Atsuomi Kimura

Analysis of the effect of foreign gases in the production of hyperpolarized 129Xe gas on a simple system working under atmospheric pressure

Experimental conditions that affect the degree of polarization of 129Xe gas were tested for a higher degree of polarization to facilitate a laboratory use of 129Xe NMR, primarily on the effect of addition of foreign gases. When He, N(2), or D(2) gas was added separately to pure Xe gas with natural isotope abundance, D(2) gas gave better results than the others in enhancing the degree of polarization in 129Xe atom. When these gases were added in mixture, however, N(2) plus He was proved to be more efficient than D(2) or He in enhancing the degree of polarization. As a result, the degree of polarization was found to be increased by more than an order, when diluent gases were properly mixed; polarization as high as 35% was reached at gas composition of 5% Xe, 10% N(2), and 85% He, whereas only a few percent was attainable when Xe gas was polarized without mixing any foreign gases [J. Magn. Reson. 150 (2), 156-160 (2001)]. These results were discussed on a basis of quenching and buffer effects of foreign gases. Polarization was also measured after separating the pure Xe gas from the mixture; value of 22% was obtained for the Xe gas isolated after solidification in liquid nitrogen trap. Build-up time of the polarization was also tested, which did not change remarkably depending on the gas composition.

Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration.

In the present study, a chemical shift saturation recovery method in hyperpolarized 129Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase‐induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, Vs/Va, and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase‐treated mice. Our results showed that Vs/Va was significantly reduced in elastase‐treated mice, reflecting emphysema‐like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized 129Xe MR spectroscopy to a mouse model of emphysema and shows that the Vs/Va volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents. Magn Reson Med, 2010.

The study of Xe adsorption behavior in meso-size pores of carbon black materials using laser-polarized 129Xe NMR spectroscopy.

The meso size pores of carbon black materials with Pt critically affect catalysts which play an important role for fuel cells of electric vehicles. Time-consuming BET methods are usually used to measure the physisorption enthalpy which determines the characteristics of catalysts. The laser polarized method enhances 129Xe polarization by 4 orders of magnitude, overcoming a low sensitivity, making this measurement technique faster than conventional experiments. In this paper, we first demonstrate Laser-Polarized 129Xe NMR Spectroscopy for studying carbon black materials with Pt of fuel cells of electric vehicles in order to determine the physisorption enthalpy. At the same time, T1 experiments using Laser-Polarized 129Xe will be discussed in order to clarify the surface condition and adsorption behavior.

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system.

To apply a continuous flow‐type hyperpolarizing (CF‐HP) system to lung imaging and investigate the feasibility of hyperpolarized 129Xe MRI at a low xenon concentration.

Hyperpolarized 129Xe lung MRI in spontaneously breathing mice with respiratory gated fast imaging and its application to pulmonary functional imaging

In the present study, a balanced steady‐state free precession pulse sequence combined with compressed sensing was applied to hyperpolarized 129Xe lung imaging in spontaneously breathing mice. With the aid of fast imaging techniques, the temporal resolution was markedly improved in the resulting images. Using these protocols and respiratory gating, 129Xe lung images in end‐inspiratory and end‐expiratory phases were obtained successfully. The application of these techniques for pulmonary functional imaging made it possible to simultaneously evaluate regional ventilation and gas exchange in the same animal. A comparative study between healthy and elastase‐induced mouse models of emphysema showed abnormal ventilation as well as gas exchange in elastase‐treated mice. Copyright

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema.

MRI of hyperpolarized 129Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T  2* and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo‐time sequence was introduced, and its feasibility to quantitatively assess emphysema‐like pulmonary tissue destruction by a combination of dissolved‐ and gas‐phase 129Xe lung MRI was investigated. The ultrashort echo‐time has made it possible to acquire dissolved 129Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm2 and to obtain T  2* of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of 129Xe magnetization that diffused into the septa relative to the gas‐phase magnetization F was regionally evaluated. The mean F value of elastase‐treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface‐to‐volume ratio. Magn Reson Med, 2013.

