Ultra-sensitive magnetometry based on free precession of nuclear spins

We discuss the design and performance of a very sensitive low-field magnetometer based on the detection of free spin precession of gaseous, nuclear polarized ³He or ¹²⁹Xe samples with a SQUID as magnetic flux detector. The device will be employed to control fluctuating magnetic fields and gradients in a new experiment searching for a permanent electric dipole moment of the neutron. Furthermore, with the detection of the free precession of co-located ³He/¹²⁹Xe nuclear spins it can be used as ultra-sensitive probe for non-magnetic spin interactions, since the magnetic dipole interaction (Zeeman-term) drops out. Characteristic spin precession times T₂ ^* of up to 60 h were measured. The achieved signal-to-noise ratio of more than 5000:1 leads to an expected sensitivity level (Cramer-Rao lower bound) of δB≈1 fT after an integration time of 220 s and of δB≈10^-4 fT after one day. By means of a co-located ³He/¹²⁹Xe magnetometer, noise sources inherent in the magnetometer could be investigated, showing that CRLB is fulfilled, at least down to δB≈10^-2 fT. The reason for such a high sensitivity is that free precessing ³He (¹²⁹Xe) nuclear spins are almost completely decoupled from the environment. Therefore, this type of magnetometer is particularly attractive for precision field measurements where long-term stability is required.     

Magnetic resonance imaging of dissolved hyperpolarized Xe using a membrane-based continuous flow system

A technique for continuous production of solutions containing hyperpolarized ¹²⁹Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized ¹²⁹Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of ¹²⁹Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized ¹²⁹Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.     

A new search for the atomic EDM of 129Xe at FRM-II

Permanent electric dipole moments (EDMs) arise due to the breaking of time-reversal or, equivalently, CP-symmetry. Although EDM searches have so far only set upper limits, which are many orders of magnitude larger than Standard Model (SM) predictions, the motivation for more sensitive searches is stronger than ever. A new effort at FRM-II incorporating ¹²⁹Xe and ³He as a co-magnetometer can potentially improve the current limit. The noble gas mixture of ¹²⁹Xe and ³He is simultanously polarized by spin-exchange optical pumping and then transferred into a high-performance magnetically shielded room. Inside, both species can freely precess in the presence of applied magnetic and electric fields. The precession signals are detected by LTc SQUID sensors. In EDM cells with silicon electrodes we observed spin lifetimes in excess of 2500 s without and with high-voltage applied. This meets one requirement to achieve our goal of improving the EDM limit on ¹²⁹Xe by several orders of magnitude.     

Novel MRI applications of laser-polarized noble gases

Gas-phase nuclear magnetic resonance (NMR) has great potential as a probe for a variety of interesting physical and biomedical problems that are not amenable to study by water or similar liquid. However, NMR of gases was largely neglected due to the low signal obtained from the thermally polarized gases with very low sample density. The advent of optical pumping techniques for enhancing the polarization of the noble gases³He and¹²⁹Xe has bought new life to this field, especially in medical imaging where³He lung inhalation imaging is approaching a clinical application. However, there are numerous applications in materials science that also benefit from the use of these gases. We review primarily nonmedical applications of laser-polarized noble gases for both NMR imaging and spectroscopy and highlight progress with examples from our laboratory including high-resolution imaging at millitesla applied field strength and velocity imaging of convective flow. Porous media microstucture has been probed with both thermal and laser-polarized xenon, as xenon is an ideal probe due to low surface interaction with the grains of the porous media.     

Alkali lasers for magnetic resonance imaging

Spin-polarized nuclei of such gases as ³He and ¹²⁹Xe are successfully used for magnetic resonance imaging of lungs and other organs of human body. To produce large numbers of spin-polarized nuclei required for this medical application, a high power narrowband tunable laser source is required. Diode pumped alkali lasers, developed during last several years can be an ideal source for this application. In this paper we present our latest achievements in diode pumped alkali lasers development. We describe optically pumped Cs laser tunable in the range of 14 GHz and operating in single transverse mode with a linewidth less than 3 MHz. We also present continuous wave diode pumped Rb and Cs lasers with output power 17 W and 20 W.     

