Distribution and Dynamics of Laser-Polarized 129 Xe Magnetization In Vivo Scott D. Swanson, 1 * Matthew S. Rosen, 2 Kevin P. Coulter, 2 Robert C. Welsh, 2 and Timothy E. Chupp 2 The first magnetic resonance imaging studies of laser-polarized 129 Xe, dissolved in the blood and tissue of the lungs and the heart of Sprague-Dawley rats, are described. 129 Xe resonances at 0, 192, 199, and 210 ppm were observed and assigned to xenon in gas, fat, tissue, and blood, respectively. One-dimen- sional chemical-shift imaging (CSI) reveals xenon magnetiza- tion in the brain, kidney, and lungs. Coronal and axial two- dimensional CSI show 129 Xe dissolved in blood and tissue in the thorax. Images of the blood resonance show xenon in the lungs and the heart ventricle. Images of the tissue resonance reveal xenon in lung parenchyma and myocardium. The 129 Xe spec- trum from a voxel located in the heart ventricle shows a single blood resonance. Time-resolved spectroscopy shows that the dynamics of the blood resonance match the dynamics of the gas resonance and demonstrates efficient diffusion of xenon gas to the lung parenchyma and then to pulmonary blood. These observations demonstrate the utility of laser-polarized 129 Xe to detect exchange across the gas-blood barrier in the lungs and perfusion into myocardial tissue. Applications to measurement of lung function, kidney perfusion, myocardial perfusion, and regional cerebral blood flow are discussed. Magn Reson Med 42:1137–1145, 1999.  1999 Wiley-Liss, Inc. Key words: tissue perfusion; xenon; laser-polarized; hyperpolar- ized; lung function The biological properties of xenon and the ability to create high levels of nuclear polarization in noble gases combine to make magnetic resonance imaging (MRI) of laser- polarized 129 Xe an exciting field of research. Freely diffus- ible across biological membranes and metabolically inert, xenon dissolves in blood (1), travels to distant organs, and accumulates in tissue. By applying the principles of diffusible indicators first outlined by Kety (2), radio- active 133 Xe has been used in nuclear medicine to mea- sure kidney perfusion (3), cardiac perfusion (4), regional cerebral blood flow (rCBF) (5), and lung ventilation (6). These measurements are possible because the tissue distribution (7) and dynamics of 133 Xe in vivo are well understood. To make similar perfusion measurements us- ing MRI of laser-polarized 129 Xe, the distribution and dynamics of xenon magnetization in vivo must first be determined. The most exciting medical applications for laser- polarized (also called hyperpolarized) 129 Xe nuclear mag- netic resonance (NMR) lie in imaging xenon dissolved in tissue or blood. Previous spectroscopy studies of 129 Xe in vivo in the mouse body (8), rat body (9), rat brain (10,11), and human brain and chest (12) demonstrated that xenon in blood, tissue, and gas resonates at different frequencies and suggest that the different frequency components can be selectively imaged. In vitro studies of xenon dissolved in blood have revealed two components, plasma and red blood cell, exchanging rapidly with respect to T 1 but slowly with respect to the inverse frequency separation (13,14). Additional in vitro work has measured the T 1 of xenon dissolved in tissue samples (15). Our initial work focused on imaging 129 Xe in the rat brain after inhalation and resulted in the first, chemical-shift resolved image of laser-polarized 129 Xe dissolved in tissue (10). No informa- tion has been published to date concerning the spatial distribution of xenon magnetization in the whole body in vivo. The tissue distribution of 129 Xe magnetization in vivo will be much different than the distribution of xenon (7) because xenon polarization decays once injected or in- haled. The value of the decay rate differs in the lungs, blood, tissue, and fat. Measuring the xenon magnetization distribution is needed to determine which organs will be suitable for perfusion measurement with laser-polarized 129 Xe. Understanding the dynamics of 129 Xe magnetization in vivo is essential to new imaging methods that measure tissue perfusion with MRI of laser-polarized 129 Xe. This paper presents the first chemical-shift resolved images of 129 Xe in blood, tissue, and gas in the thorax, assignments for the in vivo blood and tissue resonances, and a study of the dynamics of laser-polarized 129 Xe in vivo. We also discuss how MRI of laser-polarized 129 Xe may be used in the future to measure rCBF, cardiac perfusion, kidney perfusion, and lung function. MATERIALS AND METHODS Xenon Polarization and Delivery Xenon was polarized and delivered to Sprague-Dawley rats (200–250 g) by an apparatus previously described (10) and recently modified (11). The current device makes multiple, 165-ml batches of laser-polarized, naturally-abundant xe- non ( 129 Xe 26.44% ) at a rate of approximately one batch per 5 minutes. 129 Xe polarization is typically 5%. Each batch was frozen and stored as xenon ice (T 1  1 hour at 50 mT and 77 K). Between two and five batches of polarized 129 Xe were used for each experiment presented here. After freezing of multiple batches, polarized xenon ice was warmed, and the gas expanded into a one-liter glass cylinder sealed by a Teflon piston. A series of automated valves regulated delivery of a 50/50 xenon/oxygen mixture to the animal. Mixing with oxygen occurred just before 1 Department of Radiology, The University of Michigan, Ann Arbor, Michigan. 2 Department of Physics, The University of Michigan, Ann Arbor, Michigan. Grant sponsor: National Institutes of Health; Grant number: GM-48633; Grant sponsor: National Science Foundation; Grant number: PHY-9514340. *Correspondence to: Scott D. Swanson, Ph.D., Department of Radiology, The University of Michigan, Ann Arbor, MI 48109-0553. E-mail: sswanson@umich.edu Received 24 November 1998; revised 9 August 1999; accepted 10 August 1999. Magnetic Resonance in Medicine 42:1137–1145 (1999) 1137  1999 Wiley-Liss, Inc.