerted simultaneously on the smooth muscle and on the cholinergic excitatory pathways which innervate it.

Nerve-mediated descending inhibition in the proximal colon of the rabbit.

PubMed Central

Julé, Y

1980-01-01

1. Descending inhibition in the rabbit proximal colon, evoked by distension, was studied in vivo by recording extracellularly electrical activity from pressure electrodes placed on the serosa. 2. Distention produced, blow the level of the balloon, a brief hyperpolarization of smooth muscle fibres which could be recorded up to 20 cm from the point of distension. 3. This hyperpolarization like that produced by vagal stimulation (inhibitory junction potentials) persisted in the presence of sympathetic blocking agents and atropine, and was produced by non-adrenergic non-cholinergic intramural neurones. 4. In the presence of vagally evoked excitatory junction potentials (e.j.p.s), distension produced a transient inhibition of e.j.p.s, in addition to the hyperpolarization of smooth muscle. 5. The inhibition of these e.j.p.s persisted in the presence of sympathetic blocking agents, but in contrast to the hyperpolarization of smooth muscle produced by distension alone, was modulated by drugs interfering with 5-HT synthesis, re-uptake and activity. 6. The results indicate that descending inhibition in the rabbit proximal colon was produced by two distinct neuronal non-adrenergic inhibitory mechanisms exerted simultaneously on the smooth muscle and on the cholinergic excitatory pathways which innervate it. PMID:6454779

Anoxia increases potassium conductance in hippocampal nerve cells.

PubMed

Hansen, A J; Hounsgaard, J; Jahnsen, H

1982-07-01

The effect of anoxia on nerve cell function was studied by intra- and extracellular microelectrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission. Mn++, Mg++ and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyperpolarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Patchy intergalactic He II absorption in HE 2347-4342. II. The possible discovery of the epoch of He-reionization

NASA Astrophysics Data System (ADS)

Reimers, D.; Kohler, S.; Wisotzki, L.; Groote, D.; Rodriguez-Pascual, P.; Wamsteker, W.

1997-11-01

We report on observations of redshifted Heii303.8 Angstroms absorption in the high-redshift QSO HE2347-4342 (z=2.885, V=16.1) with the Goddard High Resolution Spectrograph on board HST in its low resolution mode (bigtriangleup lambda = 0.7 Angstroms). With f_λ=3.6\\ 10(-15) ergcm(-2) s(-1) Angstroms(-1) at the expected position of Heii304 Angstroms absorption it is the most UV-bright high redshift QSO discovered so far. We show that the Heii opacity as a function of redshift is patchy showing spectral regions with low Heii opacity (``voids'') and regions with high Heii opacity (blacked-out ``troughs'') and no detectable flux. Combination with high-resolution optical spectra of the Lyalpha forest using CASPEC at the 3.6m telescope shows that the voids can be explained either exclusively by Lyalpha forest cloud absorption with a moderate N_{subs {He{sc ii}}}/N_{subs {H{sc i}}} ratio eta <=100 and turbulent line broadening or by a combination of Lyalpha forest with eta = 45 and thermal broadening plus a diffuse medium with tau_ {subs {GP}}({subs {He{sc ) ii}}} ~ 0.3. Since the latter is a minimum assumption for the Lyalpha forest, a strict upper limit to a diffuse medium is Omega_ {subs {diff}}<0.02 h50(-1.5) at z=2.8. In the troughs in addition to the Lyalpha forest opacity a continuous Heii 304 Angstroms opacity tau = 4.8(+infty }_{-2) is required. In case of photoionization, the troughs would require a diffuse component with a density close to Omega =~ 0.077(eta /45)(-0.5) h50(-1.5) , i.e. all baryons in the universe, which is inconsistent, however, with the observed absence of such a component in the voids. A tentative interpretation is that we observe the epoch of partial Heii reionization of the universe with patches not yet reionized. In that case a diffuse component with Omega_ {subs {diff}}>= 1.3\\ 10(-4) h(-1}_{50) would be sufficient to explain the ``trough'' opacity. The size of the 1163--1172 Angstroms trough is ~ 6 h50(-1) Mpc or ~ 2300 kms(-1) , respectively. We also discuss partially resolved Heii absorption of a high-ionization associated absorption system. Despite its high luminosity HE2347-4342 does not show a Heii proximity effect. A possible reason is that the strong associated system shields the Heii ionizing continuum. Based on observations collected at the European Southern Observatory, La Silla, Chile (ESO No.\\ 58.B--0116). Based on IUE observations collected at the ESA VILSPA ground station near Madrid, Spain. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by Aura, Inc., under NASA contract NAS 5--26\\,555.

Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h

NASA Technical Reports Server (NTRS)

Clark, J. M.; Jackson, R. M.; Lambertsen, C. J.; Gelfand, R.; Hiller, W. D. B.; Unger, M.

1991-01-01

A complete description of pulmonary measurements obtained after continuous O2 exposure of 13 healthy men at 3.0 ATA for 3.5 h is presented. Measurements included flow-volume loops, spirometry, and airway resistance(n = 12); CO diffusing capacity (n = 11); closing volumes (n= 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). The average difference in maximum mid expiratory flows at 50 percent vital capacity on air and HeO2 was found to be significantly reduced postexposure by 18 percent. Raw and CO diffusing capacity were not changed postexposure. It is concluded that the relatively large change in forced expiratory flow at 25-75 percent of vital capacity compared with the mean forced expiratory volume in 1 s, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow.

Screening and Monitoring Response to Treatment Using Subsecond Molecular Imaging and Hyperpolarized Contrast Agents

DTIC Science & Technology

2013-05-01

Magnetization transfer MRI in multiple sclerosis . J Neuroimaging. 2007;17 Suppl 1:S22–S26. 82. Filippi M, Rocca MA. Magnetization transfer magnetic resonance... multiple sclerosis . Neuroimaging Clin N Am. 2009;19(1):27–36. 84. Lundbom N. Determination of magnetization transfer contrast in tissue: an MR... multiple RF coils intended for optimal direct and indirect detection of hyperpolarized contrast agents in vivo. 4.b. Y1Q3-Y1Q4. Low field MRI: pre

He, U, and Th Depth Profiling of Apatite and Zircon Using Laser Ablation Noble Gas Mass Spectrometry and SIMS

NASA Astrophysics Data System (ADS)

Monteleone, B. D.; van Soest, M. C.; Hodges, K. V.; Hervig, R.; Boyce, J. W.

2008-12-01

Conventional (U-Th)/He thermochronology utilizes single or multiple grain analyses of U- and Th-bearing minerals such as apatite and zircon and does not allow for assessment of spatial variation in concentration of He, U, or Th within individual crystals. As such, age calculation and interpretation require assumptions regarding 4He loss through alpha ejection, diffusive redistribution of 4He, and U and Th distribution as an initial condition for these processes. Although models have been developed to predict 4He diffusion parameters, correct for the effect of alpha ejection on calculated cooling ages, and account for the effect of U and Th zonation within apatite and zircon, measurements of 4He, U, and Th distribution have not been combined within a single crystal. We apply ArF excimer laser ablation, combined with noble gas mass spectrometry, to obtain depth profiles within apatite and zircon crystals in order to assess variations in 4He concentration with depth. Our initial results from pre-cut, pre-heated slabs of Durango apatite, each subjected to different T-t schedules, suggest a general agreement of 4He profiles with those predicted by theoretical diffusion models (Farley, 2000). Depth profiles through unpolished grains give reproducible alpha ejection profiles in Durango apatite that deviate from alpha ejection profiles predicted for ideal, homogenous crystals. SIMS depth profiling utilizes an O2 primary beam capable of sputtering tens of microns and measuring sub-micron resolution variation in [U], [Th], and [Sm]. Preliminary results suggest that sufficient [U] and [Th] zonation is present in Durango apatite to influence the form of the 4He alpha ejection profile. Future work will assess the influence of measured [U] and [Th] zonation on previously measured 4He depth profiles. Farley, K.A., 2000. Helium diffusion from apatite; general behavior as illustrated by Durango fluorapatite. J. Geophys. Res., B Solid Earth Planets 105 (2), 2903-2914.

Postural headache in a patient with Marfan's syndrome.

PubMed

Ferrante, E; Citterio, A; Savino, A; Santalucia, P

2003-09-01

A 26-year-old man with Marfan's syndrome had postural headache. Brain MRI with gadolinium showed diffuse pachymeningeal enhancement. MRI myelography revealed bilateral multiple large meningeal diverticula at sacral nerve roots level. He was suspected to have spontaneous intracranial hypotension syndrome. Eight days later headache improved with bed rest and hydration. One month after the onset he was asymptomatic and 3 months later brain MRI showed no evidence of diffuse pachymeningeal enhancement. The 1-year follow-up revealed no neurological abnormalities. The intracranial hypotension syndrome likely resulted from a CSF leak from one of the meningeal diverticula. In conclusion patients with spinal meningeal diverticula (frequently seen in Marfan's syndrome) might be at increased risk of developing CSF leaks, possibly secondary to Valsalva maneuver or minor unrecognized trauma.

LIGHT-SABRE enables efficient in-magnet catalytic hyperpolarization.

PubMed

Theis, Thomas; Truong, Milton; Coffey, Aaron M; Chekmenev, Eduard Y; Warren, Warren S

2014-11-01

Nuclear spin hyperpolarization overcomes the sensitivity limitations of traditional NMR and MRI, but the most general method demonstrated to date (dynamic nuclear polarization) has significant limitations in scalability, cost, and complex apparatus design. As an alternative, signal amplification by reversible exchange (SABRE) of parahydrogen on transition metal catalysts can hyperpolarize a variety of substrates, but to date this scheme has required transfer of the sample to low magnetic field or very strong RF irradiation. Here we demonstrate "Low-Irradiation Generation of High Tesla-SABRE" (LIGHT-SABRE) which works with simple pulse sequences and low power deposition; it should be usable at any magnetic field and for hyperpolarization of many different nuclei. This approach could drastically reduce the cost and complexity of producing hyperpolarized molecules. Copyright © 2014 Elsevier Inc. All rights reserved.

Silicon nanoparticles as hyperpolarized magnetic resonance imaging agents.

PubMed

Aptekar, Jacob W; Cassidy, Maja C; Johnson, Alexander C; Barton, Robert A; Lee, Menyoung; Ogier, Alexander C; Vo, Chinh; Anahtar, Melis N; Ren, Yin; Bhatia, Sangeeta N; Ramanathan, Chandrasekhar; Cory, David G; Hill, Alison L; Mair, Ross W; Rosen, Matthew S; Walsworth, Ronald L; Marcus, Charles M

2009-12-22

Magnetic resonance imaging of hyperpolarized nuclei provides high image contrast with little or no background signal. To date, in vivo applications of prehyperpolarized materials have been limited by relatively short nuclear spin relaxation times. Here, we investigate silicon nanoparticles as a new type of hyperpolarized magnetic resonance imaging agent. Nuclear spin relaxation times for a variety of Si nanoparticles are found to be remarkably long, ranging from many minutes to hours at room temperature, allowing hyperpolarized nanoparticles to be transported, administered, and imaged on practical time scales. Additionally, we demonstrate that Si nanoparticles can be surface functionalized using techniques common to other biologically targeted nanoparticle systems. These results suggest that Si nanoparticles can be used as a targetable, hyperpolarized magnetic resonance imaging agent with a large range of potential applications.

In situ and ex situ low-field NMR spectroscopy and MRI endowed by SABRE hyperpolarization.

PubMed

Barskiy, Danila A; Kovtunov, Kirill V; Koptyug, Igor V; He, Ping; Groome, Kirsten A; Best, Quinn A; Shi, Fan; Goodson, Boyd M; Shchepin, Roman V; Truong, Milton L; Coffey, Aaron M; Waddell, Kevin W; Chekmenev, Eduard Y

2014-12-15

By using 5.75 and 47.5 mT nuclear magnetic resonance (NMR) spectroscopy, up to 10(5)-fold sensitivity enhancement through signal amplification by reversible exchange (SABRE) was enabled, and subsecond temporal resolution was used to monitor an exchange reaction that resulted in the buildup and decay of hyperpolarized species after parahydrogen bubbling. We demonstrated the high-resolution low-field proton magnetic resonance imaging (MRI) of pyridine in a 47.5 mT magnetic field endowed by SABRE. Molecular imaging (i.e. imaging of dilute hyperpolarized substances rather than the bulk medium) was conducted in two regimes: in situ real-time MRI of the reaction mixture (in which pyridine was hyperpolarized), and ex situ MRI (in which hyperpolarization decays) of the liquid hyperpolarized product. Low-field (milli-Tesla range, e.g. 5.75 and 47.5 mT used in this study) parahydrogen-enhanced NMR and MRI, which are free from the limitations of high-field magnetic resonance (including susceptibility-induced gradients of the static magnetic field at phase interfaces), potentially enables new imaging applications as well as differentiation of hyperpolarized chemical species on demand by exploiting spin manipulations with static and alternating magnetic fields. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Apatite (U-Th)/He thermochronology dataset interpretation: New insights from physical point of view

NASA Astrophysics Data System (ADS)

Gautheron, Cécile; Mbongo-Djimbi, Duval; Gerin, Chloé; Roques, Jérôme; Bachelet, Cyril; Oliviero, Erwan; Tassan-Got, Laurent

2015-04-01

The apatite (U-Th)/He (AHe) system has rapidly become a very popular thermochronometer to constrain burial and exhumation phases in a variety of geological contexts. However, the interpretation of AHe data depends on a precise knowledge of He diffusion in apatite. Several studies suggest that radiation damage generated by U and Th decay can create traps for He atoms, increasing He retention for irradiated minerals. The radiation damage also anneals with temperature and the amount of damage in an apatite crystal is at any time a balance between production and annealing, controlled by U-Th concentration, grain chemistry and thermal history (Flowers et al., 2009; Gautheron et al., 2009; 2013). However the models are not well constrained and do not fully explain the mechanism of He retention. In order to have a deeper insight on this issue, multidisciplinary studies on apatite combining diffusion experiments by Elastic Recoil Diffusion Analysis (ERDA) with a multi-scale theoretical diffusion calculation based on Density Functional Theory (DFT) and Kinetic Monte Carlo were performed. ERDA experiments were conducted on different macro-crystals, and we probed the shape of a He profile implanted into a planar and polished surface of the crystal. The helium profile evolves with temperature and allows quantifying the He diffusivity and damage impact. Additionally, DFT calculations of a damage-free crystal of apatite with different F and Cl compositions, in similar proportion as natural ones, have been run to find the favored paths of a helium atom between interstitial sites, leading to a computation of the activation energy and the diffusion coefficient. We show that damage free apatite crystals are characterized by low retention behavior and closure temperature range from 33-36°C for pure F-apatite to higher value for Cl riche apatite (up to 12°C higher), for typical grain size and cooling rate (Mbongo-Djimbi et al., in review). Using ERDA and DFT approaches, we demonstrate that in addition to grain chemistry, He diffusivity will be strongly influenced by damage and propose a new physical model. Finally, we propose a new way of interpreting AHe datasets and practical geological examples will be given. Flowers, R., Ketcham, R.A., Shuster, D., Farley, K.A., 2009. Apatite (U-Th)/He thermochronology using a radiation damage accumulation and annealing model. Geochimica et Cosmochimica Acta 73, 2347-2365. Gautheron, C., Tassan-got, L., Barbarand, J., Pagel, M., 2009. Effect of alpha-damage annealing on apatite (U-Th)/He thermochronology. Chemical Geology 266, 166-179. Gautheron, C., Barbarand, J., Ketcham R.A., Tassan-got, L., van der Beek, P., Pagel, M., Pinna-Jamme, R., Couffignal, F., Fialin, M., 2013. Chemical influence on α-recoil damage annealing in apatite: implications for (U-Th)/He dating. Chemical Geology 351, 257-267. Mbongo-Djimbi D., Gautheron C., Roques, J., Tassan-Got, L., Gerin, C., Simoni, E.. Apatite composition effect on (U-Th)/He thermochronometer: an atomistic point of view. In review at Geochimica Cosmochimica Acta.

Reconstructing mantle volatile contents through the veil of degassing

NASA Astrophysics Data System (ADS)

Tucker, J.; Mukhopadhyay, S.; Gonnermann, H. M.

2014-12-01

The abundance of volatile elements in the mantle reveals critical information about the Earth's origin and evolution such as the chemical constituents that built the Earth and material exchange between the mantle and exosphere. However, due to magmatic degassing, volatile element abundances measured in basalts usually do not represent those in undegassed magmas and hence in the mantle source of the basalts. While estimates of average mantle concentrations of some volatile species can be obtained, such as from the 3He flux into the oceans, volatile element variability within the mantle remains poorly constrained. Here, we use CO2-He-Ne-Ar-Xe measurements in basalts and a new degassing model to reconstruct the initial volatile contents of 8 MORBs from the Mid-Atlantic Ridge and Southwest Indian Ridge that span a wide geochemical range from depleted to enriched MORBs. We first show that equilibrium degassing (e.g. Rayleigh degassing), cannot simultaneously fit the measured CO2-He-Ne-Ar-Xe compositions in MORBs and argue that kinetic fractionation between bubbles and melt lowers the dissolved ratios of light to heavy noble gas species in the melt from that expected at equilibrium. We present a degassing model (after Gonnermann and Mukhopadhyay, 2007) that explicitly accounts for diffusive fractionation between melt and bubbles. The model computes the degassed composition based on an initial volatile composition and a diffusive timescale. To reconstruct the undegassed volatile content of a sample, we find the initial composition and degassing timescale which minimize the misfit between predicted and measured degassed compositions. Initial 3He contents calculated for the 8 MORB samples vary by a factor of ~7. We observe a correlation between initial 3He and CO2 contents, indicating relatively constant CO2/3He ratios despite the geochemical diversity and variable gas content in the basalts. Importantly, the gas-rich popping rock from the North Atlantic, as well as the average mantle ratio computed from the ridge 3He flux and independently estimated CO2 content fall along the same correlation. This observation suggests that undegassed CO2 and noble gas concentrations can be reconstructed in individual samples through measurement of noble gases and CO2 in erupted basalts.

Rapid prototyping raw models on the basis of high resolution computed tomography lung data for respiratory flow dynamics.

PubMed

Giesel, Frederik L; Mehndiratta, Amit; von Tengg-Kobligk, Hendrik; Schaeffer, A; Teh, Kevin; Hoffman, E A; Kauczor, Hans-Ulrich; van Beek, E J R; Wild, Jim M

2009-04-01

Three-dimensional image reconstruction by volume rendering and rapid prototyping has made it possible to visualize anatomic structures in three dimensions for interventional planning and academic research. Volumetric chest computed tomography was performed on a healthy volunteer. Computed tomographic images of the larger bronchial branches were segmented by an extended three-dimensional region-growing algorithm, converted into a stereolithography file, and used for computer-aided design on a laser sintering machine. The injection of gases for respiratory flow modeling and measurements using magnetic resonance imaging were done on a hollow cast. Manufacturing the rapid prototype took about 40 minutes and included the airway tree from trackea to segmental bronchi (fifth generation). The branching of the airways are clearly visible in the (3)He images, and the radial imaging has the potential to elucidate the airway dimensions. The results for flow patterns in the human bronchial tree using the rapid-prototype model with hyperpolarized helium-3 magnetic resonance imaging show the value of this model for flow phantom studies.

Direct enhancement of nitrogen-15 targets at high-field by fast ADAPT-SABRE

NASA Astrophysics Data System (ADS)

Roy, Soumya S.; Stevanato, Gabriele; Rayner, Peter J.; Duckett, Simon B.

2017-12-01

Signal Amplification by Reversible Exchange (SABRE) is an attractive nuclear spin hyperpolarization technique capable of huge sensitivity enhancement in nuclear magnetic resonance (NMR) detection. The resonance condition of SABRE hyperpolarization depends on coherent spin mixing, which can be achieved naturally at a low magnetic field. The optimum transfer field to spin-1/2 heteronuclei is technically demanding, as it requires field strengths weaker than the earth's magnetic field for efficient spin mixing. In this paper, we illustrate an approach to achieve strong 15N SABRE hyperpolarization at high magnetic field by a radio frequency (RF) driven coherent transfer mechanism based on alternate pulsing and delay to achieve polarization transfer. The presented scheme is found to be highly robust and much faster than existing related methods, producing ∼ 3 orders of magnitude 15N signal enhancement within 2 s of RF pulsing.

Direct enhancement of nitrogen-15 targets at high-field by fast ADAPT-SABRE.

PubMed

Roy, Soumya S; Stevanato, Gabriele; Rayner, Peter J; Duckett, Simon B

2017-12-01

Signal Amplification by Reversible Exchange (SABRE) is an attractive nuclear spin hyperpolarization technique capable of huge sensitivity enhancement in nuclear magnetic resonance (NMR) detection. The resonance condition of SABRE hyperpolarization depends on coherent spin mixing, which can be achieved naturally at a low magnetic field. The optimum transfer field to spin-1/2 heteronuclei is technically demanding, as it requires field strengths weaker than the earth's magnetic field for efficient spin mixing. In this paper, we illustrate an approach to achieve strong 15 N SABRE hyperpolarization at high magnetic field by a radio frequency (RF) driven coherent transfer mechanism based on alternate pulsing and delay to achieve polarization transfer. The presented scheme is found to be highly robust and much faster than existing related methods, producing ∼3 orders of magnitude 15 N signal enhancement within 2 s of RF pulsing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cosmogenic 3He in detrital gold

NASA Astrophysics Data System (ADS)

Stuart, Finlay; Yakubovich, Olga; Caracedo, Ana; Nesterenok, Alexander

2017-04-01

Since the measurement of cosmogenic He in an alluvial diamond by McConville and Reynolds (1996) the application of cosmogenic noble gases to individual detrital grains to quantify surface processes has not been vigorously pursued. The likely low rate of diffusion of cosmogenic He in native metals, and their resistance to weathering and disintegration during erosion and transport, makes them a potential record of long-term Earth surface processes. In an effort to assess the extent that detrital refractory metals record the exposure history during transport and storage we have undertaken a reconnaissance study of the He isotope composition in 18 grains (2-200 mg) of native gold, copper, silver, and PtPd, Pt3Fe and OsIr alloys from alluvial placer deposits from around the world. 4He is dominantly the result of U and Th decay within the grains, or decay of 190Pt in the Pt-rich alloys. 3He is measurable in 13 grains, concentrations range up to 2.7E+6 atoms/g. 3He/4He are always in excess of the crustal radiogenic ratio, up to 306 Ra. Although nucleogenic 3He produced by (n,α) reactions on 6Li, and 3He from trapped hydrothermal fluids, are present, the majority of the 3He is cosmogenic in origin. Using newly calculated cosmogenic 3He production rates in heavy metals, and a determination of the effect of implantation based on the stopping distances of spallogenic 3He and 3H, the grains have 3Hecos concentrations that are equivalent to 0.35 to 1.5 Ma exposure at Earth's surface. In a study of detrital gold grains from several sites in Scotland we have found that 10 % have 3He concentrations that are significantly in excess of that generated since the Last Glacial Maximum. These studies demonstrate that, with refinement, cosmogenic 3He in refractory detrital minerals can be used to quantify sediment transport and storage on the 1-10 Ma timescale. P. McConville & J.H. Reynolds (1989). Geochim. Cosmochim. Acta, 53, 2365-75.

Efficient Synthesis of Molecular Precursors for Para-Hydrogen-Induced Polarization of Ethyl Acetate-1-(13) C and Beyond.

PubMed

Shchepin, Roman V; Barskiy, Danila A; Coffey, Aaron M; Manzanera Esteve, Isaac V; Chekmenev, Eduard Y

2016-05-10

A scalable and versatile methodology for production of vinylated carboxylic compounds with (13) C isotopic label in C1 position is described. It allowed synthesis of vinyl acetate-1-(13) C, which is a precursor for preparation of (13) C hyperpolarized ethyl acetate-1-(13) C, which provides a convenient vehicle for potential in vivo delivery of hyperpolarized acetate to probe metabolism in living organisms. Kinetics of vinyl acetate molecular hydrogenation and polarization transfer from para-hydrogen to (13) C via magnetic field cycling were investigated. Nascent proton nuclear spin polarization (%PH ) of ca. 3.3 % and carbon-13 polarization (%P13C ) of ca. 1.8 % were achieved in ethyl acetate utilizing 50 % para-hydrogen corresponding to ca. 50 % polarization transfer efficiency. The use of nearly 100% para-hydrogen and the improvements of %PH of para-hydrogen-nascent protons may enable production of (13) C hyperpolarized contrast agents with %P13C of 20-50 % in seconds using this chemistry. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The functional organization of the crayfish lamina ganglionaris. I. Nonspiking monopolar cells.

PubMed

Wang-Bennett, L T; Glantz, R M

1987-06-01

The light responses of the second order lamina monopolar neurons were examined in the crayfish compound eye. Single cartridge monopolar neurons (M1-M4) exhibited nonspiking hyperpolarizing light responses; for M1, M3 and M4 the transient 'on' response operated over the same intensity range as the receptor, 3.5 log units. M2 operated in a much narrower intensity range (1.5 log unit). The 'on' responses were associated with a 19% increase in conductance. The hyperpolarizing 'on' response can be reversed at 18 mV below the resting membrane potential. The half-angular sensitivity width of monopolar cells (in partially dark-adapted eyes) is 15 degrees X 8 degrees (horizontal by vertical). Off axis stimuli elicit attenuated hyperpolarizing responses associated with a diminished conductance increase or depolarizing responses associated with a net decrease in conductance. The latter result is consistent with the presynaptic inhibition of a 'back-ground' transmitter release which normally persists in the dark. Lateral inhibition is elicited from the area immediately surrounding the excitatory field, and it is associated with diminished transient responses and an accelerated decay of the response. Inhibitory stimuli decrease the conductance change associated with the hyperpolarizing response. The surround stimuli can also elicit depolarizing 'off' responses with reversal potentials positive to the membrane resting potential. It is concluded that the rapidly repolarizing monopolar cell response is modulated by both pre- and postsynaptic inhibitory mechanisms. A compartment model indicates that signal attenuation along a 500 microns length of monopolar cell axon is 22-34%. Simulation of steady-state signal transmission suggests that passive (decremental) conduction is sufficient to convey 66 to 78% of the monopolar cell signal from lamina to medulla. The current-voltage relation in current clamp is linear over the physiological operating range, and there is no evidence for rectification. Hyperpolarization of single monopolar cells (M1-M4) provides a polysynaptic excitatory signal to the medullary sustaining fibers.

Hyperpolarized (129)Xe T (1) in oxygenated and deoxygenated blood

NASA Technical Reports Server (NTRS)

Albert, M. S.; Balamore, D.; Kacher, D. F.; Venkatesh, A. K.; Jolesz, F. A.

2000-01-01

The viability of the new technique of hyperpolarized (129)Xe MRI (HypX-MRI) for imaging organs other than the lungs depends on whether the spin-lattice relaxation time, T(1), of (129)Xe is sufficiently long in the blood. In previous experiments by the authors, the T(1) was found to be strongly dependent upon the oxygenation of the blood, with T(1) increasing from about 3 s in deoxygenated samples to about 10 s in oxygenated samples. Contrarily, Tseng et al. (J. Magn. Reson. 1997; 126: 79-86) reported extremely long T(1) values deduced from an indirect experiment in which hyperpolarized (129)Xe was used to create a 'blood-foam'. They found that oxygenation decreased T(1). Pivotal to their experiment is the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles); this necessitated a complicated analysis to extract the T(1) of (129)Xe in blood. In the present study, the experimental design minimizes gas exchange after the initial bolus of hyperpolarized (129)Xe has been bubbled through the sample. This study confirms that oxygenation increases the T(1) of (129)Xe in blood, from about 4 s in freshly drawn venous blood, to about 13 s in blood oxygenated to arterial levels, and also shifts the red blood cell resonance to higher frequency. Copyright 2000 John Wiley & Sons, Ltd. Abbreviations used BOLD blood oxygen level dependent NOE nuclear overhouses effect PO(2) oxygen partial pressure RBC red blood cells RF radio frequency SNR signal-to-noise ratio.

Muscle Contraction during Hyperpolarizing Currents in the Crab

PubMed Central

Uchitel, O. D.; García, H.

1974-01-01

Isolated muscle fibers from the motor legs of the crab Trichodactilus dilocarcinus were submitted to strong hyperpolarizing currents of varied intensities which produced tension during the current pulse. Threshold for tension was obtained with intensities of about 0.2 x 10–5 A, changing Em to ca. –150 mV (starting from a resting potential ofca. –80 mV). At the closure of the anodic square pulse, a second phase of tension usually appeared superimposed upon the one obtained during hyperpolarization. The first phase of tension increased with the increase of Ca++ concentration in the bath. Sr++ produced the same type of mechanical output as Ca++. When added to the normal Ca++ concentration, Ba++ and Mn++ in low concentrations (up to 21.5 mM) also increased the tension of this phase, but at higher concentrations they blocked both phases while Mg++ did not alter the tension. Of all the divalent cations employed, only Sr++ is capable of developing tension as a substitute for Ca++ in the external media. Procaine administered in a dosage (5 x 10–3 W/V)which would suppress the contracture due to caffeine (10 mM), did not modify the tension developed during the hyperpolarization. The preceding data indicate that the Ca++ required for tension during hyperpolarization comes from sites which would differ from those usually postulated for tension due to depolarization in the muscle fibers of other crustaceans (American crayfish). Furthermore, the external source of Ca++ appears to be one mainly implicated in the induction of tension due to inward current pulses. PMID:4810206

Muscle contraction during hyperpolarizing currents in the crab.

PubMed

Uchitel, O D; García, H

1974-01-01

Isolated muscle fibers from the motor legs of the crab Trichodactilus dilocarcinus were submitted to strong hyperpolarizing currents of varied intensities which produced tension during the current pulse. Threshold for tension was obtained with intensities of about 0.2 x 10(-5) A, changing E(m) to ca. -150 mV (starting from a resting potential ofca. -80 mV). At the closure of the anodic square pulse, a second phase of tension usually appeared superimposed upon the one obtained during hyperpolarization. The first phase of tension increased with the increase of Ca(++) concentration in the bath. Sr(++) produced the same type of mechanical output as Ca(++). When added to the normal Ca(++) concentration, Ba(++) and Mn(++) in low concentrations (up to 21.5 mM) also increased the tension of this phase, but at higher concentrations they blocked both phases while Mg(++) did not alter the tension. Of all the divalent cations employed, only Sr(++) is capable of developing tension as a substitute for Ca(++) in the external media. Procaine administered in a dosage (5 x 10(-3) W/V)which would suppress the contracture due to caffeine (10 mM), did not modify the tension developed during the hyperpolarization. The preceding data indicate that the Ca(++) required for tension during hyperpolarization comes from sites which would differ from those usually postulated for tension due to depolarization in the muscle fibers of other crustaceans (American crayfish). Furthermore, the external source of Ca(++) appears to be one mainly implicated in the induction of tension due to inward current pulses.

Spontaneous 15N Nuclear Spin Hyperpolarization in Metal-Free Activation of Parahydrogen by Molecular Tweezers

PubMed Central

2018-01-01

The ability of frustrated Lewis pairs (FLPs) to activate H2 is of significant interest for metal-free catalysis. The activation of H2 is also the key element of parahydrogen-induced polarization (PHIP), one of the nuclear spin hyperpolarization techniques. It is demonstrated that o-phenylene-based ansa-aminoboranes (AABs) can produce 1H nuclear spin hyperpolarization through a reversible interaction with parahydrogen at ambient temperatures. Heteronuclei are useful in NMR and MRI as well because they have a broad chemical shift range and long relaxation times and may act as background-free labels. We report spontaneous formation of 15N hyperpolarization of the N–H site for a family of AABs. The process is efficient at the high magnetic field of an NMR magnet (7 T), and it provides up to 350-fold 15N signal enhancements. Different hyperpolarization effects are observed with various AAB structures and in a broad temperature range. Spontaneous hyperpolarization, albeit an order of magnitude weaker than that for 15N, was also observed for 11B nuclei. PMID:29401399

Hyperpolarized Magnetic Resonance: A Novel Technique for the In Vivo Assessment of Cardiovascular Disease

PubMed Central

Schroeder, Marie A.; Clarke, Kieran; Neubauer, Stefan; Tyler, Damian J.

2011-01-01

Non-invasive imaging plays a central role in cardiovascular disease for determining diagnosis, prognosis, and optimizing patient management. Recent experimental studies have demonstrated that monitoring hyperpolarized 13C-labelled tracers with magnetic resonance imaging and spectroscopy (MRI and MRS) offers a new way to investigate the normal and diseased heart, and that the technology may be useful in patients with heart disease. In this review, we show how hyperpolarized 13C-labelled tracers are generated and have been applied experimentally, and outline the methodological advances currently underway to enable translation of hyperpolarized 13C MRI and MRS into the clinic. Using hyperpolarized 13C-labelled metabolites and metabolic MRI and MRS could help assessment of many human cardiovascular diseases, including coronary artery disease, heart failure and metabolic cardiomyopathies. We discuss the clinical areas in which the technology may, in the future, aid in the diagnosis and management of patients with cardiovascular diseases, including dynamic investigations of in vivo metabolism, coronary angiography and quantitative perfusion imaging. It is possible that, in the future, hyperpolarized magnetic resonance will play a major role in clinical cardiology. PMID:21969318

Synaptic delay in the heart: an ionophoretic study.

PubMed Central

Hill-Smith, I; Purves, R D

1978-01-01

1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats. 2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec. 3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more. 4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells. 5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane. 6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux. PMID:209176

Reconstructing temperatures in the Maritime Alps, Italy, since the Last Glacial Maximum using cosmogenic noble gas paleothermometry

NASA Astrophysics Data System (ADS)

Tremblay, Marissa; Spagnolo, Matteo; Ribolini, Adriano; Shuster, David

2016-04-01

The Gesso Valley, located in the southwestern-most, Maritime portion of the European Alps, contains an exceptionally well-preserved record of glacial advances during the late Pleistocene and Holocene. Detailed geomorphic mapping, geochronology of glacial deposits, and glacier reconstructions indicate that glaciers in this Mediterranean region responded to millennial scale climate variability differently than glaciers in the interior of the European Alps. This suggests that the Mediterranean Sea somehow modulated the climate of this region. However, since glaciers respond to changes in temperature and precipitation, both variables were potentially influenced by proximity to the Sea. To disentangle the competing effects of temperature and precipitation changes on glacier size, we are constraining past temperature variations in the Gesso Valley since the Last Glacial Maximum (LGM) using cosmogenic noble gas paleothermometry. The cosmogenic noble gases 3He and 21Ne experience diffusive loss from common minerals like quartz and feldspars at Earth surface temperatures. Cosmogenic noble gas paleothermometry utilizes this open-system behavior to quantitatively constrain thermal histories of rocks during exposure to cosmic ray particles at the Earth's surface. We will present measurements of cosmogenic 3He in quartz sampled from moraines in the Gesso Valley with LGM, Bühl stadial, and Younger Dryas ages. With these 3He measurements and experimental data quantifying the diffusion kinetics of 3He in quartz, we will provide a preliminary temperature reconstruction for the Gesso Valley since the LGM. Future work on samples from younger moraines in the valley system will be used to fill in details of the more recent temperature history.

Alpha-Recoil Damage Annealing Effecfs on Zircon Crystallinity and He Diffusivity: Improving Damage-Diffusivity Models

NASA Astrophysics Data System (ADS)

Thurston, O. G.; Guenthner, W.; Garver, J. I.

2017-12-01

The effects of radiation damage on He diffusion in zircon has been a major research focus in thermochronology over the past decade. In the zircon-He system, alpha-recoil damage effects He diffusivity in two ways: a decrease in He diffusivity at low radiation damage levels, and an increase in He diffusivity at high radiation damage levels. The radiation damage accumulation process within zircon is well understood; however, the kinetics of annealing of alpha-recoil damage at geologic timescales as they pertain to damage-diffusivity models, and for metamict zircon (i.e. transition from crystalline to amorphous glass via damage accumulation), has not been well constrained. This study aims to develop a more complete model that describes the annealing kinetics for zircon grains with a broad range of pre-annealing, alpha-induced radiation damage. A suite of zircon grains from the Lucerne pluton, ME were chosen for this study due to their simple thermal history (monotonic cooling), notable range of effective uranium (eU, eU = [U] +0.235*[Th]) (15 - 34,239 ppm eU), and large range of radiation damage as measured by Raman shift from crystalline (>1005 cm-1) to metamict (<1000 cm-1). The zircon grains selected represent the full range of eU and radiation damage present in the pluton. The zircon grains were first mapped for overall crystallinity using Raman spectroscopy, then annealed at different time-temperature (t-T) schedules from 1 hr to 24 hrs at temperatures ranging from 700-1100 °C, followed by remapping with Raman spectroscopy to track the total Raman shift for each t-T step. The temperature window selected is at the "roll-over" point established in prior studies (Zhang et al., 2000), at which most laboratory annealing occurs. Our data show that high radiation damage zircon grains show larger Raman shifts than low radiation damage zircon grains when exposed to the same t-T step. The high damage zircon grains typically show a Raman shift of 4 cm-1 toward crystalline, while low radiation damage grains show a shift of 2 cm-1. These shifts suggest that the annealing process occurs at a faster rate in high damage zircon grains, and slower rates in more crystalline grains. That is, the initial level of radiation damage prior to annealing must be considered in damage-diffusivity models that contain thermal histories from zircon-He dates.

Cryogenic buffer-gas loading and magnetic trapping of CrH and MnH molecules

NASA Astrophysics Data System (ADS)

Stoll, Michael; Bakker, Joost M.; Steimle, Timothy C.; Meijer, Gerard; Peters, Achim

2008-09-01

We report on the buffer-gas cooling and trapping of CrH and MnH molecules in a magnetic quadrupole trap with densities on the order of 106cm-3 at a temperature of 650mK . Storage times of up to 180ms have been observed, corresponding to a 20-fold lifetime enhancement with respect to the field-free diffusion through the He3 buffer-gas. Using Monte Carlo trajectory simulations, inelastic molecule- He3 collision cross sections of 1.6×10-18 and 3.1×10-17cm2 are extracted for CrH and MnH, respectively. Furthermore, elastic molecule- He3 collision cross sections of 1.4(±0.5)×10-14cm2 are determined for both species. We conclude that the confinement time of these molecules in a magnetic trapping field is limited by inelastic collisions with the helium atoms leading to Zeeman relaxation.

Expression of a functional hyperpolarization-activated current (Ih) in the mouse nucleus reticularis thalami.

PubMed

Rateau, Y; Ropert, N

2006-05-01

The GABAergic neurons of the nucleus reticularis thalami (nRT) express the type 2 hyperpolarization-activated cAMP-sensitive (HCN2) subunit mRNA, but surprisingly, they were reported to lack the hyperpolarization-activated (Ih) current carried by this subunit. Using the voltage-clamp recordings in the thalamocortical slice preparation of the newborn and juvenile mice (P6-P23), we demonstrate that, in the presence of 1 mM barium (Ba2+), the nRT neurons express a slow hyperpolarization-activated inward current, suggesting that the Ih is present but masked in control conditions by K+ leak currents. We investigate the identity of the hyperpolarization-activated current in the nRT by studying its physiological and pharmacological profile in presence of Ba2+. We show that it has voltage- and time-dependent properties typical of the Ih, that it is blocked by cesium and ZD7288, two blockers of the Ih, and that it is carried both by the K+ and Na+ ions. We could also alter the gating characteristics of the hyperpolarization-activated current in the nRT by adding a nonhydrolysable analogue of cAMP to the pipette solution. Finally, using the current-clamp recording, we showed that blocking the hyperpolarization-activated current induced an hyperpolarization correlated with an increase of the R(in) of the nRT neurons. In conclusion, our results demonstrate that the nRT neurons express the Ih with slow kinetics similar to those described for the homomeric HCN2 channels, and we show that the Ih of the nRT contributes to the excitability of the nRT neurons in normal conditions.

Hyperpolarized nanodiamond with long spin-relaxation times

NASA Astrophysics Data System (ADS)

Rej, Ewa; Gaebel, Torsten; Boele, Thomas; Waddington, David E. J.; Reilly, David J.

2015-10-01

The use of hyperpolarized agents in magnetic resonance, such as 13C-labelled compounds, enables powerful new imaging and detection modalities that stem from a 10,000-fold boost in signal. A major challenge for the future of the hyperpolarization technique is the inherently short spin-relaxation times, typically <60 s for 13C liquid-state compounds, which limit the time that the signal remains boosted. Here we demonstrate that 1.1% natural abundance 13C spins in synthetic nanodiamond can be hyperpolarized at cryogenic and room temperature without the use of free radicals, and, owing to their solid-state environment, exhibit relaxation times exceeding 1 h. Combined with the already established applications of nanodiamonds in the life sciences as inexpensive fluorescent markers and non-cytotoxic substrates for gene and drug delivery, these results extend the theranostic capabilities of nanoscale diamonds into the domain of hyperpolarized magnetic resonance.

VERTICAL DIFFUSION IN SMALL STRATIFIED LAKES: DATA AND ERROR ANALYSIS

EPA Science Inventory

Water temperature profiles were measured at 2-min intervals in a stratified temperate lake with a surface area of 0.06 km2 and a aximum depth of 10 m from May 7 to August 9, 1989. he data were used to calculate the vertical eddy diffusion coefficient K2 in the hypolimnion. he dep...

Variability of intensity ratios of H to He and He to ions with Z not smaller than 3 in solar energetic particle events

NASA Technical Reports Server (NTRS)

Van Allen, J. A.; Venkatarangan, P.; Venkatesan, D.

1974-01-01

Data from the solid-state detector on Explorer 35 are applied to a study of two intensity ratios in the sub-MeV per nucleon specific kinetic energy range for several energetic particle events. It is found that the intensity ratios vary markedly from event to event, particularly during the time history of the individual events. This implies that the ratios have no simple relationship to 'solar abundances' in the usual sense of the term. The pattern of the variability of each ratio is established; the ratio of He to ions with Z not smaller than 3 starts with a low value and increases as the event proceeds. The H/He ratio exhibits a qualitatively similar time history with marked relative enhancement of He early in an event. Differential diffusion of the various ionic species with differing magnetic rigidities is seen to be the dominant physical cause for the variabilities observed.

Tunneling-thermally activated vacancy diffusion mechanism in quantum crystals

NASA Astrophysics Data System (ADS)

Natsik, V. D.; Smirnov, S. N.

2017-10-01

We consider a quasiparticle model of a vacancy in a quantum crystal, with metastable quantum states localized at the lattice sites in potential wells of the crystal field. It is assumed that the quantum dynamics of such vacancies can be described in the semi-classical approximation, where its spectrum consists of a broad band with several split-off levels. The diffusive movement of the vacancy in the crystal volume is reduced to a sequence of tunneling and thermally activated hops between the lattice cites. The temperature dependence of the vacancy diffusion coefficient shows a monotonic decrease during cooling with a sharp transition from an exponential dependence that is characteristic of a high-temperature thermally activated diffusion, to a non-thermal tunneling process in the region of extremely low temperatures. Similar trends have been recently observed in an experimental study of mass-transfer in the 4He and 3He crystals [V. A. Zhuchkov et al., Low Temp. Phys. 41, 169 (2015); Low Temp. Phys. 42, 1075 (2016)]. This mechanism of vacancy diffusion and its analysis complement the concept of a diffusional flow of a defection-quasiparticle quantum gas with a band energy spectrum proposed by Andreev and Lifshitz [JETP 29, 1107 (1969)] and Andreev [Sov. Phys. Usp. 19, 137 (1976)].