Imaging of a mixture of hyperpolarized 3He and 129Xe

With the use of hyperpolarized gases, a great number of experiments have been carried out in order to improve the diagnostics of the lung, both from a structural and a functional point of view. 3He is best suited for structural studies, whereas 129Xe gives more detailed information about the functionality of the lung because it enters the bloodstream. In this work, we propose the use of a gas mixture to perform consecutive analysis of lung structure and functionality upon the delivery of a single bolus of gas. We show images of a helium-xenon gas mixture in the presence of a small amount of liquid toluene in order to demonstrate how both nuclei can be detected independently, extracting the spectroscopic information provided by the 129Xe spectra and obtaining an image with high sensitivity for 3He. A second experiment performed on a dissected mouse lung was used to demonstrate how the mixture of gases can enhance sensitivity in the larger airways of the lung.     

Searches for Lorentz violation in 3He/129Xe clock comparison experiments

We discuss the design and performance of a very sensitive low-field magnetometer based on the detection of free spin precession of gaseous, nuclear polarized ³He or ¹²⁹Xe samples with a SQUID as magnetic flux detector. Characteristic spin precession times $T_2^\ast$ of up to 115 h were measured in low magnetic fields (about 1 μT) and in the regime of motional narrowing. With the detection of the free precession of co-located ³He/¹²⁹Xe nuclear spins (clock comparison), the device can be used as ultra-sensitive probe for non-magnetic spin interactions, since the magnetic dipole interaction (Zeeman-term) drops out in the weighted frequency difference, i.e., Δω?=?ω _He ???γ _He /γ _Xe ·ω _Xe . We report on searches for Lorentz violating signatures by monitoring the Larmor frequencies of co-located ³He/¹²⁹Xe spin samples as the laboratory reference frame rotates with respect to distant stars (sidereal modulation).     

Nuclear Spin Maser Oscillation of 129Xe by Means of Optical-Detection Feedback

We have developed the nuclear spin maser oscillating at a low frequency of 34 Hz with highly polarized nuclear spins of the noble gas element ¹²⁹Xe. The system is advantageous for detecting a small frequency shift of the nuclear spin precession. We are thus planning to apply this system to the search for an atomic electric dipole moment of ¹²⁹Xe. We here report the development of the system and its performance.     

MEASUREMENTS OF RELAXATION OF SPIN POLARIZED 129Xe NUCLEI IN HIGH MAGNETIC FIELDS

We observed the NMR signal of low-pressure gas ¹²⁹Xe by laser enhanced method on an MSL-400 NMR spectrometer and measured nuclear spin relaxations of ¹²⁹Xe gas at various temperatures. The relaxation rate constant of ¹²⁹Xe-¹³³Cs spin exchange was obtained as (6.8±0.5)×10^-16cm^-3s^-1.     

Production of nitrogen-free, hyperpolarized 129Xe gas

129 Xe with a nuclear polarization far above the thermal equilibrium value (hyperpolarized) is used in NMR studies to increase sensitivity. Gaseous, adsorbed, or dissolved xenon is utilized in physical, chemical, and medical applications. With the aim in mind to study single-crystal surfaces by NMR of adsorbed hyperpolarized ¹²⁹Xe, three problems have to be solved. The reliable production of ¹²⁹Xe with highest nuclear polarization possible, the separation of the xenon gas from the necessary quench gas nitrogen without polarization loss, and the dosing/delivery of small amounts of polarized xenon gas to a sample surface. Here we describe an optical pumping setup that regularly produces xenon gas with a ¹²⁹Xe nuclear polarization of 0.7(±0.07). We show that a freeze–pump–thaw separation of xenon and nitrogen is feasible without a significant loss in xenon polarization. The nitrogen partial pressure can be suppressed by a factor of 400 in a single separation cycle. Dosing is achieved by using the low vapor pressure of a frozen hyperpolarized xenon sample. Received: 12 June 1998     

