Detection of tobacco smoke deposition by hyperpolarized krypton-83 MRI

Despite the importance of the tobacco smoke particulate matter in the lungs to the etiology of pulmonary disease in cigarette smokers, little is currently known about the spatial distribution of particle deposition or the persistence of the resulting deposits in humans, and no satisfactory technique currently exists to directly observe tobacco smoke condensate in airways. In this proof-of-principle work, hyperpolarized (hp) 83Kr MRI and NMR spectroscopy are introduced as probes for tobacco smoke deposition in porous media. A reduction in the hp-83Kr longitudinal (T1) relaxation of up to 95% under near-ambient humidity, pressure and temperature conditions was observed when the krypton gas was brought into contact with surfaces that had been exposed to cigarette smoke. This smoke-induced acceleration of the 83Kr self-relaxation was observed for model glass surfaces that, in some experiments, were coated with bovine lung surfactant extract. However, a similar effect was not observed with hp-(129)Xe indicating that the 83Kr sensitivity to smoke deposition was not caused by paramagnetic species but rather by quadrupolar relaxation due to high adsorption affinity for the smoke deposits. The 83Kr T1 differences between smoke-treated and untreated surfaces were sufficient to produce a strong contrast in variable flip angle FLASH hp-83Kr MRI, suggesting that hp-83Kr may be a promising contrast agent for in vivo pulmonary MRI.     

Quadrupolar relaxation of hyperpolarized krypton-83 as a probe for surfaces

This work reports the first systematic study of relaxation experienced by the hyperpolarized (hp) noble gas isotope (83)Kr (I=9/2) in contact with surfaces. The spin-lattice relaxation of (83)Kr is found to depend strongly on the chemical composition of the surfaces in the vicinity of the gas. This effect is caused by quadrupolar interactions during brief periods of surface adsorption that are the dominating source of longitudinal spin relaxation in the (83)Kr atoms. Simple model systems of closest packed glass beads with uniform but variable bead sizes are used for the relaxation measurements. The observed relaxation rates depend strongly on the chemical treatment of the glass surfaces and on the surface to volume ratio. Hp (83)Kr NMR relaxation measurements of porous polymers with pore sizes of 70-250 microm demonstrate the potential use of this new technique for material sciences applications.     

Exploring hyperpolarized 83Kr by remotely detected NMR relaxometry

For the first time, a hyperpolarized (hp) noble gas with a nuclear electric quadrupole moment is available for high-field nuclear-magnetic-resonance (NMR) spectroscopy and magnetic-resonance imaging. Hp (83)Kr (I=92) is generated by spin-exchange optical pumping and separated from the rubidium vapor used in the pumping process. Optical pumping occurs under the previously unstudied condition of high krypton gas densities. Signal enhancements of more than three orders of magnitude compared to the thermal equilibrium (83)Kr signal at 9.4 T magnetic-field strength are obtained. The spin-lattice relaxation of (83)Kr is caused primarily by quadrupolar couplings during the brief adsorption periods of the krypton atoms on the surrounding container walls and significantly limits the currently obtained spin polarization. Measurements in macroscopic glass containers and in desiccated canine lung tissue at field strengths between 0.05 and 3 T using remotely detected hp (83)Kr NMR spectroscopy reveal that the longitudinal relaxation dramatically accelerates as the magnetic-field strength decreases.     

Hyperpolarized 83Kr MRI of lungs

Hyperpolarized (hp) ⁸³Kr (spin I = 9/2) is a promising gas-phase contrast agent that displays sensitivity to the surface chemistry, surface-to-volume ratio, and surface temperature of the surrounding environment. This proof-of-principle study demonstrates the feasibility of ex vivo hp ⁸³Kr magnetic resonance imaging (MRI) of lungs using natural abundance krypton gas (11.5% ⁸³Kr) and excised, but otherwise intact, rat lungs located within a custom designed ventilation chamber. Experiments comparing the ⁸³Kr MR signal intensity from lungs to that arising from a balloon with no internal structure inflated to the same volume with krypton gas mixture suggest that most of the observed signal originated from the alveoli and not merely the conducting airways. The ⁸³Kr longitudinal relaxation times in the rat lungs ranged from 0.7 to 3.7 s but were reproducible for a given lung. Although the source of these variations was not explored in this work, hp ⁸³Kr T₁ differences may ultimately lead to a novel form of MRI contrast in lungs. The currently obtained 1200-fold signal enhancement for hp ⁸³Kr at 9.4 T field strength is found to be 180 times below the theoretical upper limit.     