Hyperpolarized 129Xe dynamic study in mouse lung under spontaneous respiration: Application to murine tumor B16BL6 melanoma

This is a study on the analysis of hyperpolarized (HP) (129)Xe dynamics applied in the lung of a pathological model mouse under spontaneous respiration. A novel parameter k(1)k(2) - a product of the rate constant for Xe transfer from gas to dissolved phase (k(1)) and from dissolved to gas phase (k(2)) - was shown to be derived successfully from the analysis of the HP (129)Xe dynamic MR experiment in the mouse lung under spontaneous respiration with the aid of a selective pre-saturation technique. A comparative study using healthy mice and model mice induced with lung cancer (by injection of murine tumor B16BL6 melanoma) was performed and a significant difference was found in the k(1)k(2) values of the two groups, that is, 0.020+/-0.007s(-2) (n=4) for healthy mice and 0.032+/-0.04s(-2) (n=3) for lung cancer model mice (p=0.04). Thus, the parameter obtained by our proposed method is considered useful for detection of lung tumors.

Regional fractional ventilation mapping in spontaneously breathing mice using hyperpolarized 129Xe MRI

The feasibility of ventilation imaging with hyperpolarized (HP) 129Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP 129Xe delivered continuously from a 129Xe polarizer. A series of 129Xe ventilation images was obtained by varying the number of breaths before the 129Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE‐treated group. The whole‐lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE‐treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents. Copyright

Development of a fast method for quantitative measurement of hyperpolarized 129Xe dynamics in mouse brain

A fast method has been established for the precise measurement and quantification of the dynamics of hyperpolarized (HP) xenon‐129 (129Xe) in the mouse brain. The key technique is based on repeatedly applying radio frequency (RF) pulses and measuring the decrease of HP 129Xe magnetization after the brain Xe concentration has reached a steady state due to continuous HP 129Xe ventilation. The signal decrease of the 129Xe nuclear magnetic resonance (NMR) signal was well described by a simple theoretical model. The technique made it possible to rapidly evaluate the rate constant α, which is composed of cerebral blood flow (CBF), the partition coefficient of Xe between the tissue and blood (λi), and the longitudinal relaxation time (T1i) of HP 129Xe in the brain tissue, without any effect of depolarization by RF pulses and the dynamics in the lung. The technique enabled the precise determination of α as 0.103 ± 0.018 s‐1 (± SD, n = 5) on healthy mice. To investigate the potential of this method for detecting physiological changes in the brain of a kainic acid (KA) ‐induced mouse model of epilepsy, an attempt was made to follow the time course of α after KA injection. It was found that the α value changes characteristically with time, reflecting the change in the physiological state of the brain induced by KA injection. By measuring CBF using 1H MRI and 129Xe dynamics simultaneously and comparing these results, it was suggested that the reduction of T1i, in addition to the increase of CBF due to KA‐induced epilepsy, are possible causes of the change in 129Xe dynamics. Thus, the present method would be useful to detect a pathophysiological state in the brain and provide a novel tool for future brain study. Copyright

Hyperpolarized 129Xe MRI using isobutene as a new quenching gas

The use of a quenching gas, isobutene, with a low vapor pressure was investigated to enhance the utility of hyperpolarized 129Xe (HP Xe) MRI. Xenon mixed with isobutene was hyperpolarized using a home‐built apparatus for continuously producing HP Xe. The isobutene was then readily liquefied and separated almost totally by continuous condensation at about 173 K, because the vapor pressure of isobutene (0.247 kPa) is much lower than that of Xe (157 kPa). Finally, the neat Xe gas was continuously delivered to mice by spontaneous inhalation. The HP Xe MRI was enhanced twofold in polarization level and threefold in signal intensity when isobutene was adopted as the quenching gas instead of N2. The usefulness of the HP Xe MRI was verified by application to pulmonary functional imaging of spontaneously breathing mice, where the parameters of fractional ventilation (ra) and gas exchange (fD) were evaluated, aiming at future extension to preclinical studies. This is the first application of isobutene as a quenching gas for HP Xe MRI.