Optically polarized 3He.

This article reviews the physics and technology of producing large quantities of highly spin-polarized 3He nuclei using spin-exchange (SEOP) and metastability-exchange (MEOP) optical pumping. Both technical developments and deeper understanding of the physical processes involved have led to substantial improvements in the capabilities of both methods. For SEOP, the use of spectrally narrowed lasers and K-Rb mixtures has substantially increased the achievable polarization and polarizing rate. For MEOP nearly lossless compression allows for rapid production of polarized 3He and operation in high magnetic fields has likewise significantly increased the pressure at which this method can be performed, and revealed new phenomena. Both methods have benefitted from development of storage methods that allow for spin-relaxation times of hundreds of hours, and specialized precision methods for polarimetry. SEOP and MEOP are now widely applied for spin-polarized targets, neutron spin filters, magnetic resonance imaging, and precision measurements.

Organic electronics. Room-temperature coupling between electrical current and nuclear spins in OLEDs.

The effects of external magnetic fields on the electrical conductivity of organic semiconductors have been attributed to hyperfine coupling of the spins of the charge carriers and hydrogen nuclei. We studied this coupling directly by implementation of pulsed electrically detected nuclear magnetic resonance spectroscopy in organic light-emitting diodes (OLEDs). The data revealed a fingerprint of the isotope (protium or deuterium) involved in the coherent spin precession observed in spin-echo envelope modulation. Furthermore, resonant control of the electric current by nuclear spin orientation was achieved with radiofrequency pulses in a double-resonance scheme, implying current control on energy scales one-millionth the magnitude of the thermal energy.

Collisional 3He and 129Xe frequency shifts in Rb-noble-gas mixtures.

The Fermi-contact interaction that characterizes collisional spin exchange of a noble gas with an alkali-metal vapor also gives rise to NMR and EPR frequency shifts of the noble-gas nucleus and the alkali-metal atom, respectively. We have measured the enhancement factor κ0 that characterizes these shifts for Rb-129Xe to be 493±31, making use of the previously measured value of κ0 for Rb-3He. This result allows accurate 129Xe polarimetry with no need to reference a thermal-equilibrium NMR signal.

Universal long-time behavior of nuclear spin decays in a solid.

Magnetic resonance studies of nuclear spins in solids are exceptionally well suited to probe the limits of statistical physics. We report experimental results indicating that isolated macroscopic systems of interacting nuclear spins possess the following fundamental property: spin decays that start from different initial configurations quickly evolve towards the same long-time behavior. This long-time behavior is characterized by the shortest ballistic microscopic time scale of the system and therefore falls outside of the validity range for conventional approximations of statistical physics. We find that the nuclear free-induction decay and different solid echoes in hyperpolarized solid xenon all exhibit sinusoidally modulated exponential long-time behavior characterized by identical time constants. This universality was previously predicted on the basis of analogy with resonances in classical chaotic systems.

Wall relaxation of 3He in spin-exchange cells.

The 3He longitudinal spin-relaxation rate T1-1 is crucial for production of highly polarized 3He by spin-exchange optical pumping. We show that T1-1 is increased by a factor of 2-20 solely by exposure of spin-exchange cells to a few-kG magnetic field. The original T1-1 can be restored by degaussing the cell. The effect is attributed to magnetic surface sites and has been observed in both Pyrex and aluminosilicate-glass cells. Our results both advance the understanding of wall relaxation and demonstrate the use of 3He as an extremely sensitive probe of surface magnetism.

MR imaging of diffusion of (3)He gas in healthy and diseased lungs.

Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed, the mean value of D(e) in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174-179, 2000.

Dynamic echo planar MR imaging of lung ventilation with hyperpolarized (3)He in normal subjects and patients with severe emphysema.

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized (3)He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized (3)He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm(2) (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 degrees, echo train length = 32, matrix = 32 x 64, field of view = 225 x 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, (3)He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic (3)He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology.

Rapid imaging of hyperpolarized gas using EPI.

