Thomas Meersmann

Perspectives of hyperpolarized noble gas MRI beyond 3He

Graphical abstract Highlights ► Advances in hyperpolarization have reduced the SNR gap between 3He and 129Xe. ► 129Xe offers additional information useful in materials and biomedical sciences. ► Non-invasive techniques with 129Xe probe lung morphometry and offer new biomarkers. ► 83Kr with a nuclear electric quadrupole moment provides surface sensitive contrast.

Spin-exchange optical pumping of high-density xenon-129

Gas mixtures with high xenon densities are explored for continuous flow spin-exchange optical pumping. It is shown that the 129Xe-NMR signal increases significantly with increasing xenon partial pressures up to about 200 kPa, despite a decreasing spin-polarization. Comparison of the rubidium infrared D2 emission with the xenon polarization demonstrates that radiation quenching by molecular nitrogen is of no substantial benefit for the pumping process at xenon pressures above 100 kPa. This reflects a diminished importance of spin-depolarization by radiation trapping due to the increased significance of spin-relaxation by rubidium-xenon collisions at high xenon densities. A quantitative expression for this effect is provided.

Pathway to Cryogen Free Production of Hyperpolarized Krypton-83 and Xenon-129

Hyperpolarized (hp) 129Xe and hp 83Kr for magnetic resonance imaging (MRI) are typically obtained through spin-exchange optical pumping (SEOP) in gas mixtures with dilute concentrations of the respective noble gas. The usage of dilute noble gases mixtures requires cryogenic gas separation after SEOP, a step that makes clinical and preclinical applications of hp 129Xe MRI cumbersome. For hp 83Kr MRI, cryogenic concentration is not practical due to depolarization that is caused by quadrupolar relaxation in the condensed phase. In this work, the concept of stopped flow SEOP with concentrated noble gas mixtures at low pressures was explored using a laser with 23.3 W of output power and 0.25 nm linewidth. For 129Xe SEOP without cryogenic separation, the highest obtained MR signal intensity from the hp xenon-nitrogen gas mixture was equivalent to that arising from 15.5±1.9% spin polarized 129Xe in pure xenon gas. The production rate of the hp gas mixture, measured at 298 K, was 1.8 cm3/min. For hp 83Kr, the equivalent of 4.4±0.5% spin polarization in pure krypton at a production rate of 2 cm3/min was produced. The general dependency of spin polarization upon gas pressure obtained in stopped flow SEOP is reported for various noble gas concentrations. Aspects of SEOP specific to the two noble gas isotopes are discussed and compared with current theoretical opinions. A non-linear pressure broadening of the Rb D1 transition was observed and taken into account for the qualitative description of the SEOP process.

Hyperpolarized 131Xe NMR spectroscopy

Hyperpolarized (hp) 131Xe 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 T1 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 131Xe 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 129Xe SEOP. 131Xe 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 131Xe 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 131Xe spectrum shows differential line broadening, suggesting the presence of strong adsorption sites. Beyond hp 131Xe NMR spectroscopy studies, a general equation for the high temperature, thermal spin polarization, P, for spin I⩾1/2 nuclei is presented.

Exploring hyperpolarized Kr83 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 Kr83 (I=9∕2) 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 Kr83 signal at 9.4T magnetic-field strength are obtained. The spin-lattice relaxation of Kr83 is caused primarly 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 3T using remotely detected hp Kr83 NMR spectroscopy reveal that the longitudinal relax...

Cryogenics free production of hyperpolarized 129Xe and 83Kr for biomedical MRI applications

As an alternative to cryogenic gas handling, hyperpolarized (hp) gas mixtures were extracted directly from the spin exchange optical pumping (SEOP) process through expansion followed by compression to ambient pressure for biomedical MRI applications. The omission of cryogenic gas separation generally requires the usage of high xenon or krypton concentrations at low SEOP gas pressures to generate hp (129)Xe or hp (83)Kr with sufficient MR signal intensity for imaging applications. Two different extraction schemes for the hp gasses were explored with focus on the preservation of the nuclear spin polarization. It was found that an extraction scheme based on an inflatable, pressure controlled balloon is sufficient for hp (129)Xe handling, while (83)Kr can efficiently be extracted through a single cycle piston pump. The extraction methods were tested for ex vivo MRI applications with excised rat lungs. Precise mixing of the hp gases with oxygen, which may be of interest for potential in vivo applications, was accomplished during the extraction process using a piston pump. The (83)Kr bulk gas phase T1 relaxation in the mixtures containing more than approximately 1% O2 was found to be slower than that of (129)Xe in corresponding mixtures. The experimental setup also facilitated (129)Xe T1 relaxation measurements as a function of O2 concentration within excised lungs.