Surface damages of polycrystalline W and La2O3-doped W induced by high-flux He plasma irradiation

NASA Astrophysics Data System (ADS)

Liu, Lu; Li, Shouzhe; Liu, Dongping; Benstetter, Günther; Zhang, Yang; Hong, Yi; Fan, Hongyu; Ni, Weiyuan; Yang, Qi; Wu, Yunfeng; Bi, Zhenhua

2018-04-01

In this study, polycrystalline tungsten (W) and three oxide dispersed strengthened W with 0.1 vol %, 1.0 vol % and 5.0 vol % lanthanum trioxide (La2O3) were irradiated with low-energy (200 eV) and high-flux (5.8 × 1021 or 1.4 × 1022 ions/m2ṡs) He+ ions at elevated temperature. After He+ irradiation at a fluence of 3.0 × 1025/m2, their surface damages were observed by scanning electron microscopy, energy dispersive spectroscopy, scanning electron microscopy-electron backscatter diffraction, and conductive atomic force microscopy. Micron-sized holes were formed on the surface of W alloys after He+ irradiation at 1100 K. Analysis shows that the La2O3 grains doped in W were sputtered preferentially by the high-flux He+ ions when compared with the W grains. For irradiation at 1550 K, W nano-fuzz was formed at the surfaces of both polycrystalline W and La2O3-doped W. The thickness of the fuzz layers formed at the surface of La2O3-doped W is 40% lower than the one of polycrystalline W. The presence of La2O3 could suppress the diffusion and coalescence of He atoms inside W, which plays an important role in the growth of nanostructures fuzz.

Objective estimates of mantle 3He in the ocean and implications for constraining the deep ocean circulation

NASA Astrophysics Data System (ADS)

Holzer, Mark; DeVries, Timothy; Bianchi, Daniele; Newton, Robert; Schlosser, Peter; Winckler, Gisela

2017-01-01

Hydrothermal vents along the ocean's tectonic ridge systems inject superheated water and large amounts of dissolved metals that impact the deep ocean circulation and the oceanic cycling of trace metals. The hydrothermal fluid contains dissolved mantle helium that is enriched in 3He relative to the atmosphere, providing an isotopic tracer of the ocean's deep circulation and a marker of hydrothermal sources. This work investigates the potential for the 3He/4He isotope ratio to constrain the ocean's mantle 3He source and to provide constraints on the ocean's deep circulation. We use an ensemble of 11 data-assimilated steady-state ocean circulation models and a mantle helium source based on geographically varying sea-floor spreading rates. The global source distribution is partitioned into 6 regions, and the vertical profile and source amplitude of each region are varied independently to determine the optimal 3He source distribution that minimizes the mismatch between modeled and observed δ3He. In this way, we are able to fit the observed δ3He distribution to within a relative error of ∼15%, with a global 3He source that ranges from 640 to 850 mol yr-1, depending on circulation. The fit captures the vertical and interbasin gradients of the δ3He distribution very well and reproduces its jet-sheared saddle point in the deep equatorial Pacific. This demonstrates that the data-assimilated models have much greater fidelity to the deep ocean circulation than other coarse-resolution ocean models. Nonetheless, the modelled δ3He distributions still display some systematic biases, especially in the deep North Pacific where δ3He is overpredicted by our models, and in the southeastern tropical Pacific, where observed westward-spreading δ3He plumes are not well captured. Sources inferred by the data-assimilated transport with and without isopycnally aligned eddy diffusivity differ widely in the Southern Ocean, in spite of the ability to match the observed distributions of CFCs and radiocarbon for either eddy parameterization.

NMR Hyperpolarization Techniques for Biomedicine

PubMed Central

Nikolaou, Panayiotis; Goodson, Boyd M.

2015-01-01

Recent developments in NMR hyperpolarization have enabled a wide array of new in vivo molecular imaging modalities—ranging from functional imaging of the lungs to metabolic imaging of cancer. This Concept article explores selected advances in methods for the preparation and use of hyperpolarized contrast agents, many of which are already at or near the phase of their clinical validation in patients. PMID:25470566

Transmission of Helium Isotopes through Graphdiyne Pores: Tunneling versus Zero Point Energy Effects.

PubMed

Hernández, Marta I; Bartolomei, Massimiliano; Campos-Martínez, José

2015-10-29

Recent progress in the production of new two-dimensional (2D) nanoporous materials is attracting considerable interest for applications to isotope separation in gases. In this paper we report a computational study of the transmission of (4)He and (3)He through the (subnanometer) pores of graphdiyne, a recently synthesized 2D carbon material. The He-graphdiyne interaction is represented by a force field parametrized upon ab initio calculations, and the (4)He/(3)He selectivity is analyzed by tunneling-corrected transition state theory. We have found that both zero point energy (of the in-pore degrees of freedom) and tunneling effects play an extraordinary role at low temperatures (≈20-30 K). However, both quantum features work in opposite directions in such a way that the selectivity ratio does not reach an acceptable value. Nevertheless, the efficiency of zero point energy is in general larger, so that (4)He tends to diffuse faster than (3)He through the graphdiyne membrane, with a maximum performance at 23 K. Moreover, it is found that the transmission rates are too small in the studied temperature range, precluding practical applications. It is concluded that the role of the in-pore degrees of freedom should be included in computations of the transmission probabilities of molecules through nanoporous materials.

Gravity-induced changes in intracellular potentials in elongating cortical cells of mung bean roots

NASA Technical Reports Server (NTRS)

Ishikawa, H.; Evans, M. L.

1990-01-01

Gravity-induced changes in intracellular potentials in primary roots of 2-day-old mung bean (Vigna mungo L. cv. black matpe) seedlings were investigated using glass microelectrodes held by 3-dimensional hydraulic micro-drives. The electrodes were inserted into outer cortical cells within the elongation zone. Intracellular potentials, angle of root orientation with respect to gravity, and position within the root of the impaled cortical cell were measured simultaneously. Gravistimulation caused intracellular potential changes in cortical cells of the elongation zone. When the roots were oriented vertically, the intracellular potentials of the outer cortical cells (2 mm behind the root apex) were approximately - 115 mV. When the roots were placed horizontally cortical cells on the upper side hyperpolarized to - 154 mV within 30 s while cortical cells on the lower side depolarized to about - 62 mV. This electrical asymmetry did not occur in cells of the maturation zone. Because attempts to insert the electrode into cells of the root cap were unsuccessful, these cells were not measured. The hyperpolarization of cortical cells on the upper side was greatly reduced upon application of N,N'-dicyclohexylcarbodiimide (DCCD), an inhibitor of respiratory energy coupling. When stimulated roots were returned to the vertical, the degree of hyperpolarization of cortical cells on the previous upper side decreased within 30 s and approached that of cortical cells in non-stimulated roots. This cycle of hyperpolarization/loss of hyperpolarization was repeatable at least ten times by alternately turning the root from the vertical to the horizontal and back again. The very short (<30 s) lag period of these electrical changes indicates that they may result from stimulus-perception and transduction within the elongation zone rather than from transmission of a signal from the root cap.

Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR.

PubMed

Witte, C; Kunth, M; Rossella, F; Schröder, L

2014-02-28

Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of (129)Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

1H-NMR and Hyperpolarized 13C-NMR Assays of Pyruvate-Lactate Exhange: a comparative study

PubMed Central

Orton, Matthew R.; Tardif, Nicolas; Parkes, Harold G.; Robinson, Simon P.; Leach, Martin O.; Chung, Yuen-Li; Eykyn, Thomas R.

2015-01-01

Pyruvate-lactate exchange is mediated by the enzyme lactate dehydrogenase (LDH) and is central to the altered energy metabolism in cancer cells. Measurement of exchange kinetics using hyperpolarized 13C NMR has provided a biomarker of response to novel therapeutics. In this study we investigated an alternative in vitro 1H assay, using [3-13C]pyruvate, and compared the measured kinetics with a hyperpolarized 13C-NMR assay, using [1-13C]pyruvate, under the same conditions in human colorectal carcinoma SW1222 cells. The apparent forward reaction rate constants (kPL) derived from the two assays showed no significant difference, and both assays had similar reproducibility (kPL = 0.506 ± 0.054 and kPL = 0.441 ± 0.090 nmol/s/106 cells, (mean ± standard deviation, n = 3); 1H, 13C assays respectively). The apparent backward reaction rate constant (kLP) could only be measured with good reproducibility using the 1H-NMR assay (kLP = 0.376 ± 0.091 nmol/s/106 cells, (mean ± standard deviation, n = 3)). The 1H-NMR assay has adequate sensitivity to measure real-time pyruvate-lactate exchange kinetics in vitro, offering a complementary and accessible assay of apparent LDH activity. PMID:23712817

Achieving High Levels of NMR-Hyperpolarization in Aqueous Media With Minimal Catalyst Contamination Using SABRE.

PubMed

Iali, Wissam; Olaru, Alexandra M; Green, Gary G R; Duckett, Simon B

2017-08-04

Signal amplification by reversible exchange (SABRE) is shown to allow access to strongly enhanced 1 H NMR signals in a range of substrates in aqueous media. To achieve this outcome, phase-transfer catalysis is exploited, which leads to less than 1.5×10 -6  mol dm -3 of the iridium catalyst in the aqueous phase. These observations reflect a compelling route to produce a saline-based hyperpolarized bolus in just a few seconds for subsequent in vivo MRI monitoring. The new process has been called catalyst separated hyperpolarization through signal amplification by reversible exchange or CASH-SABRE. We illustrate this method for the substrates pyrazine, 5-methylpyrimidine, 4,6-d 2 -methyl nicotinate, 4,6-d 2 -nicotinamide and pyridazine achieving 1 H signal gains of approximately 790-, 340-, 3000-, 260- and 380-fold per proton at 9.4 T at the time point at which phase separation is complete. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Electrophysiological and mechanical effects of substance P and acetylcholine on rabbit aorta.

PubMed Central

Bény, J L; Brunet, P C

1988-01-01

1. The mechanical and electrical properties of smooth muscle cells of the rabbit aorta were recorded simultaneously using respectively a force transducer and a 3 M-KCl-filled glass microelectrode. 2. Acetylcholine had two effects depending on concentration. At low concentration, it caused a persistent endothelium-dependent relaxation and hyperpolarization. At higher concentrations the acetylcholine endothelium-dependent relaxation summed with an endothelium-independent contraction. 3. Substance P caused a transient endothelium-dependent relaxation and hyperpolarization. 4. Acetylcholine and substance P depolarized and contracted de-endothelialized smooth muscle. When the de-endothelialized strip was pre-contracted by noradrenaline, acetylcholine depolarized the muscle but substance P did not. 5. In a 'cascade' experiment, the perfusate from an upstream intact aorta passed over a downstream de-endothelialized strip. Acetylcholine and substance P relaxed the downstream strip showing that they released an endothelial humoral factor which relaxes smooth muscle. 6. The results suggest a constant release of a factor from the endothelial cells which hyperpolarizes the smooth muscle cells in the media. Activation of acetylcholine and substance P receptors on the endothelium accelerates the release of this factor and causes vasodilatation. PMID:2455799

WE-AB-202-07: Ventilation CT: Voxel-Level Comparison with Hyperpolarized Helium-3 & Xenon-129 MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tahir, B; Marshall, H; Hughes, P

Purpose: To compare the spatial correlation of ventilation surrogates computed from inspiratory and expiratory breath-hold CT with hyperpolarized Helium-3 & Xenon-129 MRI in a cohort of lung cancer patients. Methods: 5 patients underwent expiration & inspiration breath-hold CT. Xenon-129 & {sup 1}H MRI were also acquired at the same inflation state as inspiratory CT. This was followed immediately by acquisition of Helium-3 & {sup 1}H MRI in the same breath and at the same inflation state as inspiratory CT. Expiration CT was deformably registered to inspiration CT for calculation of ventilation CT from voxel-wise differences in Hounsfield units. Inspiration CTmore » and the Xenon-129’s corresponding anatomical {sup 1}H MRI were registered to Helium-3 MRI via the same-breath anatomical {sup 1}H MRI. This enabled direct comparison of CT ventilation with Helium-3 MRI & Xenon-129 MRI for the median values in corresponding regions of interest, ranging from finer to coarser in-plane dimensions of 10 by 10, 20 by 20, 30 by 30 and 40 by 40, located within the lungs as defined by the same-breath {sup 1}H MRI lung mask. Spearman coefficients were used to assess voxel-level correlation. Results: The median Spearman’s coefficients of ventilation CT with Helium-3 & Xenon-129 MRI for ROIs of 10 by 10, 20 by 20, 30 by 30 and 40 by 40 were 0.52, 0.56, 0.60 and 0.68 and 0.40, 0.42, 0.52 and 0.70, respectively. Conclusion: This work demonstrates a method of acquiring CT & hyperpolarized gas MRI (Helium-3 & Xenon-129 MRI) in similar breath-holds to enable direct spatial comparison of ventilation maps. Initial results show moderate correlation between ventilation CT & hyperpolarized gas MRI, improving for coarser regions which could be attributable to the inherent noise in CT intensity, non-ventilatory effects and registration errors at the voxel-level. Thus, it may be more beneficial to quantify ventilation at a more regional level.« less

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

PubMed

Seki, Takunori; Goto, Kenichi; Kiyohara, Kanako; Kansui, Yasuo; Murakami, Noboru; Haga, Yoshie; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

2017-01-01

Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca 2+ -activated K + channels (SK Ca and IK Ca ) underpins EDH-mediated responses. It was recently reported that Ca 2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SK Ca /IK Ca in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IK Ca , using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SK Ca /IK Ca blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SK Ca activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SK Ca protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IK Ca were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SK Ca input to EDH. © 2016 American Heart Association, Inc.

Etudes des Reactions de Transfert LITHIUM-7/LITHIUM -6

NASA Astrophysics Data System (ADS)

Baddou, Djafer

Les reactions de transfert de deux nucleons ^7Li/^6Li(^3He, rm p)^8Be/^9Be ont ete effectuees a partir d'um faisceau d'^3He initialement polarise et d'energie incidente egale a 4.58 MeV au centre de la cible. Le faisceau d'^3He est simplement ionise et il est accelere par l'accelerateur Van de Graaff de l'Universite Laval. Ce faisceau d' ^3He est de polarisation egale a 40% et il est obtenu a partir d'une source d'^3He a l'etat metastable. Nous avons decrit la reaction depuis la production et le transport du faisceau initial de l'^3 He jusqu'a la chambre de reaction. Par la suite, nous avons obtenu les distributions angulaires de la section efficace differentielle et du pouvoir d'analyse de ces reactions. Elles ont ete comparees a la theorie DWBA a l'approximation zero. La theorie a montre qu'il s'agit d'un transfert de deux particules independants (neutron, proton) pour le cas de la reaction ^7Li( ^3He,rm p)^9Be et d'un transfert de "cluster" deuteron pour le cas de la reaction ^6Li(^3He, rm p)^8Be. Notons que pour cette reaction l'instabilite du ^8Be ne nous permet pas d'avoir une diffusion elastique permettant la determination des parametres du modele optique entre ce noyau et la particule diffusee. Afin de contourner cette difficulte, nous supposons que le ^8 Be est un noyau compose de deux particules alpha et nous avons teste cette hypothese avec les reactions ^6Li(^3He, rm p)^8Be et ^7Li( ^3He,rm d)^8Be. Nous mentionnons a la fin que nous avons observe que l'etat fondamental de la reaction ^6Li( ^3He,rm p)^8Be et l'etat excite 2.43 MeV de la reaction ^7Li(^3He,rm p)^9Be sont des reactions directes alors que le premier etat excite (2.96 MeV) de la reaction ^6Li(^3He,rm p)^8Be et l'etat fondamental de la reaction ^7Li(^3He,rm p)^9Be peuvent etre domines par une reaction a noyau compose.

Optical transmembrane potential measurements during defibrillation-strength shocks in perfused rabbit hearts.

PubMed

Zhou, X; Ideker, R E; Blitchington, T F; Smith, W M; Knisley, S B

1995-09-01

To study the optical transmembrane potential change (delta F) induced during shocks, optical recordings were obtained in 15 isolated perfused rabbit hearts treated with the potentiometric dye di-4-ANEPPS and diacetyl monoxime. Shock electrodes were sutured on the right and left ventricles. A laser beam 30 microns in diameter was used to optically excite di-4-ANEPPS. Fluorescence from a region 150 microns in diameter was recorded during a shock. In the macroscopic study (six animals), there were nine recording spots that were 3 mm apart between the two shock electrodes. In the microscopic study, there were three recording regions that were 3 mm away from either shock electrode and midway between them, with nine recording spots that were 30 microns (three animals), 100 microns (three animals), and 300 microns (three animals) apart in each region. After 20 S1 stimuli, a 10-ms truncated exponential S2 shock of defibrillation-threshold strength was given during the plateau of the last S1 action potential. In the microscopic study, shocks were also given during diastole, with delta F recordings at the three recording regions. Shocks of both polarities were tested. delta F during the shock was expressed as a percentage of the fluorescence change during the S1 upstroke action potential amplitude (the S1 Fapa), ie, delta F/Fapa%. In the macroscopic study, the magnitudes of delta F/Fapa% from recording spots 1 to 9, numbered from the left to the right ventricular electrodes, were 77 +/- 41%, 46 +/- 32%, 32 +/- 27%, 28 +/- 20%, 37 +/- 25%, 24 +/- 20%, 33 +/- 22%, 37 +/- 25%, and 59 +/- 29%, respectively (P < .05 among the nine spots). Depolarization or hyperpolarization could occur near either shock electrode with both shock polarities, but the magnitude of hyperpolarization was 1.8 +/- 0.9 times that of depolarization at the same recording spot when the shock polarity was reversed (P < .01). In the microscopic study, the change in delta F/Fapa% varied significantly over the microscopic regions examined. The maximum values of delta F/Fapa% for hyperpolarizing shocks during diastole reached only 7 +/- 10% of those for shocks during the plateau (P < .01). During diastole, the time until a new action potential occurred after the beginning of the shock was shorter when the membrane was depolarized (1.1 +/- 0.5 ms) than when it was hyperpolarized (12.8 +/- 9.1 ms, P < .01). Conclusions are as follows: (1) A shock can induce either hyperpolarization or depolarization. (2) Hyperpolarization or depolarization during a shock can occur near either the anodal or cathodal shock electrode. (3) Variation of delta F/Fapa% exists within a microscopic region.(ABSTRACT TRUNCATED AT 400 WORDS)

[Effect of nitric oxide on the somatic membrane of rat DRG neurons].

PubMed

Cheng, Hong-Ju; Ma, Ke-Tao; Zhao, Lei; Li, Li; Cao, Ying-Ying; Si, Jun-Qiang

2009-11-01

To observe the role of nitric oxide in dorsal root ganglion (DRG) neurons and its related ionic mechanisms, and explore the function of NO in pain transmission process. In freshly isolated rat DRG samples, using intracellular recording technique, we perfused sodium nitroprusside (NO donor) to observe the role of NO in DRG neurons. In 77.45% of the bath cells, application of sodium nitroprusside (10 -100 mmol/L) induced concentration-dependent membrane hyperpolarization (79/102), and remaining neurons had no response. The membrane conductance increased from control value of (21.06 +/- 1.94) nS to (23.08 +/- 0.92) nS during sodium nitroprusside induced hyperpolarization. L-NAME (1 mmol/L), CdCl2 (0.1 mmol/L) and non-sodium BSS failed to change the amplitude of sodium nitroprusside induced hyperpolarization. When BSS containing 10 mmol/L TEA was used, sodium nitroprusside induced hyperpolarization was obviously inhibited. Sodium nitroprusside could cause concentration-dependent hyperpolarization in DRG neurons by activating K+ channels.

Thermal annihilation of photo-induced radicals following dynamic nuclear polarization to produce transportable frozen hyperpolarized 13C-substrates

PubMed Central

Capozzi, Andrea; Cheng, Tian; Boero, Giovanni; Roussel, Christophe; Comment, Arnaud

2017-01-01

Hyperpolarization via dynamic nuclear polarization (DNP) is pivotal for boosting magnetic resonance imaging (MRI) sensitivity and dissolution DNP can be used to perform in vivo real-time 13C MRI. The type of applications is however limited by the relatively fast decay time of the hyperpolarized spin state together with the constraint of having to polarize the 13C spins in a dedicated apparatus nearby but separated from the MRI magnet. We herein demonstrate that by polarizing 13C with photo-induced radicals, which can be subsequently annihilated using a thermalization process that maintains the sample temperature below its melting point, hyperpolarized 13C-substrates can be extracted from the DNP apparatus in the solid form, while maintaining the enhanced 13C polarization. The melting procedure necessary to transform the frozen solid into an injectable solution containing the hyperpolarized 13C-substrates can therefore be performed ex situ, up to several hours after extraction and storage of the polarized solid. PMID:28569840

3D Time-lapse Imaging and Quantification of Mitochondrial Dynamics

NASA Astrophysics Data System (ADS)

Sison, Miguel; Chakrabortty, Sabyasachi; Extermann, Jérôme; Nahas, Amir; James Marchand, Paul; Lopez, Antonio; Weil, Tanja; Lasser, Theo

2017-02-01

We present a 3D time-lapse imaging method for monitoring mitochondrial dynamics in living HeLa cells based on photothermal optical coherence microscopy and using novel surface functionalization of gold nanoparticles. The biocompatible protein-based biopolymer coating contains multiple functional groups which impart better cellular uptake and mitochondria targeting efficiency. The high stability of the gold nanoparticles allows continuous imaging over an extended time up to 3000 seconds without significant cell damage. By combining temporal autocorrelation analysis with a classical diffusion model, we quantify mitochondrial dynamics and cast these results into 3D maps showing the heterogeneity of diffusion parameters across the whole cell volume.

NMR hyperpolarization techniques for biomedicine.

PubMed

Nikolaou, Panayiotis; Goodson, Boyd M; Chekmenev, Eduard Y

2015-02-16

Recent developments in NMR hyperpolarization have enabled a wide array of new in vivo molecular imaging modalities, ranging from functional imaging of the lungs to metabolic imaging of cancer. This Concept article explores selected advances in methods for the preparation and use of hyperpolarized contrast agents, many of which are already at or near the phase of their clinical validation in patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Concentric Rings K-Space Trajectory for Hyperpolarized 13C MR Spectroscopic Imaging

PubMed Central

Jiang, Wenwen; Lustig, Michael; Larson, Peder E.Z.

2014-01-01

Purpose To develop a robust and rapid imaging technique for hyperpolarized 13C MR Spectroscopic Imaging (MRSI) and investigate its performance. Methods A concentric rings readout trajectory with constant angular velocity is proposed for hyperpolarized 13C spectroscopic imaging and its properties are analyzed. Quantitative analyses of design tradeoffs are presented for several imaging scenarios. The first application of concentric rings on 13C phantoms and in vivo animal hyperpolarized 13C MRSI studies were performed to demonstrate the feasibility of the proposed method. Finally, a parallel imaging accelerated concentric rings study is presented. Results The concentric rings MRSI trajectory has the advantages of acquisition timesaving compared to echo-planar spectroscopic imaging (EPSI). It provides sufficient spectral bandwidth with relatively high SNR efficiency compared to EPSI and spiral techniques. Phantom and in vivo animal studies showed good image quality with half the scan time and reduced pulsatile flow artifacts compared to EPSI. Parallel imaging accelerated concentric rings showed advantages over Cartesian sampling in g-factor simulations and demonstrated aliasing-free image quality in a hyperpolarized 13C in vivo study. Conclusion The concentric rings trajectory is a robust and rapid imaging technique that fits very well with the speed, bandwidth, and resolution requirements of hyperpolarized 13C MRSI. PMID:25533653

Characterization and optimization of the visualization performance of continuous flow overhauser DNP hyperpolarized water MRI: Inversion recovery approach.

PubMed

Terekhov, Maxim; Krummenacker, Jan; Denysenkov, Vasyl; Gerz, Kathrin; Prisner, Thomas; Schreiber, Laura Maria

2016-03-01

Overhauser dynamic nuclear polarization (DNP) allows the production of liquid hyperpolarized substrate inside the MRI magnet bore as well as its administration in continuous flow mode to acquire MR images with enhanced signal-to-noise ratio. We implemented inversion recovery preparation in order to improve contrast-to-noise ratio and to quantify the overall imaging performance of Overhauser DNP-enhanced MRI. The negative enhancement created by DNP in combination with inversion recovery (IR) preparation allows canceling selectively the signal originated from Boltzmann magnetization and visualizing only hyperpolarized fluid. The theoretical model describing gain of MR image intensity produced by steady-state continuous flow DNP hyperpolarized magnetization was established and proved experimentally. A precise quantification of signal originated purely from DNP hyperpolarization was achieved. A temperature effect on longitudinal relaxation had to be taken into account to fit experimental results with numerical prediction. Using properly adjusted IR preparation, the complete zeroing of thermal background magnetization was achieved, providing an essential increase of contrast-to-noise ratio of DNP-hyperpolarized water images. To quantify and optimize the steady-state conditions for MRI with continuous flow DNP, an approach similar to that incorporating transient-state thermal magnetization equilibrium in spoiled fast field echo imaging sequences can be used. © 2015 Wiley Periodicals, Inc.

Using parahydrogen to hyperpolarize amines, amides, carboxylic acids, alcohols, phosphates, and carbonates

PubMed Central

Iali, Wissam; Rayner, Peter J.; Duckett, Simon B.

2018-01-01

Hyperpolarization turns weak nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) responses into strong signals, so normally impractical measurements are possible. We use parahydrogen to rapidly hyperpolarize appropriate 1H, 13C, 15N, and 31P responses of analytes (such as NH3) and important amines (such as phenylethylamine), amides (such as acetamide, urea, and methacrylamide), alcohols spanning methanol through octanol and glucose, the sodium salts of carboxylic acids (such as acetic acid and pyruvic acid), sodium phosphate, disodium adenosine 5′-triphosphate, and sodium hydrogen carbonate. The associated signal gains are used to demonstrate that it is possible to collect informative single-shot NMR spectra of these analytes in seconds at the micromole level in a 9.4-T observation field. To achieve these wide-ranging signal gains, we first use the signal amplification by reversible exchange (SABRE) process to hyperpolarize an amine or ammonia and then use their exchangeable NH protons to relay polarization into the analyte without changing its identity. We found that the 1H signal gains reach as high as 650-fold per proton, whereas for 13C, the corresponding signal gains achieved in a 1H-13C refocused insensitive nuclei enhanced by polarization transfer (INEPT) experiment exceed 570-fold and those in a direct-detected 13C measurement exceed 400-fold. Thirty-one examples are described to demonstrate the applicability of this technique. PMID:29326984

Evaluation of argon ages and integrity of fluid-inclusion compositions: Stepwise noble gas heating experiments on 1.87 Ga alunite from Tapajós Province, Brazil

USGS Publications Warehouse

Landis, G.P.; Snee, L.W.; Juliani, Caetano

2005-01-01

Diffusion coefficients and activation energies for the diffusion of Ar and He, as determined using Arrhenius plots, indicate two distinct groups definable by their differences in activation energies. Argon log Do=2.45 and 15.33, with activation energies of 225 and 465 kJ mol−1, respectively; the diffusion of He in alunite is quantified with log Do=−4.33 and E=106.8 kJ mol−1. Model calculations of simplistic 1/e-folding times and diffusion distance–time curves indicate that He should remain in alunite for millions of years at ≤100°C, whereas at <200–220°C, the alunite will retain Ar almost indefinitely. The data demonstrate why alunite is suitable for Ar geochronological applications and also show that, unless the alunite is subjected to metamorphic deformation, the inclusion fluids should retain their primary compositions.

GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+ exchanger and endoplasmic reticulum Ca2+ refilling.

PubMed

Bondarenko, Alexander I; Montecucco, Fabrizio; Panasiuk, Olga; Sagach, Vadim; Sidoryak, Nataliya; Brandt, Karim J; Mach, François

2017-02-01

Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)-induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na + /Ca 2+ exchanged (NCX) currents in a concentration-dependent manner. The inhibition is non-mode-specific and unaffected by intracellular GDPβS infusion and tempol, a superoxide dismutase mimetic. In excised mouse aorta, LPI strongly inhibits the sustained and the peak endothelial hyperpolarization induced by Ach, but not by SKA-31, an opener of Ca 2+ -dependent K + channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca 2+ -re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca 2+ -re-addition following Ca 2+ stores depletion. These finding indicate that LPC and LPI inhibit endothelial hyperpolarization to Ach and histamine independently of G-protein coupled receptors and superoxide anions. Reversed NCX is critical for ER Ca 2+ refilling in EC. The inhibition of NCX by LPI and LPC underlies diminished endothelium-dependent responses and endothelial dysfunction accompanied by increased levels of these lipids in the blood. Copyright © 2017 Elsevier Inc. All rights reserved.

Mouse Sperm Membrane Potential Hyperpolarization Is Necessary and Sufficient to Prepare Sperm for the Acrosome Reaction*

PubMed Central

De La Vega-Beltran, Jose Luis; Sánchez-Cárdenas, Claudia; Krapf, Darío; Hernandez-González, Enrique O.; Wertheimer, Eva; Treviño, Claudia L.; Visconti, Pablo E.; Darszon, Alberto

2012-01-01

Mammalian sperm are unable to fertilize the egg immediately after ejaculation; they acquire this capacity during migration in the female reproductive tract. This maturational process is called capacitation and in mouse sperm it involves a plasma membrane reorganization, extensive changes in the state of protein phosphorylation, increases in intracellular pH (pHi) and Ca2+ ([Ca2+]i), and the appearance of hyperactivated motility. In addition, mouse sperm capacitation is associated with the hyperpolarization of the cell membrane potential. However, the functional role of this process is not known. In this work, to dissect the role of this membrane potential change, hyperpolarization was induced in noncapacitated sperm using either the ENaC inhibitor amiloride, the CFTR agonist genistein or the K+ ionophore valinomycin. In this experimental setting, other capacitation-associated processes such as activation of a cAMP-dependent pathway and the consequent increase in protein tyrosine phosphorylation were not observed. However, hyperpolarization was sufficient to prepare sperm for the acrosome reaction induced either by depolarization with high K+ or by addition of solubilized zona pellucida (sZP). Moreover, K+ and sZP were also able to increase [Ca2+]i in non-capacitated sperm treated with these hyperpolarizing agents but not in untreated cells. On the other hand, in conditions that support capacitation-associated processes blocking hyperpolarization by adding valinomycin and increasing K+ concentrations inhibited the agonist-induced acrosome reaction as well as the increase in [Ca2+]i. Altogether, these results suggest that sperm hyperpolarization by itself is key to enabling mice sperm to undergo the acrosome reaction. PMID:23095755

Ultrasound Attenuation in Normal Fluid 3He in 98% Aerogel: Knudsen-to-Hydrodynamic Crossover

NASA Astrophysics Data System (ADS)

Lee, Yoonseok; Choi, H. C.; Moon, B. H.; Masuhara, N.; Meisel, M. W.; Takeuchi, H.; Higashitani, S.; Nagai, K.; Mulders, N.

2014-03-01

Mass flow in porous media is a widely occurring phenomenon as in water flow in aquifers, blood flow in vessels, and petroleum flow through sandstones. However, the understanding of these phenomena is a challenging task. In particular, when the mean free path of the fluid particles exceeds the pore size, the hydrodynamic description breaks down and the fluid mass is carried by the Knudsen diffusion. The 3He-aerogel system offers an opportunity that allows a systematic investigation of a wide range flow phenomena from the hydrodynamic to Knudsen regime owing to the strongly temperature dependent mean free path in liquid 3He at low temperatures. In this paper, we present ultrasound attenuation measurements of liquid 3He in 98% aerogel. The Knudsen-hydrodynamic crossover is clearly demonstrated in a drastic change in the temperature dependence in attenuation observed in this system. H. Takeuchi et al., Phys. Rev. Lett. 108, 225307 (2012). Grant-in-Aid for Scientific Research No. 21540365 and No. 22103003 by MEXT of Japan and NSF DMR-0803516, DMR-0654118, and the State of Florida.

Synaptic hyperpolarization and inhibition of turtle cochlear hair cells.

PubMed

Art, J J; Fettiplace, R; Fuchs, P A

1984-11-01

Intracellular recordings were made from turtle cochlear hair cells in order to examine the properties of the post-synaptic potentials evoked by electrical stimulation of the efferent axons. Single shocks to the efferents generated a hair cell membrane hyperpolarization with an average amplitude generally less than 1 mV and lasting for about 100 ms. With short trains of shocks, the size of the post-synaptic potential grew markedly to a maximum of 20-30 mV. The interaction between pairs of shocks separated by a varying interval was studied. For an interval of 4 ms, the response to the second shock was increased on average by a factor of 3 and the conditioning effect of the first shock decayed with a time constant of about 100 ms. We suggest the augmentation in response to trains of shocks may be partly due to facilitation of efferent transmitter release. The efferent post-synaptic potentials could be reversibly abolished by perfusion with perilymphs containing 3 microM-curare or atropine, and infusion of acetylcholine gave a transient membrane hyperpolarization. These observations are consistent with efferent action being mediated via a cholinergic synapse onto the hair cells. The post-synaptic potentials could be reversed in polarity by injection of hyperpolarizing currents through the recording electrode. The reversal potential was estimated as about -80 mV, 30 mV negative to the resting potential. Near reversal, a small brief depolarization was evident and may constitute a minor component of the synaptic response. The value of the reversal potential was unaffected by substitution of the perilymphatic chloride, but was altered in a predictable manner by changes in extracellular potassium concentration indicating that the post-synaptic potentials arise mainly by an increase in the permeability of the hair cell membrane to potassium ions. Throughout the post-synaptic hyperpolarization there was a reduction in the sensitivity of the hair cell to tones at its characteristic frequency. The desensitization, maximal for low sound pressures, varied in different cells from a factor of 1.6 to 28. At the peak of the largest synaptic potentials, the receptor potential remained negative to the resting potential with all but the loudest characteristic frequency tone s. We suggest that there are two factors in efferent inhibition; one a r duction in the receptor potential at the hair cell's characteristic frequency and the other a hyperpolarization of its membrane potential which should reduce the release of excitatory transmitter onto the afferent terminals.

Coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma with antecedent chronic lymphocytic leukemia: a case report and review of the literature.

PubMed

Abuelgasim, Khadega A; Rehan, Hinna; Alsubaie, Maha; Al Atwi, Nasser; Al Balwi, Mohammed; Alshieban, Saeed; Almughairi, Areej

2018-03-11

Chronic lymphocytic leukemia and chronic myeloid leukemia are the most common types of adult leukemia. However, it is rare for the same patient to suffer from both. Richter's transformation to diffuse large B-cell lymphoma is frequently observed in chronic lymphocytic leukemia. Purine analog therapy and the presence of trisomy 12, and CCND1 gene rearrangement have been linked to increased risk of Richter's transformation. The coexistence of chronic myeloid leukemia and diffuse large B-cell lymphoma in the same patient is extremely rare, with only nine reported cases. Here, we describe the first reported case of concurrent chronic myeloid leukemia and diffuse large B-cell lymphoma in a background of chronic lymphocytic leukemia. A 60-year-old Saudi man known to have diabetes, hypertension, and chronic active hepatitis B was diagnosed as having Rai stage II chronic lymphocytic leukemia, with trisomy 12 and rearrangement of the CCND1 gene in December 2012. He required no therapy until January 2016 when he developed significant anemia, thrombocytopenia, and constitutional symptoms. He received six cycles of fludarabine, cyclophosphamide, and rituximab, after which he achieved complete remission. One month later, he presented with progressive leukocytosis (mostly neutrophilia) and splenomegaly. Fluorescence in situ hybridization from bone marrow aspirate was positive for translocation (9;22) and reverse transcription polymerase chain reaction detected BCR-ABL fusion gene consistent with chronic myeloid leukemia. He had no morphologic or immunophenotypic evidence of chronic lymphocytic leukemia at the time. Imatinib, a first-line tyrosine kinase inhibitor, was started. Eight months later, a screening imaging revealed new liver lesions, which were confirmed to be diffuse large B-cell lymphoma. In chronic lymphocytic leukemia, progressive leukocytosis and splenomegaly caused by emerging chronic myeloid leukemia can be easily overlooked. It is unlikely that chronic myeloid leukemia arose as a result of clonal evolution secondary to fludarabine treatment given the very short interval after receiving fludarabine. It is also unlikely that imatinib contributed to the development of diffuse large B-cell lymphoma; rather, diffuse large B-cell lymphoma arose as a result of Richter's transformation. Fludarabine, trisomy 12, and CCND1 gene rearrangement might have increased the risk of Richter's transformation in this patient.

Improved hatch rate in helium-oxygen by reducing shell diffusion area.

PubMed

Weiss, H S

1975-03-01

For eggs incubating in a He atmosphere (79% He/21% O2), covering approximately 50% of the shell with melted paraffin improves hatch rate to control values (from 20% to 74%) and decreases egg weight loss to control values (from 17% to 9%). In air (79% N2/21% O2) the same paraffin treatment depresses hatch rate. The role of the inert gases in incubation appears to be an indirect one related to their modification of the rate of gaseous flux across the shell with the adverse effects of He due to excessively rapid diffusion.

Oxygen depletion speeds and simplifies diffusion in HeLa cells.

PubMed

Edwald, Elin; Stone, Matthew B; Gray, Erin M; Wu, Jing; Veatch, Sarah L

2014-10-21

Many cell types undergo a hypoxic response in the presence of low oxygen, which can lead to transcriptional, metabolic, and structural changes within the cell. Many biophysical studies to probe the localization and dynamics of single fluorescently labeled molecules in live cells either require or benefit from low-oxygen conditions. In this study, we examine how low-oxygen conditions alter the mobility of a series of plasma membrane proteins with a range of anchoring motifs in HeLa cells at 37°C. Under high-oxygen conditions, diffusion of all proteins is heterogeneous and confined. When oxygen is reduced with an enzymatic oxygen-scavenging system for ≥ 15 min, diffusion rates increase by > 2-fold, motion becomes unconfined on the timescales and distance scales investigated, and distributions of diffusion coefficients are remarkably consistent with those expected from Brownian motion. More subtle changes in protein mobility are observed in several other laboratory cell lines examined under both high- and low-oxygen conditions. Morphological changes and actin remodeling are observed in HeLa cells placed in a low-oxygen environment for 30 min, but changes are less apparent in the other cell types investigated. This suggests that changes in actin structure are responsible for increased diffusion in hypoxic HeLa cells, although superresolution localization measurements in chemically fixed cells indicate that membrane proteins do not colocalize with F-actin under either experimental condition. These studies emphasize the importance of controls in single-molecule imaging measurements, and indicate that acute response to low oxygen in HeLa cells leads to dramatic changes in plasma membrane structure. It is possible that these changes are either a cause or consequence of phenotypic changes in solid tumor cells associated with increased drug resistance and malignancy.

(U-Th-Sm)/He thermochronological age distribution in a slowly cooled plutonic complex (Ploumanac'h intrusion, France): insights into helium diffusion processes.

NASA Astrophysics Data System (ADS)

Recanati, A. C.; Gautheron, C.; Barbarand, J.; Tassan-Got, L.; Missenard, Y.; Pinna-Jamme, R.

2015-12-01

(U-Th-Sm)/He thermochronology is widely used to determine the thermal histories of mountain ranges and sedimentary basins. Apatite crystals retain helium at low temperatures, thus giving an insight into upper crustal evolution (e.g. exhumation, subsidence, erosion). Advanced models predict He production and diffusion rates in apatite crystals, thereby allowing determination of helium dates by integration over time/temperature paths (e.g. Gautheron et al., 2009). However, scattered dates and discordance between predicted and measured dates suggest that other parameters than time or temperature may also influence helium contents in apatite. The present study determines the variables that affect He diffusion in apatite over long timescales. We report the (U-Th-Sm)/He date distribution within a slowly cooled intrusion, along with AFT data, as well as extensive petrological and chemical characterization. The Ploumanac'h site (Brittany, France) was chosen because it includes small-scale spatial variations in petrology and chemistry (6-9106 tracks/cm2). GAUTHERON C., TASSAN-GOT L., BARBARAND J., PAGEL M., 2009. Effect of alpha-damage annealing on apatite (U-Th)/He thermochronology. Chem. Geol. 266, 166-179.

Blockade of hyperpolarization-activated channels modifies the effect of beta-adrenoceptor stimulation.

PubMed

Zefirov, T L; Ziyatdinova, N I; Gainullin, A A; Zefirov, A L

2002-05-01

Experiments on rats showed that blockade of hyperpolarization-activated currents moderates tachycardia induced by beta-adrenoceptor agonist isoproterenol and potentiates the increase in stroke volume produced by this agonist. Electrical stimulation of the vagus nerve against the background of isoproterenol treatment augmented bradycardia and increased stroke volume. Blockade of hyperpolarization-activated currents followed by application of isoproterenol moderated vagus-induced bradycardia and had no effect on the dynamics of stroke volume.

Selective detection of hyperpolarized NMR signals derived from para-hydrogen using the Only Para-hydrogen SpectroscopY (OPSY) approach.

PubMed

Aguilar, Juan A; Adams, Ralph W; Duckett, Simon B; Green, Gary G R; Kandiah, Rathika

2011-01-01

A new family of NMR pulse sequences is reported for the recording of para-hydrogen enhanced NMR spectra. This Only Para-hydrogen SpectroscopY (OPSY) approach uses coherence selection to separate hyperpolarized signals from those of fully relaxed and thermally equilibrated protons. Sequence design, performance, practical aspects and applicability to other hyperpolarization techniques are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

Single voxel localization for dynamic hyperpolarized 13C MR spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Albert P.; Cunningham, Charles H.

2015-09-01

The PRESS technique has been widely used to achieve voxel localization for in vivo1H MRS acquisitions. However, for dynamic hyperpolarized 13C MRS experiments, the transition bands of the refocusing pulses may saturate the pre-polarized substrate spins flowing into the voxel. This limitation may be overcome by designing refocusing pulses that do not perturb the resonance of the hyperpolarized substrate, but selectively refocuses the spins of the metabolic products. In this study, a PRESS pulse sequence incorporating spectral-spatial refocusing pulses that have a stop band ('notch') at the substrate resonance is tested in vivo using hyperpolarized [1-13C]pyruvate. Higher metabolite SNR was observed in experiments using the spectral-spatial refocusing pulses as compared to conventional refocusing pulses.

Helium isotopes in matrix pore fluids from SAFOD drill core samples suggest mantle fluids cannot be responsible for fault weakening

NASA Astrophysics Data System (ADS)

Ali, S.; Stute, M.; Torgersen, T.; Winckler, G.

2008-12-01

To quantify fluid flow in the San Andreas Fault (SAF) (and since direct fracture fluid sampling of the fault zone was not available), we have adapted a method to extract rare gases from matrix fluids of whole rocks by diffusion. Helium was measured on drill core samples obtained from 3054 m (Pacific Plate) to 3990 m (North American Plate) through the San Andreas Fault Zone (SAFZ) ~3300 m during SAFOD Phases I (2004), II (2005), III (2007). Samples were typically collected as 2.54 cm diameter subcores drilled into the ends of the cores, or from the core catcher and drillcore fragments within <2hr after core recovery. The samples were placed into ultra high vacuum stainless steel containers, flushed with ultra high purity nitrogen and immediately evacuated. Helium isotopes of the extracted matrix pore fluids and the solid matrix were determined by mass spectrometery at LDEO. Matrix porefluid 3He/4He ratios are ~0.4 - 0.5xRa (Ra: atmospheric 3He/4He = 1.384 x 10-6) in the Pacific Plate, increasing toward the SAFZ, while pore fluids in the North American Plate have a 3He/4He range of 0.7-0.9Ra, increasing away from the SAFZ (consistent with results from mud gas samples (Wiersberg and Erzinger, 2007) and direct fluid samples (Kennedy et al., 2007)). Helium isotope ratios of the solid matrix are less than 0.06Ra across the SAF in samples from both the North American and the Pacific plates, thereby excluding the host matrix as source for the enhanced isotopic signature. If the system is assumed to be in steady state, then the flux of mantle helium must be from the North American Plate to the Pacific plate. The steeper gradient in the Pacific Plate relative to the North American plate is consistent with a porosity corrected effective diffusivity. The source for this mantle helium in the North American Plate is likely related to a low crustal conductivity zone identified by magnetotelluric signals (Becken et al., 2008) that provides a channel for transport of mantle helium within brittle crust under high strain rates (Kennedy et al., 2007). The helium isotope gradients suggest that fault weakening by mantle-derived fluid pressure is unlikely. More likely, mantle fluids "bleed" into the North American plate below seismogenic depths and are transported across the fault by nonseismic, diffusive processes.

