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.

The nuclear spin polarization of the noble gas isotopes 3 He and 129 Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments. MRI has been extremely successful at diagnosing soft tissue disease since its discovery in 1972 (1). However, MRI is not as sensitive in comparison with other biomedical imaging techniques, such as CT, positron-emission tomography, or single-photon emission computed tomography. This is a consequence of a very small signal from a small population difference between nuclear energy states. For a spin-1/2 system, the "nuclear spin polarization", P N , is defined as:where N ϩ and N Ϫ denote populations with magnetic spin quantum numbers ϩ1/2 and Ϫ1/2, respectively. Typically, the thermal energy of the sample at temperature T exceeds the energy difference between the nuclear spin states in a magnetic field B 0 by several orders of magnitude ("hightemperature approximation") and the equilibrium polarization can be written as:where ␥ is the magnetogyric ratio, ប is Planck's constant divided by 2 , and k B is Boltzmann's constant. As an example, P N,0 Ϸ 5 ppm is predicted with Eq.[2] for protons ( 1 H) at body temperature (T ϭ 37°C) and B 0 ϭ 1.5T. In view of the inherent sensitivity problem, increasing the signalto-noise ratio (SNR) has been a field of continuous research since the discovery of NMR. Recently, the use of optically polarized noble gas isotopes 3 He and 129 Xe has attracted increasing interest for use in a variety of promising MR applications. These systems exhibit polarizations exceeding the thermal levels by several orders of magnitude. While the use of such "hyperpolarized" (HP) gases for MRI is a recent development, it is based on a solid foundation of work in atomic physics. The groundwork was laid by Kastler (2) more than 50 years ago by demonstrating transfer of angular momentum from circularly polarized light to the electron and nuclear spins of atoms, a process called "optical pumping" (OP). Since 1991, exploitation of OP as a means of enhancing signal initiated the development of a novel field in NMR (3,4). Research involving HP noble gases has been exceptionally fruitful in biomedical MRI as well as providing applications for investigation of materials (5-8).In the context of proton MRI, the lung is a particularly challenging area to study (9). Even at end expiration, the overall density is ...

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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.

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.