Hyperpolarized Xenon-129 Lung and/or Brain Magnetic Resonance Imaging: Healthy Adult Volunteer Pilot Study

With the emergence of novel hardware and software image acquisition improvements, magnetic resonance imaging (MRI) has the potential to become an important tool for assessing lung structure and function. In particular, the use of a hyperpolarized noble gas such as 129Xe has been used to explore structural and functional relationships in the lungs of both healthy subjects and patients with lung disease (1,2). In contrast to proton-based MRI imaging, 129Xe gas is used as a "contrast agent" to directly visualize the airways, and thus image ventilation. Whereas the normal density of gas is too low to produce an easily detectable signal, this is overcome by artificially increasing the amount of polarization per unit volume using optical pumping (3).

Hyperpolarized noble gas MR lung imaging is a relatively new imaging method that allows depiction of both lung function and morphology [4-9]. Hyperpolarized gases are a new class of MR contrast agent which, when inhaled, provide high temporal and spatial resolution MR images of the lung airspaces. Since no ionizing radiation is involved, hyperpolarized gas MR imaging is ideal for the evaluation of lung diseases. With hyperpolarized gases, the nuclear spins of the gas atoms are brought into alignment outside of the MR scanner via a process called optical pumping; this yields high polarizations and permits visualization of the lung airspaces with MR imaging (despite the low physical density of the gas in the lung). Two non-radioactive (i.e. stable) isotopes of noble gases 3He and 129Xe can be hyperpolarized. Until recently, higher polarizations could be achieved with 3He than with 129Xe, so in humans, 3He was more commonly used for hyperpolarized gas MR imaging of the lungs [10-15]. Recently, the technology has been developed to provide large quantities of highly polarized 129Xe [16].

Several applications of 129Xe MRI imaging are under development, including diffusion-weighted and relaxation-weighted imaging (17-19). These techniques take advantage of the fact that the rate of loss of 129Xe polarization is significantly influenced by the local blood flow and concentration of molecular oxygen, as well as the restriction of 129Xe diffusion by small airway space dimensions. These data can be used to create maps of the lung reflecting regional ventilation/perfusion and micro-airway sizes. Other data that can be obtained with 129Xe MRI include the volumes of ventilated and unventilated lungs which can subsequently be analyzed to determine the homogeneity of gas distribution within the airspaces (17).

Another emergent application of 129Xe exploits the solubility of xenon in biological tissues and blood. This allows for the detection of 129Xe signals from beyond the airspaces, in the parenchymal lung tissue and red blood cells of the pulmonary vasculature. This enables the direct imaging and quantification of gas exchange capability of the lungs. Furthermore, xenon dissolved in the blood is carried away from the lungs to distal organs by the cardiovascular system (e.g., heart, kidneys). One organ that has seen a recent intensification of research with 129Xe is in the brain. HP 129Xe MRI of the brain holds promise for the evaluation of brain perfusion and function (31-33). Xenon dissolved in brain tissues exhibits a rich chemical shift spectrum allowing for the detection of signal from various biochemical compartments such as RBCs, cerebrospinal fluid, and white/gray matter, among others. Additionally, HP 129Xe can passively transit the blood-brain barrier in a manner that is not possible with other exogenous tracers (e.g., gadolinium-based contrast). Preliminary clinical investigations have demonstrated novelty in stroke, Alzheimer's disease, and functional brain imaging (31-33).

Objectives of the study are:

To quantitatively evaluate a 3T 129Xe radiofrequency coils (lung and/or brain) for image quality and coil comfort/performance.

To prototype and determine the range of possible novel lung and brain pulse sequences in combination with the coil and inhalation of 129Xe gas in healthy volunteers.