Photothermal Beam Deflection Spectroscopy for the Determination of Thermal Diffusivity of Soils and Soil Aggregates

NASA Astrophysics Data System (ADS)

Proskurnin, M. A.; Korte, D.; Rogova, O. B.; Volkov, D. S.; Franko, M.

2018-07-01

Photothermal beam deflection spectroscopy (BDS) with a red He-Ne laser (632.8 nm, 35 mW) as an excitation beam source and a green He-Ne laser (543.1 nm, 2 mW) as a probe was used for estimating thermal diffusivity of several types of soil samples and individual soil aggregates with small surfaces (2 × 2 mm). It is shown that BDS can be used on demand for studies of changes in properties of soil entities of different hierarchical levels under the action of agrogenesis. It is presented that BDS clearly distinguishes between thermal diffusivities of different soil types: Sod-podzolic [Umbric Albeluvisols, Abruptic], 29 ± 3; Chernozem typical [Voronic Chernozems, Pachic], 9.9 ± 0.9; and Light Chestnut [Haplic Kastanozems, Chromic], 9.7 ± 0.9 cm2·h-1. Aggregates of chernozem soil show a significantly higher thermal diffusivity compared to the bulk soil. Thermal diffusivities of aggregates of Chernozem for virgin and bare fallow samples differ, 53 ± 4 cm2·h-1 and 45 ± 4 cm2·h-1, respectively. Micromonoliths of different Sod-podzolic soil horizons within the same profile (topsoil, depth 10-14 cm, and a parent rock with Fe illuviation, depth 180-185 cm) also show a significant difference, thermal diffusivities are 9.5 ± 0.8 cm2·h-1 and 27 ± 2 cm2·h-1, respectively. For soil micromonoliths, BDS is capable to distinguish the difference in thermal diffusivity resulting from the changes in the structure of aggregates.

A Bloody Mess: An Unusual Case of Diffuse Alveolar Hemorrhage Because of Warfarin Overdose.

PubMed

Heffler, Enrico; Campisi, Raffaele; Ferri, Sebastian; Crimi, Nunzio

2016-01-01

We herein present the case of a patient with frank hemoptysis and hematuria, dyspnea, and cough. The patient was known to be affected by Chronic Obstructive Pulmonary Disease (COPD) and dilated cardiomyopathy with atrial fibrillation. For this latter condition, he was supposed to take 1.25 mg warfarin daily. Laboratory findings revealed very high levels of International Normalized Ratio (INR) (16), and the patient referred that he self-increased warfarin dose to 5 mg daily since 8 days before the onset of symptoms. Computed tomography scan revealed diffuse bilateral signs of alveolar hemorrhage with hydroaerial levels within emphysematous cysts. Wafarin was immediately stopped and changed with 220 mg dabigatran daily, and he was properly treated to restore a normal coagulation status. We concluded for a case of diffuse alveolar hemorrhage because of warfarin overdose.

Role of collateral paths in long-range diffusion in lungs

PubMed Central

Bartel, Seth-Emil T.; Haywood, Susan E.; Woods, Jason C.; Chang, Yulin V.; Menard, Christopher; Yablonskiy, Dmitriy A.; Gierada, David S.; Conradi, Mark S.

2010-01-01

The long-range apparent diffusion coefficient (LRADC) of 3He gas in lungs, measured over times of several seconds and distances of 1–3 cm, probes the connections between the airways. Previous work has shown the LRADC to be small in health and substantially elevated in emphysema, reflecting tissue destruction, which is known to create collateral pathways. To better understand what controls LRADC, we report computer simulations and measurements of 3He gas diffusion in healthy lungs. The lung is generated with a random algorithm using well-defined rules, yielding a three-dimensional set of nodes or junctions, each connected by airways to one parent node and two daughters; airway dimensions are taken from published values. Spin magnetization in the simulated lung is modulated sinusoidally, and the diffusion equation is solved to 1,000 s. The modulated magnetization decays with a time constant corresponding to an LRADC of ~0.001 cm2/s, which is smaller by a factor of ~20 than the values in healthy lungs measured here and previously in vivo and in explanted lungs. It appears that collateral gas pathways, not present in the simulations, are functional in healthy lungs; they provide additional and more direct routes for long-range motion than the canonical airway tree. This is surprising, inasmuch as collateral ventilation is believed to be physiologically insignificant in healthy lungs. We discuss the effect on LRADC of small collateral connections through airway walls and rule out other possible mechanisms. The role of collateral paths is supported by measurements of smaller LRADC in pigs, where collateral ventilation is known to be smaller. PMID:18292298

Exact quantum scattering calculation of transport properties for free radicals: OH(X2Π)-helium.

PubMed

Dagdigian, Paul J; Alexander, Millard H

2012-09-07

Transport properties for OH-He are computed through quantum scattering calculations using the ab initio potential energy surfaces determined by Lee et al. [J. Chem. Phys. 113, 5736 (2000)]. To gauge the importance of the open-shell character of OH and the anisotropy of the potential on the transport properties, including the collision integrals Ω((1,1)) and Ω((2,2)), as well as the diffusion coefficient, calculations were performed with the full potential, with the difference potential V(dif) set to zero, and with only the spherical average of the potential. Slight differences (3%-5%) in the computed diffusion coefficient were found between the values obtained using the full potential and the truncated potentials. The computed diffusion coefficients were compared to recent experimental measurements and those computed with a Lennard-Jones (LJ) 12-6 potential. The values obtained with the full potential were slightly higher than the experimental values. The LJ 12-6 potential was found to underestimate the variation in temperature as compared to that obtained using the full OH-He ab initio potential.

Structural Measurements from Images of Noble Gas Diffusion

NASA Astrophysics Data System (ADS)

Cadman, Robert V.; Kadlecek, Stephen J.; Emami, Kiarash; MacDuffie Woodburn, John; Vahdat, Vahid; Ishii, Masaru; Rizi, Rahim R.

2009-03-01

Magnetic resonance imaging of externally polarized noble gases such as ^3He has been used for pulmonary imaging for more than a decade. Because gas diffusion is impeded by the alveoli, the diffusion coefficient of gas in the lung, measured on a time scale of milliseconds, is reduced compared to that of the same gas mixture in the absence of restrictions. When the alveolar walls decay, as in emphysema, diffusivity in the lung increases. In this paper, the relationship between diffusion measurements and the size of the restricting structures will be discussed. The simple case of diffusion in an impermeable cylinder, a structure similar to the upper respiratory airways in mammals, has been studied. A procedure will be presented by which airways of order 2 mm in diameter may be accurately measured; demonstration experiments with plastic tubes will also be presented. The additional developments needed before this technique becomes practical will be briefly discussed.

Effects of alloying and transmutation impurities on stability and mobility of helium in tungsten under a fusion environment

NASA Astrophysics Data System (ADS)

Wu, Xuebang; Kong, Xiang-Shan; You, Yu-Wei; Liu, C. S.; Fang, Q. F.; Chen, Jun-Ling; Luo, G.-N.; Wang, Zhiguang

2013-07-01

The behaviour of helium in metals is particularly significant in fusion research due to the He-induced degradation of materials. A small amount of impurities introduced either by intentional alloying or by transmutation reactions, will interact with He and lead the microstructure and mechanical properties of materials to change. In this paper, we present the results of first-principles calculations on the interactions of He with impurities and He diffusion around them in tungsten (W), including the interstitials Be, C, N, O, and substitutional solutes Re, Ta, Tc, Nb, V, Os, Ti, Si, Zr, Y and Sc. We find that the trapping radii of interstitial atoms on He are much larger than those of substitutional solutes. The binding energies between the substitutional impurities and He increase linearly with the relative charge densities at the He occupation site, indicating that He atoms easily aggregate at the low charge density site. The sequence of diffusion energy barriers of He around the possible alloying elements is Ti > V > Os > Ta > Re. The present results suggest that Ta might be chosen as a relatively suitable alloying element compared with other possible ones.

High Field Small Animal Magnetic Resonance Oncology Studies

PubMed Central

Bokacheva, Louisa; Ackerstaff, Ellen; LeKaye, H. Carl; Zakian, Kristen; Koutcher, Jason A.

2014-01-01

This review focuses on the applications of high magnetic field magnetic resonance imaging (MRI) and spectroscopy (MRS) to cancer studies in small animals. High field MRI can provide information about tumor physiology, the microenvironment, metabolism, vascularity and cellularity. Such studies are invaluable for understanding tumor growth and proliferation, response to treatment and drug development. The MR techniques reviewed here include 1H, 31P, Chemical Exchange Saturation Transfer (CEST) imaging, and hyperpolarized 13C MR spectroscopy as well as diffusion-weighted, Blood Oxygen Level Dependent (BOLD) contrast imaging, and dynamic contrast-enhanced MR imaging. These methods have been proven effective in animal studies and are highly relevant to human clinical studies. PMID:24374985

FROM THE HISTORY OF PHYSICS: Mysteries of diffusion and labyrinths of destiny

NASA Astrophysics Data System (ADS)

Bakunin, Oleg G.

2003-03-01

The role of prominent Soviet physicist B I Davydov in the development of our understanding of diffusion is briefly reviewed, with emphasis on the ideas he put forward in the 1930s: introducing additional partial derivatives into diffusion equations and extending diffusion concepts to phase space.

Cases from the Osler Medical Service at Johns Hopkins University.

PubMed

Blank, Susan; Le, Dung; Hemnes, Anna

2004-07-01

PRESENTING FEATURES: An 18-year-old white man was admitted to the Osler Medical Service with the chief complaint of back pain. Two weeks prior to admission, the patient developed diffuse and aching upper back pain. Over the next couple of days, he also developed severe anterior chest pain that was somewhat pleuritic in nature but diffuse and extending bilaterally into the shoulders. One week prior to admission, he developed intermittent fevers and night sweats. The patient denied any lymphadenopathy, pharyngitis, sick contacts, shortness of breath, rash, or bleeding. He was seen by a physician and told that he had thrombocytopenia. There was no history of recent or remote unusual bleeding episodes. His medical history was unremarkable except for a childhood diagnosis of attention deficit/hyperactivity disorder. He was not taking any medications and had no history of tobacco, alcohol, or illicit drug use. He had no risk factors for human immunodeficiency virus infection. Physical examination showed that he was afebrile and had normal vital signs. He was a well-appearing man who was lying still because of pain. HEENT examination was unremarkable. There was no pharyngeal erythema or exudates. His lungs were clear. His neck was supple and without lymphadenopathy. Examination of his back and chest revealed no focal tenderness. There was no hepatosplenomegaly, and his skin was without petechiae or rashes. Examination of the patient's joints showed pain on passive and active movement of his shoulders bilaterally, but no frank arthritis. There was no rash, petechiae, or echymoses. Chest radiograph and electrocardiogram were unremarkable. On admission, the laboratory examination was notable for a hematocrit level of 32.5%, with a mean corpuscular volume of 79 fL, and white blood cell count of 2.8 x 10(3)/microL. Platelet count was 75 x 10(3)/microL. A white blood cell differential revealed 7% bands, 53% polys, 34% lymphs, 5% atypical lymphocytes, 2% nucleated red cells, and a few young unidentified cells. His chemistry studies were unremarkable. What is the diagnosis?

Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate

PubMed Central

Nelson, Sarah J.; Kurhanewicz, John; Vigneron, Daniel B.; Larson, Peder E. Z.; Harzstark, Andrea L.; Ferrone, Marcus; van Criekinge, Mark; Chang, Jose W.; Bok, Robert; Park, Ilwoo; Reed, Galen; Carvajal, Lucas; Small, Eric J.; Munster, Pamela; Weinberg, Vivian K.; Ardenkjaer-Larsen, Jan Henrik; Chen, Albert P.; Hurd, Ralph E.; Odegardstuen, Liv-Ingrid; Robb, Fraser J.; Tropp, James; Murray, Jonathan A.

2014-01-01

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo 13C MR data, it is possible to evaluate the distribution of agents such as [1-13C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-13C]lactate in tumor, with the ratio of [1-13C]lactate/[1-13C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect 13C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-13C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-13C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-13C]lactate/[1-13C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials. PMID:23946197

Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate

NASA Astrophysics Data System (ADS)

Cavallari, Eleonora; Carrera, Carla; Aime, Silvio; Reineri, Francesca

2018-04-01

The use of [1-13C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP polarizer is quite high and the speed of hyperpolarization process is relatively slow, meaning that its use is limited to few research laboratories. ParaHydrogen Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is a cost effective and easy-to-handle method that produces 13C-MR hyperpolarization in [1-13C]pyruvate and other metabolites. This work aims to identify the main determinants of the hyperpolarization levels observed in C13-pyruvate using this method. By dissecting the various steps of the PHIP-SAH procedure, it has been possible to assess the role of several experimental parameters whose optimization must be pursued if this method is to be made suitable for future translational steps. The search for possible solutions has led to improvements in the polarization of sodium [1-13C]pyruvate from 2% to 5%. Moreover, these results suggest that observed polarization levels could be increased considerably by an automatized procedure which would reduce the time required for the work-up passages that are currently carried out manually. The results reported herein mean that the attainment of polarization levels suitable for the metabolic imaging applications of these hyperpolarized substrates show significant promise.

129 Xe chemical shift in human blood and pulmonary blood oxygenation measurement in humans using hyperpolarized 129 Xe NMR.

PubMed

Norquay, Graham; Leung, General; Stewart, Neil J; Wolber, Jan; Wild, Jim M

2017-04-01

To evaluate the dependency of the 129 Xe-red blood cell (RBC) chemical shift on blood oxygenation, and to use this relation for noninvasive measurement of pulmonary blood oxygenation in vivo with hyperpolarized 129 Xe NMR. Hyperpolarized 129 Xe was equilibrated with blood samples of varying oxygenation in vitro, and NMR was performed at 1.5 T and 3 T. Dynamic in vivo NMR during breath hold apnea was performed at 3 T on two healthy volunteers following inhalation of hyperpolarized 129 Xe. The 129 Xe chemical shift in RBCs was found to increase nonlinearly with blood oxygenation at 1.5 T and 3 T. During breath hold apnea, the 129 Xe chemical shift in RBCs exhibited a periodic time modulation and showed a net decrease in chemical shift of ∼1 ppm over a 35 s breath hold, corresponding to a decrease of 7-10 % in RBC oxygenation. The 129 Xe-RBC signal amplitude showed a modulation with the same frequency as the 129 Xe-RBC chemical shift. The feasibility of using the 129 Xe-RBC chemical shift to measure pulmonary blood oxygenation in vivo has been demonstrated. Correlation between 129 Xe-RBC signal and 129 Xe-RBC chemical shift modulations in the lung warrants further investigation, with the aim to better quantify temporal blood oxygenation changes in the cardiopulmonary vascular circuit. Magn Reson Med 77:1399-1408, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Hyperpolarizing and age-dependent depolarizing responses of cultured locus coeruleus neurons to noradrenaline.

PubMed

Finlayson, P G; Marshall, K C

1984-08-01

The electrical activity and responses to noradrenaline (NA) of locus coeruleus (LC) neurons have been studied in organotypic cultures using intracellular recording. Most LC neurons were predominantly quiescent, though occasional bursts of activity were observed; a few cells were tonically active at rates of 0.5-5/s. In most cells tested, iontophoretic application of NA evoked responses which were initially hyperpolarizing, sometimes followed by a depolarizing phase and frequently followed by a period of increased excitatory synaptic activity. The enhanced synaptic activity appeared to be an indirect effect since it was blocked by bath application of tetrodotoxin (TTX). In the presence of TTX, responses to NA of all but one cell were simple hyperpolarizations or biphasic (hyperpolarization/depolarization) responses. The presence of the depolarizing component appeared to be age-dependent, since it was frequently observed in cultures grown in vitro for less than 26 days, while neurons in older cultures exhibited only hyperpolarizing responses. If such age-dependent depolarizing responses are present in vivo, they would represent a unique example of a transmitter response which is present only during a transient developmental phase.

Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates

NASA Astrophysics Data System (ADS)

Xing, Yan; Reed, Galen D.; Pauly, John M.; Kerr, Adam B.; Larson, Peder E. Z.

2013-09-01

In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral-spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-13C]lactate generated from [1-13C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.

Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging

PubMed Central

Eichhorn, Tim R.; Takado, Yuhei; Salameh, Najat; Capozzi, Andrea; Cheng, Tian; Hyacinthe, Jean-Noël; Mishkovsky, Mor; Roussel, Christophe; Comment, Arnaud

2013-01-01

Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization have been proposed as magnetic resonance imaging (MRI) agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo. The use of potentially toxic persistent radicals to hyperpolarize substrates was hitherto required. We demonstrate that by shining UV light for an hour on a frozen pure endogenous substance, namely the glucose metabolic product pyruvic acid, it is possible to generate a concentration of photo-induced radicals that is large enough to highly enhance the 13C polarization of the substance via dynamic nuclear polarization. These radicals recombine upon dissolution and a solution composed of purely endogenous products is obtained for performing in vivo metabolic hyperpolarized 13C MRI with high spatial resolution. Our method opens the way to safe and straightforward preclinical and clinical applications of hyperpolarized MRI because the filtering procedure mandatory for clinical applications and the associated pharmacological tests necessary to prevent contamination are eliminated, concurrently allowing a decrease in the delay between preparation and injection of the imaging agents for improved in vivo sensitivity. PMID:24145405

Proton magnetic resonance imaging with para-hydrogen induced polarization.

PubMed

Dechent, Jan F; Buljubasich, Lisandro; Schreiber, Laura M; Spiess, Hans W; Münnemann, Kerstin

2012-02-21

A major challenge in imaging is the detection of small amounts of molecules of interest. In the case of magnetic resonance imaging (MRI) their signals are typically concealed by the large background signal of e.g. the body. This problem can be tackled by hyperpolarization which increases the NMR signals up to several orders of magnitude. However, this strategy is limited for (1)H, the most widely used nucleus in NMR and MRI, because the enormous number of protons in the body screens the small amount of hyperpolarized ones. Here, we describe a method giving rise to high (1)H MRI contrast for hyperpolarized molecules against a large background signal. The contrast is based on the J-coupling induced rephasing of the NMR signal of molecules hyperpolarized via PHIP and it can easily be implemented in common pulse sequences. We discuss several scenarios with different or equal dephasing times T(2)* for the hyperpolarized and thermally polarized compounds and verify our approach by experiments. This method may open up unprecedented opportunities to use the standard MRI nucleus (1)H for e.g. metabolic imaging in the future.

Zeeman relaxation of cold atomic iron and nickel in collisions with He3

NASA Astrophysics Data System (ADS)

Johnson, Cort; Newman, Bonna; Brahms, Nathan; Doyle, John M.; Kleppner, Daniel; Greytak, Thomas J.

2010-06-01

We have measured the ratio γ of the diffusion cross section to the angular momentum reorientation cross section in the colliding Fe-He3 and Ni-He3 systems. Nickel (Ni) and iron (Fe) atoms are introduced via laser ablation into a cryogenically cooled experimental cell containing cold (<1 K) He3 buffer gas. Elastic collisions rapidly cool the translational temperature of the ablated atoms to the He3 temperature. γ is extracted by measuring the decays of the atomic Zeeman sublevels. For our experimental conditions, thermal energy is comparable to the Zeeman splitting. As a result, thermal excitations between Zeeman sublevels significantly impact the observed decay. To determine γ accurately, we introduce a model of Zeeman-state dynamics that includes thermal excitations. We find γNi-3He=5×103 and γFe-3He⩽3×103 at 0.75 K in a 0.8-T magnetic field. These measurements are interpreted in the context of submerged shell suppression of spin relaxation, as studied previously in transition metals and rare-earth-metal atoms [C. I. Hancox, S. C. Doret, M. T. Hummon, R. V. Krems, and J. M. Doyle, Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.94.013201 94, 013201 (2005); C. I. Hancox, S. C. Doret, M. T. Hummon, L. Luo, and J. M. Doyle, Nature (London)NATUAS0028-083610.1038/nature02938 431, 281 (2004); A. Buchachenko, G. Chaasiski, and M. Szczniak, Eur. Phys. J. DEPJDF61434-606010.1140/epjd/e2006-00263-3 45, 147 (2007)].

Inductive Measurement of Optically Hyperpolarized Phosphorous Donor Nuclei in an Isotopically Enriched Silicon-28 Crystal

NASA Astrophysics Data System (ADS)

Gumann, P.; Patange, O.; Ramanathan, C.; Haas, H.; Moussa, O.; Thewalt, M. L. W.; Riemann, H.; Abrosimov, N. V.; Becker, P.; Pohl, H.-J.; Itoh, K. M.; Cory, D. G.

2014-12-01

We experimentally demonstrate the first inductive readout of optically hyperpolarized phosphorus-31 donor nuclear spins in an isotopically enriched silicon-28 crystal. The concentration of phosphorus donors in the crystal was 1.5 ×1 015 cm-3 , 3 orders of magnitude lower than has previously been detected via direct inductive detection. The signal-to-noise ratio measured in a single free induction decay from a 1 cm3 sample (≈1015 spins) was 113. By transferring the sample to an X -band ESR spectrometer, we were able to obtain a lower bound for the nuclear spin polarization at 1.7 K of ˜64 % . The 31P -T2 measured with a Hahn echo sequence was 420 ms at 1.7 K, which was extended to 1.2 s with a Carr Purcell cycle. The T1 of the 31P nuclear spins at 1.7 K is extremely long and could not be determined, as no decay was observed even on a time scale of 4.5 h. Optical excitation was performed with a 1047 nm laser, which provided above-band-gap excitation of the silicon. The buildup of the hyperpolarization at 4.2 K followed a single exponential with a characteristic time of 577 s, while the buildup at 1.7 K showed biexponential behavior with characteristic time constants of 578 and 5670 s.

Magnetic Resonance Microscopy of the Lung

NASA Astrophysics Data System (ADS)

Johnson, G. Allan

1999-11-01

The lung presents both challenges and opportunities for study by magnetic resonance imaging (MRI). The technical challenges arise from respiratory and cardiac motion, limited signal from the tissues, and unique physical structure of the lung. These challenges are heightened in magnetic resonance microscopy (MRM) where the spatial resolution may be up to a million times higher than that of conventional MRI. The development of successful techniques for MRM of the lung present enormous opportunities for basic studies of lung structure and function, toxicology, environmental stress, and drug discovery by permitting investigators to study this most essential organ nondestructively in the live animal. Over the last 15 years, scientists at the Duke Center for In Vivo Microscopy have developed techniques for MRM in the live animal through an interdisciplinary program of biology, physics, chemistry, electrical engineering, and computer science. This talk will focus on the development of specialized radiofrequency coils for lung imaging, projection encoding methods to limit susceptibility losses, specialized support structures to control and monitor physiologic motion, and the most recent development of hyperpolarized gas imaging with ^3He and ^129Xe.

Mechanisms of inhibition in cat visual cortex.

PubMed Central

Berman, N J; Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Neurones from layers 2-6 of the cat primary visual cortex were studied using extracellular and intracellular recordings made in vivo. The aim was to identify inhibitory events and determine whether they were associated with small or large (shunting) changes in the input conductance of the neurones. 2. Visual stimulation of subfields of simple receptive fields produced depolarizing or hyperpolarizing potentials that were associated with increased or decreased firing rates respectively. Hyperpolarizing potentials were small, 5 mV or less. In the same neurones, brief electrical stimulation of cortical afferents produced a characteristic sequence of a brief depolarization followed by a long-lasting (200-400 ms) hyperpolarization. 3. During the response to a stationary flashed bar, the synaptic activation increased the input conductance of the neurone by about 5-20%. Conductance changes of similar magnitude were obtained by electrically stimulating the neurone. Neurones stimulated with non-optimal orientations or directions of motion showed little change in input conductance. 4. These data indicate that while visually or electrically induced inhibition can be readily demonstrated in visual cortex, the inhibition is not associated with large sustained conductance changes. Thus a shunting or multiplicative inhibitory mechanism is not the principal mechanism of inhibition. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1804983

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

PubMed

Hundshammer, Christian; Düwel, Stephan; Ruseckas, David; Topping, Geoffrey; Dzien, Piotr; Müller, Christoph; Feuerecker, Benedikt; Hövener, Jan B; Haase, Axel; Schwaiger, Markus; Glaser, Steffen J; Schilling, Franz

2018-02-15

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (p K a ). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the p K a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1- 13 C]serine amide and [1- 13 C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei ( 13 C, 15 N, 31 P) with high sensitivity up to 4.8 ppm/pH and we show that 13 C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Modeling and Measuring the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2016-12-01

Understanding helium diffusion kinetics in apatite is critical for the accurate interpretation of (U-Th)/He thermochronometric data. This problem is complicated by the observation that helium diffusivity is not a simple function of temperature, but may evolve as a function of damage to the apatite crystal lattice resulting from alpha recoil. This `radiation damage' increases as a function of the amount of radiometric parent products, or effective uranium concentration, and time, but decreases due to thermal annealing of damage, necessitating a detailed understanding of radiation damage production and annealing in cases of burial heating over geologic timescales. Published observations [1,2] suggest that annealing rates of damage caused by alpha recoil and fission tracks in apatite differ. Existing models, however, assume the diffusion kinetics resulting from the two sources of damage are identical [3], demonstrating the need for further investigation of these damage sources. We present modeling and experimental work designed to interrogate the effects of radiation damage and its annealing on helium diffusion kinetics in apatite. Using previously published results [4] that investigated the effects of annealing temperature and duration on measured helium diffusivity, we fit a set of functions that are then integrated into a numerical model that tracks the evolution of radiation damage and apparent (U-Th)/He age. We compare the results of this model calibration to existing models [3]. In addition, we present data from two suites of diffusion experiments. The first suite, intended to test the published methodology and results, uses Durango apatite, while the second uses Sierran (CA) granite as a first test to determine if apatite of varying chemistry and age responds differently to the thermal annealing of radiation damage. Ultimately, the updated model and experimental results will benefit the interpretation of the effects of radiation damage accumulation and annealing in apatite and expand the range of geologic settings that can be studied using low-temperature thermochronology. References: [1] Fox, M., Shuster, D. (2014), EPSL 397, 174-183; [2] Gautheron, C. et al. (2013), Chem. Geol. 351, 257-267; [3] Flowers, R. et al. (2009), GCA 73, 2347-2365; [4] Shuster, D., Farley, K. (2009), GCA 73, 6183-6196.

What is the Efficiency of ATP Signaling from Erythrocytes to Regulate Distribution of O2 Supply within the Microvasculature?

PubMed Central

C.G., Ellis; S., Milkovich; D., Goldman

2012-01-01

Erythrocytes appear to be ideal sensors for regulating microvascular O2 supply since they release the potent vasodilator adenosine 5′-triphosphate (ATP) in an O2 saturation dependent manner. Whether erythrocytes play a significant role in regulating O2 supply in the complex environment of diffusional O2 exchange among capillaries, arterioles and venules, depends on the efficiency with which erythrocytes signal the vascular endothelium. If one assumes that the distribution of purinergic receptors is uniform throughout the microvasculature, then the most efficient site for signaling should occur in capillaries, where the erythrocyte membrane is in close proximity to the endothelium. ATP released from erythrocytes would diffuse a short distance to P2y receptors inducing an increase in blood flow possibly the result of endothelial hyperpolarization. We hypothesize that this hyperpolarization varies across the capillary bed dependent upon erythrocyte supply rate and the flux of O2 from these erythrocytes to support O2 metabolism. This would suggest that the capillary bed would be the most effective site for erythrocytes to communicate tissue oxygen needs. Electrically coupled endothelial cells conduct the integrated signal upstream where arterioles adjust vascular resistance, thus enabling ATP released from erythrocytes to regulate the magnitude and distribution of O2 supply to individual capillary networks. PMID:22587367

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies

NASA Astrophysics Data System (ADS)

Flori, Alessandra; Giovannetti, Giulio; Santarelli, Maria Filomena; Aquaro, Giovanni Donato; De Marchi, Daniele; Burchielli, Silvia; Frijia, Francesca; Positano, Vincenzo; Landini, Luigi; Menichetti, Luca

2018-06-01

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid

PubMed Central

Düwel, Stephan; Hundshammer, Christian; Gersch, Malte; Feuerecker, Benedikt; Steiger, Katja; Buck, Achim; Walch, Axel; Haase, Axel; Glaser, Steffen J.; Schwaiger, Markus; Schilling, Franz

2017-01-01

Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance. PMID:28492229

Characteristics of hyperpolarization-activated cyclic nucleotide-gated channels in dorsal root ganglion neurons at different ages and sizes.

PubMed

Hou, Baohua; Chen, Hengling; Qu, Xiangwei; Lin, Xianguang; Luo, Fang; Li, Chenhong

2015-11-11

In rat's sensory neurons, hyperpolarization-activated inward currents (Ih) play an essential role in mediating action potentials and contributing to neuronal excitability. Classified by the size of neurons and ages, we studied the Ih and transcription levels of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels using electrophysiology and the single-cell RT-PCR. In voltage-clamp studies, Ih and half-maximal activation voltage (V1/2) changed with age and size. An analysis of all HCN subtypes in dorsal root ganglion (DRG) neurons by single-cell RT-PCR was carried out. HCN1 and HCN3 in medium-small elderly neurons had a weak expression. HCN2 in newborns and HCN4 in elderly rats also had a weak expression. The aim of this study is to examine the age-related Ih and HCN channels subunits in different ages and sizes of DRG neurons. The results would be significant in understanding the physiological and pathophysiological function of different sizes of DRG neurons in different age periods.

Diffuse large B cell lymphoma of the mesentery: an unusual presentation and review of the literature.

PubMed

Salemis, Nikolaos S; Gourgiotis, Stavros; Tsiambas, Evangelos; Karagkiouzis, Grigorios; Nakos, Georgios; Karathanasis, Vasilios

2009-01-01

Diffuse large B cell lymphoma is the most commonly diagnosed non-Hodgkin's lymphoma, whereas lymphoma is the most common cause of mesenteric masses. We herein present a very rare case of a young male patient with a giant diffuse large B cell lymphoma of the mesentery that was incidentally diagnosed during his admission for a road traffic accident. At laparotomy, a huge tumor measuring 18 x 14 x 10 cm was found originating from the jejunal mesentery. Despite the giant size of the tumor, the patient was completely asymptomatic. After complete surgical recection with clear margins, he recieved six cycles of CHOP chemotherapy in the pre-rituximab era. He remained disease-free 2 years after surgery, but unfortunately, he relapsed with disseminated disease and died 6 months later. Mesenteric lymphomas may remain asymptomatic until they reach a large size. The presence of a bulky mesenteric mass is a poor prognostic indicator. Although chemotherapy is the treatment of choice for diffuse large B cell lymphoma, in some cases radical surgery has a role in establishing a definitive diagnosis.

Polarized Helium to Image the Lung

NASA Astrophysics Data System (ADS)

Leduc, Michèle; Nacher, Pierre Jean

2005-05-01

The main findings of the european PHIL project (Polarised Helium to Image the Lung) are reported. State of the art optical pumping techniques for polarising 3He gas are described. MRI methodological improvements allow dynamical ventilation images with a good resolution, ultimately limited by gas diffusion. Diffusion imaging appears as a robust method of lung diagnosis. A discussion of the potential advantage of low field MRI is presented. Selected PHIL results for emphysema are given, with the perspectives that this joint work opens up for the future of respiratory medicine.

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model.

PubMed

Park, Jae Mo; Josan, Sonal; Jang, Taichang; Merchant, Milton; Watkins, Ron; Hurd, Ralph E; Recht, Lawrence D; Mayer, Dirk; Spielman, Daniel M

2016-03-01

MRS of hyperpolarized [2-(13)C]pyruvate can be used to assess multiple metabolic pathways within mitochondria as the (13)C label is not lost with the conversion of pyruvate to acetyl-CoA. This study presents the first MR spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate in glioma-bearing brain. Spiral chemical shift imaging with spectrally undersampling scheme (1042 Hz) and a hard-pulse excitation was exploited to simultaneously image [2-(13)C]pyruvate, [2-(13)C]lactate, and [5-(13)C]glutamate, the metabolites known to be produced in brain after an injection of hyperpolarized [2-(13)C]pyruvate, without chemical shift displacement artifacts. A separate undersampling scheme (890 Hz) was also used to image [1-(13)C]acetyl-carnitine. Healthy and C6 glioma-implanted rat brains were imaged at baseline and after dichloroacetate administration, a drug that modulates pyruvate dehydrogenase kinase activity. The baseline metabolite maps showed higher lactate and lower glutamate in tumor as compared to normal-appearing brain. Dichloroacetate led to an increase in glutamate in both tumor and normal-appearing brain. Dichloroacetate-induced %-decrease of lactate/glutamate was comparable to the lactate/bicarbonate decrease from hyperpolarized [1-(13)C]pyruvate studies. Acetyl-carnitine was observed in the muscle/fat tissue surrounding the brain. Robust volumetric imaging with hyperpolarized [2-(13)C]pyruvate and downstream products was performed in glioma-bearing rat brains, demonstrating changes in mitochondrial metabolism with dichloroacetate. © 2015 Wiley Periodicals, Inc.

In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

NASA Astrophysics Data System (ADS)

Schmidt, Rita; Laustsen, Christoffer; Dumez, Jean-Nicolas; Kettunen, Mikko I.; Serrao, Eva M.; Marco-Rius, Irene; Brindle, Kevin M.; Ardenkjaer-Larsen, Jan Henrik; Frydman, Lucio

2014-03-01

Hyperpolarized metabolic imaging is a growing field that has provided a new tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized 13C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-13C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7 T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7 T from a murine lymphoma tumor model.

In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

PubMed Central

Schmidt, Rita; Laustsen, Christoffer; Dumez, Jean-Nicolas; Kettunen, Mikko I.; Serrao, Eva M.; Marco-Rius, Irene; Brindle, Kevin M.; Ardenkjaer-Larsen, Jan Henrik; Frydman, Lucio

2016-01-01

Hyperpolarized metabolic imaging is a growing field that has provided a tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized 13C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-13C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7 T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7 T from a murine lymphoma tumor model. PMID:24486720

Analytical W-He and H-He interatomic potentials for a W-H-He system

NASA Astrophysics Data System (ADS)

Li, Xiao-Chun; Shu, Xiaolin; Liu, Yi-Nan; Yu, Yi; Gao, F.; Lu, Guang-Hong

2012-07-01

We have constructed W-He and H-He analytical bond-order potentials for a W-H-He system. In combination with the previously self-developed W-H potential [X.-C. Li, X. Shu, Y.-N. Liu, F. Gao, G.-H. Lu, J. Nucl. Mater. 408 (2011) 12] and the Hartree-Fock-dispersion pair potential (Aziz-potential) for He-He interactions, we demonstrate that such potentials behave well for reproducing various properties of the W-H-He system such as defect formation energies, structural properties, and diffusion barriers. Such potentials can be employed to model both the He behaviours and the H-He synergetic effects in the W-H-He system.

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib.

PubMed

Yamada, Tadaaki; Ohtsubo, Koushiro; Izumi, Kouji; Takeuchi, Shinji; Mouri, Hisatsugu; Yamashita, Kaname; Yasumoto, Kazuo; Ghenev, Peter; Kitagawa, Satoshi; Yano, Seiji

2010-12-01

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Intensity correction for multichannel hyperpolarized 13C imaging of the heart.

PubMed

Dominguez-Viqueira, William; Geraghty, Benjamin J; Lau, Justin Y C; Robb, Fraser J; Chen, Albert P; Cunningham, Charles H

2016-02-01

Develop and test an analytic correction method to correct the signal intensity variation caused by the inhomogeneous reception profile of an eight-channel phased array for hyperpolarized (13) C imaging. Fiducial markers visible in anatomical images were attached to the individual coils to provide three dimensional localization of the receive hardware with respect to the image frame of reference. The coil locations and dimensions were used to numerically model the reception profile using the Biot-Savart Law. The accuracy of the coil sensitivity estimation was validated with images derived from a homogenous (13) C phantom. Numerical coil sensitivity estimates were used to perform intensity correction of in vivo hyperpolarized (13) C cardiac images in pigs. In comparison to the conventional sum-of-squares reconstruction, improved signal uniformity was observed in the corrected images. The analytical intensity correction scheme was shown to improve the uniformity of multichannel image reconstruction in hyperpolarized [1-(13) C]pyruvate and (13) C-bicarbonate cardiac MRI. The method is independent of the pulse sequence used for (13) C data acquisition, simple to implement and does not require additional scan time, making it an attractive technique for multichannel hyperpolarized (13) C MRI. © 2015 Wiley Periodicals, Inc.

Inverted Apatite (U-Th)/He and Fission-track Dates from the Rae craton, Baffin Island, Canada and Implications for Apatite Radiation Damage-He Diffusivity Models

NASA Astrophysics Data System (ADS)

Ault, A. K.; Reiners, P. W.; Thomson, S. N.; Miller, G. H.

2015-12-01

Coupled apatite (U-Th)/He and fission-track (AFT) thermochronology data from the same sample can be used to decipher complex low temperature thermal histories and evaluate compatibility between these two methods. Existing apatite He damage-diffusivity models parameterize radiation damage annealing as fission-track annealing and yield inverted apatite He and AFT dates for samples with prolonged residence in the He partial retention zone. Apatite chemistry also impacts radiation damage and fission-track annealing, temperature sensitivity, and dates in both systems. We present inverted apatite He and AFT dates from the Rae craton, Baffin Island, Canada, that cannot be explained by apatite chemistry or existing damage-diffusivity and fission track models. Apatite He dates from 34 individual analyses from 6 samples range from 237 ± 44 Ma to 511 ± 25 Ma and collectively define a positive date-eU relationship. AFT dates from these same samples are 238 ± 15 Ma to 350 ± 20 Ma. These dates and associated track length data are inversely correlated and define the left segment of a boomerang diagram. Three of the six samples with 20-90 ppm eU apatite grains yield apatite He and AFT dates inverted by 300 million years. These samples have average apatite Cl chemistry of ≤0.02 wt.%, with no correlation between Cl content and Dpar. Thermal history simulations using geologic constraints, an apatite He radiation damage accumulation and annealing model, apatite He dates with the range of eU values, and AFT date and track length data, do not yield any viable time-temperature paths. Apatite He and AFT data modeled separately predict thermal histories with Paleozoic-Mesozoic peaks reheating temperatures differing by ≥15 °C. By modifying the parameter controlling damage annealing (Rmr0) from the canonical 0.83 to 0.5-0.6, forward models reproduce the apatite He date-eU correlation and AFT dates with a common thermal history. Results imply apatite radiation damage anneals at higher temperatures than fission-track damage and the impact on coupled apatite He and AFT dates is magnified for protracted cooling histories. Further experimental and field-based tests are important for refining radiation damage and fission-track annealing parameters for accurate interpretation of apatite He- and AFT-derived thermal histories.

Helium self-trapping and diffusion behaviors in deformed 316L stainless steel exposed to high flux and low energy helium plasma

NASA Astrophysics Data System (ADS)

Gong, Yihao; Jin, Shuoxue; Zhu, Te; Cheng, Long; Cao, Xingzhong; You, Li; Lu, Guanghong; Guo, Liping; Wang, Baoyi

2018-04-01

A large number of dislocation networks were introduced in to 316L stainless steel by cold rolling. Subsequently, low energy (40 eV) helium ions were implanted by exposing the steel to helium plasma. Thermal desorption and positron annihilation spectroscopy were used to study the behavior of helium in the presence of dislocations, with emphasis on helium self-trapping and migration behaviors. Helium desorption behaviour from different helium trapping states was measured by the thermal desorption spectroscopy. Most of the helium desorbed from the He m V n clusters, and the corresponding desorption peak is located at ~650 K. The desorption peak from helium-dislocation clusters (He m D) is at approximately 805 K. The effect of annealing on the defect evolution was investigated by positron annihilation spectroscopy. For the specimen exposed to helium plasma without displacement damage, the increment of S parameter meant the existence of helium self-trapping behavior (He m V n ). Helium atoms could diffuse two to three orders of magnitude deeper than the implantation depth calculated by SRIM. The diffusing helium atoms were gradually trapped by dislocation lines and formed He m D. Elevated temperatures enhance the self-trapping behavior and cause helium atoms to dissociate/desorb from the He m V n clusters, increasing the S parameters at 473-673 K. The gradual recovery of vacancies in the He m V n clusters decreased the S parameter above 673 K.

A case of recurrent encephalopathy with SCN2A missense mutation.

PubMed

Fukasawa, Tatsuya; Kubota, Tetsuo; Negoro, Tamiko; Saitoh, Makiko; Mizuguchi, Masashi; Ihara, Yukiko; Ishii, Atsushi; Hirose, Shinichi

2015-06-01

Voltage-gated sodium channels regulate neuronal excitability, as well as survival and the patterning of neuronal connectivity during development. Mutations in SCN2A, which encodes the Na(+) channel Nav1.2, cause epilepsy syndromes and predispose children to acute encephalopathy. Here, we report the case of a young male with recurrent acute encephalopathy who carried a novel missense mutation in the SCN2A gene. He was born by normal delivery and developed repetitive apneic episodes at 2days of age. Diffusion-weighted imaging revealed high-intensity areas in diffuse subcortical white matter, bilateral thalami, and basal nuclei. His symptoms improved gradually without any specific treatment, but he exhibited a motor milestone delay after the episode. At the age of 10months, he developed acute cerebellopathy associated with a respiratory syncytial viral infection. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy and seemed to have no obvious sequelae after the episode. He then developed severe diffuse encephalopathy associated with gastroenteritis at the age of 14months. He received high-dose intravenous gammaglobulin and methylprednisolone pulse therapy but was left with severe neurological sequelae. PCR-based analysis revealed a novel de novo missense mutation, c.4979T>G (p.Leu1660Trp), in the SCN2A gene. This case suggests that SCN2A mutations might predispose children to repetitive encephalopathy with variable clinical and imaging findings. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Apatite (U-Th)/He thermochronometry using a radiation damage accumulation and annealing model

NASA Astrophysics Data System (ADS)

Flowers, Rebecca M.; Ketcham, Richard A.; Shuster, David L.; Farley, Kenneth A.