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized Kr

Hyperpolarized ⁸³Kr has previously been demonstrated to enable MRI contrast that is sensitive to the chemical composition of the surface in a porous model system. Methodological advances have lead to a substantial increase in the ⁸³Kr hyperpolarization and the resulting signal intensity. Using the improved methodology for spin exchange optical pumping of isotopically enriched ⁸³Kr, internal anatomical details of ex vivo rodent lung were resolved with hyperpolarized ⁸³Kr MRI after krypton inhalation. Different ⁸³Kr relaxation times were found between the main bronchi and the parenchymal regions in ex vivo rat lungs. The T₁ weighted hyperpolarized ⁸³Kr MRI provided a first demonstration of surface quadrupolar relaxation (SQUARE) pulmonary MRI contrast.     

Hyperpolarized (131)Xe NMR spectroscopy

Hyperpolarized (hp) (131)Xe with up to 2.2% spin polarization (i.e., 5000-fold signal enhancement at 9.4 T) was obtained after separation from the rubidium vapor of the spin-exchange optical pumping (SEOP) process. The SEOP was applied for several minutes in a stopped-flow mode, and the fast, quadrupolar-driven T(1) relaxation of this spin I = 3/2 noble gas isotope required a rapid subsequent rubidium removal and swift transfer into the high magnetic field region for NMR detection. Because of the xenon density dependent (131)Xe quadrupolar relaxation in the gas phase, the SEOP polarization build-up exhibits an even more pronounced dependence on xenon partial pressure than that observed in (129)Xe SEOP. (131)Xe is the only stable noble gas isotope with a positive gyromagnetic ratio and shows therefore a different relative phase between hp signal and thermal signal compared to all other noble gases. The gas phase (131)Xe NMR spectrum displays a surface and magnetic field dependent quadrupolar splitting that was found to have additional gas pressure and gas composition dependence. The splitting was reduced by the presence of water vapor that presumably influences xenon-surface interactions. The hp (131)Xe spectrum shows differential line broadening, suggesting the presence of strong adsorption sites. Beyond hp (131)Xe NMR spectroscopy studies, a general equation for the high temperature, thermal spin polarization, P, for spin I ≥ 1/2 nuclei is presented.     

Tests for specific nonparametric relations between two distribution functions with applications

Let (X,Y) be a random vector and let G and H be the marginal distributions of X and Y, respectively. In this paper, we propose two tests, one of Kolmogorov‐Smirnov type and the other of Wilcoxon type, for the null hypothesis Ψ(G) = H against the alternative Ψ(G) < H, where Ψ() is a function such that Ψ(G) is a distribution function. The tests are based on the empirical distribution functions of the observations on X and Y, which are dependent. We obtain their asymptotic null distributions. A suspected relationship between the distribution functions of two dependent outcomes can be specified as a hypothesis to be tested in examples like the load sharing models, record values, and auction bidding models. As an application, we consider in detail the problem of testing the effect of load sharing in two component parallel systems.     

Hyperpolarized 83Kr and 129Xe NMR relaxation measurements of hydrated surfaces: implications for materials science and pulmonary diagnostics

In this proof of principle work, a technique is introduced to study hydrated surfaces using hyperpolarized (hp) 83Kr NMR spectroscopy. The longitudinal (T1) relaxation of hp-83Kr is shown to be extremely sensitive to the presence of adsorbed water on hydrophilic borosilicate and hydrophobic siliconized glass surfaces. The krypton surface relaxation is found to be largely independent of the total gas pressure applied to the studied materials, and the presented technique is therefore fairly robust. However, the relaxational properties of hp-83Kr can be "tuned" by adjusting the composition of the optical pumping gas mixture. This effect may be important for practical applications such as hp-83Kr MR imaging and can be achieved without sacrificing signal intensity. Complementary information to that of hp-83Kr surface relaxation data can be obtained from hp-129Xe relaxation measurements that are sensitive to the presence of paramagnetic surface sites. In contrast to the signal decay of hp-129Xe, the longitudinal relaxation of 83Kr is largely unaffected by paramagnetic impurities, and in some materials, 83Kr and 129Xe show comparable T1 times that are caused by two completely different relaxation mechanisms. Finally, the relaxation times of 83Kr in contact with bovine lung surfactant coated glass pores that are similar in size to mammalian alveoli are presented. The results suggest that in vivo MR studies may be feasible and could provide valuable information about changes in pulmonary surface chemistry.