Temporal Dynamics of Hyperpolarized129Xe Resonances in Living Rats

Abstract

temperature, with minimal loss of its hyperpolarization after Recent development of a magnetic-resonance technique sublimation. The hyperpolarized Xe gas was transferred using hyperpolarized noble gases (He and Xe) has ento a 50 cm glass syringe prior to use. abled imaging of the lung gas space (1, 2) . While the exSprague–Dawley rats (400–500 g) were anesthetized tremely low solubility of He in the blood (3) precludes its with intramuscular injections of ketamine (24 mg/kg) and use as a tissue imaging probe, Xe is highly lipophilic and xylazine (6 mg/kg). A 14 gauge Teflon catheter was insoluble in blood and tissue, and thus holds promise for tissue serted into the trachea, and silk ligatures were tied around imaging and physiological studies such as white matter perthe endotracheal tube. The animal was then placed in a short fusion, heretofore not possible. Recently, hyperpolarized birdcage detector coil covering only the thorax. The hyperXe tissue signals were reported from a live mouse (4) . It polarized Xe gas was delivered from the syringe to the remains unclear, however, what the lifetimes of different animal’s lungs via a 24 gauge catheter that was inserted hyperpolarized Xe tissue resonances will be in vivo, and coaxially into the 14 gauge catheter. The animal breathed which tissue will yield distinguishable signals. In this paper, naturally through the open end of the 14 gauge catheter. we report measurements of the xenon exchange and accumuIn each spectroscopy experiment, four 10 cm boluses of lation in the pulmonary tissue by examination of the washhyperpolarized Xe were administered at 4–5 s intervals. in and wash-out dynamics of hyperpolarized Xe signals The use of an open delivery system allowed excess xenon and their lifetimes in living rats. The in vivo spectra exhibited to escape without injuring the animal from a dangerous builtfour resolved peaks of hyperpolarized Xe resonances from up pressure. Furthermore, the excess xenon gas was expelled gas, blood, and tissue phases (5, 6) . In addition, imaging of outside the pickup coil. All rats showed no discomfort after the lung gas space was performed using hyperpolarized Xe. These results suggest applications of the hyperpolarthe xenon delivery, indicating that the xenon ventilation and the method of delivery were well tolerated. The care and ized Xe MRI technique for ventilation–perfusion studies of the lung. use of animals in these experiments were approved by the Harvard Medical School Standing Animal Committee and The novel technique of noble gas hyperpolarization, by conformed with the guidelines set forth by the National Insticollisional spin exchange with optically pumped rubidium tute of Health (11) . vapor, yields up to a hundred thousandfold enhancement in spin polarization and MR detectability (7–10) . We used Xe spectra were obtained at 55.35 MHz on a 4.7 T Omega spectroscopy/imaging system (Bruker Instruments, natural-abundance xenon (26% Xe), which was contained in a 25 cm cylindrical glass cell, at 3 atm, along with N2 Fremont, California) . A spectral window of 25.0 kHz covered both gas and tissue Xe resonances. The transmitter buffer gas and a small quantity of solid Rb. Xe was hyperpolarized in the fringe field of a 4.7 T superconducting magfrequency was set to 160 ppm downfield from the gas resonance. Free-induction decay data were acquired with low net (Oxford Instruments, Oxford, UK). Circularly polarized 795 nm light from diode laser arrays (Optopower, Tucson, flip-angle (267) rectangular pulses (pulse width, 100 ms) at 1–3 s intervals. The data were baseline corrected, apodized Arizona) was used for optical pumping of the Rb vapor. After 30 min of optical pumping at 90–1007C, the glass cell by Gaussian multiplication (50 Hz for Figs. 1 and 2), and Fourier transformed. Hyperpolarization lifetimes were estiwas rapidly cooled in ice water to remove the Rb vapor by condensation onto the cell walls. The hyperpolarized Xe mated by the method of least squares for single-exponential line fitting for decaying signals, after correcting the signal was extracted by connecting a 25 cm glass cell immersed in liquid nitrogen, for cryopumping the Xe from the hypermagnitudes of each spectral peak for the amount of depolarization induced by the RF excitations. polarization cell. The frozen Xe was then warmed to room