Hyperpolarized xenon and helium have both demonstrated utility in functional lung imaging and quantifying lung disease. Hyperpolarized xenon offers advantages of a low diffusion constant and availability from natural sources. It also has applications in dissolved state imaging, with a high solubility in fluids and tissues and a characteristic chemical shift, revealing its microscopic environment. Comparison of the dissolved and gaseous signals in lungs, for example, offers a precise measure of surface-to-volume ratio. A protocol involving a suite of lung images in three-dimensions or a program to investigate dissolved- phase imaging of perfused organs in humans could beneficially utilize large quantities of highly polarized xenon. The UNH group has developed a new type of xenon polarizer that flows the gas mixture at relatively high velocity and low pressure along a direction opposite to the laser beam, producing polarization of over 60% for small quantities and 22% for a production rate of six liters per hour. The figure-of-merit (polarization times production rate) of this polarizer presently exceeds all other polarizer technologies by an order of magnitude. The 500 torr operating pressure represents a compromise between higher laser absorption (at higher pressure) and faster spin-exchange rates (at lower pressure). Our numerical simulations indicate that magnetization output scales with absorbed laser power, that is, power within a narrow range around the spectral absorption band. Using STTR Phase I funding we have further developed our high-power spectrally narrowed laser technology for spin-exchange optical pumping of hyperpolarized gas. We scaled up our spectrally narrowed laser technology to 480W. Separately, we adapted our 5 bar 130 watt and 9 bar 270 watt lasers to investigate two new technologies to reduce the mode structure of the output beam for better collimation. We recently installed our 270 watt laser on the polarizer, and we expect polarization figures for both lasers once calibrations are set. For Phase II we will complete our study of the mode reduction technology to achieve a narrow spectral output with nearly ideal collimation. We will measure laser output as a function of mode and spectral constraints. We will investigate polarizer output as a function of laser power. We will test two different polarizer column diameters and two different polarizer column lengths to optimize the physical properties of the polarizer for increased output. We expect to come close to the goal of real-time hyperpolarized xenon production, 60 L/hr at ~50% polarization. This research to develop a high power laser will increase the production rate for producing hyperpolarized xenon. Hyperpolarized Xenon Magnetic Resonance Imaging (MRI) was recently demonstrated as an exquisitely sensitive method for assessment of lung ventilation and tissue health, with applications to quantifying obstructive lung disease and emphysema.
The specific aim of the current work is to increase the production rate of hyperpolarized xenon to greater than 60 L/hr, allowing an imaging subject to breathe the gas directly from the polarizer in real time. High-volume, cost-effective production of hyperpolarized xenon will also provide a new background-free, non-recirculating contrast agent for blood and tissues which may offer unique contrast for diagnosing a broad spectrum of diseases. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
2R42ES014005-02
Application #
7156869
Study Section
Special Emphasis Panel (ZRG1-SBIB-Q (13))
Program Officer
Heindel, Jerrold
Project Start
2005-09-30
Project End
2008-11-30
Budget Start
2007-05-11
Budget End
2007-12-14
Support Year
2
Fiscal Year
2007
Total Cost
$282,207
Indirect Cost
Name
Xemed, LLC
Department
Type
DUNS #
152959891
City
Durham
State
NH
Country
United States
Zip Code
03824
Hersman, F William; Ruset, Iulian C; Ketel, Stephen et al. (2008) Large production system for hyperpolarized 129Xe for human lung imaging studies. Acad Radiol 15:683-92
Patz, Samuel; Hersman, F William; Muradian, Iga et al. (2007) Hyperpolarized (129)Xe MRI: a viable functional lung imaging modality? Eur J Radiol 64:335-44