2009-04-01

Helium diffusion from apatite is a sensitive function of the volume fraction of radiation damage to the crystal, a quantity that varies over the lifetime of the apatite. Using recently published laboratory data we develop and investigate a new kinetic model, the radiation damage accumulation and annealing model (RDAAM), that adopts the effective fission-track density as a proxy for accumulated radiation damage. This proxy incorporates creation of crystal damage proportional to α-production from U and Th decay, and the elimination of that damage governed by the kinetics of fission-track annealing. The RDAAM is a version of the helium trapping model (HeTM; Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249, 148-161), calibrated by helium diffusion data in natural and partially annealed apatites. The chief limitation of the HeTM, now addressed by RDAAM, is its use of He concentration as the radiation damage proxy for circumstances in which radiation damage and He are not accumulated and lost proportionately from the crystal. By incorporating the RDAAM into the HeFTy computer program, we explore its implications for apatite (U-Th)/He thermochronometry. We show how (U-Th)/He dates predicted from the model are sensitive to both effective U concentration (eU) and details of the temperature history. The RDAAM predicts an effective He closure temperature of 62 °C for a 28 ppm eU apatite of 60 μm radius that experienced a 10 °C/Ma monotonic cooling rate; this is 8 °C lower than the 70 °C effective closure temperature predicted using commonly assumed Durango diffusion kinetics. Use of the RDAAM is most important for accurate interpretation of (U-Th)/He data for apatite suites that experienced moderate to slow monotonic cooling (1-0.1 °C/Ma), prolonged residence in the helium partial retention zone, or a duration at temperatures appropriate for radiation damage accumulation followed by reheating and partial helium loss. Under common circumstances the RDAAM predicts (U-Th)/He dates that are older, sometimes much older, than corresponding fission-track dates. Nonlinear positive correlations between apatite (U-Th)/He date and eU in apatites subjected to the same temperature history are a diagnostic signature of the RDAAM for many but not all thermal histories. Observed date-eU correlations in four different localities can be explained with the RDAAM using geologically reasonable thermal histories consistent with independent fission-track datasets. The existence of date-eU correlations not only supports a radiation damage based kinetic model, but can significantly limit the range of acceptable time-temperature paths that account for the data. In contrast, these datasets are inexplicable using the Durango diffusion model. The RDAAM helps reconcile enigmatic data in which apatite (U-Th)/He dates are older than expected using the Durango model when compared with thermal histories based on apatite fission-track data or other geological constraints. It also has the potential to explain at least some cases in which (U-Th)/He dates are actually older than the corresponding fission-track dates.

Magnetic resonance imaging with hyperpolarized agents: methods and applications

NASA Astrophysics Data System (ADS)

Adamson, Erin B.; Ludwig, Kai D.; Mummy, David G.; Fain, Sean B.

2017-07-01

In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into (1) a brief introduction, (2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, (3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, (4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study: (5) metabolic pathways in cancer and cardiac disease and (6) lung function in both pre-clinical and clinical research studies, concluding with (7) some future directions and challenges, and (8) an overall summary.

Hyperpolarized 13C pyruvate mouse brain metabolism with absorptive-mode EPSI at 1 T

NASA Astrophysics Data System (ADS)

Miloushev, Vesselin Z.; Di Gialleonardo, Valentina; Salamanca-Cardona, Lucia; Correa, Fabian; Granlund, Kristin L.; Keshari, Kayvan R.

2017-02-01

The expected signal in echo-planar spectroscopic imaging experiments was explicitly modeled jointly in spatial and spectral dimensions. Using this as a basis, absorptive-mode type detection can be achieved by appropriate choice of spectral delays and post-processing techniques. We discuss the effects of gradient imperfections and demonstrate the implementation of this sequence at low field (1.05 T), with application to hyperpolarized [1-13C] pyruvate imaging of the mouse brain. The sequence achieves sufficient signal-to-noise to monitor the conversion of hyperpolarized [1-13C] pyruvate to lactate in the mouse brain. Hyperpolarized pyruvate imaging of mouse brain metabolism using an absorptive-mode EPSI sequence can be applied to more sophisticated murine disease and treatment models. The simple modifications presented in this work, which permit absorptive-mode detection, are directly translatable to human clinical imaging and generate improved absorptive-mode spectra without the need for refocusing pulses.

Utilization of SABRE-derived hyperpolarization to detect low-concentration analytes via 1D and 2D NMR methods.

PubMed

Lloyd, Lyrelle S; Adams, Ralph W; Bernstein, Michael; Coombes, Steven; Duckett, Simon B; Green, Gary G R; Lewis, Richard J; Mewis, Ryan E; Sleigh, Christopher J

2012-08-08

The characterization of materials by the inherently insensitive method of NMR spectroscopy plays a vital role in chemistry. Increasingly, hyperpolarization is being used to address the sensitivity limitation. Here, by reference to quinoline, we illustrate that the SABRE hyperpolarization technique, which uses para-hydrogen as the source of polarization, enables the rapid completion of a range of NMR measurements. These include the collection of (13)C, (13)C{(1)H}, and NOE data in addition to more complex 2D COSY, ultrafast 2D COSY and 2D HMBC spectra. The observations are made possible by the use of a flow probe and external sample preparation cell to re-hyperpolarize the substrate between transients, allowing repeat measurements to be made within seconds. The potential benefit of the combination of SABRE and 2D NMR methods for rapid characterization of low-concentration analytes is therefore established.

Hyperpolarized Porous Silicon Nanoparticles: Potential Theragnostic Material for ²⁹Si Magnetic Resonance Imaging.

PubMed

Seo, Hyeonglim; Choi, Ikjang; Whiting, Nicholas; Hu, Jingzhe; Luu, Quy Son; Pudakalakatti, Shivanand; McCowan, Caitlin; Kim, Yaewon; Zacharias, Niki; Lee, Seunghyun; Bhattacharya, Pratip; Lee, Youngbok

2018-05-20

Porous silicon nanoparticles have recently garnered attention as potentially-promising biomedical platforms for drug delivery and medical diagnostics. Here, we demonstrate porous silicon nanoparticles as contrast agents for ²⁹Si magnetic resonance imaging. Size-controlled porous silicon nanoparticles were synthesized by magnesiothermic reduction of silica nanoparticles and were surface activated for further functionalization. Particles were hyperpolarized via dynamic nuclear polarization to enhance their ²⁹Si MR signals; the particles demonstrated long ²⁹Si spin-lattice relaxation (T₁) times (~ 25 mins), which suggests potential applicability for medical imaging. Furthermore, ²⁹Si hyperpolarization levels were sufficient to allow ²⁹Si MRI in phantoms. These results underscore the potential of porous silicon nanoparticles that, when combined with hyperpolarized magnetic resonance imaging, can be a powerful theragnostic deep tissue imaging platform to interrogate various biomolecular processes in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of temperature during He+ implantation on deuterium retention in tungsten, tungsten with carbon deposit and tungsten carbide

NASA Astrophysics Data System (ADS)

Oya, Yasuhisa; Sato, Misaki; Li, Xiaochun; Yuyama, Kenta; Fujita, Hiroe; Sakurada, Shodai; Uemura, Yuki; Hatano, Yuji; Yoshida, Naoaki; Ashikawa, Naoko; Sagara, Akio; Chikada, Takumi

2016-02-01

Temperature dependence on deuterium (D) retention for He+ implanted tungsten (W) was studied by thermal desorption spectroscopy (TDS) to evaluate the tritium retention behavior in W. The activation energies were evaluated using Hydrogen Isotope Diffusion and Trapping (HIDT) simulation code and found to be 0.55 eV, 0.65 eV, 0.80 eV and 1.00 eV. The heating scenarios clearly control the D retention behavior and, dense and large He bubbles could work as a D diffusion barrier toward the bulk, leading to D retention enhancement at lower temperature of less than 430 K, even if the damage was introduced by He+ implantation. By comparing the D retention for W, W with carbon deposit and tungsten carbide (WC), the dense carbon layer on the surface enhances the dynamic re-emission of D as hydrocarbons, and induces the reduction of D retention. However, by He+ implantation, the D retention was increased for all the samples.

Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus.

PubMed

Tyzio, Roman; Minlebaev, Marat; Rheims, Sylvain; Ivanov, Anton; Jorquera, Isabelle; Holmes, Gregory L; Zilberter, Yuri; Ben-Ari, Yehezkiel; Khazipov, Rustem

2008-05-01

During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

Revisiting point FRAP to quantitatively characterize anomalous diffusion in live cells.

PubMed

Daddysman, Matthew K; Fecko, Christopher J

2013-02-07

Fluorescence recovery after photobleaching (FRAP) is widely used to interrogate diffusion and binding of proteins in live cells. Herein, we apply two-photon excited FRAP with a diffraction limited bleaching and observation volume to study anomalous diffusion of unconjugated green fluorescence protein (GFP) in vitro and in cells. Experiments performed on dilute solutions of GFP reveal that reversible fluorophore bleaching can be mistakenly interpreted as anomalous diffusion. We derive a reaction-diffusion FRAP model that includes reversible photobleaching, and demonstrate that it properly accounts for these photophysics. We then apply this model to investigate the diffusion of GFP in HeLa cells and polytene cells of Drosophila larval salivary glands. GFP exhibits anomalous diffusion in the cytoplasm of both cell types and in HeLa nuclei. Polytene nuclei contain optically resolvable chromosomes, permitting FRAP experiments that focus separately on chromosomal or interchrosomal regions. We find that GFP exhibits anomalous diffusion in chromosomal regions but diffuses normally in regions devoid of chromatin. This observation indicates that obstructed transport through chromatin and not crowding by macromolecules is a source of anomalous diffusion in polytene nuclei. This behavior is likely true in other cells, so it will be important to account for this type of transport physics and for reversible photobleaching to properly interpret future FRAP experiments on DNA-binding proteins.

Evaluation of the Catalytic Activity and Cytotoxicity of Palladium Nanocubes. The Role of Oxygen

PubMed Central

Dahal, Eshan; Curtiss, Jessica; Subedi, Deepak; Chen, Gen; Houston, Jessica P.; Smirnov, Sergei

2015-01-01

Recently it has been reported that palladium nanocubes (PdNC) are capable of generating singlet oxygen without photo-excitation simply via chemisorption of molecular oxygen on its surface. Such a trait would make PdNC a highly versatile catalyst suitable in organic synthesis and a Reactive Oxygen Species (ROS) inducing cancer treatment reagent. Here we thoroughly investigated the catalytic activity of PdNC with respect to their ability to produce singlet oxygen and to oxidize 3,5,3′,5′-tetramethyl-benzidine (TMB), as well as, analyzed the cytotoxic properties of PdNC on HeLa cells. Our findings showed no evidence of singlet oxygen production by PdNC. The nanocubes’ activity is not necessarily linked to activation of oxygen. The oxidation of substrate on PdNC can be a first step followed by PdNC regeneration with oxygen or other oxidant. The catalytic activity of PdNC towards oxidation of TMB is very high and shows direct two-electrons oxidation when the surface of PdNC is clean and the ratio of TMB/PdNC is not very high. Sequential one electron oxidation is observed when the pristine quality of PdNC surface is compromised by serum or uncontrolled impurities and/or the ratio of TMB/PdNC is high. Clean PdNC in serum-free media efficiently induce apoptosis of HeLa cells. It is the primary route of cell death and is associated with hyperpolarization of mitochondria, contrary to a common mitochondrial depolarization initiated by ROS. Again, the effects are very sensitive to how well the pristine surface of PdNC is preserved, suggesting that PdNC can be used as an apoptosis inducing agent but only with appropriate drug delivery system. PMID:25886644

Chemical compatibility study between ceramic breeder and EUROFER97 steel for HCPB-DEMO blanket

NASA Astrophysics Data System (ADS)

Mukai, Keisuke; Sanchez, Fernando; Knitter, Regina

2017-05-01

Chemical compatibility between ceramic breeder (Li4SiO4 + 20 mol% addition of Li2TiO3) and EUROFER97 steel was examined in this study. These materials were contacted and heated at 623, 823 and 1073 K under He + 0.1 vol.% H2 atmosphere for up to 12 weeks. Limited influence was found in the breeder specimens, although losses of the constituent elements appeared near the surface of the breeder pellets heated at 1073 K. For the EUROFER specimens with formation of a corrosion layer, element diffusivity was estimated based on diffusion kinetics. In the temperature range, effective diffusion coefficients of oxygen into EUROFER steel were in the range from 3.5 × 10-14 to 2.5 × 10-12 cm2/s and found to be faster than that of Li. The coefficients yielded an activation energy of 0.93 eV for oxygen diffusion into EUROFER steel and predicted the possible thickness of the corrosion layer after operational periods.

Diffusion in thorium carbide: A first-principles study

NASA Astrophysics Data System (ADS)

Pérez Daroca, D.; Llois, A. M.; Mosca, H. O.

2015-12-01

The prediction of the behavior of Th compounds under irradiation is an important issue for the upcoming Generation-IV nuclear reactors. The study of self-diffusion and hetero-diffusion is a central key to fulfill this goal. As a first approach, we obtained, by means of first-principles methods, migration and activation energies of Th and C atoms self-diffusion and diffusion of He atoms in ThC. We also calculate diffusion coefficients as a function of temperature.

Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.

PubMed

Sjöstrand, F S

2002-01-01

Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.

Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-{sup 13}C] pyruvate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Chung-Man; Oh, Chang-Hyun; Ahn, Kyu-Youn

Hyperpolarized {sup 13}C magnetic resonance spectroscopy (MRS) to assess hepatic metabolism in non-alcoholic fatty liver disease (NAFLD) has not been reported. This study searched for cellular metabolism-based biomarkers for NAFLD induced by a high-fat diet (HFD) in rats. Also, correlations of the biomarkers with enzyme levels and histopathology were identified during a 6-week follow-up. Six rats were fed a control diet (CD) and seven rats were fed the HFD for 6 weeks. Hyperpolarized {sup 13}C dynamic MRS was performed on rat liver following an injection of hyperpolarized [1-{sup 13}C] pyruvate. Compared with CD-fed rats, HFD-fed rats showed significant increases inmore » the levels of serum alanine aminotransferase and low-density lipoprotein cholesterol at weeks 4 and 6 of follow-up. After the 6-week HFD, the ratios of [1-{sup 13}C] alanine/pyruvate and [1-{sup 13}C] lactate/pyruvate were significantly increased, as were the levels of alanine aminotransferase and lactate dehydrogenase, which are potentially associated with hepatosteatosis. The results implicate [1-{sup 13}C] alanine and [1-{sup 13}C] lactate as potentially useful noninvasive biomarkers of hepatosteatosis occurring in NAFLD. - Highlights: • Hyperpolarized {sup 13}C-alanine and lactate are noninvasive biomarkers on hepatosteatosis. • During the course of HFD feeding, {sup 13}C-alanine and lactate were increased in HFD-rats. • Hyperpolarized {sup 13}C dynamic MRS will be helpful to monitor the progression of NAFLD.« less

Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes

PubMed Central

Akuzawa-Tateyama, M; Tateyama, M; Ochi, R

1998-01-01

The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique.Decreasing [K+]o from the normal level of 5.4 mm to 0.1 mm increased resting membrane potential (Vrest) from −75.6 ± 0.3 to −140.3 ± 1.9 mV (means ± s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 ± 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 ± 1.5 mV (n = 72) and sustained plateaux.Addition of 0.1 mm La3+ in the presence of 0.1 mm[K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials.Replacement of external Na+ or Cl− with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mm EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes.Hyperpolarizing voltage clamp pulses to potentials between −110 and −200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mm La3+.The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane. PMID:9824717

Monitoring diffuse He degassing from the summit crater of Pico do Fogo volcano, Cape Verde

NASA Astrophysics Data System (ADS)

Alonso, Mar; Dionis, Samara; Fernandes, Paulo; Melián, Gladys; Asensio-Ramos, María; Padilla, Germán D.; Hernández, Pedro A.; Pérez, Nemesio M.; Silva, Sonia

2017-04-01

Fogo (476km2) is one of the Sotavento islands of Cape Verde archipelago. The main geomorphological feature is the presence of a 9 km wide caldera hosting one of the world's most active volcanoes, Pico do Fogo (2829 m.a.s.l.), with the last eruption occurring on November 2014. Pico do Fogo volcano is characterized by the existence of a fumarolic field situated NW inside the summit crater and composed by low- and high-temperature gas discharges (90 to above 200oC respectively) with widespread sulfur precipitates at the surface, typical of hydrothermal alteration. As part of the geochemical monitoring program for the volcanic surveillance of Fogo volcano, twelve surveys of diffuse Helium (He) emission through the surface of the crater have been performed since 2008. He emission has been measured because it is considered as an excellent geochemical indicator (Pogorsky and Quirt 1981) due to its geochemical properties. Recent results clearly show the importance of helium emission studies for the prediction of major volcanic events and the importance of continuous monitoring of this gas in active volcanic regions (Padrón et al. 2013). Soil He emission rates were measured always at the same 63 sampling sites distributed inside the crater and covering an area of 0.142km2. At each measurement site, soil gas was collected in 10 cc glass vials with a hypodermic syringe by inserting to 40 cm depth a 50 cm stainless probe and later analyzed for He content by a quadrupole mass spectrometer Pfeiffer Omnistar 422. Diffusive and convective emission values were estimated at each sampling site following the Fick and Darcy's laws. The He emission rate through the crater was estimated after making the spatial interpolation maps using sequential Gaussian simulation. The average emission rate during these eight years of study is 3.3 kg d-1. The emission rate showed an important increase (up to 5.7 kg d-1) eight months before the 2014 eruption onset. During the eruptive period the crater released the highest value (up to 8 kg d-1), followed by a decrease after the eruption. The last emission value was measured in October 2016 and represents the lowest value of the series (1 kg d-1). This data suggest that monitoring of He degassing rate in volcanic areas is an excellent warning geochemical precursory signal for volcanic unrest. This work demonstrates and reinforces the importance of performing helium emission studies as an important promising volcano monitoring technique that might help to detect early warning signals of volcanic unrest in oceanic volcanic islands.

Enhanced Sensitivity to Hyperpolarizing Inhibition in Mesoaccumbal Relative to Nigrostriatal Dopamine Neuron Subpopulations

PubMed Central

2017-01-01

Midbrain dopamine neurons recorded in vivo pause their firing in response to reward omission and aversive stimuli. While the initiation of pauses typically involves synaptic or modulatory input, intrinsic membrane properties may also enhance or limit hyperpolarization, raising the question of how intrinsic conductances shape pauses in dopamine neurons. Using retrograde labeling and electrophysiological techniques combined with computational modeling, we examined the intrinsic conductances that shape pauses evoked by current injections and synaptic stimulation in subpopulations of dopamine neurons grouped according to their axonal projections to the nucleus accumbens or dorsal striatum in mice. Testing across a range of conditions and pulse durations, we found that mesoaccumbal and nigrostriatal neurons differ substantially in rebound properties with mesoaccumbal neurons displaying significantly longer delays to spiking following hyperpolarization. The underlying mechanism involves an inactivating potassium (IA) current with decay time constants of up to 225 ms, and small-amplitude hyperpolarization-activated currents (IH), characteristics that were most often observed in mesoaccumbal neurons. Pharmacological block of IA completely abolished rebound delays and, importantly, shortened synaptically evoked inhibitory pauses, thereby demonstrating the involvement of A-type potassium channels in prolonging pauses evoked by GABAergic inhibition. Therefore, these results show that mesoaccumbal and nigrostriatal neurons display differential responses to hyperpolarizing inhibitory stimuli that favors a higher sensitivity to inhibition in mesoaccumbal neurons. These findings may explain, in part, observations from in vivo experiments that ventral tegmental area neurons tend to exhibit longer aversive pauses relative to SNc neurons. SIGNIFICANCE STATEMENT Our study examines rebound, postburst, and synaptically evoked inhibitory pauses in subpopulations of midbrain dopamine neurons. We show that pauses in dopamine neuron firing, evoked by either stimulation of GABAergic inputs or hyperpolarizing current injections, are enhanced by a subclass of potassium conductances that are recruited at voltages below spike threshold. Importantly, A-type potassium currents recorded in mesoaccumbal neurons displayed substantially slower inactivation kinetics, which, combined with weaker expression of hyperpolarization-activated currents, lengthened hyperpolarization-induced delays in spiking relative to nigrostriatal neurons. These results suggest that input integration differs among dopamine neurons favoring higher sensitivity to inhibition in mesoaccumbal neurons and may partially explain in vivo observations that ventral tegmental area neurons exhibit longer aversive pauses relative to SNc neurons. PMID:28219982

Monitoring quiescent volcanoes by diffuse He degassing: case study Teide volcano

NASA Astrophysics Data System (ADS)

Pérez, Nemesio M.; Melián, Gladys; Asensio-Ramos, María; Padrón, Eleazar; Hernández, Pedro A.; Barrancos, José; Padilla, Germán; Rodríguez, Fátima; Calvo, David; Alonso, Mar

2016-04-01

Tenerife (2,034 km2), the largest of the Canary Islands, is the only island that has developed a central volcanic complex (Teide-Pico Viejo stratovolcanoes), characterized by the eruption of differentiated magmas. This central volcanic complex has been built in the intersection of the three major volcanic rift-zones of Tenerife, where most of the historical volcanic activity has taken place. The existence of a volcanic-hydrothermal system beneath Teide volcano is suggested by the occurrence of a weak fumarolic system, steamy ground and high rates of diffuse CO2 degassing all around the summit cone of Teide (Pérez et al., 2013). Diffuse emission studies of non-reactive and/or highly mobile gases such as helium have recently provided promising results to detect changes in the magmatic gas component at surface related to volcanic unrest episodes (Padrón et al., 2013). The geochemical properties of He minimize the interaction of this noble gas on its movement toward the earth's surface, and its isotopic composition is not affected by subsequent chemical reactions. It is highly mobile, chemically inert, physically stable, non-biogenic, sparingly soluble in water under ambient conditions, almost non-adsorbable, and highly diffusive with a diffusion coefficient ˜10 times that of CO2. As part of the geochemical monitoring program for the volcanic surveillance of Teide volcano, yearly surveys of diffuse He emission through the surface of the summit cone of Teide volcano have been performed since 2006. Soil He emission rate was measured yearly at ˜130 sampling sites selected in the surface environment of the summit cone of Teide volcano (Tenerife, Canary Islands), covering an area of ˜0.5 km2, assuming that He emission is governed by convection and diffusion. The distribution of the sampling sites was carefully chosen to homogeneously cover the target area, allowing the computation of the total He emission by sequential Gaussian simulation (sGs). Nine surveys have been carried out since 2006, showing an average emission rate of 8.0 kg/d. This value showed an anomalous increase up to 29 kg/d in the summer of 2010. The number of seismic events registered in and around Tenerife Island by the National Geographic Institute (IGN) reached also the highest value (1,176) in 2010. This excellent agreement between both times series suggest that the anomalous seismicity registered in 2010 was likely due to strain/stress changes caused by input of magmatic fluids beneath the central volcanic system of the island. These results suggest that monitoring of He degassing rates in oceanic volcanic islands is an excellent early warning geochemical precursory signal for volcanic unrest. References Padrón et al., 2013. Geology, DOI: 10.1130/G34027.1. Pérez et al., 2013. J. Geol. Soc., DOI: 10.1144/jgs2012-125.

Gas Chemistry of Submarine Hydrothermal Venting at Maug Caldera, Mariana Arc

NASA Astrophysics Data System (ADS)

Embley, R. W.; Lupton, J. E.; Butterfield, D. A.; Lilley, M. D.; Evans, L. J.; Olson, E. J.; Resing, J. A.; Buck, N.; Larson, B. I.; Young, C.

2014-12-01

Maug volcano consists of 3 islands that define the perimeter of a submerged caldera that was formed by an explosive eruption. The caldera reaches a depth of ~225 meters, and has a prominent central cone or pinnacle that ascends within 20 meters of the sea surface. Our exploration of Maug began in 2003, when a single hydrocast in the caldera detected a strong suspended particle and helium plume reaching a maximum of δ3He = 250% at ~180 meters depth, clearly indicating hydrothermal activity within the caldera. In 2004 we returned armed with the ROPOS ROV, and two ROPOS dives discovered and sampled low temperature (~4 °C) diffuse venting associated with bacterial mats on the NE flank of the central pinnacle at 145 m depth. Samples collected with titanium gas tight bottles were badly diluted with ambient seawater but allowed an estimate of end-member 3He/4He of 7.3 Ra. Four vertical casts lowered into the caldera in 2004 all had a strong 3He signal (δ3He = 190%) at 150-190 meters depth. A recent expedition in 2014 focused on the shallow (~10 m) gas venting along the caldera interior. Scuba divers were able to collect samples of the gas bubbles using evacuated SS bottles fitted with plastic funnels. The gas samples had a consistent ~170 ppm He, 8 ppmNe, 60% CO2, 40%N2, and 0.8% Ar, and an end-member 3He/4He ratio of 6.9 Ra. This 3He/4He ratio falls within the range for typical arc volcanoes. The rather high atmospheric component (N2, Ar, Ne) in these samples is not contamination but appears to be derived from subsurface exchange between the ascending CO2 bubbles and air saturated seawater. A single vertical cast in 2014 had a maximum δ3He = 55% at 140 m depth, much lower than in 2003 and 2004. This decrease is possibly due to recent flushing of the caldera by a storm event, or may reflect a decrease in the deep hydrothermal activity. This area of shallow CO2 venting in Maug caldera is of particular interest as a natural laboratory for studying the effects of ocean acidification on corals.

He isotope ratios in the Nankai Trough and Costa Rica subduction zones - implications for volatile cycling

NASA Astrophysics Data System (ADS)

Kastner, M.; Hilton, D. R.; Jenkins, W. J.; Solomon, E. A.; Spivack, A. J.

2013-12-01

The noble gas 3He is a clear indicator of primordial volatile flux from the mantle, thus providing important insights on the interaction between Earth's interior and exterior reservoirs. Volatile cycling at ridge-crests and its impact on the evolution of seawater chemistry is rather well known as constrained by the 3He flux, whereas the impact of volatile cycling at subduction zones (SZs) on seawater chemistry is as yet poorly known. Constraining chemical and isotopic cycling at SZs is important for understanding the evolution of the mantle-crust and ocean-atmosphere systems. To gain insights on volatile cycling in SZs, pore fluids were sampled for He concentration and isotopic analyses at two tectonically contrasting SZs, Nankai Trough (offshore Japan, Muroto and Kumano transects), an accretionary SZ, and Costa Rica (Offshore Osa Peninsula), an erosional SZ. Sampling for He was achieved by rapidly subsampling core sediments, cleaning and transferring these samples into Ti squeezers in a glove bag, and storing the squeezed pore fluids in crimped Cu tubes for shore-based He concentration and isotope ratio analyses. At the Nankai Trough SZ there is a remarkable range of He isotopic values. The 3He/4He ratios relative to atmospheric ratio (RA) range from mostly crustal 0.47 RA to 4.30 RA which is ~55% of the MORB value of 8 RA. Whereas at the Costa Rica SZ, offshore Osa Peninsula, the ratios range from 0.86 to 1.14 RA, indicating the dominance of crustal radiogenic 4He that is from U and Th decay. The distribution of the He isotope values at Nankai Trough is most interesting, fluids that contain significant mantle 3He components (3He/4He >1) were sampled along and adjacent to fluid conduits that were identified by several chemical and isotopic data (i.e. Cl, B, and Li), including the presence of thermogenic hydrocarbons. Whereas the fluids dominated by 4He (3He/4He ≤1) were obtained from sediment sections that were between the fluid conduits. At Costa Rica, however, even along conduits, the fluids were not greatly enriched in 3He, hence there is no evidence for fluid advection from the subducting Cocos Ridge and numerous seamounts into the sediments, suggesting greatly diminished hydrothermal activity. Focused flow along faults, the décollement, splay and out of sequence faults, and fractured and permeable horizons at SZs play a key role in controlling fluid and heat transport, including mantle He, whereas diffuse flow plays a minor role; mud volcanoes and seeps as well play some role in volatile cycling.

Multiband Spectral-Spatial RF Excitation for Hyperpolarized [2-13C]Dihydroxyacetone 13C-MR Metabolism Studies

PubMed Central

Marco-Rius, Irene; Cao, Peng; von Morze, Cornelius; Merrit, Matthew; Moreno, Karlos X; Chang, Gene-Yuan; Ohliger, Michael A.; Pearce, David; Kurhanewicz, John; Larson, Peder E. Z.; Vigneron, Daniel B.

2016-01-01

Purpose To develop a specialized multislice, single-acquisition approach to detect the metabolites of hyperpolarized [2-13C]dihydroxyacetone (DHAc) to probe gluconeogenesis in vivo, which have a broad 144 ppm spectral range (~4.6 KHz at 3T). A novel multiband RF excitation pulse was designed for independent flip angle control over 5-6 spectral-spatial (SPSP) excitation bands, each corrected for chemical shift misregistration effects. Methods Specialized multi-band SPSP RF pulses were designed, tested and applied to investigate hyperpolarized [2-13C]DHAc metabolism in kidney and liver of fasted rats with dynamic 13C-MRS and an optimal flip angle scheme. For comparison, experiments were also performed with narrow-band slice-selective RF pulses and a sequential change of the frequency offset to cover the five frequency bands of interest. Results The SPSP pulses provided a controllable spectral profile free of baseline distortion with improved signal to noise of the metabolite peaks, allowing for quantification of the metabolic products. We observed organ-specific differences in DHAc metabolism. There was 2-5 times more [2-13C]phosphoenolpyruvate and about 19 times more [2-13C]glycerol 3-phosphate in the liver than in the kidney. Conclusion A multiband SPSP RF pulse covering a spectral range over 144 ppm enabled in vivo characterization of HP [2-13C]dihydroxyacetone metabolism in rat liver and kidney. PMID:27017966

Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

NASA Astrophysics Data System (ADS)

Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

BK Channel-Mediated Relaxation of Urinary Bladder Smooth Muscle: A Novel Paradigm for Phosphodiesterase Type 4 Regulation of Bladder Function

PubMed Central

Xin, Wenkuan; Li, Ning; Cheng, Qiuping

2014-01-01

Elevation of intracellular cAMP and activation of protein kinase A (PKA) lead to activation of large conductance voltage- and Ca2+-activated K+ (BK) channels, thus attenuation of detrusor smooth muscle (DSM) contractility. In this study, we investigated the mechanism by which pharmacological inhibition of cAMP-specific phosphodiesterase 4 (PDE4) with rolipram or Ro-20-1724 (C15H22N2O3) suppresses guinea pig DSM excitability and contractility. We used high-speed line-scanning confocal microscopy, ratiometric fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp techniques on freshly isolated DSM cells, along with isometric tension recordings of DSM isolated strips. Rolipram caused an increase in the frequency of Ca2+ sparks and the spontaneous transient BK currents (TBKCs), hyperpolarized the cell membrane potential (MP), and decreased the intracellular Ca2+ levels. Blocking BK channels with paxilline reversed the hyperpolarizing effect of rolipram and depolarized the MP back to the control levels. In the presence of H-89 [N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride], a PKA inhibitor, rolipram did not cause MP hyperpolarization. Rolipram or Ro-20-1724 reduced DSM spontaneous and carbachol-induced phasic contraction amplitude, muscle force, duration, and frequency, and electrical field stimulation-induced contraction amplitude, muscle force, and tone. Paxilline recovered DSM contractility, which was suppressed by pretreatment with PDE4 inhibitors. Rolipram had reduced inhibitory effects on DSM contractility in DSM strips pretreated with paxilline. This study revealed a novel cellular mechanism whereby pharmacological inhibition of PDE4 leads to suppression of guinea pig DSM contractility by increasing the frequency of Ca2+ sparks and the functionally coupled TBKCs, consequently hyperpolarizing DSM cell MP. Collectively, this decreases the global intracellular Ca2+ levels and DSM contractility in a BK channel-dependent manner. PMID:24459245

A parameter free model for HgMn stars

NASA Astrophysics Data System (ADS)

Michaud, G.

Consideration is given to hydrodynamic and radiative acceleration calculations that may be performed within the context of a parameter-free model of HgMn stars. The model accounts for the formation of HgMn stars at temperatures too high to support an outer hydrogen convection zone by the settling of helium through a He II convection zone which eventually disappears, leaving a diffusive atmosphere with envelope heavy element abundances. Calculations of meridional circulation and the He II diffusion velocity are presented which demonstrate that the He II convection zone can disappear for equatorial rotation velocities less than or equal to 90 km/sec. Detailed radiative acceleration calculations performed for various elements are then reviewed which have reproduced the maximum anomalies observed for He, B, Si, Ca, Sr and Mn abundances in HgMn stars. The parameter-free model is noted to fail, however, in the case of Be.

Empirical constraints on the effects of radiation damage on helium diffusion in zircon

NASA Astrophysics Data System (ADS)

Anderson, Alyssa J.; Hodges, Kip V.; van Soest, Matthijs C.

2017-12-01

In this study, we empirically evaluate the impact of radiation damage on zircon (U-Th)/He closure temperatures for a suite of zircon crystals from the slowly cooled McClure Mountain syenite of south-central Colorado, USA. We present new zircon, titanite, and apatite conventional (U-Th)/He dates, zircon laser ablation (U-Th)/He and U-Pb dates, and zircon Raman spectra for crystals from the syenite. Titanite and apatite (U-Th)/He dates range from 447 to 523 Ma and 88.0 to 138.9 Ma, respectively, and display no clear correlation between (U-Th)/He date and effective uranium concentration. Conventional zircon (U-Th)/He dates range from 230.3 to 474 Ma, while laser ablation zircon (U-Th)/He dates show even greater dispersion, ranging from 5.31 to 520 Ma. Dates from both zircon (U-Th)/He datasets decrease with increasing alpha dose, indicating that most of the dispersion can be attributed to radiation damage. Alpha dose values for the dated zircon crystals range from effectively zero to 2.15 × 1019 α /g, spanning the complete damage spectrum. We use an independently constrained thermal model to empirically assign a closure temperature to each dated zircon grain. If we assume that this thermal model is robust, the zircon radiation damage accumulation and annealing model of Guenthner et al. (2013) does not accurately predict closure temperatures for many of the analyzed zircon crystals. Raman maps of the zircons dated by laser ablation document complex radiation damage zoning, sometimes revealing crystalline zones in grains with alpha dose values suggestive of amorphous material. Such zoning likely resulted in heterogeneous intra-crystalline helium diffusion and may help explain some of the discrepancies between our empirical findings and the Guenthner et al. (2013) model predictions. Because U-Th zoning is a common feature in zircon, radiation damage zoning is likely to be a concern for most ancient, slowly cooled zircon (U-Th)/He datasets. Whenever possible, multiple mineral-isotopic systems should be employed to add additional, independent constraints to a sample's thermal history.

Synthesis of long T₁ silicon nanoparticles for hyperpolarized ²⁹Si magnetic resonance imaging.

PubMed

Atkins, Tonya M; Cassidy, Maja C; Lee, Menyoung; Ganguly, Shreyashi; Marcus, Charles M; Kauzlarich, Susan M

2013-02-26

We describe the synthesis, materials characterization, and dynamic nuclear polarization (DNP) of amorphous and crystalline silicon nanoparticles for use as hyperpolarized magnetic resonance imaging (MRI) agents. The particles were synthesized by means of a metathesis reaction between sodium silicide (Na₄Si₄) and silicon tetrachloride (SiCl₄) and were surface functionalized with a variety of passivating ligands. The synthesis scheme results in particles of diameter ∼10 nm with long size-adjusted ²⁹Si spin-lattice relaxation (T₁) times (>600 s), which are retained after hyperpolarization by low-temperature DNP.

Synthesis of Long-T1 Silicon Nanoparticles for Hyperpolarized 29Si Magnetic Resonance Imaging

PubMed Central

Atkins, Tonya M.; Cassidy, Maja C.; Lee, Menyoung; Ganguly, Shreyashi; Marcus, Charles M.; Kauzlarich, Susan M.

2013-01-01

We describe the synthesis, materials characterization and dynamic nuclear polarization (DNP) of amorphous and crystalline silicon nanoparticles for use as hyperpolarized magnetic resonance imaging (MRI) agents. The particles were synthesized by means of a metathesis reaction between sodium silicide (Na4Si4) and silicon tetrachloride (SiCl4) and were surface functionalized with a variety of passivating ligands. The synthesis scheme results in particles of diameter ~10 nm with long size-adjusted 29Si spin lattice relaxation (T1) times (> 600 s), which are retained after hyperpolarization by low temperature DNP. PMID:23350651

LabVIEW-based control software for para-hydrogen induced polarization instrumentation.

PubMed

Agraz, Jose; Grunfeld, Alexander; Li, Debiao; Cunningham, Karl; Willey, Cindy; Pozos, Robert; Wagner, Shawn

2014-04-01

The elucidation of cell metabolic mechanisms is the modern underpinning of the diagnosis, treatment, and in some cases the prevention of disease. Para-Hydrogen induced polarization (PHIP) enhances magnetic resonance imaging (MRI) signals over 10,000 fold, allowing for the MRI of cell metabolic mechanisms. This signal enhancement is the result of hyperpolarizing endogenous substances used as contrast agents during imaging. PHIP instrumentation hyperpolarizes Carbon-13 ((13)C) based substances using a process requiring control of a number of factors: chemical reaction timing, gas flow, monitoring of a static magnetic field (Bo), radio frequency (RF) irradiation timing, reaction temperature, and gas pressures. Current PHIP instruments manually control the hyperpolarization process resulting in the lack of the precise control of factors listed above, resulting in non-reproducible results. We discuss the design and implementation of a LabVIEW based computer program that automatically and precisely controls the delivery and manipulation of gases and samples, monitoring gas pressures, environmental temperature, and RF sample irradiation. We show that the automated control over the hyperpolarization process results in the hyperpolarization of hydroxyethylpropionate. The implementation of this software provides the fast prototyping of PHIP instrumentation for the evaluation of a myriad of (13)C based endogenous contrast agents used in molecular imaging.

Parahydrogen-induced polarization of carboxylic acids: a pilot study of valproic acid and related structures.

PubMed

Lego, Denise; Plaumann, Markus; Trantzschel, Thomas; Bargon, Joachim; Scheich, Henning; Buntkowsky, Gerd; Gutmann, Torsten; Sauer, Grit; Bernarding, Johannes; Bommerich, Ute

2014-07-01

Parahydrogen-induced polarization (PHIP) is a promising new tool for medical applications of MR, including MRI. The PHIP technique can be used to transfer high non-Boltzmann polarization, derived from parahydrogen, to isotopes with a low natural abundance or low gyromagnetic ratio (e.g. (13)C), thus improving the signal-to-noise ratio by several orders of magnitude. A few molecules acting as metabolic sensors have already been hyperpolarized with PHIP, but the direct hyperpolarization of drugs used to treat neurological disorders has not been accomplished until now. Here, we report on the first successful hyperpolarization of valproate (valproic acid, VPA), an important and commonly used antiepileptic drug. Hyperpolarization was confirmed by detecting the corresponding signal patterns in the (1)H NMR spectrum. To identify the optimal experimental conditions for the conversion of an appropriate VPA precursor, structurally related molecules with different side chains were analyzed in different solvents using various catalytic systems. The presented results include hyperpolarized (13)C NMR spectra and proton images of related systems, confirming their applicability for MR studies. PHIP-based polarization enhancement may provide a new MR technique to monitor the spatial distribution of valproate in brain tissue and to analyze metabolic pathways after valproate administration. Copyright © 2014 John Wiley & Sons, Ltd.

Boosting the signal: Endothelial inward rectifier K+ channels.

PubMed

Jackson, William F

2017-04-01

Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of K IR 2 subunits. These two-membrane spanning domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K + channel (K IR ) currents display a region of negative slope conductance at membrane potentials positive to the K + equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K IR to amplify hyperpolarization induced by other K + channels and ion transporters. Increases in extracellular K + concentration activate K IR allowing them to sense extracellular K + concentration and transduce this change into membrane hyperpolarization. These properties position K IR to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. The expression of K IR in capillaries in electrically active tissues may allow K IR to sense extracellular K + , contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K IR will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for the development of therapeutics in the future. © 2016 John Wiley & Sons Ltd.

LabVIEW-based control software for para-hydrogen induced polarization instrumentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agraz, Jose, E-mail: joseagraz@ucla.edu; Grunfeld, Alexander; Li, Debiao

2014-04-15

The elucidation of cell metabolic mechanisms is the modern underpinning of the diagnosis, treatment, and in some cases the prevention of disease. Para-Hydrogen induced polarization (PHIP) enhances magnetic resonance imaging (MRI) signals over 10 000 fold, allowing for the MRI of cell metabolic mechanisms. This signal enhancement is the result of hyperpolarizing endogenous substances used as contrast agents during imaging. PHIP instrumentation hyperpolarizes Carbon-13 ({sup 13}C) based substances using a process requiring control of a number of factors: chemical reaction timing, gas flow, monitoring of a static magnetic field (B{sub o}), radio frequency (RF) irradiation timing, reaction temperature, and gas pressures.more » Current PHIP instruments manually control the hyperpolarization process resulting in the lack of the precise control of factors listed above, resulting in non-reproducible results. We discuss the design and implementation of a LabVIEW based computer program that automatically and precisely controls the delivery and manipulation of gases and samples, monitoring gas pressures, environmental temperature, and RF sample irradiation. We show that the automated control over the hyperpolarization process results in the hyperpolarization of hydroxyethylpropionate. The implementation of this software provides the fast prototyping of PHIP instrumentation for the evaluation of a myriad of {sup 13}C based endogenous contrast agents used in molecular imaging.« less

3D Compressed Sensing for Highly Accelerated Hyperpolarized 13C MRSI With In Vivo Applications to Transgenic Mouse Models of Cancer

PubMed Central

Hu, Simon; Lustig, Michael; Balakrishnan, Asha; Larson, Peder E. Z.; Bok, Robert; Kurhanewicz, John; Nelson, Sarah J.; Goga, Andrei; Pauly, John M.; Vigneron, Daniel B.

2010-01-01

High polarization of nuclear spins in liquid state through hyperpolarized technology utilizing dynamic nuclear polarization has enabled the direct monitoring of 13C metabolites in vivo at a high signal-to-noise ratio. Acquisition time limitations due to T1 decay of the hyperpolarized signal require accelerated imaging methods, such as compressed sensing, for optimal speed and spatial coverage. In this paper, the design and testing of a new echo-planar 13C three-dimensional magnetic resonance spectroscopic imaging (MRSI) compressed sensing sequence is presented. The sequence provides up to a factor of 7.53 in acceleration with minimal reconstruction artifacts. The key to the design is employing x and y gradient blips during a fly-back readout to pseudorandomly undersample kf-kx-ky space. The design was validated in simulations and phantom experiments where the limits of undersampling and the effects of noise on the compressed sensing nonlinear reconstruction were tested. Finally, this new pulse sequence was applied in vivo in preclinical studies involving transgenic prostate cancer and transgenic liver cancer murine models to obtain much higher spatial and temporal resolution than possible with conventional echo-planar spectroscopic imaging methods. PMID:20017160

Construction and 13C NMR signal-amplification efficiency of a dynamic nuclear polarizer at 6.4 T and 1.4 K

NASA Astrophysics Data System (ADS)

Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Ferguson, Sarah; Taylor, David; McDonald, George; Lumata, Lloyd

Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging technique in biomedical and metabolic imaging since it amplifies the liquid-state nuclear magnetic resonance (NMR) and imaging (MRI) signals by >10,000-fold. Originally used in nuclear scattering experiments, DNP works by creating a non-Boltzmann nuclear spin distribution by transferring the high electron (γ = 28,000 MHz/T) thermal polarization to the nuclear spins via microwave irradiation of the sample at high magnetic field and low temperature. A dissolution device is used to rapidly dissolve the frozen sample and consequently produces an injectable ``hyperpolarized'' liquid at physiologically-tolerable temperature. Here we report the construction and performance evaluation of a dissolution DNP hyperpolarizer at 6.4 T and 1.4 K using a continuous-flow cryostat. The solid and liquid-state 13C NMR signal enhancement levels of 13C acetate samples doped with trityl OX063 and 4-oxo-TEMPO free radicals will be discussed and compared with the results from the 3.35 T commercial hyperpolarizer. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

Magnetic resonance imaging of (1)H long lived states derived from parahydrogen induced polarization in a clinical system.