Hyperpolarized 83Kr MRI of lungs

Hyperpolarized (hp) (83)Kr (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 (83)Kr magnetic resonance imaging (MRI) of lungs using natural abundance krypton gas (11.5% (83)Kr) and excised, but otherwise intact, rat lungs located within a custom designed ventilation chamber. Experiments comparing the (83)Kr 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 (83)Kr longitudinal relaxation times in the rat lungs ranged from 0.7 to 3.7s but were reproducible for a given lung. Although the source of these variations was not explored in this work, hp (83)Kr T(1) differences may ultimately lead to a novel form of MRI contrast in lungs. The currently obtained 1200-fold signal enhancement for hp (83)Kr at 9.4T field strength is found to be 180 times below the theoretical upper limit.

Studying porous materials with krypton-83 NMR spectroscopy

This report is the first review of 83Kr nuclear magnetic resonance as a new and promising technique for exploring the surfaces of solid materials. In contrast to the spin I = 1/2 nucleus of 129Xe, 83Kr has a nuclear spin of I = 9/2 and therefore possesses a nuclear electric quadrupole moment. Interactions of the quadrupole moment with the electronic environment are modulated by surface adsorption processes and therefore affect the 83Kr relaxation rate and spectral lineshape. These effects are much more sensitive probes for surfaces than the 129Xe chemical shielding and provide unique insights into macroporous materials in which the 129Xe chemical shift is typically of little diagnostic value. The first part of this report reviews the effect of quadrupolar interactions on the 83Kr linewidth in zeolites and also the 83Kr chemical shift behavior that is distinct from that of its 129Xe cousin in some of these materials. The second part reviews hyperpolarized (hp) 83Kr NMR spectroscopy of macroporous materials in which the longitudinal relaxation is typically too slow to allow sufficient averaging of thermally polarized 83Kr NMR signals. The quadrupolar‐driven T1 relaxation times of hp 83Kr in these materials are sensitive to surface chemistry, surface‐to‐volume ratios, coadsorption of other species on surfaces, and surface temperature. Thus, 83Kr T1 relaxation can provide information about surfaces and chemical processes in macroscopic pores and can generate surface‐sensitive contrast in hp 83Kr MRI. Copyright

Effects of pulmonary inhalation on hyperpolarized krypton-83 magnetic resonance T1 relaxation

The (83)Kr magnetic resonance (MR) relaxation time T(1) of krypton gas in contact with model surfaces was previously found to be highly sensitive to surface composition, surface-to-volume ratio, and surface temperature. The work presented here explored aspects of pulmonary (83)Kr T(1) relaxation measurements in excised lungs from healthy rats using hyperpolarized (hp) (83)Kr with approximately 4.4% spin polarization. MR spectroscopy without spatial resolution was applied to the ex vivo lungs that actively inhale hp (83)Kr through a custom designed ventilation system. Various inhalation schemes were devised to study the influence of anatomical dead space upon the measured (83)Kr T(1) relaxation times. The longitudinal (83)Kr relaxation times in the distal airways and the respiratory zones were independent of the lung inhalation volume, with T(1) = 1.3 s and T(1) = 1.0 s, depending only on the applied inhalation scheme. The obtained data were highly reproducible between different specimens. Further, the (83)Kr T(1) relaxation times in excised lungs were unaffected by the presence of up to 40% oxygen in the hp gas mixture. The results support the possible importance of (83)Kr as a biomarker for evaluating lung function.

Pulmonary MRI contrast using Surface Quadrupolar Relaxation (SQUARE) of hyperpolarized 83Kr

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.