Dilip Balamore

Development of hyperpolarized noble gas MRI.

Magnetic resonance imaging using the MR signal from hyperpolarized noble gases 129Xe and 3He may become an important new diagnostic technique. Alex Pines (adapting the hyperpolarization technique pioneered by William Happer) presented MR spectroscopy studies using hyperpolarized 129Xe. The current authors recognized that the enormous enhancement in the delectability of 129Xe, promised by hyperpolarization, would solve the daunting SNR problems impeding their attempts to use 129Xe as an in vivo MR probe, especially in order to study the action of general anesthetics. It was hoped that hyperpolarized 129Xe MRI would yield resolutions equivalent to that achievable with conventional 1H2O MRI, and that xenons solubility in lipids would facilitate investigations of lipid-rich tissues that had as yet been hard to image. The publication of hyperpolarized 129Xe images of excised mouse lungs heralded the emergence of hyperpolarized noble-gas MRI. Using hyperpolarized 3He, researchers have obtained images of the lung gas space of guinea pigs and of humans. Lung gas images from patients with pulmonary disease have recently been reported. 3He is easier to hyperpolarize than 129Xe, and it yields a stronger MR signal, but its extremely low solubility in blood precludes its use for the imaging of tissue. Xenon, however, readily dissolves in blood, and the T1, of dissolved 129Xe is long enough for sufficient polarization to be carried by the circulation to distal tissues. Hyperpolarized 129Xe dissolved-phase tissue spectra from the thorax and head of rodents and humans have been obtained, as have chemical shift 129 Xe images from the head of rats. Lung gas 129Xe images of rodents, and more recently of humans, have been reported. Hyperpolarized 129Xe MRI (HypX-MRI) may elucidate the link between the structure of the lung and its function. The technique may also be useful in identifying ventilation-perfusion mismatch in patients with pulmonary embolism, in staging and tracking the success of therapeutic approaches in patients with chronic obstructive airway diseases, and in identifying candidates for lung transplantation or reduction surgery. The high lipophilicity of xenon may allow MR investigations of the integrity and function of excitable lipid membranes. Eventually, HypX-MRI may permit better imaging of the lipid-rich structures of the brain. Cortical brain function is one perfusion-dependent phenomena that may be explored with hyperpolarized 129Xe MR. This leads to the exciting possibility of conducting hyperpolarized 129Xe functional MRI (HypX-fMRI) studies.

MRI of the lung gas-space at very low-field using hyperpolarized noble gases

In hyperpolarized (HP) noble-gas magnetic resonance imaging, large nuclear spin polarizations, about 100,000 times that ordinarily obtainable at thermal equilibrium, are created in 3He and 129Xe. The enhanced signal that results can be employed in high-resolution MRI studies of void spaces such as in the lungs. In HP gas MRI the signal-to-noise ratio (SNR) depends only weakly on the static magnetic field (B(0)), making very low-field (VLF) MRI possible; indeed, it is possible to contemplate portable MRI using light-weight solenoids or permanent magnets. This article reports the first in vivo VLF MR images of the lungs in humans and in rats, obtained at a field of only 15 millitesla (150 Gauss).

Evaluation of carrier agents for hyperpolarized xenon MRI

Several biocompatible carrier agents, in which xenon is highly soluble and has a long T1, were tested, and injected in living rats. These included saline, Intralipid suspension, perfluorocarbon emulsion and 129Xe gas‐filled liposomes. The T1 of 129Xe in these compounds ranged from 47 to 116 s. Vascular injection of these carrier agents was tolerated well, encouraging their use for further experiments in live animals. In vivo spectra, obtained from gas‐filled liposomes and perfluorocarbon solutions, suggest that these carrier agents have potential for use in angiography and perfusion imaging. Copyright

Hyperpolarized (129)Xe T (1) in oxygenated and deoxygenated blood

The viability of the new technique of hyperpolarized 129Xe MRI (HypX‐MRI) for imaging organs other than the lungs depends on whether the spin–lattice relaxation time, T1, of 129Xe is sufficiently long in the blood. In previous experiments by the authors, the T1 was found to be strongly dependent upon the oxygenation of the blood, with T1 increasing from about 3 s in deoxygenated samples to about 10 s in oxygenated samples. Contrarily, Tseng et al. (J. Magn. Reson. 1997; 126: 79–86) reported extremely long T1 values deduced from an indirect experiment in which hyperpolarized 129Xe was used to create a ‘blood‐foam’. They found that oxygenation decreased T1. Pivotal to their experiment is the continual and rapid exchange of hyperpolarized 129Xe between the gas phase (within blood‐foam bubbles) and the dissolved phase (in the skin of the bubbles); this necessitated a complicated analysis to extract the T1 of 129Xe in blood. In the present study, the experimental design minimizes gas exchange after the initial bolus of hyperpolarized 129Xe has been bubbled through the sample. This study confirms that oxygenation increases the T1 of 129Xe in blood, from about 4 s in freshly drawn venous blood, to about 13 s in blood oxygenated to arterial levels, and also shifts the red blood cell resonance to higher frequency. Copyright