PubMed

Graafen, Dirk; Franzoni, María Belén; Schreiber, Laura M; Spiess, Hans W; Münnemann, Kerstin

2016-01-01

Hyperpolarization is a powerful tool to overcome the low sensitivity of nuclear magnetic resonance (NMR). However, applications are limited due to the short lifetime of this non equilibrium spin state caused by relaxation processes. This issue can be addressed by storing hyperpolarization in slowly decaying singlet spin states which was so far mostly demonstrated for non-proton spin pairs, e.g. (13)C-(13)C. Protons hyperpolarized by parahydrogen induced polarization (PHIP) in symmetrical molecules, are very well suited for this strategy because they naturally exhibit a long-lived singlet state. The conversion of the NMR silent singlet spin state to observable magnetization can be achieved by making use of singlet-triplet level anticrossings. In this study, a low-power radiofrequency pulse sequence is used for this purpose, which allows multiple successive singlet-triplet conversions. The generated magnetization is used to record proton images in a clinical magnetic resonance imaging (MRI) system, after 3min waiting time. Our results may open unprecedented opportunities to use the standard MRI nucleus (1)H for e.g. metabolic imaging in the future. Copyright © 2016. Published by Elsevier Inc.

Electroporation of DC-3F cells is a dual process.

PubMed

Wegner, Lars H; Frey, Wolfgang; Silve, Aude

2015-04-07

Treatment of biological material by pulsed electric fields is a versatile technique in biotechnology and biomedicine used, for example, in delivering DNA into cells (transfection), ablation of tumors, and food processing. Field exposure is associated with a membrane permeability increase usually ascribed to electroporation, i.e., formation of aqueous membrane pores. Knowledge of the underlying processes at the membrane level is predominantly built on theoretical considerations and molecular dynamics (MD) simulations. However, experimental data needed to monitor these processes with sufficient temporal resolution are scarce. The whole-cell patch-clamp technique was employed to investigate the effect of millisecond pulsed electric fields on DC-3F cells. Cellular membrane permeabilization was monitored by a conductance increase. For the first time, to our knowledge, it could be established experimentally that electroporation consists of two clearly separate processes: a rapid membrane poration (transient electroporation) that occurs while the membrane is depolarized or hyperpolarized to voltages beyond so-called threshold potentials (here, +201 mV and -231 mV, respectively) and is reversible within ∼100 ms after the pulse, and a long-term, or persistent, permeabilization covering the whole voltage range. The latter prevailed after the pulse for at least 40 min, the postpulse time span tested experimentally. With mildly depolarizing or hyperpolarizing pulses just above threshold potentials, the two processes could be separated, since persistent (but not transient) permeabilization required repetitive pulse exposure. Conductance increased stepwise and gradually with depolarizing and hyperpolarizing pulses, respectively. Persistent permeabilization could also be elicited by single depolarizing/hyperpolarizing pulses of very high field strength. Experimental measurements of propidium iodide uptake provided evidence of a real membrane phenomenon, rather than a mere patch-clamp artifact. In short, the response of DC-3F cells to strong pulsed electric fields was separated into a transient electroporation and a persistent permeabilization. The latter dominates postpulse membrane properties but to date has not been addressed by electroporation theory or MD simulations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Comparison of age distributions estimated from environmental tracers by using binary-dilution and numerical models of fractured and folded karst: Shenandoah Valley of Virginia and West Virginia, USA

USGS Publications Warehouse

Yager, Richard M.; Plummer, Niel; Kauffman, Leon J.; Doctor, Daniel H.; Nelms, David L.; Schlosser, Peter

2013-01-01

Measured concentrations of environmental tracers in spring discharge from a karst aquifer in the Shenandoah Valley, USA, were used to refine a numerical groundwater flow model. The karst aquifer is folded and faulted carbonate bedrock dominated by diffuse flow along fractures. The numerical model represented bedrock structure and discrete features (fault zones and springs). Concentrations of 3H, 3He, 4He, and CFC-113 in spring discharge were interpreted as binary dilutions of young (0–8 years) water and old (tracer-free) water. Simulated mixtures of groundwater are derived from young water flowing along shallow paths, with the addition of old water flowing along deeper paths through the model domain that discharge to springs along fault zones. The simulated median age of young water discharged from springs (5.7 years) is slightly older than the median age estimated from 3H/3He data (4.4 years). The numerical model predicted a fraction of old water in spring discharge (0.07) that was half that determined by the binary-dilution model using the 3H/3He apparent age and 3H and CFC-113 data (0.14). This difference suggests that faults and lineaments are more numerous or extensive than those mapped and included in the numerical model.

High-field Overhauser dynamic nuclear polarization in silicon below the metal-insulator transition.

PubMed

Dementyev, Anatoly E; Cory, David G; Ramanathan, Chandrasekhar

2011-04-21

Single crystal silicon is an excellent system to explore dynamic nuclear polarization (DNP), as it exhibits a continuum of properties from metallic to insulating as a function of doping concentration and temperature. At low doping concentrations DNP has been observed to occur via the solid effect, while at very high-doping concentrations an Overhauser mechanism is responsible. Here we report the hyperpolarization of (29)Si in n-doped silicon crystals, with doping concentrations in the range of (1-3) × 10(17) cm(-3). In this regime exchange interactions between donors become extremely important. The sign of the enhancement in our experiments and its frequency dependence suggest that the (29)Si spins are directly polarized by donor electrons via an Overhauser mechanism within exchange-coupled donor clusters. The exchange interaction between donors only needs to be larger than the silicon hyperfine interaction (typically much smaller than the donor hyperfine coupling) to enable this Overhauser mechanism. Nuclear polarization enhancement is observed for a range of donor clusters in which the exchange energy is comparable to the donor hyperfine interaction. The DNP dynamics are characterized by a single exponential time constant that depends on the microwave power, indicating that the Overhauser mechanism is a rate-limiting step. Since only about 2% of the silicon nuclei are located within 1 Bohr radius of the donor electron, nuclear spin diffusion is important in transferring the polarization to all the spins. However, the spin-diffusion time is much shorter than the Overhauser time due to the relatively weak silicon hyperfine coupling strength. In a 2.35 T magnetic field at 1.1 K, we observed a DNP enhancement of 244 ± 84 resulting in a silicon polarization of 10.4 ± 3.4% following 2 h of microwave irradiation.

Experimental determination of pore shapes using phase retrieval from q -space NMR diffraction

NASA Astrophysics Data System (ADS)

Demberg, Kerstin; Laun, Frederik Bernd; Bertleff, Marco; Bachert, Peter; Kuder, Tristan Anselm

2018-05-01

This paper presents an approach to solving the phase problem in nuclear magnetic resonance (NMR) diffusion pore imaging, a method that allows imaging the shape of arbitrary closed pores filled with an NMR-detectable medium for investigation of the microstructure of biological tissue and porous materials. Classical q -space imaging composed of two short diffusion-encoding gradient pulses yields, analogously to diffraction experiments, the modulus squared of the Fourier transform of the pore image which entails an inversion problem: An unambiguous reconstruction of the pore image requires both magnitude and phase. Here the phase information is recovered from the Fourier modulus by applying a phase retrieval algorithm. This allows omitting experimentally challenging phase measurements using specialized temporal gradient profiles. A combination of the hybrid input-output algorithm and the error reduction algorithm was used with dynamically adapting support (shrinkwrap extension). No a priori knowledge on the pore shape was fed to the algorithm except for a finite pore extent. The phase retrieval approach proved successful for simulated data with and without noise and was validated in phantom experiments with well-defined pores using hyperpolarized xenon gas.

Experimental determination of pore shapes using phase retrieval from q-space NMR diffraction.

PubMed

Demberg, Kerstin; Laun, Frederik Bernd; Bertleff, Marco; Bachert, Peter; Kuder, Tristan Anselm

2018-05-01

This paper presents an approach to solving the phase problem in nuclear magnetic resonance (NMR) diffusion pore imaging, a method that allows imaging the shape of arbitrary closed pores filled with an NMR-detectable medium for investigation of the microstructure of biological tissue and porous materials. Classical q-space imaging composed of two short diffusion-encoding gradient pulses yields, analogously to diffraction experiments, the modulus squared of the Fourier transform of the pore image which entails an inversion problem: An unambiguous reconstruction of the pore image requires both magnitude and phase. Here the phase information is recovered from the Fourier modulus by applying a phase retrieval algorithm. This allows omitting experimentally challenging phase measurements using specialized temporal gradient profiles. A combination of the hybrid input-output algorithm and the error reduction algorithm was used with dynamically adapting support (shrinkwrap extension). No a priori knowledge on the pore shape was fed to the algorithm except for a finite pore extent. The phase retrieval approach proved successful for simulated data with and without noise and was validated in phantom experiments with well-defined pores using hyperpolarized xenon gas.

Uncontrolled pneumonia in a 49-year-old white man.

PubMed

Taghizadeh, Farnoush; Raghuwanshi M, Raghuraj S

2014-01-01

A 49-year-old white man. Shortness of breath, fever, and ongoing unintended weight loss. The patient had arrived at the emergency department of a hospital in St. Augustine, Florida with coughing and progressive shortness of breath. He reported that he had been experiencing these symptoms for the past 6 weeks. He was examined by his primary physician, who had prescribed him a course of antibiotics and treated him on an outpatient basis. The patient reported no improvement in his symptoms at present, despite the antibiotics. He mentioned that he had traveled to St. Augustine, Florida approximately 10 days previously. Medical personnel in the emergency department subsequently performed a chest x-ray on the patient, as well as computed tomography (CT) scanning of his lymphadenopathy. MEDICAL AND FAMILY HISTORY: Positive for hypertension, diabetes mellitus, and osteoporosis. He reported that he has chewed 2 packs of chewing tobacco per day for the past 30 years, occasionally drinks alcohol, and is a nonsmoker with no known allergies. Noncontributory. Noncontributory. The patient exhibited mild respiratory distress; however, he was awake, alert, and oriented, with a temperature of 37.3°C. He also exhibited poor respiratory effort with diffuse expiratory rhonchi. His heart rate and heart rhythm were regular, with no murmurs, gallops, or rubs. His bowel sounds were positive; he exhibited no organomegaly and no cyanosis, clubbing, or edema of his extremities.

(De)coupled zircon metamictization, radiation damage, and He diffusivity

NASA Astrophysics Data System (ADS)

Ault, A. K.; Guenthner, W.; Reiners, P. W.; Moser, A. C.; Miller, G. H.; Refsnider, K. A.

2017-12-01

We develop and apply a new protocol for targeting crystals for the zircon (U-Th)/He (He) thermochronometry to maximize effective U (eU) and corresponding closure temperature variability to develop zircon He date-eU correlations observed in some datasets. Our approach exploits visual proxies for radiation damage accumulation (metamictization) during zircon selection. We show that by purposefully targeting a spectrum of zircon textures from pristine to metamict grains, it is possible to generate broad eU variation in suites of zircon from a single sample and zircon He date-eU-metamictization trends that can be exploited to resolve increasingly complex thermal histories. We present plane light photographs, eU concentration, and zircon He results from 59 individual zircons from nine crystalline rock samples. Six of the nine samples come from exposed Proterozoic granitoids on SE Baffin Island, Canada; Boulder Creek, CO; Sandia Mountains, NM; and Mecca Hills, CA. We report data from three Archean Baffin samples to compare with the Proterozoic Baffin sample date-eU-metamictization trend. In each Proterozoic sample, target zircons display a spectrum of metamictization from pristine, transparent crystals to purple-brown, translucent grains. Progressive loss of transparency and increase in discoloration consistently corresponds to an increase in eU in all samples. Individual zircon eU varies from 89-1885 ppm and, within each sample, the total eU spread is 538 ppm to 1374 ppm. For any given eU value, the Archean zircon appear comparatively more metamict than the Proterozoic Baffin grains and samples collectively define a 1681 ppm range in eU, with more restrictive intrasample eU spreads (199-1120 ppm). Proterozoic samples from Baffin, Sandia, and Front Range yield negative zircon He date-eU correlations with intrasample date ranges of 90-783 Ma. Increasing eU and younger dates correspond with increasing metamictization. In contrast, all three Proterozoic Mecca Hills samples yield uniform 25 Ma zircon He dates over 1800 ppm eU. We apply simple thermal history models that account for the coevolution of zircon radiation damage and He-diffusivity to demonstrate that visible zircon metamictization and He diffusivity can be either coupled or decoupled depending on a sample's thermal history.

Laser depth profiling of diffusion and alpha ejection profiles in Durango apatite: testing the fundamental parameters of apatite (U-Th)/He dating

NASA Astrophysics Data System (ADS)

van Soest, M. C.; Monteleone, B. D.; Boyce, J. W.; Hodges, K.

2009-12-01

Since its development (e.g. Zeitler et al., 1987, Lippolt et al., 1994, Farley et al., 1996, Wolf et al., 1996) as a viable low temperature thermochronological method (U-Th)/He dating of apatite has become a popular and widely applied low temperature thermochronometer. The method has been applied with success to a great variety of geological problems, and the fundamental parameters of the method: the bulk diffusion parameters of helium in apatite, and the calculated theoretical helium stopping distance in apatite used to correct the ages for the effects of alpha ejection appear sound. However, the development of the UV laser microprobe technique for the (U-Th)/He method (Boyce et al., 2006) allows for in-situ testing of the helium bulk diffusion parameters (Farley, 2000) and can provide a direct measurement of the alpha ejection distance in apatite. So, with the ultimate goal of further developing the in-situ (U-Th)/He dating method and micro-analytical depth profiling techniques to constrain cooling histories in natural grains, we conducted a helium depth profiling study of induced diffusion and natural alpha ejection profiles in Durango apatite. For the diffusion depth profiling, a Durango crystal was cut in slabs oriented parallel and perpendicular to the crystal c-axis. The slabs were polished and heated using different temperature and time schedules to induce predictable diffusion profiles based on the bulk helium diffusion parameters in apatite. Depth profiling of the 4He diffusion profiles was done using an ArF excimer laser. The measured diffusion depth profiles at 350°, 400°, and 450° C coincide well with the predicted bulk diffusion curves, independent of slab orientation, but the 300° C profiles consistently deviate significantly. The possible cause for this deviation is currently being investigated. Alpha ejection profiling was carried out on crystal margins from two different Durango apatite crystals, several faces from each crystal were analyzed to evaluate the potential effects of crystallographic orientation on alpha ejection. The results from both crystals were very reproducible irrespective of crystal surface used and confirm the findings of Monteleone et al. (2008) that the measured alpha ejection profiles deviate significantly from and are shorter than the calculated theoretical average value. Efforts are currently underway to better constrain the measured alpha ejection distance and measure alpha ejection profiles in apatite crystals other than Durango apatite. References: Boyce, J. et al. (2006) GCA 70, pp. 3031-3039. Farley, K. et al. (1996) GCA 60, pp. 4223-4229. Farley, K. (2006) JGR SE 105, p. 2903-2914. Lippolt, H. et al. (1994) Chem Geol 112, pp. 179-191. Monteleone, B. et al. (2008) Eos Trans AGU, 89 Fall Meeting V53B-2162. Wolf, R. et al. (1996) GCA 60, pp. 4231-4240. Zeitler, P. et al. (1987) GCA 51, pp. 2865-2868.

SU-E-QI-11: Measurement of Renal Pyruvate-To-Lactate Exchange with Hyperpolarized 13C MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, E; Johnson, K; Fain, S

Purpose: Previous work [1] modeling the metabolic flux between hyperpolarized [1-13C]pyruvate and [1-13C]lactate in magnetic resonance spectroscopic imaging (MRSI) experiments failed to account for vascular signal artifacts. Here, we investigate a method to minimize the vascular signal and its impact on the fidelity of metabolic modeling. Methods: MRSI was simulated for renal metabolism in MATLAB both with and without bipolar gradients. The resulting data were fit to a two-site exchange model [1], and the effects of vascular partial volume artifacts on kinetic modeling were assessed. Bipolar gradients were then incorporated into a gradient echo sequence to validate the simulations experimentally.more » The degree of diffusion weighting (b = 32 s/mm{sup 2}) was determined empirically from 1H imaging of murine renal vascular signal. The method was then tested in vivo using MRSI with bipolar gradients following injection of hyperpolarized [1-{sup 13}C]pyruvate (∼80 mM at 20% polarization). Results: In simulations, vascular signal contaminated the renal metabolic signal at resolutions as high as 2 × 2 mm{sup 2} due to partial volume effects. The apparent exchange rate from pyruvate to lactate (k{sub p}) was underestimated in the presence of these artifacts due to contaminating pyruvate signal. Incorporation of bipolar gradients suppressed vascular signal and improved the accuracy of kp estimation. Experimentally, the in vivo results supported the ability of bipolar gradients to suppress vascular signal. The in vivo exchange rate increased, as predicted in simulations, from k{sub p} = 0.012 s-{sup 1} to k{sub p} = 0.020-{sup 1} after vascular signal suppression. Conclusion: We have demonstrated the limited accuracy of the two-site exchange model in the presence of vascular partial volume artifacts. The addition of bipolar gradients suppressed vascular signal and improved model accuracy in simulations. Bipolar gradients largely affected kp estimation in vivo. Currently, slow-flowing spins in small vessels and capillaries are only partially suppressed, so further improvement is possible. Funding support: Seed Grant from the Radiological Society of North America, GE Healthcare, University of Wisconsin Graduate School.« less

Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence

NASA Astrophysics Data System (ADS)

Milshteyn, Eugene; von Morze, Cornelius; Reed, Galen D.; Shang, Hong; Shin, Peter J.; Larson, Peder E. Z.; Vigneron, Daniel B.

2018-05-01

Acceleration of dynamic 2D (T2 Mapping) and 3D hyperpolarized 13C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2-13C]pyruvate, [1-13C]lactate, [13C, 15N2]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T2 maps.

A fast field-cycling device for high-resolution NMR: Design and application to spin relaxation and hyperpolarization experiments

NASA Astrophysics Data System (ADS)

Kiryutin, Alexey S.; Pravdivtsev, Andrey N.; Ivanov, Konstantin L.; Grishin, Yuri A.; Vieth, Hans-Martin; Yurkovskaya, Alexandra V.

2016-02-01

A device for performing fast magnetic field-cycling NMR experiments is described. A key feature of this setup is that it combines fast switching of the external magnetic field and high-resolution NMR detection. The field-cycling method is based on precise mechanical positioning of the NMR probe with the mounted sample in the inhomogeneous fringe field of the spectrometer magnet. The device enables field variation over several decades (from 100 μT up to 7 T) within less than 0.3 s; progress in NMR probe design provides NMR linewidths of about 10-3 ppm. The experimental method is very versatile and enables site-specific studies of spin relaxation (NMRD, LLSs) and spin hyperpolarization (DNP, CIDNP, and SABRE) at variable magnetic field and at variable temperature. Experimental examples of such studies are demonstrated; advantages of the experimental method are described and existing challenges in the field are outlined.

Measurement and significance of the reversal potential for the pace-maker current (iK2) in sheep Purkinje fibres.

PubMed

DiFrancesco, D; Ohba, M; Ojeda, C

1979-12-01

1. The apparent reversal potential (Erev) of the pace-maker current (iK2) is found to depend on the experimental protocol used for its measurement. Evidence is presented showing that depolarizing (hyperpolarizing) pulses given before a test hyperpolarization used to determine Erev, shift Erev to more negative (positive) values. These shifts are opposite to those expected if the only effect of pre-pulses were to change the concentration of potassium in extracellular clefts ([K]c) via accumulation and depletion processes. 2. This effect is shown to be due to the fact that Erev is dependent on s0, the degree of activation of iK2 at the start of the test hyperpolarization. 3. When a suitable protocol is used, depletion of cleft K can be demonstrated to take place during a large hyperpolarization. Changes in the level of [K]c induced by pre-pulses must therefore also affect the Erev determination. 4. A simplified three-compartment model has been used to investigate how K accumulation and depletion can affect the time course of iK2, with particular reference to the problem of Erev determination. Computed examples show that the model is able to reproduce the main features of the time course of iK2 recorded near its reversal potential and the changes induced by pre-pulses on Erev measuremnet. By contrast, simulation on a linear cable model rules out the possibility that such results are due to voltage non-uniformity. 5. The three-compartment model predicts that the measured value of Erev differs from EK2 for two reasons: (1) when the recorded current trace is flat iK2 is still outward and decaying, and (2) the K equilibrium potential shifts to more negative values while the test hyperpolarization is applied. 6. The finding that Erev is directly affected by changes in s at the beginning of the test pulse is discussed in relation to the action of agents (such as Ca2+, H+, salicylate, adrenaline and ouabain) which are found to shift both the s00 curve and Erev.

Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine

PubMed Central

Gerschenfeld, H. M.; Tritsch, Danièle Paupardin

1974-01-01

1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5-hydroxytryptamine (5-HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed. 2. Four of the responses to 5-HT (named A, A′, B and C) are consequent upon an increase in membrane conductance whereas the other two (named α and β) are caused by a decrease in membrane conductance. 3. The A-response to 5-HT consists of a `fast' depolarization due to an increase mainly in Na+-conductance; the A′-response is a `slow' depolarization also associated with a Na+-conductance increase. Receptors mediating the A- and A′-depolarizations have different pharmacological properties and may exist side by side on the same neurone. 4. Both the B- and C-responses are inhibitory. The B-response is a `slow' hyperpolarization due to an increase in K+-conductance, the C-response is a fast hyperpolarization associated with an increase in Cl--conductance. 5. The α-response to 5-HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at -75 mV; it is caused by a decrease in K+-conductance. The β-response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at -20/-30 mV. It results from a decrease in conductance to both Na+ and K+ ions. 6. The receptors involved in the 5-HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7-methyltryptamine blocks only the A-receptors, 5-methoxygramine only the B-receptors and neostigmine only the C-receptors. Curare blocks the A- and C-receptors and bufotenine, the A-, A′- and B-receptors. No specific antagonists have yet been found for the 5-HT responses caused by a conductance decrease. 7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper. PMID:4155767

Traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Inoue, Hirofumi; Hasegawa, Shunji; Kajimoto, Madoka; Matsushige, Takeshi; Ichiyama, Takashi

2014-10-01

Many studies have reported acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with viral infection at onset, but few studies have reported AESD without infection. We report the case of a 9-month-old boy who had a clinical course mimicking AESD after a traffic accident. The traffic accident caused a mild subdural hematoma without neurological abnormalities on admission. The boy became unconscious on the second day, and he was diagnosed with non-convulsive status epilepticus on the third day. Diffusion-weighted imaging showed reduced water diffusion in the subcortical white matter. On laboratory analysis interleukin (IL)-6 was elevated in the cerebrospinal fluid (CSF), but not in the serum. He had severe neurological sequelae with mental retardation, spastic tetraplegia, and epilepsy. We suggest that brain damage mimicking AESD was caused by the traffic accident and the prolonged seizure during infancy. © 2014 Japan Pediatric Society.

Signal Amplification by Reversible Exchange (SABRE): From Discovery to Diagnosis.

PubMed

Rayner, Peter J; Duckett, Simon B

2018-06-04

Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity because of its speed and simplicity. This Minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009 to the point in which 50 % 1 H polarization levels have been achieved in a di-deuterio-nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient 15 N hyperpolarization and the creation of hyperpolarized long-lived magnetic states are illustrated. To conclude, we describe how the recently reported SABRE-RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids, and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pulsed Magnetic Resonance to Signal-Enhance Metabolites within Seconds by utilizing para-Hydrogen.

PubMed

Korchak, Sergey; Yang, Shengjun; Mamone, Salvatore; Glöggler, Stefan

2018-05-01

Diseases such as Alzheimer's and cancer have been linked to metabolic dysfunctions, and further understanding of metabolic pathways raises hope to develop cures for such diseases. To broaden the knowledge of metabolisms in vitro and in vivo, methods are desirable for direct probing of metabolic function. Here, we are introducing a pulsed nuclear magnetic resonance (NMR) approach to generate hyperpolarized metabolites within seconds, which act as metabolism probes. Hyperpolarization represents a magnetic resonance technique to enhance signals by over 10 000-fold. We accomplished an efficient metabolite hyperpolarization by developing an isotopic labeling strategy for generating precursors containing a favorable nuclear spin system to add para -hydrogen and convert its two-spin longitudinal order into enhanced metabolite signals. The transfer is performed by an invented NMR experiment and 20 000-fold signal enhancements are achieved. Our technique provides a fast way of generating hyperpolarized metabolites by using para -hydrogen directly in a high magnetic field without the need for field cycling.

A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1-¹³C]-pyruvate.

PubMed

Walker, Christopher M; Lee, Jaehyuk; Ramirez, Marc S; Schellingerhout, Dawid; Millward, Steven; Bankson, James A

2013-01-01

In vivo real time spectroscopic imaging of hyperpolarized ¹³C labeled metabolites shows substantial promise for the assessment of physiological processes that were previously inaccessible. However, reliable and reproducible methods of measurement are necessary to maximize the effectiveness of imaging biomarkers that may one day guide personalized care for diseases such as cancer. Animal models of human disease serve as poor reference standards due to the complexity, heterogeneity, and transient nature of advancing disease. In this study, we describe the reproducible conversion of hyperpolarized [1-¹³C]-pyruvate to [1-¹³C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction can be controlled and tuned to mimic normal or pathologic conditions of varying degree. Variations observed in the use of this phantom compare favorably against within-group variations observed in recent animal studies. This novel phantom system provides crucial capabilities as a reference standard for the optimization, comparison, and certification of quantitative imaging strategies for hyperpolarized tracers.

Room-temperature in situ nuclear spin hyperpolarization from optically pumped nitrogen vacancy centres in diamond

DOE PAGES

King, Jonathan P.; Jeong, Keunhong; Vassiliou, Christophoros C.; ...

2015-12-07

Low detection sensitivity stemming from the weak polarization of nuclear spins is a primary limitation of magnetic resonance spectroscopy and imaging. Methods have been developed to enhance nuclear spin polarization but they typically require high magnetic fields, cryogenic temperatures or sample transfer between magnets. Here we report bulk, room-temperature hyperpolarization of 13C nuclear spins observed via high-field magnetic resonance. The technique harnesses the high optically induced spin polarization of diamond nitrogen vacancy centres at room temperature in combination with dynamic nuclear polarization. We observe bulk nuclear spin polarization of 6%, an enhancement of ~170,000 over thermal equilibrium. The signal ofmore » the hyperpolarized spins was detected in situ with a standard nuclear magnetic resonance probe without the need for sample shuttling or precise crystal orientation. In conclusion, hyperpolarization via optical pumping/dynamic nuclear polarization should function at arbitrary magnetic fields enabling orders of magnitude sensitivity enhancement for nuclear magnetic resonance of solids and liquids under ambient conditions.« less

JET (3He)-D scenarios relying on RF heating: survey of selected recent experiments

NASA Astrophysics Data System (ADS)

Van Eester, D.; Lerche, E.; Andrew, Y.; Biewer, T. M.; Casati, A.; Crombé, K.; de la Luna, E.; Ericsson, G.; Felton, R.; Giacomelli, L.; Giroud, C.; Hawkes, N.; Hellesen, C.; Hjalmarsson, A.; Joffrin, E.; Källne, J.; Kiptily, V.; Lomas, P.; Mantica, P.; Marinoni, A.; Mayoral, M.-L.; Ongena, J.; Puiatti, M.-E.; Santala, M.; Sharapov, S.; Valisa, M.; JET EFDA contributors

2009-04-01

Recent JET experiments have been devoted to the study of (3He)-D plasmas involving radio frequency (RF) heating. This paper starts by discussing the RF heating efficiency theoretically expected in such plasmas, covering both relevant aspects of wave and of particle dynamics. Then it gives a concise summary of the main conclusions drawn from recent experiments that were either focusing on studying RF heating physics aspects or that were adopting RF heating as a tool to study plasma behavior. Depending on the minority concentration chosen, different physical phenomena are observed. At very low concentration (X[3He] < 1%), energetic tails are formed which trigger MHD activity and result in loss of fast particles. Alfvén cascades were observed and gamma ray tomography indirectly shows the impact of sawtooth crashes on the fast particle orbits. Low concentration (X[3He] < 10%) favors minority heating while for X[3He] Gt 10% electron mode conversion damping becomes dominant. Evidence for the Fuchs et al standing wave effect (Fuchs et al 1995 Phys. Plasmas 2 1637-47) on the absorption is presented. RF induced deuterium tails were observed in mode conversion experiments with large X[3He] (≈18%). As tentative modeling shows, the formation of these tails can be explained as a consequence of wave power absorption by neutral beam particles that efficiently interact with the waves well away from the cold D cyclotron resonance position as a result of their substantial Doppler shift. As both ion and electron RF power deposition profiles in (3He)-D plasmas are fairly narrow—giving rise to localized heat sources—the RF heating method is an ideal tool for performing transport studies. Various of the experiments discussed here were done in plasmas with internal transport barriers (ITBs). ITBs are identified as regions with locally reduced diffusivity, where poloidal spinning up of the plasma is observed. The present know-how on the role of RF heating for impurity transport is also briefly summarized.

Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer.

PubMed

Chen, Hsin-Yu; Larson, Peder E Z; Gordon, Jeremy W; Bok, Robert A; Ferrone, Marcus; van Criekinge, Mark; Carvajal, Lucas; Cao, Peng; Pauly, John M; Kerr, Adam B; Park, Ilwoo; Slater, James B; Nelson, Sarah J; Munster, Pamela N; Aggarwal, Rahul; Kurhanewicz, John; Vigneron, Daniel B

2018-03-25

The purpose of this study was to develop a new 3D dynamic carbon-13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1- 13 C]pyruvate to [1- 13 C]lactate with whole gland coverage at high spatial and temporal resolution. A 3D dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized sterile GMP [1- 13 C]pyruvate. 3D dynamic 13 C CS-EPSI data were acquired starting 5 s after injection throughout the gland with a spatial resolution of 0.5 cm 3 , 18 time frames, 2-s temporal resolution, and 36 s total acquisition time. Through preclinical testing, the 3D CS-EPSI sequence developed in this project was shown to provide the desired spectral, temporal, and spatial 5D HP 13 C MR data. In human studies, the 3D dynamic HP CS-EPSI approach provided first-ever simultaneously volumetric and dynamic images of the LDH-catalyzed conversion of [1- 13 C]pyruvate to [1- 13 C]lactate in a biopsy-proven prostate cancer patient with full gland coverage. The results demonstrate the feasibility to characterize prostate cancer metabolism in animals, and now patients using this new 3D dynamic HP MR technique to measure k PL , the kinetic rate constant of [1- 13 C]pyruvate to [1- 13 C]lactate conversion. © 2018 International Society for Magnetic Resonance in Medicine.

Incorporation of Prior Knowledge of Signal Behavior Into the Reconstruction to Accelerate the Acquisition of Diffusion MRI Data.

PubMed

Abascal, Juan F P J; Desco, Manuel; Parra-Robles, Juan

2018-02-01

Diffusion MRI data are generally acquired using hyperpolarized gases during patient breath-hold, which yields a compromise between achievable image resolution, lung coverage, and number of -values. In this paper, we propose a novel method that accelerates the acquisition of diffusion MRI data by undersampling in both the spatial and -value dimensions and incorporating knowledge about signal decay into the reconstruction (SIDER). SIDER is compared with total variation (TV) reconstruction by assessing its effect on both the recovery of ventilation images and the estimated mean alveolar dimensions (MADs). Both methods are assessed by retrospectively undersampling diffusion data sets ( =8) of healthy volunteers and patients with Chronic Obstructive Pulmonary Disease (COPD) for acceleration factors between x2 and x10. TV led to large errors and artifacts for acceleration factors equal to or larger than x5. SIDER improved TV, with a lower solution error and MAD histograms closer to those obtained from fully sampled data for acceleration factors up to x10. SIDER preserved image quality at all acceleration factors, although images were slightly smoothed and some details were lost at x10. In conclusion, we developed and validated a novel compressed sensing method for lung MRI imaging and achieved high acceleration factors, which can be used to increase the amount of data acquired during breath-hold. This methodology is expected to improve the accuracy of estimated lung microstructure dimensions and provide more options in the study of lung diseases with MRI.

In vivo detection of cucurbit[6]uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor

PubMed Central

Hane, Francis T.; Li, Tao; Smylie, Peter; Pellizzari, Raiili M.; Plata, Jennifer A.; DeBoef, Brenton; Albert, Mitchell S.

2017-01-01

The Hyperpolarized gas Chemical Exchange Saturation Transfer (HyperCEST) Magnetic Resonance (MR) technique has the potential to increase the sensitivity of a hyperpolarized xenon-129 MRI contrast agent. Signal enhancement is accomplished by selectively depolarizing the xenon within a cage molecule which, upon exchange, reduces the signal in the dissolved phase pool. Herein we demonstrate the in vivo detection of the cucurbit[6]uril (CB6) contrast agent within the vasculature of a living rat. Our work may be used as a stepping stone towards using the HyperCEST technique as a molecular imaging modality. PMID:28106110

Gamma rays and the case for baryon symmetric big-bang cosmology

NASA Technical Reports Server (NTRS)

Stecker, F. W.

1977-01-01

The baryon symmetric big-bang cosmologies offer an explanation of the present photon-baryon ratio in the universe, the best present explanation of the diffuse gamma-ray background spectrum in the 1 to 200 MeV range, and a mechanism for galaxy formation. In the context of an open universe model, the value of omega which best fits the present gamma-ray data is omega equals approx. 0.1 which does not conflict with upper limits on Comptonization distortion of the 3K background radiation. In regard to He production, evidence is discussed that nucleosynthesis of He may have taken place after the galaxies were formed.

A comparison of quantitative methods for clinical imaging with hyperpolarized (13)C-pyruvate.

PubMed

Daniels, Charlie J; McLean, Mary A; Schulte, Rolf F; Robb, Fraser J; Gill, Andrew B; McGlashan, Nicholas; Graves, Martin J; Schwaiger, Markus; Lomas, David J; Brindle, Kevin M; Gallagher, Ferdia A

2016-04-01

Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized (13)C-labelled molecules, such as the conversion of [1-(13)C]pyruvate to [1-(13)C]lactate, to be dynamically and non-invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model-free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two-way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time-to-peak and the lactate-to-pyruvate area under the curve ratio were simple model-free approaches that accurately represented the full reaction, with the time-to-peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized (13)C data. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

Enhanced Oxygen Diffusion Within the Internal Oxidation Zone of Alloy 617 in Controlled Impurity Helium Environments from 1023 K to 1123 K (750 °C to 850 °C)

NASA Astrophysics Data System (ADS)

Gulsoy, Gokce; Was, Gary S.

2015-04-01

Alloy 617 was exposed to He-CO-CO2 environments with of either 9 or 1320 at temperatures from 1023 K to 1123 K (750 °C to 850 °C) to determine the oxygen diffusion coefficients within the internal oxidation zone of the alloy. The oxygen diffusion coefficients determined based on both intergranular and transgranular oxidation rates were several orders of magnitude greater than those reported in pure nickel and in nickel-based binary alloys, indicating that the rapid internal aluminum oxidation of Alloy 617 was primarily due to enhanced oxygen diffusion along the incoherent Al2O3-alloy interfaces. The range of activation energy values determined for oxygen diffusion associated with the intergranular aluminum oxidation was from 149.6 to 154.7 kJ/mol, and that associated with the transgranular aluminum oxidation was from 244.7 to 283.5 kJ/mol.

Vertical groundwater flow estimated from the bomb pulse of 36Cl and tritiogenic 3He

NASA Astrophysics Data System (ADS)

Mahara, Y.; Ohta, T.

2011-12-01

The boring well was approximately excavated to 400 m depth from the ground surface on the tableland in the Central Shimokita Peninsula, Japan. Collecting pore-water, some fresh boring cores were sampled on the site during the excavation of borehole. Samples of groundwater were collected by using the sampling device with the water inflating packer system to protect various contaminations, after excavating the borehole. The atmospheric maximum concentration in bomb pulse in the northern hemisphere was reported to observe in 1955 for 36Cl and in 1963 for 3H, respectively. Since the half-life of 36Cl is much longer than 3H, the decay loss of 36Cl was negligible small for a short time until sampling groundwater in 2001 and 2003. On the other hand, the half-life of 3H is very short compared with that of 36Cl. Most of 3H was converted into the tritiogenic 3He in groundwater for the past 38 years after rainwater infiltrating toward the groundwater table. Profiles of dissolved 4He concentration, tritiogenic 3He and 36Cl/Cl ratio were observed in groundwater of the borehole. The total dissolved 4He concentration ranged from 5.8×10-8 at the ground surface to 7.5×10-8 ccSTP/g at the depth of 200 m below the ground surface and it was almost equilibrated with the atmospheric 4He in pore-water (Fig. 1). The bomb pulses of tritiogenic 3He and 36Cl were left from the depth of 101 m below the ground surface to the depth of 132 m, respectively (Figs. 2 and 3). There was a slight difference in the location between the bomb pulse of 36Cl and that of tritiogenic 3He. The downward flow velocity of groundwater were simply estimated to be 2.8 m/y from the marked position of bomb pulse in the profile of 36Cl/Cl ratio and to be 2.7 m/y from the position of the bomb pulse peak of tritiogenic 3He, separately. These two rough estimations were good agreed with each other. The estimation suggests that the vertical flow of groundwater on the tableland is approximated with the downward piston flow with small diffusion without turbulence.

Fumarole/plume and diffuse CO2 emission from Sierra Negra caldera, Galapagos archipelago

NASA Astrophysics Data System (ADS)

Padrón, Eleazar; Hernández, Pedro A.; Pérez, Nemesio M.; Toulkeridis, Theofilos; Melián, Gladys; Barrancos, José; Virgili, Giorgio; Sumino, Hirochika; Notsu, Kenji

2012-08-01

Measurements of visible and diffuse gas emission were conducted in 2006 at the summit of Sierra Negra volcano, Galapagos, with the aim to better characterize degassing after the 2005 eruption. A total SO2 emission of 11 ± 2 t day-1 was derived from miniature differential optical absorption spectrometer (mini-DOAS) ground-based measurements of the plume emanating from the Mini Azufral fumarolic area, the most important site of visible degassing at Sierra Negra volcano. Using a portable multigas system, the H2S/SO2, CO2/SO2, and H2O/SO2 molar ratios in the Mina Azufral plume emissions were found to be 0.41, 52.2, and 867.9, respectively. The corresponding H2O, CO2, and H2S emission rates were 562, 394, and 3 t day-1, respectively. The total output of diffuse CO2 emissions from the summit of Sierra Negra volcano was 990 ± 85 t day-1, with 605 t day-1 being released by a deep source. The diffuse-to-plume CO2 emission ratio was about 1.5. Mina Azufral fumaroles released gasses containing 73.6 mol% of H2O; the main noncondensable components amounted to 97.4 mol% CO2, 1.5 mol% SO2, 0.6 mol% H2S, and 0.35 mol% N2. The higher H2S/SO2 ratio values found in 2006 as compared to those reported before the 2005 eruption reveal a significant hydrothermal contribution to the fumarolic emissions. 3He/4He ratios measured at Mina Azufral fumarolic discharges showed values of 17.88 ± 0.25 R A , indicating a mid-ocean ridge basalts (MORB) and a Galapagos plume contribution of 53 and 47 %, respectively.

A case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion.

PubMed

Hazama, Kyoko; Shiihara, Takashi; Tsukagoshi, Hiroyuki; Hasegawa, Shunji; Dowa, Yuri; Watanabe, Mio

2017-10-01

Mumps is a common childhood viral disease characterized by fever and swelling of the parotid gland. The prognosis is generally good, although some complications, such as encephalitis (0.1%), exist. Acute encephalopathy with biphasic seizures and late reduced diffusion is the most common type of acute encephalopathy. However, this type of encephalopathy has not been reported in association with mumps infection. A previously healthy 3-year-old Japanese boy had a brief convulsion after fever for 3days, and then had conscious disturbance and parotitis. After several days, he had a second brief convulsion and was admitted. Increased serum amylase levels and presence of anti-mumps immunoglobulin M antibody confirmed mumps parotitis. The patient had another brief seizure later the day of admission. He did not have status or cluster seizures, although the biphasic nature of his seizures, conscious disturbance between the seizures, no pleocytosis in cerebrospinal fluid, and brain magnetic resonance images were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion. In Japan, the mumps vaccine is not administered as a part of routine immunizations. It thus has low coverage (30-40%), and as a result, mumps infections are still common. However, this is the first case of mumps-related acute encephalopathy with biphasic seizures and late reduced diffusion. This case may be representative of only a minority of patients with mumps-associated central nervous system involvement. Nevertheless, this diagnostic possibility may be considered. In order to prevent mumps-related complications, routine mumps vaccination might be warranted. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Rapid assessment of pulmonary gas transport with hyperpolarized 129Xe MRI using a 3D radial double golden-means acquisition with variable flip angles.

PubMed

Ruppert, Kai; Amzajerdian, Faraz; Hamedani, Hooman; Xin, Yi; Loza, Luis; Achekzai, Tahmina; Duncan, Ian F; Profka, Harrilla; Siddiqui, Sarmad; Pourfathi, Mehrdad; Cereda, Maurizio F; Kadlecek, Stephen; Rizi, Rahim R

2018-04-22

To demonstrate the feasibility of using a 3D radial double golden-means acquisition with variable flip angles to monitor pulmonary gas transport in a single breath hold with hyperpolarized xenon-129 MRI. Hyperpolarized xenon-129 MRI scans with interleaved gas-phase and dissolved-phase excitations were performed using a 3D radial double golden-means acquisition in mechanically ventilated rabbits. The flip angle was either held fixed at 15 ° or 5 °, or it was varied linearly in ascending or descending order between 5 ° and 15 ° over a sampling interval of 1000 spokes. Dissolved-phase and gas-phase images were reconstructed at high resolution (32 × 32 × 32 matrix size) using all 1000 spokes, or at low resolution (22 × 22 × 22 matrix size) using 400 spokes at a time in a sliding-window fashion. Based on these sliding-window images, relative change maps were obtained using the highest mean flip angle as the reference, and aggregated pixel-based changes were tracked. Although the signal intensities in the dissolve-phase maps were mostly constant in the fixed flip-angle acquisitions, they varied significantly as a function of average flip angle in the variable flip-angle acquisitions. The latter trend reflects the underlying changes in observed dissolve-phase magnetization distribution due to pulmonary gas uptake and transport. 3D radial double golden-means acquisitions with variable flip angles provide a robust means for rapidly assessing lung function during a single breath hold, thereby constituting a particularly valuable tool for imaging uncooperative or pediatric patient populations. © 2018 International Society for Magnetic Resonance in Medicine.

Hyperpolarized 13C NMR lifetimes in the liquid-state: relating structures and T1 relaxation times

NASA Astrophysics Data System (ADS)

Parish, Christopher; Niedbalski, Peter; Hashami, Zohreh; Fidelino, Leila; Kovacs, Zoltan; Lumata, Lloyd

Among the various attempts to solve the insensitivity problem in nuclear magnetic resonance (NMR), the physics-based technique dissolution dynamic nuclear polarization (DNP) is probably the most successful method of hyperpolarization or amplifying NMR signals. Using this technique, liquid-state NMR signal enhancements of several thousand-fold are expected for low-gamma nuclei such as carbon-13. The lifetimes of these hyperpolarized 13C NMR signals are directly related to their 13C spin-lattice relaxation times T1. Depending upon the 13C isotopic location, the lifetimes of hyperpolarized 13C compounds can range from a few seconds to minutes. In this study, we have investigated the hyperpolarized 13C NMR lifetimes of several 13C compounds with various chemical structures from glucose, acetate, citric acid, naphthalene to tetramethylallene and their deuterated analogs at 9.4 T and 25 deg C. Our results show that the 13C T1s of these compounds can range from a few seconds to more than 60 s at this field. Correlations between the chemical structures and T1 relaxation times will be discussed and corresponding implications of these results on 13C DNP experiments will be revealed. US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture.

