Hyperpolarized 129Xe gas magnetic resonance imaging (MRI) is a medical imaging technique used to visualize the anatomy and physiology of body regions that are difficult to image with standard proton MRI. In particular, the lung, which lacks substantial density of protons, is particularly useful to be visualized with 129Xe gas MRI. This technique has promise as an early-detection technology for chronic lung diseases and imaging technique for processes and structures reliant on dissolved gases. 129Xe is a stable, naturally occurring isotope of xenon with 26.44% isotope abundance. It is one of two Xe isotopes, along with 131Xe, that has non-zero spin, which allows for magnetic resonance. 129Xe is used for MRI because its large electron cloud permits hyperpolarization and a wide range of chemical shifts. The hyperpolarization creates a large signal intensity, and the wide range of chemical shifts allows for identifying when the 129Xe associates with molecules like hemoglobin. 129Xe is preferred over 131Xe for MRI because 129Xe has spin 1/2 (compared to 3/2 for 131Xe), a longer T1, and 3.4 times larger gyromagnetic ratio (11.78 MHz/T).
Uses
Medical uses
Xenon Xe 129 hyperpolarized, sold under the brand name Xenoview, is a hyperpolarized contrast agent indicated for use with magnetic resonance imaging (MRI) for evaluation of lung ventilation, and approved for people aged twelve years of age and older. It was approved for medical use in the US in December 2022. The most common side effects include mouth and throat pain, headache, and dizziness. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication. The FDA approved Xenoview based on evidence from two clinical trials in 83 participants with various lung disorders who were being evaluated for possible lung resection or lung transplantation. The trials were conducted at five sites in the United States and assessed both efficacy and safety of Xenoview. Xenoview was evaluated in two clinical trials of 83 adults with pulmonary disorders who each underwent sequential lung ventilation imaging with Xenoview with MRI and an approved comparator, Xe 133 scintigraphy. In study 1, participants were imaged to help plan possible lung resection. To determine the benefit of Xenoview, estimates of the percentage of lung ventilation predicted to remain after surgery made with Xenoview with MRI and comparator imaging were evaluated for equivalence. In study 2, participants were imaged to help plan possible lung transplantation. To determine the benefit of Xenoview, estimates of the percentage of lung ventilation contributed by the right lung made with Xenoview with MRI and comparator imaging were evaluated for equivalence.
History Hyperpolarized 129Xe is achieved through spin-exchange optical pumping, a technique developed by Grover et al. in 1978 and improved by Happer et al. in 1984. Quantification of 129Xe polarization was first described in 1982 by Bhaskar et al. The use of hyperpolarized 129Xe gas in MRI ex-vivo was first described by Albert et al. in 1994 using excised rat lungs. The first in-vivo human studies with 129Xe MRI were published by Mugler et al. in 1997. 129Xe MRI has largely begun to replace 3He gas MRI, a very similar technology that uses hyperpolarized 3He molecules instead of 129Xe. Grossman et al. began human clinical trials for 3He MRI in 1996. 3He was originally touted as the better gas for hyperpolarized gas MRI because it is more polarizable and has no effects on the body. However, 3He is mostly produced by the beta decay of tritium (3H), which is a product of nuclear warhead production. Additionally, 3He is widely used by the U.S. military to detect smuggled plutonium. These combination of increasing scarcity and increasing demand have combined to make 3He highly expensive, up to more than $1000 per liter.
Safety 129Xe is an inert, non-radioactive, non-toxic, and non-teratogenic molecule that has shown no significant adverse health effects when inhaled for MR imaging. One potential area of concern is 129Xe's anesthetic properties when a large volume is inhaled. Xenon shows blood and tissue solubility that allows it to diffuse through the lung membrane and affect the nervous system. The minimum alveolar concentration for 50% of motor response to be prevented (MAC) is 0.71, which is not reached during imaging. Further studies have shown that it provides good circulatory stability when dissolved in blood and does not affect body temperature.
Hyperpolarization When applying an external magnetic field to gas, half of the nuclear spins of the gas atoms point towards the direction of the magnetic field whereas the other half point in the opposite direction. It is slightly more energetically favorable to be aligned with the magnetic field, meaning that one of the spin states is in slight excess of the other. This excess means that the two spin-states do not completely cancel each other out, creating a magnetic signal which can be observed with MRI. However, for traditional 1H MRI, only about 4 ppm of the spin states do not cancel, so the signal is not particularly strong. This means that only regions with high densities of protons, like muscle tissue can be seen. Hyperpolarization is a means of flipping more of the atoms to have the same spin state so that less of the spin states cancel each other. In the case of 129Xe, this leads to a 104-105 improvement in signal strength.
Hyperpolarization of 129Xe is usually performed using spin-exchange optical pumping (SEOP) using circularly polarized light to add angular momentum of the atoms. However, the polarized light cannot directly transfer angular momentum to the gas nuclei, thus, an alkali metal atom is used as an intermediary. Rubidium is often used to accomplish this, where the polarized light is tuned to provide exactly the necessary energy to excite rubidium's valence electron. This process is called optical pumping. In the next step, spin exchange, gas nuclei are introduced to the system and collide with the rubidium. They receive angular momentum in the collisions with rubidium valence electrons, which, by conservation of angular momentum, is in the same direction as the rubidium. Therefore, 129Xe becomes hyperpolarized because there is a large excess of one spin state compared to the other. After this, the 129Xe is extracted, the rubidium is polarized again, and the cycle continues.
… excerpt ends here. Continue reading the full article.