Rapid repetitive MRI of hyperpolarized (HP) gases using echo-planar imaging (EPI) has been theoretically investigated and experimentally demonstrated for (3)He in human lung. A quantitative treatment of signal attenuation and magnetization consumption for the unique circumstance of a rapidly diffusing nonrenewable magnetization source has been performed. Rapid (compared to the human respiratory cycle) and repetitive imaging of the lung gas space with EPI and a single delivered bolus of HP-(3)He is feasible using low flip angles, provided the voxels are not too small. A coarse-grid (32 x 64) EPI pulse sequence has been developed and implemented to image the lungs of healthy volunteers during rebreathing of a HP-(3)He/N(2) gas mixture. A set of three 10-mm axial slices was imaged every 0.12 sec for the 36 sec duration of rebreathing, yielding a real-time visualization of ventilation. Despite some mild artifacts, the images are of good quality and show changes in gas density related to respiratory physiology. Magn Reson Med 42:507-514, 1999.

Low frequency NMR polarimeter for hyperpolarized gases.

An inexpensive and self-contained apparatus for pulsed NMR at 30-250 kHz is described. The intended application is monitoring of the spin polarization of rare gas nuclei in a laser-polarizing apparatus in fields of order 30 G. In addition, the device provides a convenient method for following the polarization decay during storage and transport. Some of the features are a flexible pulse generator, splitting of transmitter RF cycles by the RF gate, a Q switch, and a wide range of receiver gains.

Dynamics of magnetization in hyperpolarized gas MRI of the lung.

The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized 3He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution < 4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.

MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.

Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.

Longitudinal relaxation and diffusion measurements using magnetic resonance signals from laser-hyperpolarized 129Xe nuclei.

Methods for T1 relaxation and diffusion measurements based on magnetic resonance signals from laser-hyperpolarized 129Xe nuclei are introduced. The methods involve optimum use of the perishable hyperpolarized magnetization of 129Xe. The necessary theoretical framework for the methods is developed, and then the methods are applied to measure the longitudinal relaxation constant, T1, and the self-diffusion constant, D, of hyperpolarized 129Xe. In a cell containing natural abundance 129Xe at 790 Torr, the T1 value was determined to be 155 +/- 5 min at 20 degrees C and at 2.0 T field. For a second cell at 896 Torr, at the same field and temperature, the T1 value was determined to be 66 +/- 2 min. At a higher field of 7.05 T, the T1 values for the two cells were found to be 185 +/- 10 and 88 +/- 5 min, respectively. The 129Xe self-diffusion constant for the first cell was measured to be 0.057 cm2/ s and for the second cell it was 0.044 cm2/s. The methods were applied to 129Xe in the gas phase, in vitro; however, they are, in principle, applicable for in vivo or ex vivo studies. The potential role of these methods in the development of newly emerging hyper-polarized 129Xe MRI applications is discussed.

Human lung air spaces: potential for MR imaging with hyperpolarized He-3.

Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.

MR imaging with hyperpolarized 3He gas.

Magnetic resonance images of the lungs of a guinea pig have been produced using hyperpolarized helium as the source of the MR signal. The resulting images are not yet sufficiently optimized to reveal fine structural detail within the lung, but the spectacular signal from this normally signal-deficient organ system offers great promise for eventual in vivo imaging experiments. Fast 2D and 3D GRASS sequences with very small flip angles were employed to conserve the norenewable longitudinal magnetization. We discuss various unique features associated with performing MRI with hyperpolarized gases, such as the selection of the noble gas species, polarization technique, and constraints on the MR pulse sequence.

Biological magnetic resonance imaging using laser-polarized 129Xe.

As currently implemented, magnetic resonance imaging (MRI) relies on the protons of water molecules in tissue to provide the NMR signal. Protons are, however, notoriously difficult to image in some biological environments of interest, notably the lungs and lipid bilayer membranes such as those in the brain. Here we show that 129Xe gas can be used for high-resolution MRI when the nuclear-spin polarization of the atoms is increased by laser optical pumping and spin exchange. This process produces hyperpolarized 129Xe, in which the magnetization is enhanced by a factor of about 10(5). By introducing hyperpolarized 129Xe into mouse lungs we have obtained images of the lung gas space with a speed and a resolution better than those available from proton MRI or emission tomography. As xenon (a safe general anaesthetic) is rapidly and safely transferred from the lungs to blood and thence to other tissues, where it is concentrated in lipid and protein components, images of the circulatory system, the brain and other vital organs can also be obtained. Because the magnetic behaviour of 129Xe is very sensitive to its environment, and is different from that of 1H2O, MRI using hyperpolarized 129Xe should involve distinct and sensitive mechanisms for tissue contrast.