PubMed

Nin, Verónica; Hernández, Julio A; Chifflet, Silvia

2009-12-01

In previous works we showed that the depolarization of the plasma membrane potential (PMP) determines a reorganization of the cytoskeleton of diverse epithelia in culture, consisting mainly of a reallocation of peripheral actin toward the cell center, ultimately provoking intercellular disruption. In view of this evidence, we explored in this study the possible effects of membrane potential hyperpolarization on the cytoskeletal organization and adherens junction (AJ) morphology and the stability of confluent bovine corneal endothelial cells in culture. For this purpose, hyperpolarization was achieved by substitution of extracellular sodium by nondiffusible cations or via the incorporation of valinomycin to the control solution. Actin compactness at the cell periphery was assessed by quantitative analysis of fluorescence microscopy images. The stability of the AJ was challenged by calcium deprivation or temperature decrease. Our results showed that plasma membrane hyperpolarization provokes a compaction of AJ-associated actin filaments toward the plasma membrane and an increase in the stability of the AJs. We also observed that the hyperpolarizing procedures determined similar modifications in the actin cytoskeleton of endothelial cells in whole bovine corneas. Together with our previous work, the results of this study contribute to the idea that modifications in the PMP of nonexcitable cells participate in cellular adaptive responses involving reorganization of cytoskeletal components. (c) 2009 Wiley-Liss, Inc.

Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping.

PubMed

Juul, Troels; Palm, Fredrik; Nielsen, Per Mose; Bertelsen, Lotte Bonde; Laustsen, Christoffer

2017-08-01

It has been demonstrated that hyperpolarized 13 C MR is a useful tool to study cultured cells. However, cells in culture can alter phenotype, which raises concerns regarding the in vivo significance of such findings. Here we investigate if metabolic phenotyping using hyperpolarized 13 C MR is suitable for cells isolated from kidney tissue, without prior cell culture. Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system. Isolation of tubular cells from less than 2 g of kidney tissue generally resulted in more than 10 million live tubular cells. This amount of cells was enough to yield robust signals from the conversion of 13 C-pyruvate to lactate, bicarbonate and alanine, demonstrating that metabolic flux by means of both anaerobic and aerobic pathways can be quantified using this technique. Ex vivo metabolic phenotyping using hyperpolarized 13 C MR in a preclinical system is a useful technique to study energy metabolism in freshly isolated renal tubular cells. This technique has the potential to advance our understanding of both normal cell physiology as well as pathological processes contributing to kidney disease. Magn Reson Med 78:457-461, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

An optimized microfabricated platform for the optical generation and detection of hyperpolarized 129Xe

PubMed Central

Kennedy, Daniel J.; Seltzer, Scott J.; Jiménez-Martínez, Ricardo; Ring, Hattie L.; Malecek, Nicolas S.; Knappe, Svenja; Donley, Elizabeth A.; Kitching, John; Bajaj, Vikram S.; Pines, Alexander

2017-01-01

Low thermal-equilibrium nuclear spin polarizations and the need for sophisticated instrumentation render conventional nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) incompatible with small-scale microfluidic devices. Hyperpolarized 129Xe gas has found use in the study of many materials but has required very large and expensive instrumentation. Recently a microfabricated device with modest instrumentation demonstrated all-optical hyperpolarization and detection of 129Xe gas. This device was limited by 129Xe polarizations less than 1%, 129Xe NMR signals smaller than 20 nT, and transport of hyperpolarized 129Xe over millimeter lengths. Higher polarizations, versatile detection schemes, and flow of 129Xe over larger distances are desirable for wider applications. Here we demonstrate an ultra-sensitive microfabricated platform that achieves 129Xe polarizations reaching 7%, NMR signals exceeding 1 μT, lifetimes up to 6 s, and simultaneous two-mode detection, consisting of a high-sensitivity in situ channel with signal-to-noise of 105 and a lower-sensitivity ex situ detection channel which may be useful in a wider variety of conditions. 129Xe is hyperpolarized and detected in locations more than 1 cm apart. Our versatile device is an optimal platform for microfluidic magnetic resonance in particular, but equally attractive for wider nuclear spin applications benefitting from ultra-sensitive detection, long coherences, and simple instrumentation. PMID:28266629

Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast

PubMed Central

Lingwood, Mark D.; Siaw, Ting Ann; Sailasuta, Napapon; Ross, Brian D.; Bhattacharya, Pratip; Han, Songi

2016-01-01

We describe and demonstrate a system to generate hyperpolarized water in the 0.35 T fringe field of a clinical 1.5 T whole-body magnetic resonance imaging (MRI) magnet. Once generated, the hyperpolarized water is quickly and continuously transferred from the 0.35 T fringe to the 1.5 T center field of the same magnet for image acquisition using standard MRI equipment. The hyperpolarization is based on Overhauser dynamic nuclear polarization (DNP), which effectively and quickly transfers the higher spin polarization of free radicals to nuclear spins at ambient temperatures. We visualize the dispersion of hyperpolarized water as it flows through water-saturated systems by utilizing an observed −15 fold DNP signal enhancement with respect to the unenhanced 1H MRI signal of water at 1.5 T. The experimental DNP apparatus presented here is readily portable and can be brought to and used with any conventional unshielded MRI system. A new method of immobilizing radicals to gel beads via polyelectrolyte linker arms is described, which led to superior flow Overhauser DNP performance compared to previously presented gels. We discuss the general applicability of Overhauser DNP hyperpolarization of water and aqueous solutions in the fringe field of commercially available magnets with central fields up to 4.7 Tesla. PMID:20541445

An optimized microfabricated platform for the optical generation and detection of hyperpolarized 129Xe

DOE PAGES

Kennedy, Daniel J.; Seltzer, Scott J.; Jiménez-Martínez, Ricardo; ...

2017-03-07

Low thermal-equilibrium nuclear spin polarizations and the need for sophisticated instrumentation render conventional nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) incompatible with small-scale microfluidic devices. Hyperpolarized 129Xe gas has found use in the study of many materials but has required very large and expensive instrumentation. Recently a microfabricated device with modest instrumentation demonstrated all-optical hyperpolarization and detection of 129Xe gas. This device was limited by 129Xe polarizations less than 1%, 129Xe NMR signals smaller than 20 nT, and transport of hyperpolarized 129Xe over millimeter lengths. Higher polarizations, versatile detection schemes, and flow of 129Xe over larger distances are desirablemore » for wider applications. Here we demonstrate an ultra-sensitive microfabricated platform that achieves 129Xe polarizations reaching 7%, NMR signals exceeding 1 μT, lifetimes up to 6 s, and simultaneous two-mode detection, consisting of a high-sensitivity in situ channel with signal-to-noise of 10 5 and a lower-sensitivity ex situ detection channel which may be useful in a wider variety of conditions. 129Xe is hyperpolarized and detected in locations more than 1 cm apart. Our versatile device is an optimal platform for microfluidic magnetic resonance in particular, but equally attractive for wider nuclear spin applications benefitting from ultra-sensitive detection, long coherences, and simple instrumentation.« less

Rotational relaxation of fluoromethane molecules in low-temperature collisions with buffer-gas helium

NASA Astrophysics Data System (ADS)

Li, Xingjia; Xu, Liang; Yin, Yanning; Xu, Supeng; Xia, Yong; Yin, Jianping

2016-06-01

We propose a method to study the rotational relaxation of polar molecules [here taking fluoromethane (CH3F ) as an example] in collisions with 3.5 K buffer-gas helium (He) atoms by using an electrostatic guiding technique. The dependence of the guiding signal of CH3F on the injected He flux and the dependence of the guiding efficiency of CH3F on its rotational temperature are investigated both theoretically and experimentally. By comparing the experimental and simulated results, we find that the translational and rotational temperatures of the buffer-gas cooled CH3F molecules can reach to about 5.48 and 0.60 K, respectively, and the ratio between the translational and average rotational collisional cross sections of CH3F -He is γ =σt/σr=36.49 ±6.15 . In addition, the slowing, cooling, and boosting effects of the molecular beam with different injected He fluxes are also observed and their forming conditions are investigated in some detail. Our study shows that our proposed method can not only be used to measure the translational and rotational temperatures of the buffer-gas cooled molecules, but also to measure the ratio of the translational collisional cross section to the average rotational collisional cross section, and even to measure the average rotational collisional cross section when the translational collisional cross section is measured by fitting the lifetime of molecule signal to get a numerical solution from the diffusion equation of buffer-gas He atoms in the cell.

Characteristics of mucosally projecting myenteric neurones in the guinea-pig proximal colon

PubMed Central

Neunlist, Michel; Dobreva, Gisela; Schemann, Michael

1999-01-01

Using retrograde tracing with 1,1′-didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) in combination with electrophysiological and immunohistochemical techniques we determined the properties of the putative intrinsic primary afferent myenteric neurones with mucosal projections in the guinea-pig proximal colon. Eighty-four out of eighty-five DiI-labelled myenteric neurones were AH neurones with a late after-hyperpolarization. Thirty-three per cent of them exhibited atropine- and tetrodotoxin-resistant spontaneously occurring hyperpolarizing potentials (SHPs) during which the membrane resistance and excitability decreased. DiI-labelled AH neurones had multipolar Dogiel type II morphology, primarily of the dendritic type. Sixty-one per cent of the neurones were immunoreactive for choline acetyltransferase (ChAT) and calbindin (Calb) and 23% were ChAT positive but Calb negative. DiI-labelled neurones did not receive fast excitatory postsynaptic potentials but 94% (34/36) received slow excitatory postsynaptic potentials (sEPSPs). The neurokinin-3 (NK-3) agonist (MePhe7)-NKB but not the NK-1 agonist [(SAR9,Met(O2)11]-SP mimicked this response. The NK-3 receptor antagonist SR 142801 (1 μm) significantly decreased the amplitude and duration of the sEPSPs; the NK-1 receptor antagonist CP-99,994 (1 μm) was ineffective. Atropine (0.5 μm) increased the duration but not the amplitude of the sEPSPs. Microejection of 100 mM sodium butyrate onto the neurones induced in 90% of the DiI-labelled neurones a transient depolarization associated with an increased excitability. In neurones with SHPs sodium butyrate evoked, additionally, a late onset hyperpolarization. Perfusion of 0.1-10 mM sodium butyrate induced a dose-dependent increase in neuronal excitability. Sodium butyrate was ineffective when applied directly onto the mucosa. Mucosally projecting myenteric neurones of the colon are multipolar AH neurones with NK-3-mediated slow EPSPs and somal butyrate sensitivity. PMID:10332100

Observations of Solar Energetic Particles from 3He-rich Events over a Wide Range of Heliographic Longitude

NASA Astrophysics Data System (ADS)

Wiedenbeck, M. E.; Mason, G. M.; Cohen, C. M. S.; Nitta, N. V.; Gómez-Herrero, R.; Haggerty, D. K.

2013-01-01

A prevailing model for the origin of 3He-rich solar energetic particle (SEP) events attributes particle acceleration to processes associated with the reconnection between closed magnetic field lines in an active region and neighboring open field lines. The open field from the small reconnection volume then provides a path along which accelerated particles escape into a relatively narrow range of angles in the heliosphere. The narrow width (standard deviation <20°) of the distribution of X-ray flare longitudes found to be associated with 3He-rich SEP events detected at a single spacecraft at 1 AU supports this model. We report multispacecraft observations of individual 3He-rich SEP events that occurred during the solar minimum time period from 2007 January through 2011 January using instrumentation carried by the two Solar Terrestrial Relations Observatory spacecraft and the Advanced Composition Explorer. We find that detections of 3He-rich events at pairs of spacecraft are not uncommon, even when their longitudinal separation is >60°. We present the observations of the 3He-rich event of 2010 February 7, which was detected at all three spacecraft when they spanned 136° in heliographic longitude. Measured fluences of 3He in this event were found to have a strong dependence on longitude which is well fit by a Gaussian with standard deviation ~48° centered at the longitude that is connected to the source region by a nominal Parker spiral magnetic field. We discuss several mechanisms for distributing flare-accelerated particles over a wide range of heliographic longitudes including interplanetary diffusion perpendicular to the magnetic field, spreading of a compact cluster of open field lines between the active region and the source surface where the field becomes radial and opens out into the heliosphere, and distortion of the interplanetary field by a preceding coronal mass ejection. Statistical studies of additional 3He-rich events detected at multiple spacecraft will be needed to establish the relative importance of the various mechanisms.

Magma Dynamics at Mid-Ocean Ridges by Noble Gas Kinetic Fractionation: Assessment of Magmatic Ascent Rates and Mantle Composition

NASA Astrophysics Data System (ADS)

Paonita, A.; Martelli, M.

2007-12-01

Topical scientific literature on magma degassing at mid-ocean ridges more and more focuses on exsolution processes occurring under conditions that are far from thermodynamic equilibrium between bubbles and silicate melt. Indeed, the dynamics of magma ascent and decompression can be faster than that of CO2 diffusion into bubbles, in which case the diffusivity ratios among volatiles are the main control of the composition of the exsolving gas phase. We have developed a model of bubble growth in silicate melts that calculates the extent of both CO2 supersaturation and kinetic fractionation among noble gases in vesicles in relation to the decompressive rate of basaltic melts. The model predicts that, due to comparable Ar and CO2 diffusivity, magma degassing at low pressure fractionates both He/Ar and He/CO2 ratios by a similar extent, while the slower CO2 diffusion at high pressure causes early kinetic effects on Ar/CO2 ratio and dramatically changes the degassing paths. By using this tool, we have reviewed the global He-Ar-CO2 dataset of fluid inclusions in mid-ocean-ridge glasses. We display that non-equilibrium fractionations among He, Ar and CO2, driven by their different diffusivities in silicate melts, are common in most of the natural conditions of magma decompression and their signature strongly depends on pressure of degassing. The different geochemical signatures among suites of data coming from different ridge segments mainly depend on the depth of the magma chamber where the melt was stored. Moreover, variations inside a single suite emerge due to the interplay between variable ascent speed of magma and cooling rate of the emplaced lava. As a result, two data groups coming from the Pito Seamount suite (Easter Microplate East ridge), showing different degree of CO2 supersaturation and He/Ar fractionation, provide ascent rates which differ by ten folds or even more. The large variations in both the He/CO2 and Ar/CO2 ratios at almost constant He/Ar, displayed in products coming from the Mid-Atlantic Ridge 24°N segment and the Rodriguez Triple Junction, require magma storage and degassing processes occurring at high-pressure conditions. In contrast, the simultaneous increase in both He/CO2 and He/Ar of the East Pacific Rise and South-East Indian Ridge data sets suggests the dominance of low-pressure fractionation, implying that the shallow magma chambers are at a lower depth than those of the Mid-Atlantic Ridge 24°N and Rodriguez Triple Junction. Our conclusions support the presence of a relationship between spreading rate and depth of high-temperature zones below ridges, and are consistent with the depth of magma chambers as suggested from seismic studies. Finally, the non-equilibrium degassing model provides striking constraints on the compositions of noble gases and carbon in mantle-derived magmas. Our results dispense in fact with the supposed need for He-Ar-CO2 heterogeneities in the upper mantle, because the degassing of a single, popping-rock-like primary magma is able to explain all the available data.

Scaled experiments for improving diagnosis of pathological lower-airway obstruction

NASA Astrophysics Data System (ADS)

Liu, Chang; Kiger, Ken; Hariprasad, Daniel; Sul, Bora; Wallqvist, Anders; Reifman, Jaques

2017-11-01

Many lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by obstructed airflow, particularly, in the lower airway branches in the lung. Existing diagnostic tools cannot detect some diseases due to a lack of instrumentation capable of resolving the flow in the lower airways. Recent developments in MRI techniques using hyperpolarized 3He now permit measurement of velocity profiles within the trachea. Motivated by these advances, we aim to provide a better understanding of the connection between lower-airway obstruction and velocity profiles within the trachea. Specifically, we asked whether the flow deficits created by lower-airway obstructions could be detected in the trachea to permit diagnosis of the pathology. To test this idea, we used refractive index-matched materials to construct a scaled, patient-specific, transparent lung model, and coupled it to 5 independently controlled piston pumps that could generate arbitrary flow histories (healthy or diseased) for the 5 different lung lobes. Results obtained by stereo PIV within various regions of the airway network will be presented documenting the system performance and examining the detectability of under-performing lobes within the tracheal flow profile. This work supported by the Henry M. Jackson Foundation under award #3270.

Spin-driven structural effects in alkali doped (4)He clusters from quantum calculations.

PubMed

Bovino, S; Coccia, E; Bodo, E; Lopez-Durán, D; Gianturco, F A

2009-06-14

In this paper, we carry out variational Monte Carlo and diffusion Monte Carlo (DMC) calculations for Li(2)((1)Sigma(g) (+))((4)He)(N) and Li(2)((3)Sigma(u) (+))((4)He)(N) with N up to 30 and discuss in detail the results of our computations. After a comparison between our DMC energies with the "exact" discrete variable representation values for the species with one (4)He, in order to test the quality of our computations at 0 K, we analyze the structural features of the whole range of doped clusters. We find that both species reside on the droplet surface, but that their orientation is spin driven, i.e., the singlet molecule is perpendicular and the triplet one is parallel to the droplet's surface. We have also computed quantum vibrational relaxation rates for both dimers in collision with a single (4)He and we find them to differ by orders of magnitude at the estimated surface temperature. Our results therefore confirm the findings from a great number of experimental data present in the current literature and provide one of the first attempts at giving an accurate, fully quantum picture for the nanoscopic properties of alkali dimers in (4)He clusters.

Diffuse volcanic emissions of carbon dioxide from Vulcano Island, Italy.

PubMed

Baubron, J C; Allard, P; Toutain, J P

1990-03-01

RECENT investigations on Mount Etna (Sicily)(1-3) have revealed that volcanoes may release abundant carbon dioxide not only from their active craters, but also from their flanks, as diffuse soil emanations. Here we present analyses of soil gases and air in water wells on Vulcano Island which provide further evidence of such lateral degassing. Nearly pure carbon dioxide, enriched in helium and radon, escapes from the slopes of the Fossa active cone, adding a total output of 30 tonnes per day to the fumarolic crater discharge ( 180 tonnes CO(2) per day). This emanation has similar He/CO(2) and (13)C/(12)C ratios to those of the crater fumaroles (300%ndash;500 degrees C) and therefore a similar volcanic origin. Gases rich in carbon dioxide also escape at sea level along the isthmus between the Fossa and Vulcanello volcanic cones, but their depletion in both He and (13)C suggests a distinct source. Diffuse volcanic gas emanations, once their genetic link with central fumarole degassing has been demonstrated, can be used for continuous volcano monitoring, at safe distances from active craters. Such monitoring has been initiated at Vulcano, where soil and well emanations of nearly pure CO(2) themselves represent a threat to the local population.

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging

NASA Technical Reports Server (NTRS)

Ramirez, M. P.; Sigaloff, K. C.; Kubatina, L. V.; Donahue, M. A.; Venkatesh, A. K.; Albert, M. S.; ALbert, M. S. (Principal Investigator)

2000-01-01

The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments. Copyright 2000 John Wiley & Sons, Ltd.

Interlinked Test Results for Fusion Fuel Processing and Blanket Tritium Recovery Systems Using Cryogenic Molecular Sieve Bed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamanishi, Toshihiko; Hayashi, Takumi; Kawamura, Yoshinori

2005-07-15

A simulated fuel processing (cryogenic distillation columns and a palladium diffuser) and CMSB (cryogenic molecular sieve bed) systems were linked together, and were operated. The validity of the CMSB was discussed through this experiment as an integrated system for the recovery of blanket tritium. A gas stream of hydrogen isotopes and He was supplied to the CMSB as the He sweep gas in blanket of a fusion reactor. After the breakthrough of tritium was observed, regeneration of the CMSB was carried out by evacuating and heating. The hydrogen isotopes were finally recovered by the diffuser. At first, only He gasmore » was sent by the evacuating. The hydrogen isotopes gas was then rapidly released by the heating. The system worked well against the above drastic change of conditions. The amount of hydrogen isotopes gas finally recovered by the diffuser was in good agreement with that adsorbed by the CMSB. The dynamic behaviors (breakthrough and regeneration) of the system were explained well by a set of basic codes.« less

Geochemistry and fluxes of volatiles in the Magadi and Natron thermal springs, East African Rift

NASA Astrophysics Data System (ADS)

Lee, H.; Fischer, T. P.; Muirhead, J.; Ebinger, C. J.; Kattenhorn, S. A.; Sharp, Z. D.; Sano, Y.; Takahata, N.

2016-12-01

The Magadi and Natron basin (MNB) is in the earliest stages of continental rifting (<10 Ma) in the East African Rift, and is bounded by numerous normal faults releasing a significant amount of CO2 (4.05 Mt/yr). Although many thermal springs have been observed along fault zones, sources and fluxes of volatiles from these fluids are poorly known. This study reports geochemistry and fluxes of dissolved gases in thermal springs of the MNB (T = 36.8 - 83.5°C and pH = 8.5 - 10.3), including major gas chemistry, d13C-CO2, d15N-N2, and 3He/4He ratios. N2 (< 94.7 vol%) is the most abundant gas, with minor air contamination (mean value of O2 = 1.79 vol%). The majority of CO2 (mean = 11.8 vol%) is dissolved in alkaline waters. Abundant CH4 concentrations (19.3 and 25.1 vol%) are observed only in high temperature (82.3 - 83.5°C) samples. Mean values of Ar and He are 1.75 and 0.59 vol%, respectively. d13C-CO2 (-5.68 to 1.62‰) and CO2/3He (7.24 x 108 - 1.81 x 1011) values show that CO2 originates from both mantle and limestone. d15N-N2 (-1.46 to 0.35‰) and N2/3He (3.92 x 106 - 1.33 x 109) values indicate that the major source of N2 is atmospheric, with a minor input of mantle N2 (fmantle < 22%), except for an anomalous biogenic sample (d15N-N2 = 5.93‰). 3He/4He ratios (0.64 - 4.00 Ra) suggest contributions of radiogenic 4He derived from a crustal source. 4He flux rates (3.64 x 1011 - 3.34 x 1014 atoms/m2 sec) calculated using spring flow rates are much greater than reported mean of continental flux values (4.18x1010 atoms/m2 sec), implying that magma intrusions or widespread normal faulting may help to mobilize crustal 4He in the study area. Total flux values (mol/yr) of CO2, N2, 3He, and 4He are 7.91 x 106, 1.77 x 107, 8.18, and 9.33 x 104, respectively. In particular, the total CO2 flux of springs is 0.01% of the total diffuse CO2 flux reported in the region. Our results reveal an interaction between mantle-derived volatiles and continental crust during early stage continental rifting in the MNB, with their upward rise facilitated by dilatational fault systems.

Secondary Fe- and Mn-Oxides Associated with Faults Near Moab, Utah: Records of Past Fluid Flow

NASA Astrophysics Data System (ADS)

Garcia, V. H.; Reiners, P. W.

2015-12-01

Secondary Fe- and Mn-oxides are locally common near faults and fractures, and as cements within sandstones of the Colorado Plateau, and provide evidence of past fluid-flow. Here we describe textural, mineralogic, and geochronologic observations from fault-zone Fe- and Mn-oxide mineralization in Flat Iron Mesa, near Moab, Utah. Several hypotheses have been proposed for their origin, including reactions associated with the mixing of deep reduced and near-surface oxygenated waters. We integrate field observations, detailed SEM and petrographic observations, geochemical models, (U-Th)/He and Ar/Ar dating, and other data to develop interpretations of the formation of these deposits. SEM imaging shows that sandstone matrix cement adjacent to the faults follows two precipitation sequences: Fe-oxide followed by barite and Fe-oxide followed by Mn-oxide. Dense oxide layers also accumulated in cm-scale fractures near faults, and show the following precipitation sequence: Fe-oxide, barite, Ba rich Mn-oxide, and pure Mn-oxide. The latter sequence is observed at larger scale across faults in one site in Flat Iron Mesa. Our new He dates for Mn-oxides are 1.7-2.9 Ma while Fe-oxide dates are 2.7-3.0 Ma. If these dates represent formation ages, they are consistent with the interpreted precipitation sequence but would require protracted mineralization over Ma-timescales. Alternatively, they may represent varying degrees of He retentivity in earlier formed deposits. Previous Ar/Ar dates have been interpreted as a 20-25 Ma formation age. Ongoing Ar/Ar and He diffusion studies will resolve this discordance. Assuming the previous Ar dates do not reflect contamination by detrital K-bearing phases and do reflect oxide formation, potential interpretations for the younger He ages include recent U-Th addition, recrystallization, later oxide growth, or large diffusive He loss at low temperatures.

NMR/MRI with hyperpolarized gas and high Tc SQUID

DOEpatents

Schlenga, Klaus; de Souza, Ricardo E.; Wong-Foy, Annjoe; Clarke, John; Pines, Alexander

2000-01-01

A method and apparatus for the detection of nuclear magnetic resonance (NMR) signals and production of magnetic resonance imaging (MRI) from samples combines the use of hyperpolarized inert gases to enhance the NMR signals from target nuclei in a sample and a high critical temperature (Tc) superconducting quantum interference device (SQUID) to detect the NMR signals. The system operates in static magnetic fields of 3 mT or less (down to 0.1 mT), and at temperatures from liquid nitrogen (77K) to room temperature. Sample size is limited only by the size of the magnetic field coils and not by the detector. The detector is a high Tc SQUID magnetometer designed so that the SQUID detector can be very close to the sample, which can be at room temperature.

Direct modulation of tracheal Cl--channel activity by 5,6- and 11,12-EET.

PubMed

Salvail, D; Dumoulin, M; Rousseau, E

1998-09-01

Using microelectrode potential measurements, we tested the involvement of Cl- conductances in the hyperpolarization induced by 5,6- and 11,12-epoxyeicosatrienoic acid (EET) in airway smooth muscle (ASM) cells. 5,6-EET and 11,12-EET (0.75 microM) caused -5.4 +/- 1.1- and -3.34 +/- 0.95-mV hyperpolarizations, respectively, of rabbit tracheal cells (from a resting membrane potential of -53.25 +/- 0.44 mV), with significant residual repolarizations remaining after the Ca2+-activated K+ channels had been blocked by 10 nM iberiotoxin. In bilayer reconstitution experiments, we demonstrated that the EETs directly inhibit a Ca2+-insensitive Cl- channel from bovine ASM; 1 microM 5,6-EET and 1.5 microM 11,12-EET lowered the unitary current amplitude by 40 (n = 6 experiments) and 44.7% (n = 4 experiments), respectively. Concentration-dependent decreases in channel open probability were observed, with estimated IC50 values of 0.26 microM for 5,6- and 1.15 microM for 11,12-EET. Furthermore, pharmacomechanical tension measurements showed that both regioisomers induced significant bronchorelaxations in epithelium-denuded ASM strips. These results suggest that 5,6- and 11,12-EET can act in ASM as epithelium-derived hyperpolarizing factors.

COMPARISON OF NUMERICAL SCHEMES FOR SOLVING A SPHERICAL PARTICLE DIFFUSION EQUATION

EPA Science Inventory

A new robust iterative numerical scheme was developed for a nonlinear diffusive model that described sorption dynamics in spherical particle suspensions. he numerical scheme had been applied to finite difference and finite element models that showed rapid convergence and stabilit...

An ether -à-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts

PubMed Central

Bijlenga, Philippe; Occhiodoro, Teresa; Liu, Jian-Hui; Bader, Charles R; Bernheim, Laurent; Fischer-Lougheed, Jacqueline

1998-01-01

Two early signs of human myoblast commitment to fusion are membrane potential hyperpolarization and concomitant expression of a non-inactivating delayed rectifier K+ current, IK(NI). This current closely resembles the outward K+ current elicited by rat ether-à-go-go (r-eag) channels in its range of potential for activation and unitary conductance.It is shown that activation kinetics of IK(NI), like those of r-eag, depend on holding potential and on [Mg2+]o, and that IK(NI), like r-eag, is reversibly inhibited by a rise in [Ca2+].Forced expression of an isolated human ether-à-go-go K+ channel (h-eag) cDNA in undifferentiated myoblasts generates single-channel and whole-cell currents with remarkable similarity to IK(NI).h-eag current (Ih-eag) is reversibly inhibited by a rise in [Ca2+]i, and the activation kinetics depend on holding potential and [Mg2+]o.Forced expression of h-eag hyperpolarizes undifferentiated myoblasts from −9 to −50 mV, the threshold for the activation of both Ih-eag and IK(NI). Similarly, the higher the density of IK(NI), the more hyperpolarized the resting potential of fusion-competent myoblasts.It is concluded that h-eag constitutes the channel underlying IK(NI) and that it contributes to the hyperpolarization of fusion-competent myoblasts. To our knowledge, this is the first demonstration of a physiological role for a mammalian eag K+ channel. PMID:9763622

Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research

PubMed Central

Kurhanewicz, John; Vigneron, Daniel B; Brindle, Kevin; Chekmenev, Eduard Y; Comment, Arnaud; Cunningham, Charles H; DeBerardinis, Ralph J; Green, Gary G; Leach, Martin O; Rajan, Sunder S; Rizi, Rahim R; Ross, Brian D; Warren, Warren S; Malloy, Craig R

2011-01-01

A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as 13C or 15N with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism—poor sensitivity—while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care. PMID:21403835

Role of Parafacial Nuclei in Control of Breathing in Adult Rats

PubMed Central

Huckstepp, Robert T.R.; Cardoza, Kathryn P.; Henderson, Lauren E.

2015-01-01

Contiguous brain regions associated with a given behavior are increasingly being divided into subregions associated with distinct aspects of that behavior. Using recently developed neuronal hyperpolarizing technologies, we functionally dissect the parafacial region in the medulla, which contains key elements of the central pattern generator for breathing that are important in central CO2-chemoreception and for gating active expiration. By transfecting different populations of neighboring neurons with allatostatin or HM4D Gi/o-coupled receptors, we analyzed the effect of their hyperpolarization on respiration in spontaneously breathing vagotomized urethane-anesthetized rats. We identify two functionally separate parafacial nuclei: ventral (pFV) and lateral (pFL). Disinhibition of the pFL with bicuculline and strychnine led to active expiration. Hyperpolarizing pFL neurons had no effect on breathing at rest, or changes in inspiratory activity induced by hypoxia and hypercapnia; however, hyperpolarizing pFL neurons attenuated active expiration when it was induced by hypercapnia, hypoxia, or disinhibition of the pFL. In contrast, hyperpolarizing pFV neurons affected breathing at rest by decreasing inspiratory-related activity, attenuating the hypoxia- and hypercapnia-induced increase in inspiratory activity, and when present, reducing expiratory-related abdominal activity. Together with previous observations, we conclude that the pFV provides a generic excitatory drive to breathe, even at rest, whereas the pFL is a conditional oscillator quiet at rest that, when activated, e.g., during exercise, drives active expiration. PMID:25609622

In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-13C]glutamine

NASA Astrophysics Data System (ADS)

Cabella, C.; Karlsson, M.; Canapè, C.; Catanzaro, G.; Colombo Serra, S.; Miragoli, L.; Poggi, L.; Uggeri, F.; Venturi, L.; Jensen, P. R.; Lerche, M. H.; Tedoldi, F.

2013-07-01

Glutamine metabolism is, with its many links to oncogene expression, considered a crucial step in cancer metabolism and it is thereby a key target for alteration in cancer development. In particular, strong correlations have been reported between oncogene expression and expression and activity of the enzyme glutaminase. This mitochondrial enzyme, which is responsible for the deamidation of glutamine to form glutamate, is overexpressed in many tumour tissues. In animal models, glutaminase expression is correlated with tumour growth rate and it is readily possible to limit tumour growth by suppression of glutaminase activity. In principle, hyperpolarized 13C MR spectroscopy can provide insight to glutamine metabolism and should hence be a valuable tool to study changes in glutaminase activity as tumours progress. However, no such successful in vivo studies have been reported, even though several good biological models have been tested. This may, at least partly, be due to problems in preparing glutamine for hyperpolarization. This paper reports a new and improved preparation of hyperpolarized [5-13C]glutamine, which provides a highly sensitive 13C MR marker. With this preparation of hyperpolarized [5-13C]glutamine, glutaminase activity in vivo in a rat liver tumour was investigated. Moreover, this marker was also used to measure response to drug treatment in vitro in cancer cells. These examples of [5-13C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid.

Westernmost Grand Canyon incision: Testing thermochronometric resolution

NASA Astrophysics Data System (ADS)

Fox, M.; Tripathy-Lang, A.; Shuster, D. L.; Winn, C.; Karlstrom, K.; Kelley, S.

2017-09-01

The timing of carving of Grand Canyon has been debated for over 100 years with competing endmember hypotheses advocating for either a 70 Ma ("old") or <6 Ma ("young") Grand Canyon. Several geological constraints appear to support a "young" canyon model, but thermochronometric measures of cooling history and corresponding estimates of landscape evolution have been in debate. In particular, 4He/3He thermochronometric data record the distribution of radiogenic 4He (from the 238U, 235U and 232Th decay series) within an individual apatite crystal and thus are highly sensitive to the thermal history corresponding to landscape evolution. However, there are several complicating factors that make interpreting such data challenging in geologic scenarios involving reheating. Here, we analyze new data that provide measures of the cooling of basement rocks at the base of westernmost Grand Canyon, and use these data as a testbed for exploring the resolving power and limitations of 4He/3He data in general. We explore a range of thermal histories and find that these data are most consistent with a "young" Grand Canyon. A problem with the recovered thermal history, however, is that burial temperatures are under predicted based on sedimentological evidence. A solution to this problem is to increase the resistance of alpha recoil damage to annealing, thus modifying He diffusion kinetics, allowing for higher temperatures throughout the thermal history. This limitation in quantifying radiation damage (and hence crystal retentivity) introduces non-uniqueness to interpreting time-temperature paths in rocks that resided in the apatite helium partial retention zone for long durations. Another source of non-uniqueness, is due to unknown U and Th distributions within crystals. We show that for highly zoned with a decrease in effective U of 20 ppm over the outer 80% of the radius of the crystal, the 4He/3He data could be consistent with an "old" canyon model. To reduce this non-uniqueness, we obtain U and Th zonation information for separate crystals from the same rock sample through LA-ICP-MS analysis. The observed U and Th distributions are relatively uniform and not strongly zoned, thus supporting a "young" canyon model interpretation of the 4He/3He data. Furthermore, we show that for the mapped zonation, the difference between predicted 4He/3He data for a uniform crystal and a 3D model of the crystal are minimal, highlighting that zonation is unlikely to lead us to falsely infer an "old" Grand Canyon.

The origin of the post-tetanic hyperpolarization of mammalian motor nerve terminals

PubMed Central

Gage, P. W.; Hubbard, J. I.

1966-01-01

1. Motor nerve terminals in magnesium-poisoned rat hemidiaphragm-phrenic nerve preparations in vitro were stimulated with short depolarizing pulses of approximately threshold strength and the evoked antidromic responses recorded from the phrenic nerve. The percentage of these 1/sec or 0·5/sec stimuli to which there was no antidromic response was used as a quantitative measure of the terminal excitability. After standard tetanic stimulation (1000 impulses at 100/sec) the excitability of the terminals was depressed for an average duration of 60-70 sec, during most of which time no antidromic responses to stimuli of pretetanic intensity were recorded. There was no significant interaction between stimuli to the terminals at rates of 1 or 0·5/sec. 2. Potassium-free solutions at first increased, then decreased, the post-tetanic depression of excitability. Raising [K]o threefold (15 mM) abolished the post-tetanic depression and often converted it to an exaltation of excitability. 3. Polarizing currents were applied to the terminals with a second electrode. Depolarizing currents increased, while hyperpolarizing currents decreased, the post-tetanic depression of excitability. 4. In solutions with 70% of the normal NaCl content replaced by sucrose, the post-tetanic depression of excitability was reversibly prolonged. 5. In the presence of 7·7 × 10-6 M digoxin or 0·42 mM ouabain there was a small reversible reduction of post-tetanic excitability. 6. After exposure to solutions containing no glucose or to solutions containing 3-5 mM sodium azide the excitability of the terminals was not altered by the tetanus. After washing with the control solution, post-tetanic depression of excitability returned. Antimycin-A (1·8 × 10-6 M) had little or no effect upon post-tetanic excitability. 7. It was concluded that the post-tetanic depression of excitability reflected hyperpolarization of the terminals and that this hyperpolarization was caused by a shift of the membrane potential towards the potassium equilibrium potential because of an increase in potassium permeability. ImagesFig. 1 PMID:5921834

Acetylcholine-dependent upregulation of TASK-1 channels in thalamic interneurons by a smooth muscle-like signalling pathway.

PubMed

Leist, Michael; Rinné, Susanne; Datunashvili, Maia; Aissaoui, Ania; Pape, Hans-Christian; Decher, Niels; Meuth, Sven G; Budde, Thomas

2017-09-01

The ascending brainstem transmitter acetylcholine depolarizes thalamocortical relay neurons while it induces hyperpolarization in local circuit inhibitory interneurons. Sustained K + currents are modulated in thalamic neurons to control their activity modes; for the interneurons the molecular nature of the underlying ion channels is as yet unknown. Activation of TASK-1 K + channels results in hyperpolarization of interneurons and suppression of their action potential firing. The modulation cascade involves a non-receptor tyrosine kinase, c-Src. The present study identifies a novel pathway for the activation of TASK-1 channels in CNS neurons that resembles cholinergic signalling and TASK-1 current modulation during hypoxia in smooth muscle cells. The dorsal part of the lateral geniculate nucleus (dLGN) is the main thalamic site for state-dependent transmission of visual information. Non-retinal inputs from the ascending arousal system and inhibition provided by γ-aminobutyric acid (GABA)ergic local circuit interneurons (INs) control neuronal activity within the dLGN. In particular, acetylcholine (ACh) depolarizes thalamocortical relay neurons by inhibiting two-pore domain potassium (K 2P ) channels. Conversely, ACh also hyperpolarizes INs via an as-yet-unknown mechanism. By using whole cell patch-clamp recordings in brain slices and appropriate pharmacological tools we here report that stimulation of type 2 muscarinic ACh receptors induces IN hyperpolarization by recruiting the G-protein βγ subunit (Gβγ), class-1A phosphatidylinositol-4,5-bisphosphate 3-kinase, and cellular and sarcoma (c-Src) tyrosine kinase, leading to activation of two-pore domain weakly inwardly rectifying K + channel (TWIK)-related acid-sensitive K + (TASK)-1 channels. The latter was confirmed by the use of TASK-1-deficient mice. Furthermore inhibition of phospholipase Cβ as well as an increase in the intracellular level of phosphatidylinositol-3,4,5-trisphosphate facilitated the muscarinic effect. Our results have uncovered a previously unknown role of c-Src tyrosine kinase in regulating IN function in the brain and identified a novel mechanism by which TASK-1 channels are activated in neurons. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Hyperpolarized MRS: New tool to study real-time brain function and metabolism.

PubMed

Mishkovsky, Mor; Comment, Arnaud

2017-07-15

The advent of dissolution dynamic nuclear polarization (DNP) led to the emergence of a new kind of magnetic resonance (MR) measurements providing the opportunity to probe metabolism in vivo in real time. It has been shown that, following the injection of hyperpolarized substrates prepared using dissolution DNP, specific metabolic bioprobes that can be used to differentiate between healthy and pathological tissue in preclinical and clinical studies can be readily detected by MR thanks to the tremendous signal enhancement. The present article aims at reviewing the studies of cerebral function and metabolism based on the use of hyperpolarized MR. The constraints and future opportunities that this technology could offer are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperpolarized Magnetic Resonance as a Sensitive Detector of Metabolic Function

PubMed Central

2015-01-01

Hyperpolarized magnetic resonance allows for noninvasive measurements of biochemical reactions in vivo. Although this technique provides a unique tool for assaying enzymatic activities in intact organs, the scope of its application is still elusive for the wider scientific community. The purpose of this review is to provide key principles and parameters to guide the researcher interested in adopting this technology to address a biochemical, biomedical, or medical issue. It is presented in the form of a compendium containing the underlying essential physical concepts as well as suggestions to help assess the potential of the technique within the framework of specific research environments. Explicit examples are used to illustrate the power as well as the limitations of hyperpolarized magnetic resonance. PMID:25369537

Mechanisms underlying electrical and mechanical responses of the bovine retractor penis to inhibitory nerve stimulation and to an inhibitory extract.

PubMed Central

Byrne, N. G.; Muir, T. C.

1985-01-01

The response of the bovine retractor penis (BRP) to stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves and to an inhibitory extract prepared from this muscle have been studied using intracellular microelectrode, sucrose gap and conventional mechanical recording techniques. Both inhibitory nerve stimulation and inhibitory extract hyperpolarized the membrane potential and relaxed spontaneous or guanethidine (3 X 10(-5) M)-induced tone. These effects were accompanied by an increase in membrane resistance. Following membrane potential displacement from an average value of -53 +/- 7 mV (n = 184; Byrne & Muir, 1984) inhibitory potentials to nerve stimulation were abolished at approximately -30 mV; there was no evidence of reversal. Displacement by inward hyperpolarizing current over the range -45 to -60 mV increased the inhibitory response to nerve stimulation and to inhibitory extract; at more negative potential values (above approximately -60 mV) the inhibitory potential decreased and was abolished (approximately -103 mV). There was no evidence of reversal. Removal of [K+]o reversibly reduced hyperpolarization to nerve stimulation and inhibitory extract. No enhancement was observed. Increasing the [K+]o to 20 mM reduced the inhibitory potential to nerve stimulation but this was restored by passive membrane hyperpolarization. Inhibitory potentials were obtained at membrane potential values exceeding that of the estimated EK (-49 mV). [Cl-]o-free or [Cl-]o-deficient solutions reduced and abolished (after some 20-25 min) the hyperpolarization produced by inhibitory nerve stimulation or inhibitory extract. The inhibitory potential amplitude following nerve stimulation was not restored by passive displacement of the membrane potential from -26 to -104 mV approximately. Ouabain (1-5 X 10(-5) M) reduced then (45-60 min later) abolished the inhibitory potential to nerve stimulation. The effects of this drug on the extract were not investigated. It is concluded that the inhibitory response to nerve stimulation and extract in the BRP may involve several ionic species. However, unlike that in gastrointestinal muscles the NANC response in the BRP is accompanied by an increased membrane resistance and does not primarily involve K+. The underlying mechanisms for the inhibitory response to both NANC nerve stimulation and inhibitory extract appear to be similar, compatible with the view that the latter may contain the inhibitory transmitter released from these nerves in this tissue. PMID:4027462

Transport and imaging of brute-force 13C hyperpolarization

NASA Astrophysics Data System (ADS)

Hirsch, Matthew L.; Smith, Bryce A.; Mattingly, Mark; Goloshevsky, Artem G.; Rosay, Melanie; Kempf, James G.

2015-12-01

We demonstrate transport of hyperpolarized frozen 1-13C pyruvic acid from its site of production to a nearby facility, where a time series of 13C images was acquired from the aqueous dissolution product. Transportability is tied to the hyperpolarization (HP) method we employ, which omits radical electron species used in other approaches that would otherwise relax away the HP before reaching the imaging center. In particular, we attained 13C HP by 'brute-force', i.e., using only low temperature and high-field (e.g., T < ∼2 K and B ∼ 14 T) to pre-polarize protons to a large Boltzmann value (∼0.4% 1H polarization). After polarizing the neat, frozen sample, ejection quickly (<1 s) passed it through a low field (B < 100 G) to establish the 1H pre-polarization spin temperature on 13C via the process known as low-field thermal mixing (yielding ∼0.1% 13C polarization). By avoiding polarization agents (a.k.a. relaxation agents) that are needed to hyperpolarize by the competing method of dissolution dynamic nuclear polarization (d-DNP), the 13C relaxation time was sufficient to transport the sample for ∼10 min before finally dissolving in warm water and obtaining a 13C image of the hyperpolarized, dilute, aqueous product (∼0.01% 13C polarization, a >100-fold gain over thermal signals in the 1 T scanner). An annealing step, prior to polarizing the sample, was also key for increasing T1 ∼ 30-fold during transport. In that time, HP was maintained using only modest cryogenics and field (T ∼ 60 K and B = 1.3 T), for T1(13C) near 5 min. Much greater time and distance (with much smaller losses) may be covered using more-complete annealing and only slight improvements on transport conditions (e.g., yielding T1 ∼ 5 h at 30 K, 2 T), whereas even intercity transfer is possible (T1 > 20 h) at reasonable conditions of 6 K and 2 T. Finally, it is possible to increase the overall enhancement near d-DNP levels (i.e., 102-fold more) by polarizing below 100 mK, where nanoparticle agents are known to hasten T1 buildup by 100-fold, and to yield very little impact on T1 losses at temperatures relevant to transport.

Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence.

PubMed

Milshteyn, Eugene; von Morze, Cornelius; Reed, Galen D; Shang, Hong; Shin, Peter J; Larson, Peder E Z; Vigneron, Daniel B

2018-05-01

Acceleration of dynamic 2D (T 2 Mapping) and 3D hyperpolarized 13 C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm 2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2- 13 C]pyruvate, [1- 13 C]lactate, [ 13 C,  15 N 2 ]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T 2 maps. Copyright © 2018 Elsevier Inc. All rights reserved.

Population continuity, demic diffusion and Neolithic origins in central-southern Germany: the evidence from body proportions.

PubMed

Gallagher, A; Gunther, M M; Bruchhaus, H

2009-01-01

The transition to agro-pastoralism in central Europe has been framed within a dichotomy of "regional continuity" versus exogenous "demic diffusion". While substantial genetic support exists for a model of demographic diffusion from an ancestral source in the Near East, archaeological data furnish weak support for the "wave of advance" model. Nevertheless, archaeological evidence attests the widespread introduction of an exogenous "package" comprising ceramics, cereals, pulses and domesticated animals to central Europe at 5600calBCE. Body proportions are under strong climatic selection and evince remarkable stability within regional lineages. As such, they offer a viable and robust alternative to cranio-facial data in assessing hypothesised continuity and replacement with the transition to agro-pastoralism in central Europe. Humero-clavicular, brachial and crural indices in a large sample (n=75) of Linienbandkeramik (LBK), Late Neolithic and Early Bronze Age specimens from the middle Elbe-Saale-Werra valley (MESV) were compared with Eurasian and African terminal Pleistocene, European Mesolithic and geographically disparate recent human specimens. Mesolithic Europeans display considerable variation in humero-clavicular and brachial indices yet none approach the extreme "hyper-polar" morphology of LBK humans from the MESV. In contrast, Late Neolithic and Early Bronze Age peoples display elongated brachial and crural indices reminiscent of terminal Pleistocene and "tropically adapted" recent humans. These marked morphological changes likely reflect exogenous immigration during the terminal Fourth millennium cal BC. Population expansion and diffusion is a function of increased mobility and settlement dispersal concomitant with significant technological and subsistence changes in later Neolithic societies during the late fourth millennium cal BCE.

Hydrogen passivation of n+p and p+n heteroepitaxial InP solar cell structures

NASA Technical Reports Server (NTRS)

Chatterjee, B.; Ringel, S. A.; Hoffman, R., Jr.

1995-01-01

High-efficiency, heteroepitaxial (HE) InP solar cells, grown on GaAs, Si or Ge substrates, are desirable for their mechanically strong, light-weight and radiation-hard properties. However, dislocations, caused by lattice mismatch, currently limit the performance of the HE cells. This occurs through shunting paths across the active photovoltaic junction and by the formation of deep levels. In previous work we have demonstrated that plasma hydrogenation is an effective and stable means to passivate the electrical activity of dislocations in specially designed HE InP test structures. In this work, we present the first report of successful hydrogen passivation in actual InP cell structures grown on GaAs substrates by metalorganic chemical vapor deposition (MOCVD). We have found that a 2 hour exposure to a 13.56 MHz hydrogen plasma at 275 C reduces the deep level concentration in HE n+n InP cell structures from as-grown values of approximately 10(exp 15)/cm(exp -3), down to 1-2 x 10(exp 13)/cm(exp -3). The deep levels in the p-type base region of the cell structure match those of our earlier p-type test structures, which were attributed to dislocations or related point defect complexes. All dopants were successfully reactivated by a 400 C, 5 minute anneal with no detectable activation of deep levels. I-V analysis indicated a subsequent approximately 10 fold decrease in reverse leakage current at -1 volt reverse bias, and no change in the forward biased series resistance of the cell structure which indicates complete reactivation of the n+ emitter. Furthermore, electrochemical C-V profiling indicates greatly enhanced passivation depth, and hence hydrogen diffusion, for heteroepitaxial structures when compared with identically processed homoepitaxial n+p InP structures. An analysis of hydrogen diffusion in dislocated InP will be discussed, along with comparisons of passivation effectiveness for n+p versus p+n heteroepitaxial cell configurations. Preliminary hydrogen-passivated HE InP cell results will also be presented.

Iridium Cyclooctene Complex That Forms a Hyperpolarization Transfer Catalyst before Converting to a Binuclear C-H Bond Activation Product Responsible for Hydrogen Isotope Exchange.

PubMed

Iali, Wissam; Green, Gary G R; Hart, Sam J; Whitwood, Adrian C; Duckett, Simon B

2016-11-21

[IrCl(COE) 2 ] 2 (1) reacts with pyridine (py) and H 2 to form crystallographically characterized IrCl(H) 2 (COE)(py) 2 (2). 2 undergoes py loss to form 16-electron IrCl(H) 2 (COE)(py) (3), with equivalent hydride ligands. When this reaction is studied with parahydrogen, 1 efficiently achieves hyperpolarization of free py (and nicotinamide, nicotine, 5-aminopyrimidine, and 3,5-lutudine) via signal amplification by reversible exchange (SABRE) and hence reflects a simple and readily available precatayst for this process. 2 reacts further over 48 h at 298 K to form crystallographically characterized (Cl)(H)(py)(μ-Cl)(μ-H)(κ-μ-NC 5 H 4 )Ir(H)(py) 2 (4). This dimer is active in the hydrogen isotope exchange process that is used in radiopharmaceutical preparations. Furthermore, while [Ir(H) 2 (COE)(py) 3 ]PF 6 (6) forms upon the addition of AgPF 6 to 2, its stability precludes its efficient involvement in SABRE.

The Effect of Curcumin on Intracellular pH (pHi), Membrane Hyperpolarization and Sperm Motility.

PubMed

Naz, Rajesh K

2014-04-01

Curcumin has shown to affect sperm motility and function in vitro and fertility in vivo. The molecular mechanism(s) by which curcumin affects sperm motility has not been delineated. Since modulation of intracellular pH (pHi) and plasma membrane polarization is involved in sperm motility, the present study was conducted to investigate the effect of curcumin on these sperm (human and murine) parameters. The effect of curcumin on sperm forward motility was examined by counting percentages of forward moving sperm. The effect of curcumin on intracellular pH (pHi) was measured by the fluorescent pH indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein-acetoxymethyl ester (BCECF-AM). The effect of curcumin on plasma membrane polarization was examined using the fluorescence sensitive dye bis (1,3-dibarbituric acid)-trimethine oxanol [DiBAC4(3)]. Curcumin caused a concentration-dependent (p<0.05) decrease in forward motility of both human and mouse sperm. It also caused a concentration-dependent decrease in intracellular pH (pHi) in both human and mouse sperm. Curcumin induced significant (p<0.05) hyperpolarization of the plasma membrane in both human and mouse sperm. These findings indicate that curcumin inhibits sperm forward motility by intracellular acidification and hyperpolarization of sperm plasma membrane. This is the first study to our knowledge which examined the effect of curcumin on sperm pHi and membrane polarization that affect sperm forward motility. These exciting findings will have application in deciphering the signal transduction pathway involved in sperm motility and function and in development of a novel non-steroidal contraceptive for infertility.

Determining In Vivo Regulation of Cardiac Pyruvate Dehydrogenase Based on Label Flux from Hyperpolarized [1-13C]Pyruvate

PubMed Central

Heather, Lisa C.; Griffin, Julian L.; Clarke, Kieran; Radda, George K.; Tyler, Damian J.

2015-01-01

Background Pyruvate dehydrogenase (PDH) is a key regulator of cardiac substrate selection and is regulated by both pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation and feedback inhibition. The extent to which chronic upregulation of PDK protein levels, acutely increased PDK activity and acute feedback inhibition limit PDH flux remains unclear because existing in vitro assessment methods inherently disrupt the enzyme complex. We have previously demonstrated that hyperpolarized 13C-labelled metabolic tracers with magnetic resonance spectroscopy (MRS) can monitor flux through PDH in vivo. The aim of this study was to determine the relative contributions of acute and chronic changes in PDK and PDH activities to in vivo myocardial PDH flux. Methodology/Principal Findings We examined both fed and fasted rats with either hyperpolarized [1-13C]pyruvate alone or hyperpolarized [1-13C]pyruvate co-infused with malate (to modulate mitochondrial NADH/NAD+ and acetyl-CoA/CoA ratios, which alter both PDH activity and flux). To confirm the metabolic fate of infused malate, we performed in vitro 1H NMR spectroscopy on cardiac tissue extracts. We observed that in fed rats, where PDH activity was high, the presence of malate increased PDH flux by 27%, whereas in the fasted state, malate infusion had no effect on PDH flux. Conclusions/Significance These observations suggest that pyruvate oxidation is limited by feedback inhibition from acetyl-CoA only when PDH activity is high. Therefore, in the case of PDH, and potentially other enzymes, hyperpolarized 13C MR can be used to non-invasively assess enzymatic regulation. PMID:21387444

Broad Area Distributed Gain, Distributed Index Profile GaAlAs Semiconductor Laser Diodes

DTIC Science & Technology

1991-02-14

active region. The external and electron mobilities . This, along with the difference differential quantum efficiency and light-current slope ef- [91...nternotionoi .-. rnri in Circuit Thteor\\ 1991. and Aplications He also has served o~n iechnical and orovrai committees 1 -1 H C Case,, and NI B...sample temperatures. these defects are mobile and cause atomic diffusion, usually called radiation-enhanced diffusion (RED). Since this diffusion

Helium, neon, and argon composition of the solar wind as recorded in gold and other Genesis collector materials

NASA Astrophysics Data System (ADS)

Pepin, Robert O.; Schlutter, Dennis J.; Becker, Richard H.; Reisenfeld, Daniel B.

2012-07-01

We report compositions and fluxes of light noble gases in the solar wind (SW), extracted by stepped pyrolysis and amalgamation from gold collector materials carried on the Genesis Solar Wind Sample Return Mission. Results are compared with data from other laboratories on SW-He, Ne and Ar distributions implanted in Genesis aluminum, carbon, and silicon collectors and extracted by laser ablation. Corrections for mass-dependent losses (“backscatter”) of impinging SW ions due to scattering from the collector material are substantially larger for gold than for these lower atomic weight targets. We assess such losses by SRIM simulation calculations of SW backscatter from gold which are applied to the measurements to recover the composition of the incident SW. Averaged results of integrated stepped pyrolysis and single-step amalgamation measurements, with 1σ errors, are as follows: for SW-Ne and Ar isotope ratios (3He/4He was not measured), 20Ne/22Ne = 14.001 ± 0.042, 21Ne/22Ne = 0.03361 ± 0.00018, 36Ar/38Ar = 5.501 ± 0.014; for SW element ratios, 4He/20Ne = 641 ± 15, 20Ne/36Ar = 51.6 ± 0.5; and for SW fluxes in atoms cm-2 s-1 at the Genesis L1 station, 4He = 1.14 ± 0.04 × 107, 20Ne = 1.80 ± 0.06 × 104, 36Ar = 3.58 ± 0.11 × 102. Except for the 21Ne/22Ne and 20Ne/36Ar ratios, these values are in reasonable accord (within ∼1-3σ) with measurements on different collector materials reported by one or both of two other Genesis noble gas research groups. We further find, in three stepped pyrolysis experiments on gold foil, that He, Ne and Ar are released at increasing temperatures without elemental fractionation, in contrast to a pyrolytic extraction of a single non-gold collector (Al) where the release patterns point to mass-dependent thermal diffusion. The pyrolyzed gold foils exhibit enhancements, relative to sample totals, in 20Ne/22Ne and 21Ne/22Ne ratios evolved at low temperatures. The absence of elemental fractionation in pyrolytic release from gold implies that these isotope ratio enhancements, involving much smaller mass differences, do not result from preferential diffusive release of the lighter Ne isotopes. This effect, not predicted by SRIM calculations, has also been observed in stepped acid-etch releases from a different Genesis collector material in another laboratory.

A new insight into mechanisms of age-related changes in heart rate.

PubMed

Zefirov, T L; Svyatova, N V; Ziyatdinova, N I

2001-06-01

Changes in cardiac rhythm induced by blockade of hyperpolarization currents with ZD 7288 depend on animal's age. The increase in cardiointerval duration is related to prolongation of T-P segment on ECG. It is hypothesized that the age-related changes in activity of hyperpolarization channels are determined by a modulating effect of the autonomic nervous system.

The Spin-Lattice Relaxation of Hyperpolarized 89Y Complexes

NASA Astrophysics Data System (ADS)

Jindal, Ashish; Lumata, Lloyd; Xing, Yixun; Merritt, Matthew; Zhao, Piyu; Malloy, Craig; Sherry, Dean; Kovacs, Zoltan

2011-03-01

The low sensitivity of NMR can be overcome by dynamic nuclear polarization (DNP). However, a limitation to the use of hyperpolarized materials is the signal decay due to T1 relaxation. Among NMR-active nuclei, 89 Y is potentially valuable in medical imaging because in chelated form, pH-sensitive agents can be developed. 89 Y also offers many attractive features -- 100 % abundance, a 1/2 spin, and a long T1 , up to 10 min. Yet, developing new 89 Y complexes with even longer T1 values is desirable. Designing such complexes relies upon understanding the mechanism(s) responsible for T1 relaxation. We report an approach to hyperpolarized T1 measurements that enabled an analysis of relaxation mechanisms by selective deuteration of the ligand backbone, the solvent or both. Hyperpolarized 89 Y -- DTPA, DOTA, EDTA, and deuterated EDTA complexes were studied. Results suggest that substitution of low-gamma nuclei on the ligand backbone as opposed to that of the solvent most effectively increase the 89 Y T1 . These results are encouraging for in vivo applications as the presence of bound water may not dramatically affect the T1 .

Optically induced cross relaxation via nitrogen-related defects for bulk diamond 13C hyperpolarization

NASA Astrophysics Data System (ADS)

Wunderlich, Ralf; Kohlrautz, Jonas; Abel, Bernd; Haase, Jürgen; Meijer, Jan

2017-12-01

In this Rapid Communication we utilize nuclear magnetic resonance to investigate the hyperpolarization effect of negatively charged nitrogen vacancy (NV) centers on bulk 13C nuclei in a diamond single crystal. We were able to identify several polarization peaks of a different sign at different magnetic fields in a region of some tens of Gauss centered around 50 mT . The bulk 13C hyperpolarization in the investigated field range is usually attributed to the excited state level anticrossing of the NV center. However, we found that this bulk hyperpolarization is caused by optically induced cross relaxation and that it takes place in the NV center ground state. The four-spin coupling between the polarized NV electron spin, the electron spin of a substitutional nitrogen impurity (P1), as well as its 14N nuclei and the 13C nuclear spin have to be considered. We introduce a simple theoretical model which completely fits with the experimental data and which clearly shows that the P1 centers are involved in the polarization process. We expect that the current work has a significant impact on future NV-based polarization applications.

Effect of heavy atoms on photochemically induced dynamic nuclear polarization in liquids

NASA Astrophysics Data System (ADS)

Okuno, Yusuke; Cavagnero, Silvia

2018-01-01

Given its short hyperpolarization time (∼10-6 s) and mostly non-perturbative nature, photo-chemically induced dynamic nuclear polarization (photo-CIDNP) is a powerful tool for sensitivity enhancement in nuclear magnetic resonance. In this study, we explore the extent of 1H-detected 13C nuclear hyperpolarization that can be gained via photo-CIDNP in the presence of small-molecule additives containing a heavy atom. The underlying rationale for this methodology is the well-known external-heavy-atom (EHA) effect, which leads to significant enhancements in the intersystem-crossing rate of selected photosensitizer dyes from photoexcited singlet to triplet. We exploited the EHA effect upon addition of moderate amounts of halogen-atom-containing cosolutes. The resulting increase in the transient triplet-state population of the photo-CIDNP sensitizer fluorescein resulted in a significant increase in the nuclear hyperpolarization achievable via photo-CIDNP in liquids. We also explored the internal-heavy-atom (IHA) effect, which is mediated by halogen atoms covalently incorporated into the photosensitizer dye. Widely different outcomes were achieved in the case of EHA and IHA, with EHA being largely preferable in terms of net hyperpolarization.

Continuous hyperpolarization with parahydrogen in a membrane reactor

NASA Astrophysics Data System (ADS)

Lehmkuhl, Sören; Wiese, Martin; Schubert, Lukas; Held, Mathias; Küppers, Markus; Wessling, Matthias; Blümich, Bernhard

2018-06-01

Hyperpolarization methods entail a high potential to boost the sensitivity of NMR. Even though the "Signal Amplification by Reversible Exchange" (SABRE) approach uses para-enriched hydrogen, p-H2, to repeatedly achieve high polarization levels on target molecules without altering their chemical structure, such studies are often limited to batch experiments in NMR tubes. Alternatively, this work introduces a continuous flow setup including a membrane reactor for the p-H2, supply and consecutive detection in a 1 T NMR spectrometer. Two SABRE substrates pyridine and nicotinamide were hyperpolarized, and more than 1000-fold signal enhancement was found. Our strategy combines low-field NMR spectrometry and a membrane flow reactor. This enables precise control of the experimental conditions such as liquid and gas pressures, and volume flow for ensuring repeatable maximum polarization.

Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

PubMed

Meredith, Frances L; Benke, Tim A; Rennie, Katherine J

2012-12-01

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I(h)) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs(+) (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I(h) was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I(h) was -123 mV, which shifted to -114 mV in the presence of cAMP. Activation of I(h) was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at -139 mV). Activation speeded up significantly (τ=136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I(h) could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I(h) was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on Hodgkin-Huxley type ionic conductances, removal of I(h) similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.

The Role of PDH Inhibition in the Development of Hypertrophy in the Hyperthyroid Rat Heart: A Combined MRI and Hyperpolarized MRS Study

PubMed Central

Atherton, Helen J.; Dodd, Michael S.; Heather, Lisa C.; Schroeder, Marie A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Tyler, Damian J.

2015-01-01

Background Hyperthyroidism increases heart rate, contractility and cardiac output, as well as metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate utilisation. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase (PDK), thereby inhibiting glucose oxidation via pyruvate dehydrogenase (PDH). Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy (MRS) to investigate the rate and regulation of in vivo pyruvate dehydrogenase (PDH) flux in the hyperthyroid heart, and to establish whether modulation of flux through PDH would alter cardiac hypertrophy. Methods & Results Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (T3; 0.2 mg/kg/day). In vivo PDH flux, assessed using hyperpolarized MRS, was reduced by 59% in hyperthyroid animals (0.0022 ± 0.0002 s−1 vs 0.0055 ± 0.0005 s−1, P = 0.0003) and this reduction was completely reversed by both acute and chronic delivery of the PDK inhibitor, dichloroacetic acid (DCA). Hyperpolarized [2-13C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine MRI showed that chronic DCA treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100 ± 20 mg vs 200 ± 30 mg; P = 0.04) despite no change to the increase observed in cardiac output. Conclusions This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is PDK mediated. Relieving this inhibition can increase the metabolic flexibility of the hyperthyroid heart and reduce the level of hypertrophy that develops whilst maintaining the increased cardiac output required to meet the higher systemic metabolic demand. PMID:21606392

XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use.

PubMed

Nikolaou, Panayiotis; Coffey, Aaron M; Walkup, Laura L; Gust, Brogan M; Whiting, Nicholas; Newton, Hayley; Muradyan, Iga; Dabaghyan, Mikayel; Ranta, Kaili; Moroz, Gregory D; Rosen, Matthew S; Patz, Samuel; Barlow, Michael J; Chekmenev, Eduard Y; Goodson, Boyd M

2014-06-01

Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1L/h) (129)Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The 'hyperpolarizer' is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode-making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell (129)Xe nuclear spin polarization values of ~30%-90% have been measured for Xe loadings of ~300-1600Torr. Typical (129)Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long (129)Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Responses to Gamma-Aminobutyric Acid of Rat Visual Cortical Neurons in Tissue Slices

DTIC Science & Technology

1986-04-01

depolarizing afterpotentials ( DAPs ; Figure 3). The afterhyperpolarization (AHP) was defined as the hyperpolarization that follow one or more orthodromic...action potentials or action potentials elicited during a depolarizing current pulse (Figure 3). DAPs and AHPs were measured from the RMP. The term...inhibitory postsynaptic potential, DAP = depolarizing afterpotential, AHP= afterhyperpolarization. Dashed lines indicate the RMP. Asterisks indicate

Electrically-Generated Spin Polarization in Non-Magnetic Semiconductors

DTIC Science & Technology

2016-03-31

resolved Faraday rotation data due to electron spin polarization from previous pump pulses was characterized, and an analytic solution for this phase...electron spin polarization was shown to produce nuclear hyperpolarization through dynamic nuclear polarization. Time-resolved Faraday rotation...Distribution approved for public release. 3    Figure 3. Total magnetic field measured using time-resolved Faraday rotation with the electrically

Transport de Particules et Atmospheres D'etoiles Magnetiques

NASA Astrophysics Data System (ADS)

LeBlanc, Francis

1995-01-01

Les phenomenes relies a la diffusion atomique dans les etoiles sont etudies de facon intensive depuis environ un quart de siecle. La diffusion peut a la fois modifier les abondances atomiques presentes ainsi qu'affecter la structure et l'evolution stellaires. Dans cette these, nous allons etudier trois phenomenes physiques relies a la diffusion. Nous avons developpe la theorie de la derive induite par la radiation afin qu'elle soit facilement applicable dans le contexte de l'astrophysique stellaire. Des calcuis detailles furent effectues afin d'evaluer l'importance de cet effet sur la diffusion relative de l'^3 He et l'^4He et montrent que la derive induite par la radiation accelere la separation de ces deux isotopes dans une etoile de temperature effective de 18000 K. Lorsque l'^4He est present, ce phenomene augmente la vitesse de derive de l'^3He qui migre vers l'exterieur ce qui fait apparai tre la surabondance de cet isotope plus tot dans l'evolution. Des calculs sur le lithium a la base de la zone convective d'une etoile avec une temperature effective de 6700 K monuent que la derive induite par la radiation n'est pas importante dans ce cas. Ce phenomene semble aussi etre negligeable pour l'oxygene dans les etoiles de type A ainsi que pour le mercure dans les etoiles de type B. Deuxiemement nous avons construit des modeles d'atmospheres d'etoiles ayant un champ magnetique horizontal et constant en incluant l'interaction entre ce champ et la diffusion ambipolaire de l'hydrogene. Cette interaction cause une compression de la zone d'ionisation de l'hydrogene. Dans un modele de temperature effective de 10,000 K, et avec log g = 4.0 la gravite effective, c'est-a-dire la gravite plus l'acceleration causee par la force de Lorentz, en presence d'un champ magnetique de 5 kG est sept fois plus grande que la gravite. Ce phenomene affecte donc fortement la structure des etoiles Ap. Cette modification de la structure des etoiles magnetiques cause un plus grand elargissement des raies de Balmer de l'hydrogene. Puisque le champ magnetique observe n'est pas uniforme a la surface des etoiles Ap, la modification de la structure causee par l'interaction entre la diffusion ambipolaire de l'hydrogene et le champ magnetique engendre une variation de l'elargissement des raies de Balmer durant une periode de rotation. La variation causee par ce phenomene est inferieure aux variations observees. D'autres facteurs tels que des gradients horizontaux et verticaux de la metallicite et de la configuration du champ magnetique peuvent aussi influencer la variation des raies de Balmer. Des ameliorations majeures furent apportees au calcul des accelerations radiatives. Grace a des bases de donnees plus completes, il est maintenant possible de calculer l'acceleration causee par la photoionisation. De plus nous avons calcule de maniere approximative l'opacite monochromatique totale qui est un ingredient essentiel au calcul de l'acceleration radiative. Des ameliorations concernant l'elargissement des raies et la distribution de l'acceleration entre les divers ions d'un element furent aussi incluses. Des calculs detailles de l'acceleration radiative sur le fer montrent qu'une abondance consistente avec les observations peut etre supportee dans les etoiles de type A et F. L'abondance de fer supportee depend de la temperature effective et de la gravite de surface de l'etoile. Les accelerations radiatives ont ete tabulees afin d'etre facilement utilisables dans des codes d'evolution stellaire.

Mapping of intracellular pH in the in vivo rodent heart using hyperpolarized [1-13C]pyruvate.

PubMed

Lau, Angus Z; Miller, Jack J; Tyler, Damian J

2017-05-01

To demonstrate the feasibility of mapping intracellular pH within the in vivo rodent heart. Alterations in cardiac acid-base balance can lead to acute contractile depression and alterations in Ca 2+ signaling. The transient reduction in adenosine triphosphate (ATP) consumption and cardiac contractility may be initially beneficial; however, sustained pH changes can be maladaptive, leading to myocardial damage and electrical arrhythmias. Spectrally selective radiofrequency (RF) pulses were used to excite the HCO3- and CO 2 resonances individually while preserving signal from the injected hyperpolarized [1- 13 C]pyruvate. The large flip angle pulses were placed within a three-dimensional (3D) imaging acquisition, which exploited CA-mediated label exchange between HCO3- and CO 2 . Images at 4.5 × 4.5 × 5 mm 3 resolution were obtained in the in vivo rodent heart. The technique was evaluated in healthy rodents scanned at baseline and during high cardiac workload induced by dobutamine infusion. The intracellular pH was measured to be 7.15 ± 0.04 at baseline, and decreased to 6.90 ± 0.06 following 15 min of continuous β-adrenergic stimulation. Volumetric maps of intracellular pH can be obtained following an injection of hyperpolarized [1- 13 C]pyruvate. The new method is anticipated to enable assessment of stress-inducible ischemia and potential ventricular arrythmogenic substrates within the ischemic heart. Magn Reson Med 77:1810-1817, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Mechanisms defining the electrotonic potential abnormalities in simulated amyotrophic lateral sclerosis.

PubMed

Stephanova, D I; Krustev, S M; Negrev, N

2012-06-01

Electrotonic potentials allow the accommodative processes to polarizing stimuli to be assessed. Electrotonic potential transients in response to applied polarizing stimuli are caused by the kinetics of underlying axonal conductances. Here, we study these transients using our multi-layered model of the human motor nerve, in three simulated cases of the motor neuron disease amyotrophic lateral sclerosis (ALS): ALS1, ALS2 and ALS3 are three consecutively greater degrees of uniform axonal dysfunctions along the human motor nerve fibre. The results show that the responses in the ALS1 case are quite similar to the normal case. In contrast, in the ALS2 and ALS3 cases, long-lasting (100 ms) subthreshold depolarizing stimuli activate the classical "transient" Na(+) channels in the nodal and in the internodal axolemma beneath the myelin sheath; this leads to action potential generation during the early parts of the electrotonic responses in all compartments along the fibre length. The results also show that the electrotonic potentials in response to long-lasting (100 ms) subthreshold hyperpolarizing stimuli in the ALS1 and ALS2 cases are quiet similar to those of the normal case. However, the current kinetics in the ALS3 case differs from the normal case after the termination of the long-lasting hyperpolarizing stimuli. In the most abnormal ALS3 case, the activation of the Na(+) channels in the nodal and in the internodal axolemma leads to repetitive action potential generation in the late parts (100-200 ms) of the hyperpolarizing electrotonic responses. The results show that the repetitive firing, due to the progressively increased nodal and internodal ion channel dysfunction, are consistent with the loss of functional potassium channels involving both the fast and the slow potassium channel types. The results confirm that the electrotonic potentials in the three simulated ALS cases are specific indicators for the motor neuron disease ALS. The mechanisms underlying the simulated ALS are also discussed.

Development and fabrication of a diffusion welded Columbium alloy heat exchanger. [for space power generation

NASA Technical Reports Server (NTRS)

Zimmerman, W. F.; Duderstadt, E. C.; Wein, D.; Titran, R. H.

1978-01-01

A Mini Brayton space power generation system required the development of a Columbium alloy heat exchanger to transfer heat from a radioisotope heat source to a He/Xe working fluid. A light-weight design featured the simultaneous diffusion welding of 148 longitudinal fins in an annular heat exchanger about 9-1/2 in. in diameter, 13-1/2 in. in length and 1/4 in. in radial thickness. To complete the heat exchanger, additional gas ducting elements and attachment supports were added by GTA welding in a vacuum-purged inert atmosphere welding chamber. The development required the modification of an existing large size hot isostatic press to achieve HIP capabilities of 2800 F and 10,000 psi for at least 3 hr. Excellent diffusion welds were achieved in a high-quality component which met all system requirements.

Diffusive Gas Loss from Silica Glass Ampoules at Elevated Temperatures

NASA Technical Reports Server (NTRS)

Palosz, W.

1998-01-01

Changes in the pressure of hydrogen, helium and neon due to diffusion through the wall of silica crystal growth ampoules at elevated temperatures were determined experimentally. We show that, while both He- and Ne-losses closely follow conventional model of diffusive gas permeation through the wall, hydrogen losses, in particular at low fill pressures, can be much larger. This is interpreted in terms of the high solubility of hydrogen in silica glasses.

K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels

PubMed Central

Coleman, H A; Tare, Marianne; Parkington, Helena C

2001-01-01

Membrane currents attributed to endothelium-derived hyperpolarizing factor (EDHF) were recorded in short segments of submucosal arterioles of guinea-pigs using single microelectrode voltage clamp. The functional responses of arterioles and human subcutaneous, rat hepatic and guinea-pig coronary arteries were also assessed as changes in membrane potential recorded simultaneously with contractile activity. The current-voltage (I-V) relationship for the conductance due to EDHF displayed outward rectification with little voltage dependence. Components of the current were blocked by charybdotoxin (30-60 nM) and apamin (0.25-0.50 μM), which also blocked hyperpolarization and prevented EDHF-induced relaxation. The EDHF-induced current was insensitive to Ba2+ (20-100 μM) and/or ouabain (1 μM to 1 mM). In human subcutaneous arteries and guinea-pig coronary arteries and submucosal arterioles, the EDHF-induced responses were insensitive to Ba2+ and/or ouabain. Increasing [K+]o to 11-21 mM evoked depolarization under conditions in which EDHF evoked hyperpolarization. Responses to ACh, sympathetic nerve stimulation and action potentials were indistinguishable between dye-labelled smooth muscle and endothelial cells in arterioles. Action potentials in identified endothelial cells were always associated with constriction of the arterioles. 18β-Glycyrrhetinic acid (30 μM) and carbenoxolone (100 μM) depolarized endothelial cells by 31 ± 6 mV (n = 7 animals) and 33 ± 4 mV (n = 5), respectively, inhibited action potentials in smooth muscle and endothelial cells and reduced the ACh-induced hyperpolarization of endothelial cells by 56 and 58 %, respectively. Thus, activation of outwardly rectifying K+ channels underlies the hyperpolarization and relaxation due to EDHF. These channels have properties similar to those of intermediate conductance (IKCa) and small conductance (SKCa) Ca2+-activated K+ channels. Strong electrical coupling between endothelial and smooth muscle cells implies that these two layers function as a single electrical syncytium. The non-specific effects of glycyrrhetinic acid precludes its use as an indicator of the involvement of gap junctions in EDHF-attributed responses. These conclusions are likely to apply to a variety of blood vessels including those of humans. PMID:11230509

Hyperpolarization of Frozen Hydrocarbon Gases by Dynamic Nuclear Polarization at 1.2 K.

PubMed

Vuichoud, Basile; Canet, Estel; Milani, Jonas; Bornet, Aurélien; Baudouin, David; Veyre, Laurent; Gajan, David; Emsley, Lyndon; Lesage, Anne; Copéret, Christophe; Thieuleux, Chloé; Bodenhausen, Geoffrey; Koptyug, Igor; Jannin, Sami

2016-08-18

We report a simple and general method for the hyperpolarization of condensed gases by dynamic nuclear polarization (DNP). The gases are adsorbed in the pores of structured mesoporous silica matrices known as HYPSOs (HYper Polarizing SOlids) that have paramagnetic polarizing agents covalently bound to the surface of the mesopores. DNP is performed at low temperatures and moderate magnetic fields (T = 1.2 K and B0 = 6.7 T). Frequency-modulated microwave irradiation is applied close to the electron spin resonance frequency (f = 188.3 GHz), and the electron spin polarization of the polarizing agents of HYPSO is transferred to the nuclear spins of the frozen gas. A proton polarization as high as P((1)H) = 70% can be obtained, which can be subsequently transferred to (13)C in natural abundance by cross-polarization, yielding up to P((13)C) = 27% for ethylene.

Conductance changes associated with the secretory potential in the cockroach salivary gland.

PubMed

Ginsborg, B L; House, C R; Silinsky, E M

1974-02-01

1. Conductance changes in the acini of the cockroach salivary gland have been examined during nerve stimulation by means of two intracellular electrodes placed in the same acinus, the first electrode being used for recording membrane potential and the second for current injection.2. The transient hyperpolarization (secretory potential) in the acinus evoked by nerve stimuli is accompanied by a rise in membrane conductance. The conductance, however, remains high for a longer period than that of the response.3. Applying the analysis of Trautwein & Dudel (1958) to the secretory potentials recorded in the acinus (assumed to behave electrically like a single cell) gives estimates of the ;transmitter equilibrium potential'. The values indicate that the neurotransmitter increases the membrane potassium conductance.4. The hyperpolarization of the acinus evoked by 10(-6)M dopamine in the bathing fluid is also associated with an increase in membrane potassium conductance.

Parameterization of hyperpolarized (13)C-bicarbonate-dissolution dynamic nuclear polarization.

PubMed

Scholz, David Johannes; Otto, Angela M; Hintermair, Josef; Schilling, Franz; Frank, Annette; Köllisch, Ulrich; Janich, Martin A; Schulte, Rolf F; Schwaiger, Markus; Haase, Axel; Menzel, Marion I

2015-12-01

(13)C metabolic MRI using hyperpolarized (13)C-bicarbonate enables preclinical detection of pH. To improve signal-to-noise ratio, experimental procedures were refined, and the influence of pH, buffer capacity, temperature, and field strength were investigated. Bicarbonate preparation was investigated. Bicarbonate was prepared and applied in spectroscopy at 1, 3, 14 T using pure dissolution, culture medium, and MCF-7 cell spheroids. Healthy rats were imaged by spectral-spatial spiral acquisition for spatial and temporal bicarbonate distribution, pH mapping, and signal decay analysis. An optimized preparation technique for maximum solubility of 6 mol/L and polarization levels of 19-21% is presented; T1 and SNR dependency on field strength, buffer capacity, and pH was investigated. pH mapping in vivo is demonstrated. An optimized bicarbonate preparation and experimental procedure provided improved T1 and SNR values, allowing in vitro and in vivo applications.

Heterogeneous Microtesla SABRE Enhancement of 15 N NMR Signals.

PubMed

Kovtunov, Kirill V; Kovtunova, Larisa M; Gemeinhardt, Max E; Bukhtiyarov, Andrey V; Gesiorski, Jonathan; Bukhtiyarov, Valerii I; Chekmenev, Eduard Y; Koptyug, Igor V; Goodson, Boyd M

2017-08-21

The hyperpolarization of heteronuclei via signal amplification by reversible exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes=1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD=cyclooctadiene] catalyst onto silica particles modified with amine linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate a circa 100-fold enhancement of 15 N NMR signals in 15 N-pyridine at 9.4 T following parahydrogen bubbling within a magnetic shield. No 15 N NMR enhancement was observed from the supernatant liquid following catalyst separation, which along with XPS characterization supports the fact that the effects result from SABRE under heterogeneous catalytic conditions. The technique can be developed further for producing catalyst-free agents via SABRE with hyperpolarized heteronuclear spins, and thus is promising for biomedical NMR and MRI applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploration of the Transition from the Hydrodynamic-like to the Strongly Kinetic Regime in Shock-Driven Implosions

DOE PAGES

Rosenberg, M. J.; Rinderknecht, H. G.; Hoffman, N. M.; ...

2014-05-05

Clear evidence of the transition from hydrodynamiclike to strongly kinetic shock-driven implosions is, for the first time, revealed and quantitatively assessed. Implosions with a range of initial equimolar D 3He gas densities show that as the density is decreased, hydrodynamic simulations strongly diverge from and increasingly over-predict the observed nuclear yields, from a factor of ~2 at 3.1 mg/cm 3 to a factor of 100 at 0.14 mg/cm 3. (The corresponding Knudsen number, the ratio of ion mean-free path to minimum shell radius, varied from 0.3 to 9; similarly, the ratio of fusion burn duration to ion diffusion time, anothermore » figure of merit of kinetic effects, varied from 0.3 to 14.) This result is shown to be unrelated to the effects of hydrodynamic mix. As a first step to garner insight into this transition, a reduced ion kinetic (RIK) model that includes gradient-diffusion and loss-term approximations to several transport processes was implemented within the framework of a one-dimensional radiation-transport code. After empirical calibration, the RIK simulations reproduce the observed yield trends, largely as a result of ion diffusion and the depletion of the reacting tail ions.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

González, Rafael I.; Valencia, Felipe; Mella, José

The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role ofmore » nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.« less

Synaptic muscarinic response types in hippocampal CA1 interneurons depend on different levels of presynaptic activity and different muscarinic receptor subtypes

PubMed Central

Bell, L. Andrew; Bell, Karen A.; McQuiston, A. Rory

2013-01-01

Depolarizing, hyperpolarizing and biphasic muscarinic responses have been described in hippocampal inhibitory interneurons, but the receptor subtypes and activity patterns required to synaptically activate muscarinic responses in interneurons have not been completely characterized. Using optogenetics combined with whole cell patch clamp recordings in acute slices, we measured muscarinic responses produced by endogenously released acetylcholine (ACh) from cholinergic medial septum/diagonal bands of Broca inputs in hippocampal CA1. We found that depolarizing responses required more cholinergic terminal stimulation than hyperpolarizing ones. Furthermore, elevating extracellular ACh with the acetylcholinesterase inhibitor physostigmine had a larger effect on depolarizing versus hyperpolarizing responses. Another subpopulation of interneurons responded biphasically, and periodic release of ACh entrained some of these interneurons to rhythmically burst. M4 receptors mediated hyperpolarizing responses by activating inwardly rectifying K+ channels, whereas the depolarizing responses were inhibited by the nonselective muscarinic antagonist atropine but were unaffected by M1, M4 or M5 receptor modulators. In addition, activation of M4 receptors significantly altered biphasic interneuron firing patterns. Anatomically, interneuron soma location appeared predictive of muscarinic response types but response types did not correlate with interneuron morphological subclasses. Together these observations suggest that the hippocampal CA1 interneuron network will be differentially affected by cholinergic input activity levels. Low levels of cholinergic activity will preferentially suppress some interneurons via hyperpolarization and increased activity will recruit other interneurons to depolarize, possibly because of elevated extracellular ACh concentrations. These data provide important information for understanding how cholinergic therapies will affect hippocampal network function in the treatment of some neurodegenerative diseases. PMID:23747570

Optical hyperpolarization of 13C nuclear spins in nanodiamond ensembles

NASA Astrophysics Data System (ADS)

Chen, Q.; Schwarz, I.; Jelezko, F.; Retzker, A.; Plenio, M. B.

2015-11-01

Dynamical nuclear polarization holds the key for orders of magnitude enhancements of nuclear magnetic resonance signals which, in turn, would enable a wide range of novel applications in biomedical sciences. However, current implementations of DNP require cryogenic temperatures and long times for achieving high polarization. Here we propose and analyze in detail protocols that can achieve rapid hyperpolarization of 13C nuclear spins in randomly oriented ensembles of nanodiamonds at room temperature. Our protocols exploit a combination of optical polarization of electron spins in nitrogen-vacancy centers and the transfer of this polarization to 13C nuclei by means of microwave control to overcome the severe challenges that are posed by the random orientation of the nanodiamonds and their nitrogen-vacancy centers. Specifically, these random orientations result in exceedingly large energy variations of the electron spin levels that render the polarization and coherent control of the nitrogen-vacancy center electron spins as well as the control of their coherent interaction with the surrounding 13C nuclear spins highly inefficient. We address these challenges by a combination of an off-resonant microwave double resonance scheme in conjunction with a realization of the integrated solid effect which, together with adiabatic rotations of external magnetic fields or rotations of nanodiamonds, leads to a protocol that achieves high levels of hyperpolarization of the entire nuclear-spin bath in a randomly oriented ensemble of nanodiamonds even at room temperature. This hyperpolarization together with the long nuclear-spin polarization lifetimes in nanodiamonds and the relatively high density of 13C nuclei has the potential to result in a major signal enhancement in 13C nuclear magnetic resonance imaging and suggests functionalized and hyperpolarized nanodiamonds as a unique probe for molecular imaging both in vitro and in vivo.

STRETCH-DEPENDENT SENSITIZATION OF POST-JUNCTIONAL NEURAL EFFECTORS IN COLONIC MUSCLES

PubMed Central

Won, Kyung-Jong; Sanders, Kenton M.; Ward, Sean M.

2012-01-01

Background The colon undergoes distension-induced changes in motor activity as luminal contents or feces increases wall pressure. Input from enteric motor neurons regulates motility. Here we examined stretch-dependent responses in circular muscle strips of murine colon. Methods Length-ramps (6–31μm s−1) were applied in the axis of the circular muscle layer in a controlled manner until 5 mN isometric force was reached. Key Results Length-ramps produced transient membrane potential hyperpolarizations and attenuation of action potential (AP) complexes. Responses were reproducible when ramps were applied every 30s. Stretch-dependent hyperpolarization was blocked by TTX, suggesting AP-dependent release of inhibitory neurotransmitter(s). Atropine did not potentiate stretch-induced hyperpolarizations, but increased compliance of the circular layer. L-NNA inhibited stretch-dependent hyperpolarization and decreased muscle compliance, suggesting release of NO mediates stretch-dependent inhibition. Control membrane potential was restored by the NO donor SNP. Stretch-dependent hyperpolarizations were blocked by L-methionine, an inhibitor of stretch-dependent K+ (SDK) channels in colonic muscles. Loss of ICC, elicited by Kit neutralizing antibody, also inhibited responses to stretch. In presence of L-NNA and apamin, stretch responses became excitatory and were characterized by membrane depolarization and increased AP firing. A neurokinin-1 receptor antagonist inhibited this stretch-dependent increase in excitability. Conclusions & Inferences Our data show that stretch-dependent responses in colonic muscles require tonic firing of enteric inhibitory neurons, but reflex activation of neurons does not appear to be necessary. NO causes activation of SDK channels, and stretch of muscles further activates these channels, explaining the inhibitory response to stretch in colonic muscle strips. PMID:23279087

Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat.

PubMed

Zheng, Thomas W; O'Brien, Terence J; Kulikova, Sofya P; Reid, Christopher A; Morris, Margaret J; Pinault, Didier

2014-03-01

A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Bradykinin-activated transmembrane signals are coupled via N/sub o/ or N/sub i/ to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higashida, H.; Streaty, R.A.; Klee, W.