Consequences of Xe–H Cross Relaxation in Aqueous Solutions

We have investigated the transfer of polarization from ¹²⁹Xe to solute protons in aqueous solutions to determine the feasibility of using hyperpolarized xenon to enhance ¹H sensitivity in aqueous systems at or near room temperatures. Several solutes, each of different molecular weight, were dissolved in deuterium oxide and although large xenon polarizations were created, no significant proton signal enhancement was detected in -tyrosine, α-cyclodextrin, β-cyclodextrin, apomyoglobin, or myoglobin. Solute-induced enhancement of the ¹²⁹Xe spin–lattice relaxation rate was observed and depended on the size and structure of the solute molecule. The significant increase of the apparent spin–lattice relaxation rate of the solution phase ¹²⁹Xe by α-cyclodextrin and apomyoglobin indicates efficient cross relaxation. The slow relaxation of xenon in β-cyclodextrin and -tyrosine indicates weak coupling and inefficient cross relaxation. Despite the apparent cross-relaxation effects, all attempts to detect the proton enhancement directly were unsuccessful. Spin–lattice relaxation rates were also measured for Boltzmann ¹²⁹Xe in myoglobin. The cross-relaxation rates were determined from changes in ¹²⁹Xe relaxation rates in the α-cyclodextrin and myoglobin solutions. These cross-relaxation rates were then used to model ¹H signal gains for a range of ¹²⁹Xe to ¹H spin population ratios. These models suggest that in spite of very large ¹²⁹Xe polarizations, the ¹H gains will be less than 10% and often substantially smaller. In particular, dramatic ¹H signal enhancements in lung tissue signals are unlikely.     

XeNA: An automated ‘open-source’ Xe hyperpolarizer for clinical use

Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~ 1 L/h) ¹²⁹Xe 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 1800 Torr Xe in 0.5 L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell ¹²⁹Xe nuclear spin polarization values of ~ 30%–90% have been measured for Xe loadings of ~ 300–1600 Torr. Typical ¹²⁹Xe polarization build-up and T₁ relaxation time constants were ~ 8.5 min and ~ 1.9 h 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 ~ 200 W), permit such high P_Xe 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 ¹²⁹Xe relaxation times (up to nearly 6 h) were observed in Tedlar bags following transport to a clinical 3 T 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.     

Enhanced NMR signal from the laser-polarized129Xe produced by spin exchange at a high magnetic field

Nuclear-magnetic-resonance (NMR) measurement of laser-polarized gaseous¹²⁹Xe produced by spin-exchange optical pumping with a narrow-linewidth laser at a high magnetic field of 4.7 T is reported. The samples are contained in the glass tubes. The nuclear spin polarization of the laserpolarized¹²⁹Xe is 3.9%, and this corresponds to an enhancement of 9· 10³ compared to the equilibrium value at 311 K and at the same magnetic field. The laser-enhanced¹²⁹Xe NMR signals can be used in MR imaging.     

Intravascular delivery of hyperpolarized129Xenon forin vivo MRI

The nuclear polarization of¹²⁹Xe and³He can be enhanced by several orders of magnitude by using optical pumping techniques, thus allowing NMR detection of xenon and helium in very low concentrations. The benefits of optically enhanced magnetic resonance (MR) are already exploited in MR imaging of the lungs using optically polarized³He. The high solubility of xenon in blood and lipids suggests a variety ofin vivo MR applications, for instance perfusion measurements or functional MR studies. This article reviews some current work directed towards delivery of optically polarized xenon forin vivo MR applications.     

An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized ³He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B₀ coil design that produces an optimized 65 G (6.5 mT) magnetic field for ³He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D ³He images with up to 2.8 mm resolution, and present initial 2D and 3D ³He images of human lungs in both supine and upright orientations. ¹H MRI can also be performed for diagnostic and calibration reasons.     

Chemical-Shifts in Magnetic-Resonance of the 3He Nucleus in Liquid Solvents and Comparison with Other Noble Gases

Gas-to-solution solvent shifts of ³He dissolved in 17 pure liquids were measured. Two types of samples were used, under helium pressures of about 2 and 30 atm. No measurable pressure effect on the shift could be detected. The gas-to-solution shifts are dominated by the bulk susceptibility, for which correction was made. The resulting medium-shift range in our solvents is about 0.8 ppm. Hence ³He provides an excellent probe for the detection of minute local magnetic fields at the site of noble-gas atoms. For the first time shifts in liquid solvents for all four NMR-accessible noble-gas nuclei (³He, ²¹Ne, ⁸³Kr, and ¹²⁹Xe) can be compared. The medium shifts of ³He show a roughly linear correlation to medium shifts of ¹²⁹Xe, ⁸³Kr, and ²¹Ne in the same solvents. The corrected relative solvent shifts, that is, the solvent effects divided by σ_d, the diamagnetic shielding of the free atom, and by the number of nearest-neighbor solvent molecules, are approximately equal for all four noble gases.     