1986-02-01

The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or CaS into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored UVCa-labelled CaS into the cytoplasm, which activates CaS -dependent K channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of Kmore » efflux from cells and, to a lesser extent, to activation of CaS -dependent ion channels and CaS channels. In contrast, injection of inositol 1,4,5-trisphosphate or CaS into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low K/sub m/ GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. These results show that (bradykinin-receptor) complexes interact with N/sub o/ or N/sub i/ and suggest that N/sub o/ and/or N/sub i/ mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase.« less

Multidiffusion mechanisms for noble gases (He, Ne, Ar) in silicate glasses and melts in the transition temperature domain: Implications for glass polymerization

NASA Astrophysics Data System (ADS)

Amalberti, Julien; Burnard, Pete; Laporte, Didier; Tissandier, Laurent; Neuville, Daniel R.

2016-01-01

Noble gases are ideal probes to study the structure of silicate glasses and melts as the modifications of the silicate network induced by the incorporation of noble gases are negligible. In addition, there are systematic variations in noble gas atomic radii and several noble gas isotopes with which the influence of the network itself on diffusion may be investigated. Noble gases are therefore ideally suited to constrain the time scales of magma degassing and cooling. In order to document noble gas diffusion behavior in silicate glass, we measured the diffusivities of three noble gases (4He, 20Ne and 40Ar) and the isotopic diffusivities of two Ar isotopes (36Ar and 40Ar) in two synthetic basaltic glasses (G1 and G2; 20Ne and 36Ar were only measured in sample G1). These new diffusion results are used to re-interpret time scales of the acquisition of fractionated atmospheric noble gas signatures in pumices. The noble gas bearing glasses were synthesized by exposing the liquids to high noble gas partial pressures at high temperature and pressure (1750-1770 K and 1.2 GPa) in a piston-cylinder apparatus. Diffusivities were measured by step heating the glasses between 423 and 1198 K and measuring the fraction of gas released at each temperature step by noble gas mass spectrometry. In addition we measured the viscosity of G1 between 996 and 1072 K in order to determine the precise glass transition temperature and to estimate network relaxation time scales. The results indicate that, to a first order, that the smaller the size of the diffusing atom, the greater its diffusivity at a given temperature: D(He) > D(Ne) > D(Ar) at constant T. Significantly, the diffusivities of the noble gases in the glasses investigated do not display simple Arrhenian behavior: there are well-defined departures from Arrhenian behavior which occur at lower temperatures for He than for Ne or Ar. We propose that the non-Arrhenian behavior of noble gases can be explained by structural modifications of the silicate network itself as the glass transition temperature is approached: as the available free volume (available site for diffusive jumps) is modified, noble gas diffusion is no longer solely temperature-activated but also becomes sensitive to the kinetics of network rearrangements. The non-Arrhenian behavior of noble gas diffusion close to Tg is well described by a modified Vogel-Tammann-Fulcher (VTF) equation: Finally, our step heating diffusion experiments suggest that at T close to Tg, noble gas isotopes may suffer kinetic fractionation at a degree larger than that predicted by Graham's law. In the case of 40Ar and 36Ar, the traditional assumption based on Graham's law is that the ratio D40Ar/D36Ar should be equal to 0.95 (the square root of the ratio of the mass of 36Ar over the mass of 40Ar). In our experiment with glass G1, D40Ar/D36Ar rapidly decreased with decreasing temperature, from near unity (0.98 ± 0.14) at T > 1040 K to 0.76 when close to Tg (T = 1003 K). Replicate experiments are needed to confirm the strong kinetic fractionation of heavy noble gases close to the transition temperature.

Hyperpolarized 13C metabolic imaging using dissolution dynamic nuclear polarization.

PubMed

Hurd, Ralph E; Yen, Yi-Fen; Chen, Albert; Ardenkjaer-Larsen, Jan Henrik

2012-12-01

This article describes the basic physics of dissolution dynamic nuclear polarization (dissolution-DNP), and the impact of the resulting highly nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI) detection. The hardware requirements for clinical translation of this technology are also presented. For studies that allow the use of externally administered agents, hyperpolarization offers a way to overcome normal magnetic resonance sensitivity limitations, at least for a brief T(1)-dependent observation window. A 10,000-100,000-fold signal-to-noise advantage provides an avenue for real-time measurement of perfusion, metabolite transport, exchange, and metabolism. The principles behind these measurements, as well as the choice of agent, and progress toward the application of hyperpolarized (13)C metabolic imaging in oncology, cardiology, and neurology are reviewed. Copyright © 2012 Wiley Periodicals, Inc.

Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells.

PubMed

Soto-Cerrato, Vanessa; Manuel-Manresa, Pilar; Hernando, Elsa; Calabuig-Fariñas, Silvia; Martínez-Romero, Alicia; Fernández-Dueñas, Víctor; Sahlholm, Kristoffer; Knöpfel, Thomas; García-Valverde, María; Rodilla, Ananda M; Jantus-Lewintre, Eloisa; Farràs, Rosa; Ciruela, Francisco; Pérez-Tomás, Ricardo; Quesada, Roberto

2015-12-23

Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.

Effects of biradical deuteration on the performance of DNP: Towards better performing polarizing agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perras, Frédéric A.; Reinig, Regina R.; Slowing, Igor I.

2015-11-20

We study the effects of the deuteration of biradical polarizing agents on the efficiency of dynamic nuclear polarization (DNP) via the cross-effect. To this end, we synthesized a series of bTbK and TOTAPol biradicals with systematically increased deuterium substitution. The deuteration increases the radicals' relaxation time, thus contributing to a higher saturation factor and larger DNP enhancement, and reduces the pool of protons within the so-called spin diffusion barrier. Notably, we report that full or partial deuteration leads to improved DNP enhancement factors in standard samples, but also slows down the build-up of hyperpolarization. Improvements in DNP enhancements factors ofmore » up to 70% and time savings of up to 38% are obtained upon full deuteration. As a result, it is foreseen that this approach may be applied to other DNP polarizing agents thus enabling further sensitivity improvements.« less

Direct effects of glucose, insulin, GLP-1, and GIP on bulbospinal neurons in the rostral ventrolateral medulla in neonatal wistar rats.

PubMed

Oshima, Naoki; Onimaru, Hiroshi; Matsubara, Hidehito; Uchida, Takahiro; Watanabe, Atsushi; Imakiire, Toshihiko; Nishida, Yasuhiro; Kumagai, Hiroo

2017-03-06

Although patients with diabetes mellitus (DM) often exhibit hypertension, the mechanisms responsible for this correlation are not well known. We hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are affected by the levels of glucose, insulin, or incretins (glucagon like peptide-1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) in patients with DM. To investigate whether RVLM neurons are activated by glucose, insulin, GLP-1, or GIP, we examined changes in the membrane potentials of bulbospinal RVLM neurons using whole-cell patch-clamp technique during superfusion with various levels of glucose or these hormones in neonatal Wistar rats. A brainstem-spinal cord preparation was used for the experiments. A low level of glucose stimulated bulbospinal RVLM neurons. During insulin superfusion, almost all the RVLM neurons were depolarized, while during GLP-1 or GIP superfusion, almost all the RVLM neurons were hyperpolarized. Next, histological examinations were performed to examine transporters for glucose and receptors for insulin, GLP-1, and GIP on RVLM neurons. Low-level glucose-depolarized RVLM neurons exhibited the presence of glucose transporter 3 (GLUT3). Meanwhile, insulin-depolarized, GLP-1-hyperpolarized, and GIP-hyperpolarized RVLM neurons showed each of the respective specific receptor. These results indicate that a low level of glucose stimulates bulbospinal RVLM neurons via specific transporters on these neurons, inducing hypertension. Furthermore, an increase in insulin or a reduction in incretins may also activate the sympathetic nervous system and induce hypertension by activating RVLM neurons via their own receptors. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer

NASA Astrophysics Data System (ADS)

Coffey, Aaron M.; Shchepin, Roman V.; Feng, Bibo; Colon, Raul D.; Wilkens, Ken; Waddell, Kevin W.; Chekmenev, Eduard Y.

2017-11-01

Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C = 20 ± 2.5% corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.

Inhibition by enflurane and methoxyflurane of postdrive hyperpolarization in canine Purkinje fibers.

PubMed

Pratila, M; Vogel, S; Sperelakis, N

1984-05-01

When a pacemaker cell is driven with a train of stimuli at a rate faster than its own, the termination of the drive is followed by a transient hyperpolarization, due to the activity of an electrogenic Na+-K+ pump. In this study, the effect of the halogenated ethers, enflurane and methoxyflurane, on postdrive hyperpolarization (PDH) was determined in cardiac Purkinje fibers. The fibers were removed from freshly excised canine hearts and superfused with a Tyrode's solution (containing 2.7 or 3.5 mM K+). The preparation was paced at 0.2 Hz before and after drives, and at 2 Hz during drives. Under control conditions, drives of 2 min produced a PDH of 5.5 +/- 0.2 mV. Enflurane (1.5-5%) significantly reduced the PDH. At 4 to 5%, enflurane reduced the PDH to a mean value of 42% of the control. Methoxyflurane was more potent than enflurane in affecting the PDH. At 0.5 to 0.75%, methoxyflurane reduced the PDH to 5% of the control. At higher (1-1.5%) concentrations of methoxyflurane, the PDH was converted to a depolarization, which varied between 0.5 and 8.0 mV. The PDH was restored to control levels within 10 to 20 min after washout of either anesthetic agent. Methoxyflurane (0.5 or 1%) enhanced the automaticity of spontaneously firing cells (2.35 mM K+ Tyrode's solution used). This positive chronotropic action coincided with a depolarization of 2 to 8 mV. Enflurane, at concentrations of 3 to 5%, gave similar results. On the action potential, methoxyflurane, at 1%, reduced the amplitude and duration (measured at 50% repolarization) of the plateau, and also the maximal upstroke velocity (+Vmax) of the rising phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Leptin Acts via Lateral Hypothalamic Area Neurotensin Neurons to Inhibit Orexin Neurons by Multiple GABA-Independent Mechanisms

PubMed Central

Goforth, Paulette B.; Leinninger, Gina M.; Patterson, Christa M.

2014-01-01

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRbNts) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRbNts neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (KATP) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRbNts neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1–12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRbNts neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of KATP channels. PMID:25143620

A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.

PubMed

Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille

2017-07-18

Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.

High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes

NASA Astrophysics Data System (ADS)

Hermkens, Niels K. J.; Feiters, Martin C.; Rutjes, Floris P. J. T.; Wijmenga, Sybren S.; Tessari, Marco

2017-03-01

SABRE (Signal Amplification By Reversible Exchange) is a nuclear spin hyperpolarization technique based on the reversible concurrent binding of small molecules and para-hydrogen (p-H2) to an iridium metal complex in solution. At low magnetic field, spontaneous conversion of p-H2 spin order to enhanced longitudinal magnetization of the nuclear spins of the other ligands occurs. Subsequent complex dissociation results in hyperpolarized substrate molecules in solution. The lifetime of this complex plays a crucial role in attained SABRE NMR signal enhancements. Depending on the ligands, vastly different dissociation rates have been previously measured using EXSY or selective inversion experiments. However, both these approaches are generally time-consuming due to the long recycle delays (up to 2 min) necessary to reach thermal equilibrium for the nuclear spins of interest. In the cases of dilute solutions, signal averaging aggravates the problem, further extending the experimental time. Here, a new approach is proposed based on coherent hyperpolarization transfer to substrate protons in asymmetric complexes at high magnetic field. We have previously shown that such asymmetric complexes are important for application of SABRE to dilute substrates. Our results demonstrate that a series of high sensitivity EXSY spectra can be collected in a short experimental time thanks to the NMR signal enhancement and much shorter recycle delay.

Imaging Human Brain Perfusion with Inhaled Hyperpolarized 129Xe MR Imaging.

PubMed

Rao, Madhwesha R; Stewart, Neil J; Griffiths, Paul D; Norquay, Graham; Wild, Jim M

2018-02-01

Purpose To evaluate the feasibility of directly imaging perfusion of human brain tissue by using magnetic resonance (MR) imaging with inhaled hyperpolarized xenon 129 ( 129 Xe). Materials and Methods In vivo imaging with 129 Xe was performed in three healthy participants. The combination of a high-yield spin-exchange optical pumping 129 Xe polarizer, custom-built radiofrequency coils, and an optimized gradient-echo MR imaging protocol was used to achieve signal sensitivity sufficient to directly image hyperpolarized 129 Xe dissolved in the human brain. Conventional T1-weighted proton (hydrogen 1 [ 1 H]) images and perfusion images by using arterial spin labeling were obtained for comparison. Results Images of 129 Xe uptake were obtained with a signal-to-noise ratio of 31 ± 9 and demonstrated structural similarities to the gray matter distribution on conventional T1-weighted 1 H images and to perfusion images from arterial spin labeling. Conclusion Hyperpolarized 129 Xe MR imaging is an injection-free means of imaging the perfusion of cerebral tissue. The proposed method images the uptake of inhaled xenon gas to the extravascular brain tissue compartment across the intact blood-brain barrier. This level of sensitivity is not readily available with contemporary MR imaging methods. © RSNA, 2017.

Isomeric and Isotopic Effects on the Electronic Spectrum of {{\\rm{C}}}_{60}^{+}–He: Consequences for Astronomical Observations of {{\\rm{C}}}_{60}^{+}

NASA Astrophysics Data System (ADS)

Campbell, E. K.; Maier, J. P.

2018-05-01

Laboratory measurements are reported that enable a more accurate determination of the characteristics of the near-infrared absorptions of {{{C}}}60+ below 10 K. These data were obtained by photofragmentation of {{{C}}}60+{--}{He} complexes in a cryogenic trap. Asymmetry in the profiles of the observed 9577 and 9632 Å absorption bands of {{{C}}}60+{--}{He} is caused by the attachment of the weakly bound helium atom to hexagonal or pentagonal faces of {{{C}}}60+. The implication is that the FWHM of the bands in the electronic spectrum of {{{C}}}60+ below 10 K is 1.4 Å. The effect of 13C isotopes on the {{{C}}}60+ electronic spectrum is experimentally evaluated by measurement of {}12{{{C}}}60+{--}{He}, {}13{{{C}}}112{{{C}}}59+{--}{He}, and {}13{{{C}}}212{{{C}}}58+{--}{He}. Data on the 9365 Å absorption band indicate a wavelength shift of about 0.3 Å between the former and latter. This result is consistent with models used to interpret the vibrational isotope effect in the Raman spectrum of neutral C60. The influence of 13C isotopes on the 9348, 9365, 9428, 9577, and 9632 Å diffuse interstellar bands is expected to be minor considering other broadening factors that affect astronomical observations. The presented data also provide more accurate relative intensities of the five interstellar bands attributed to {{{C}}}60+.

Cerebral fat embolism and the "starfield" pattern: a case report.

PubMed

Aravapalli, Amit; Fox, James; Lazaridis, Christos

2009-11-19

Nearly all long-bone fractures are accompanied by some form of fat embolism. The rare complication of clinically significant fat embolism syndrome, however, occurs in only 0.9-2.2% of cases. The clinical triad of fat embolism syndrome consists of respiratory distress, altered mental status, and petechial rash. Cerebral fat embolism causes the neurologic involvement seen in fat embolism syndrome. A 19-year-old African-American male was admitted with gunshot wounds to his right hand and right knee. He had diffuse hyperactive deep tendon reflexes, bilateral ankle clonus and decerebrate posturing with a Glasgow Coma Scale (GCS) score of 4T. Subsequent MRI of the brain showed innumerable punctate areas of restricted diffusion consistent with "starfield" pattern. On a 10-week follow up he has a normal neurological examination and he is discharged home. Despite the severity of the neurologic insult upon initial presentation, the majority of case reports on cerebral fat embolism illustrate that cerebral dysfunction associated with cerebral fat embolism is reversible. When neurologic deterioration occurs in the non-head trauma patient, then a systemic cause such as fat emboli should be considered. We describe a patient with non-head trauma who demonstrated the classic "starfield" pattern on diffusion-weighted MRI imaging.

Analysis of electrical noise in turtle cones

PubMed Central

Lamb, T. D.; Simon, E. J.

1977-01-01

1. Properties of the light-sensitive voltage noise in cones in the retina of the turtle, Pseudemys scripta elegans, have been studied by intracellular recording. 2. Suppression of the noise by light was a function of the hyperpolarizing response of a cone but not of the size or pattern of illumination. 3. Power density spectra of the noise were fitted in many cones by the product of two Lorentzians with characteristic time constants τ1 and τ2 averaging 40 and 7 msec respectively. The spectra of some cells were peaked and could be fitted by a resonance curve. 4. Spectra in dim light exhibited decreased low frequency power. They could often be fitted by a product of two Lorentzians using the same value of τ2 as used in darkness but decreasing τ1 and the zero frequency asymptote. An e-fold reduction in τ1 occurred with lights which hyperpolarized by 4-7 mV. 5. Injection of hyperpolarizing currents of about 0·1-0·2 nA into weakly coupled cones reduced the noise, and also reduced the sensitivity to dim flashes. 6. The variance-voltage relation during steady illumination of different intensities differed from cone to cone. Dim lights increased the noise in some cells and decreased it in others, but moderately bright lights which gave steady responses of more than about one third maximal reduced the noise in all cells. 7. When the cell was transiently depolarized during the differentiated component following steady illumination, the noise was less than it was after prolonged darkness. 8. In the after-effect of bright light, the time course of recovery of noise was the same as that of flash sensitivity and voltage. The noise was reduced e-fold for hyperpolarizations averaging 3 mV while for sensitivity this reduction occurred for 1·3 mV. For a given hyperpolarization the noise was lower during the after-effect than during steady dim illumination. 9. When a series of dim flashes was delivered to a cone, no significant increase in variance over the dark noise was detected during the photo-response. This implies that each photoisomerization evokes no more than about 1·5 μV at the peak of the response in a coupled cone, corresponding to about 50 μV in an isolated cone. 10. The elementary shot events underlying the noise are about 100 μV in amplitude in an isolated cone, have a characteristic time constant of 16-60 msec and reflect unit conductance fluctuations of about 16 pS (S, Siemen ≡ Ω-1). 11. It is concluded that the noise source is internal to the cones. We postulate that the noise arises from opening and closing of the light-sensitive ionic channels in the outer segment, and that in darkness there is a residual concentration of the blocking substance which on average closes up to about one third of the channels. It seems likely that the unit event involves a considerable number of blocking molecules and ionic channels. PMID:592199

Direct monitoring of wind-induced pressure-pumping on gas transport in soil

NASA Astrophysics Data System (ADS)

Laemmel, Thomas; Mohr, Manuel; Schindler, Dirk; Schack-Kirchner, Helmer; Maier, Martin

2017-04-01

Gas exchange between soil and atmosphere is important for the biogeochemistry of soils and is commonly assumed to be governed by molecular diffusion. Yet a few previous field studies identified other gas transport processes such as wind-induced pressure-pumping to enhance soil-atmosphere fluxes significantly. However, since these wind-induced non-diffusive gas transport processes in soil often occur intermittently, the quantification of their contribution to soil gas emissions is challenging. To quantify the effects of wind-induced pressure-pumping on soil gas transport, we developed a method for in situ monitoring of soil gas transport. The method includes the use of Helium (He) as a tracer gas which was continuously injected into the soil. The resulting He steady-state concentration profile was monitored. Gas transport parameters of the soil were inversely modelled. We used our method during a field campaign in a well-aerated forest soil over three months. During periods of low wind speed, soil gas transport was modelled assuming diffusion as transport process. During periods of high wind speed, the previously steady diffusive He concentration profile showed temporary concentration decreases in the topsoil, indicating an increase of the effective gas transport rate in the topsoil up to 30%. The enhancement of effective topsoil soil gas diffusivity resulted from wind-induced air pressure fluctuations which are referred to as pressure-pumping. These air pressure fluctuations had frequencies between 0.1 and 0.01 Hz and amplitudes up to 10 Pa and occurred at above-canopy wind speeds greater than 5 m s-1. We could show the importance of the enhancement of the gas transport rate in relation with the wind intensity and corresponding air pressure fluctuations characteristics. We directly detected and quantified the pressure-pumping effect on gas transport in soil in a field study for the first time, and could thus validate and underpin the importance of this non-diffusive gas transport process. Our method can also be used to study other non-diffusive gas transport processes occurring in soil and snow, and their possible feedbacks or interactions with biogeochemical processes.

Application of combined 81Kr and 4He chronometers to the dating of old groundwater in a tectonically active region of the North China Plain

NASA Astrophysics Data System (ADS)

Matsumoto, Takuya; Chen, Zongyu; Wei, Wen; Yang, Guo-Min; Hu, Shui-Ming; Zhang, Xiangyang

2018-07-01

Groundwater dating by radio-krypton (81Kr; half-life of about 229,000 years) was applied to the sedimentary basin aquifer of the North China Plain (NCP). Krypton gas extracted from deep groundwater in the Coastal Plain was analyzed for 81Kr/Kr ratios by Atom Trap Trace Analysis, which yielded normalized ratios of 0.05 to 0.20, corresponding to groundwater residence times of 0.5-1 million years. Helium isotope compositions were determined on groundwater samples collected from the Central Plain and the Coastal Plain along a flow path of about 200 km. Helium dissolved in the groundwater samples are a mixture of atmospheric, crustal radiogenic and mantle derived sources. Mantle derived 3He contributes up to 30% of the total, and the area of occurrence coincides with zones of previous magmatic/tectonic activities. By contrast, >90% of 4He is derived from crustal reservoirs and correlates with 81Kr ages. The absolute groundwater ages (81Kr) and radiogenic 4He concentrations permit us to calibrate the 4He flux into the aquifer as well as the vertical diffusion rate of 4He to utilize the radiogenic 4He in groundwater as a quantitative age tracer. Previously, groundwater showed 14C activities near the limit of detection (30-40 k yr), in contrast Kr and radiogenic 4He data reveal progressively older ages from the recharge area to the Coastal Plain, from <20,000 yr to 0.5 to 1 Ma along the flow path of the NCP aquifers.

The abundances of hydrogen, helium, oxygen, and iron accelerated in large solar particle events

NASA Technical Reports Server (NTRS)

Mazur, J. E.; Mason, G. M.; Klecker, B.; Mcguire, R. E.

1993-01-01

Energy spectra measured in 10 large flares with the University of Maryland/Max-Planck-Institut sensors on ISEE I and Goddard Space Flight Center sensors on IMP 8 allowed us to determine the average H, He, O, and Fe abundances as functions of energy in the range of about 0.3-80 MeV/nucleon. Model fits to the spectra of individual events using the predictions of a steady state stochastic acceleration model with rigidity-dependent diffusion provided a means of interpolating small portions of the energy spectra not measured with the instrumentation. Particles with larger mass-to-charge ratios were relatively less abundant at higher energies in the flare-averaged composition. The Fe/O enhancement at low SEP energies was less than the Fe/O ratios observed in He-3-rich flares. Unlike the SEP composition averaged above 5 MeV/nucleon, the average SEP abundances above 0.3 MeV/nucleon were similar to the average solar wind.

Metal-nanotube composites as radiation resistant materials

NASA Astrophysics Data System (ADS)

González, Rafael I.; Valencia, Felipe; Mella, José; van Duin, Adri C. T.; So, Kang Pyo; Li, Ju; Kiwi, Miguel; Bringa, Eduardo M.

2016-07-01

The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

Ion transport and loss in the Earth's quiet ring current. 2: Diffusion and magnetosphere-ionosphere coupling

NASA Technical Reports Server (NTRS)

Sheldon, R. B.

1994-01-01

We have studied the transport and loss of H(+), He(+), and He(++) ions in the Earth's quiet time ring current (1 to 300 keV/e, 3 to 7 R(sub E), Kp less than 2+, absolute value of Dst less than 11, 70 to 110 degs pitchangles, all LT) comparing the standard radial diffusion model developed for the higher-energy radiation belt particles with measurements of the lower energy ring current ions in a previous paper. Large deviations of that model, which fit only 50% of the data to within a factor of 10, suggested that another transport mechanism is operating in the ring current. Here we derive a modified diffusion coefficient corrected for electric field effects on ring current energy ions that fit nearly 80% of the data to within a factor of 2. Thus we infer that electric field fluctuations from the low-latitude to midlatitude ionosphere (ionospheric dynamo) dominated the ring current transport, rather than high-latitude or solar wind fluctuations. Much of the remaining deviation may arise from convective electric field transport of the E less than 30 keV particles. Since convection effects cannot be correctly treated with this azimuthally symmetric model, we defer treatment of the lowest-energy ions to a another paper. We give chi(exp 2) contours for the best fit, showing the dependence of the fit upon the internal/external spectral power of the predicted electric and magnetic field fluctuations.

Hydrothermal germanium over the southern East pacific rise.

PubMed

Mortlock, R A; Froelich, P N

1986-01-03

Germanium enrichment in the oceanic water column above the southern axis of the East Pacific Rise results from hydrothermal solutions emanating from hot springs along the rise crest. This plume signature provides a new oceanic tracer of reactions between seawater and sea floor basalts during hydrothermal alteration. In contrast to the sharp plumes of (3)He and manganese, the germanium plume is broad and diffuse, suggesting the existence of pervasive venting of low-temperature solutions off the ridge axis.

NMR Spin-Lock Induced Crossing (SLIC) Dispersion and Long-Lived Spin States of Gaseous Propane at Low Magnetic Field (0.05 T)

PubMed Central

Barskiy, Danila A.; Salnikov, Oleg G.; Romanov, Alexey S.; Feldman, Matthew A.; Coffey, Aaron M.; Kovtunov, Kirill V.; Koptyug, Igor V.; Chekmenev, Eduard Y.

2017-01-01

When parahydrogen reacts with propylene in low magnetic fields (e.g., 0.05 T), the reaction product propane develops an overpopulation of pseudo-singlet nuclear spin states. We studied how the spin-lock induced crossing (SLIC) technique can be used to convert these pseudo-singlet spin states of hyperpolarized gaseous propane into observable magnetization and to detect 1H NMR signal directly at 0.05 T. The theoretical simulation and experimental study of the NMR signal dependence on B1 power (SLIC amplitude) exhibits a well-resolved dispersion, which is induced by the spin-spin couplings in the eight-proton spin system of propane. We also measured the exponential decay time constants (TLLSS or TS) of these pseudo-singlet long-lived spin states (LLSS) by varying the time between hyperpolarized propane production and SLIC detection. We have found that, on average, TS is approximately 3 times longer than the corresponding T1 value under the same conditions in the range of pressures studied (up to 7.6 atm). Moreover, TS may exceed 13 seconds at pressures above 7 atm in the gas phase. These results are in agreement with the previous reports, and they corroborate a great potential of long-lived hyperpolarized propane as an inhalable gaseous contrast agent for lung imaging and as a molecular tracer to study porous media using low-field NMR and MRI. PMID:28152435

NMR Spin-Lock Induced Crossing (SLIC) dispersion and long-lived spin states of gaseous propane at low magnetic field (0.05 T)

NASA Astrophysics Data System (ADS)

Barskiy, Danila A.; Salnikov, Oleg G.; Romanov, Alexey S.; Feldman, Matthew A.; Coffey, Aaron M.; Kovtunov, Kirill V.; Koptyug, Igor V.; Chekmenev, Eduard Y.

2017-03-01

When parahydrogen reacts with propylene in low magnetic fields (e.g., 0.05 T), the reaction product propane develops an overpopulation of pseudo-singlet nuclear spin states. We studied how the Spin-Lock Induced Crossing (SLIC) technique can be used to convert these pseudo-singlet spin states of hyperpolarized gaseous propane into observable magnetization and to detect 1H NMR signal directly at 0.05 T. The theoretical simulation and experimental study of the NMR signal dependence on B1 power (SLIC amplitude) exhibits a well-resolved dispersion, which is induced by the spin-spin couplings in the eight-proton spin system of propane. We also measured the exponential decay time constants (TLLSS or TS) of these pseudo-singlet long-lived spin states (LLSS) by varying the time between hyperpolarized propane production and SLIC detection. We have found that, on average, TS is approximately 3 times longer than the corresponding T1 value under the same conditions in the range of pressures studied (up to 7.6 atm). Moreover, TS may exceed 13 s at pressures above 7 atm in the gas phase. These results are in agreement with the previous reports, and they corroborate a great potential of long-lived hyperpolarized propane as an inhalable gaseous contrast agent for lung imaging and as a molecular tracer to study porous media using low-field NMR and MRI.

Magmatic unrest beneath Mammoth Mountain, California

USGS Publications Warehouse

Hill, D.P.; Prejean, S.

2005-01-01

Mammoth Mountain, which stands on the southwest rim of Long Valley caldera in eastern California, last erupted ???57,000 years BP. Episodic volcanic unrest detected beneath the mountain since late 1979, however, emphasizes that the underlying volcanic system is still active and capable of producing future volcanic eruptions. The unrest symptoms include swarms of small (M ??? 3) earthquakes, spasmodic bursts (rapid-fire sequences of brittle-failure earthquakes with overlapping coda), long-period (LP) and very-long-period (VLP) volcanic earthquakes, ground deformation, diffuse emission of magmatic CO2, and fumarole gases with elevated 3He/4He ratios. Spatial-temporal relations defined by the multi-parameter monitoring data together with earthquake source mechanisms suggest that this Mammoth Mountain unrest is driven by the episodic release of a volume of CO2-rich hydrous magmatic fluid derived from the upper reaches of a plexus of basaltic dikes and sills at mid-crustal depths (10-20 km). As the mobilized fluid ascends through the brittle-plastic transition zone and into overlying brittle crust, it triggers earthquake swarm activity and, in the case of the prolonged, 11-month-long earthquake swarm of 1989, crustal deformation and the onset of diffuse CO2 emissions. Future volcanic activity from this system would most likely involve steam explosions or small-volume, basaltic, strombolian or Hawaiaan style eruptions. The impact of such an event would depend critically on vent location and season.

Spin Noise Detection of Nuclear Hyperpolarization at 1.2 K

PubMed Central

Pöschko, Maria Theresia; Vuichoud, Basile; Milani, Jonas; Bornet, Aurélien; Bechmann, Matthias; Bodenhausen, Geoffrey; Jannin, Sami; Müller, Norbert

2015-01-01

We report proton spin noise spectra of a hyperpolarized solid sample of commonly used “DNP (dynamic nuclear polarization) juice” containing TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxide) and irradiated by a microwave field at a temperature of 1.2 K in a magnetic field of 6.7 T. The line shapes of the spin noise power spectra are sensitive to the variation of the microwave irradiation frequency and change from dip to bump, when the electron Larmor frequency is crossed, which is shown to be in good accordance with theory by simulations. Small but significant deviations from these predictions are observed, which can be related to spin noise and radiation damping phenomena that have been reported in thermally polarized systems. The non-linear dependence of the spin noise integral on nuclear polarization provides a means to monitor hyperpolarization semi-quantitatively without any perturbation of the spin system by radio frequency irradiation. PMID:26477605

T-type α1H Ca2+ channels are involved in Ca2+ signaling during terminal differentiation (fusion) of human myoblasts

PubMed Central

Bijlenga, Philippe; Liu, Jian-Hui; Espinos, Estelle; Haenggeli, Charles-Antoine; Fischer-Lougheed, Jacqueline; Bader, Charles R.; Bernheim, Laurent

2000-01-01

Mechanisms underlying Ca2+ signaling during human myoblast terminal differentiation were studied using cell cultures. We found that T-type Ca2+ channels (T-channels) are expressed in myoblasts just before fusion. Their inhibition by amiloride or Ni2+ suppresses fusion and prevents an intracellular Ca2+ concentration increase normally observed at the onset of fusion. The use of antisense oligonucleotides indicates that the functional T-channels are formed by α1H subunits. At hyperpolarized potentials, these channels allow a window current sufficient to increase [Ca2+]i. As hyperpolarization is a prerequisite to myoblast fusion, we conclude that the Ca2+ signal required for fusion is produced when the resting potential enters the T-channel window. A similar mechanism could operate in other cell types of which differentiation implicates membrane hyperpolarization. PMID:10861024

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers.

PubMed

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-03-04

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity.

Light-evoked hyperpolarization and silencing of neurons by conjugated polymers

PubMed Central

Feyen, Paul; Colombo, Elisabetta; Endeman, Duco; Nova, Mattia; Laudato, Lucia; Martino, Nicola; Antognazza, Maria Rosa; Lanzani, Guglielmo; Benfenati, Fabio; Ghezzi, Diego

2016-01-01

The ability to control and modulate the action potential firing in neurons represents a powerful tool for neuroscience research and clinical applications. While neuronal excitation has been achieved with many tools, including electrical and optical stimulation, hyperpolarization and neuronal inhibition are typically obtained through patch-clamp or optogenetic manipulations. Here we report the use of conjugated polymer films interfaced with neurons for inducing a light-mediated inhibition of their electrical activity. We show that prolonged illumination of the interface triggers a sustained hyperpolarization of the neuronal membrane that significantly reduces both spontaneous and evoked action potential firing. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity in brain slices and explanted retinas. These findings prove the ability of conjugated polymers to tune neuronal firing and suggest their potential application for the in-vivo modulation of neuronal activity. PMID:26940513

15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH

PubMed Central

2016-01-01

15N nuclear spins of imidazole-15N2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole-15N2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15N site of imidazole occurs at physiological pH (pKa ∼ 7.0), and the binding event changes the 15N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms. PMID:27379344

Diazirines as Potential Molecular Imaging Tags: Probing the Requirements for Efficient and Long-Lived SABRE-Induced Hyperpolarization.

PubMed

Shen, Kun; Logan, Angus W J; Colell, Johannes F P; Bae, Junu; Ortiz, Gerardo X; Theis, Thomas; Warren, Warren S; Malcolmson, Steven J; Wang, Qiu

2017-09-25

Diazirines are an attractive class of potential molecular tags for magnetic resonance imaging owing to their biocompatibility and ease of incorporation into a large variety of molecules. As recently reported, 15 N 2 -diazirine can be hyperpolarized by the SABRE-SHEATH method, sustaining both singlet and magnetization states, thus offering a path to long-lived polarization storage. Herein, we show the generality of this approach by illustrating that the diazirine tag alone is sufficient for achieving excellent signal enhancements with long-lasting polarization. Our investigations reveal the critical role of Lewis basic additives, including water, on achieving SABRE-promoted hyperpolarization. The application of this strategy to a 15 N 2 -diazirine-containing choline derivative demonstrates the potential of 15 N 2 -diazirines as molecular imaging tags for biomedical applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH.

PubMed

Shchepin, Roman V; Barskiy, Danila A; Coffey, Aaron M; Theis, Thomas; Shi, Fan; Warren, Warren S; Goodson, Boyd M; Chekmenev, Eduard Y

2016-06-24

15 N nuclear spins of imidazole- 15 N 2 were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A 15 N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole- 15 N 2 in methanol:aqueous buffer (∼1:1). Proton binding to a 15 N site of imidazole occurs at physiological pH (p K a ∼ 7.0), and the binding event changes the 15 N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. 15 N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.

Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates.

PubMed

Vida, Imre; Bartos, Marlene; Jonas, Peter

2006-01-05

Networks of GABAergic neurons are key elements in the generation of gamma oscillations in the brain. Computational studies suggested that the emergence of coherent oscillations requires hyperpolarizing inhibition. Here, we show that GABA(A) receptor-mediated inhibition in mature interneurons of the hippocampal dentate gyrus is shunting rather than hyperpolarizing. Unexpectedly, when shunting inhibition is incorporated into a structured interneuron network model with fast and strong synapses, coherent oscillations emerge. In comparison to hyperpolarizing inhibition, networks with shunting inhibition show several advantages. First, oscillations are generated with smaller tonic excitatory drive. Second, network frequencies are tuned to the gamma band. Finally, robustness against heterogeneity in the excitatory drive is markedly improved. In single interneurons, shunting inhibition shortens the interspike interval for low levels of drive but prolongs it for high levels, leading to homogenization of neuronal firing rates. Thus, shunting inhibition may confer increased robustness to gamma oscillations in the brain.

NEUROSCIENCE. Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics.

PubMed

Govorunova, Elena G; Sineshchekov, Oleg A; Janz, Roger; Liu, Xiaoqin; Spudich, John L

2015-08-07

Light-gated rhodopsin cation channels from chlorophyte algae have transformed neuroscience research through their use as membrane-depolarizing optogenetic tools for targeted photoactivation of neuron firing. Photosuppression of neuronal action potentials has been limited by the lack of equally efficient tools for membrane hyperpolarization. We describe anion channel rhodopsins (ACRs), a family of light-gated anion channels from cryptophyte algae that provide highly sensitive and efficient membrane hyperpolarization and neuronal silencing through light-gated chloride conduction. ACRs strictly conducted anions, completely excluding protons and larger cations, and hyperpolarized the membrane of cultured animal cells with much faster kinetics at less than one-thousandth of the light intensity required by the most efficient currently available optogenetic proteins. Natural ACRs provide optogenetic inhibition tools with unprecedented light sensitivity and temporal precision. Copyright © 2015, American Association for the Advancement of Science.

Effects of anesthetic agents on in vivo axonal HCN current in normal mice.

PubMed

Osaki, Yusuke; Nodera, Hiroyuki; Banzrai, Chimeglkham; Endo, Sachiko; Takayasu, Hirokazu; Mori, Atsuko; Shimatani, Yoshimitsu; Kaji, Ryuji

2015-10-01

The objective was to study the in vivo effects of anesthetic agents on peripheral nerve excitability. Normal male mice were anesthetized by either isoflurane inhalation or a combination of medetomidine, midazolam, and butorphanol intraperitoneal injection ("triple agents"). Immediately after induction, the tail sensory nerve action potential was recorded and its excitability was monitored. Under both anesthetic protocols, there was an interval excitability change by long hyperpolarizing currents. There was greater threshold reduction approximately 30min post induction, in comparison to immediately post induction. Other excitability parameters were stable over time. Modeling suggested interval suppression of internodal H conductance or leak current. Anesthetic agents affected responses to long hyperpolarizing currents. Axonal excitability during intraoperative monitoring may be affected by anesthetic agents. Interpretation of interval excitability changes under anesthesia requires caution, especially with long hyperpolarizing currents. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Diffuse consolidation form of bronchoalveolar carcinoma.

PubMed

Khalil, Kanwal Fatima; Saeed, Waseem; Zill-e-Hamayun

2010-03-01

This case report describes a patient with diffuse consolidation form of bronchoalveolar carcinoma (BAC) which is a rare type of adenocarcinoma of lung. He was diagnosed on the basis of findings on X-ray and high resolution CT(HRCT) chest later confirmed by open lung biopsy and immuno-histochemical staining. Only supportive treatment could be provided and the patient expired during the subsequent month of follow-up. Traditionally, diffuse consolidation is the radiological presentation in only 20% of patients with bronchoalveolar carcinoma.

Primary intestinal lymphangiectasia successfully treated by segmental resections of small bowel.

PubMed

Kim, Na Rae; Lee, Suk-Koo; Suh, Yeon-Lim

2009-10-01

Primary intestinal lymphangiectasia is a rare cause of protein-losing enteropathy and usually presents with intermittent diarrhea or malnutrition. Diagnosis depends largely on its pathologic condition demonstrating greatly dilated lymphatics mainly in the lamina propria of the mucosa. We report a case of primary intestinal lymphangiectasia, of the diffuse type, presenting with abdominal pain and voluminous diarrhea in a previously healthy 8-year-old boy. He had periumbilical pain for 3 months before presentation. He was managed by segmental bowel resections and end-to-end anastomoses. The histopathologic condition of the resected small intestine showed lymphatic dilation limited mainly to the subserosa and mesentery but was not prominent in the mucosa. Abdominal pain and diarrhea subsided postoperatively. The present case is the fourth report describing a response to operative resection.

Amiodarone-induced myxoedema coma.

PubMed

Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

2014-04-12

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3-5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.

An unusual cutaneous manifestation of Crohn's disease.

PubMed

Weiser, Jessica A; Markowitz, David M; Husain, Sameera; Grossman, Marc E

2011-01-01

A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without organisms. Tissue cultures were negative for bacterial, fungal, and mycobacterial infection. Skin biopsy taken from the central upper back demonstrated subcorneal pustules with areas of eroded epidermis and collections of neutrophils in the superficial dermis (Figure 3). Special stains were negative for organisms. He received infliximab infusion 5 mg/kg for a total dose of 420 mg over 2 hours. Within 48 hours of infusion, there was notable decrease in size of lesions, in addition to reduction of purulent drainage from both eyes. The patient was discharged home following infliximab infusion. His skin lesions resolved during a period of 2 weeks, leaving small pink atrophic scars. He received his second infusion of infliximab 2 weeks after discharge with continued improvement in his gastrointestinal symptoms.

Computational studies of the helium-lithium hydride system

NASA Astrophysics Data System (ADS)

Taylor, Brian Keith

2000-12-01

We have computed an ab initio potential energy surface for the He-LiH system. We compute the He- LiH interaction energy at the CCSD(T) level using large correlation consistent atomic basis sets supplemented with bond functions. To capture the severe anisotropy of the He-LH potential, we interpolate our ab initio points in the angular direction with cubic splines, then expand the splines in terms of Legendre polynomials. We have constructed both a He-LiH rigid rotor potential and a complete He-LiH potential where the LiH bond length is allowed to change. The resulting potential surface has a unique shape. The He- LiH rigid rotor colinear geometry has a very attractive minimum of -176.7 cm-1, while the LiH-He colinear geometry has a local minimum of only -9.8 cm -1. Using our computed He-LiH potential energy surface, we investigate the collision dynamics of He-LiH. Using a totally quantum mechanical treatment of collisions dynamics, we compute both pure rotational and rovibrational state-to-state cross sections. We integrate our rovibrational cross sections over a Maxwell-Boltzmann distribution of energies to obtain temperature dependent vibrational excitation and relaxation rate constants. The vibrational excitation rate constants are very small for temperature below 400 K, but become significant at higher temperatures. These results suggests that He-LiH collisions probably were important in the very early Universe, especially in the larger primordial gas clouds. We also investigate the structure and dynamics of small HeN-LiH clusters using diffusion quantum Monte Carlo techniques. We find that three body effects are negligible, so we take the HeN-LiH potential to be a pairwise additive potential; we use the HFD-B3-FCI1 He-He potential of Aziz and Janzen [R. A. Aziz and A. R. Janzen, Phys. Rev. Lett. 74, 1586 (1995)] and our He-LiH potential. Because of the strong He-LiH attraction, one helium is always located in the attractive well at the lithium end of the LiH.

4He permeation and H2O uptake of cyanate ester resins — an alternative to commonly used epoxy resins at low temperature

NASA Astrophysics Data System (ADS)

Nakamura, Sachiko; Fujii, Takenori; Matsukawa, Shoji; Katagiri, Masayuki; Fukuyama, Hiroshi

2018-03-01

Cyanate ester (CE) thermoset is a polymer with a high glass-transition temperature of ≈ 300 °C. CE is expected to be an alternative to Stycast 1266 as a sealing and casting glue for low temperature experiments, especially for adsorption experiments where baking of the substrate at T > 100 °C before cooling is required to eliminate surface contaminations. We experimentally confirmed that thermosets of CE monomers are non-porous and absorbs/desorbs water very little from measurements of (1) 4He permeation properties at temperatures from room temperature (RT) to 77 K and of (2) weight gains (δW) after storage for days in water and in air at RT. The 4He permeation is rather large at RT but negligibly small at T ⪅ 130 K where the diffusion constant of 4He in CE is vanishingly small. δW in water and air are 0.3–0.5% and 0.5–1.0%, respectively, which are much smaller than those of Stycast 1266. Therefore, cyanate ester is an excellent alternative to commonly used epoxy resins especially in surface-sensitive experiments at low temperature.