Relaxation Behavior of Laser-Polarized Xe Gas: Size Dependency and Wall Effect of the T1 Relaxation Time in Glass and Gelatin Bulbs

Size dependency of the relaxation time T₁ was measured for laser-polarized ¹²⁹Xe gas encapsulated in different sized cavities made by glass bulbs or gelatin capsules. The use of laser-polarized gas enhances the sensitivity a great deal, making it possible to measure the longer ¹²⁹Xe relaxation time in quite a short time. The size dependency is analyzed on the basis of the kinetic theory of gases and a relationship is derived in which the relaxation rate is connected with the square inverse of the diameter of the cavity. Such an analysis provides a novel parameter which denotes the wall effect on the relaxation rate when a gas molecule collides with the surface once in a second. The relaxation time of ¹²⁹Xe gas is also dependent on the material which forms the cavity. This dependency is large and the relaxation study using polarized ¹²⁹Xe gas is expected to offer important information about the state of the matter of the cavity wall.     

Frequency-selective laser optical pumping and spin exchange of cesium with129Xe and131Xe in a high magnetic field

We report the experimental results of frequency-selective laser optical pumping and spin exchange of Cs with¹²⁹Xe and¹³¹Xe in a high magnetic field of 11.74 T. Our results show that hyperpolarized¹²⁹Xe and¹³¹Xe nuclear magnetic resonance (NMR) signals exhibit alternating phases when the laser frequency for pumping the cesium atoms is changed, which is explained on the basis of the high-field optical pumping of Cs. We obtain about 3% polarization of the¹²⁹Xe. The electron-spin polarization of the Cs atoms has been measured to be about 22% with a simple NMR method.     

129Xe and131Xe NMR of xenon on silica surfaces at 77 K

Little is known about¹²⁹Xe NMR spectral features and spin-lattice relaxation behavior, and the dynamics of xenon atoms, for xenon adsorbed on solid surfaces at cryogenic temperatures (≤77 K), where exchange with gas-phase atoms is not a significant complication. We report¹²⁹Xe NMR experiments at 9,4 T that provide such information for xenon adsorbed onto the hydroxylated surface of a number of microporous silica samples at 77 K. A convenient design for these cryogenic experiments is described. Dynamics of surface-adsorbed xenon atoms on the time scale of seconds can be observed by¹²⁹Xe NMR hole-burning experiments; much slower dynamics occurring over hours and days are evidenced from changes with time of the¹²⁹Xe NMR chemical shifts. The peak maxima occur in the region ca. 180–316 ppm, considerably downfield of¹²⁹Xe shifts previously reported on surfaces at higher temperatures, and closer to the shift of xenon bulk solid (316.4±1 ppm). The¹²⁹Xe spin-lattice relaxation timesT ₁ range over five orders of magnitude; possible explanations for both nonexponential relaxation behavior and extremely shortT ₁ values (35 ms) are discussed. Preliminary¹³¹Xe and¹H NMR results are presented, as well as a method for greatly increasing the sensitivity of¹²⁹Xe NMR detection at low temperatures by using closely-spaced trains of rf pulses.     

Spin polarized 3He: From basic research to medical applications

Polarization of ³He gas by means of optical pumping is well known since the early 1960s with first applications in fundamental physics. Some thirty years later it was discovered, that one can use hyperpolarized ³He as contrast agent for magnetic resonance imaging of the lung. The wide interest in this new method made it necessary to find ways of polarizing ³He in large quantities with high polarization degrees. A high performance polarizing facility has been developed at the University of Mainz, designed for centralized production of hyperpolarized ³He gas. We present the Mainz concept as well as some examples of numerous applications of spin polarized ³He in fundamental research and medical applications.