Translational applications of hyperpolarized ³He and ¹²⁹Xe

Abstract

Clinical magnetic resonance imaging of the lung is technologically challenging, yet over the past two decades hyperpolarized noble gas ((3)He and (129)Xe) imaging has demonstrated the ability to measure multiple pulmonary functional biomarkers. There is a growing need for non-ionizing, non-invasive imaging techniques due to increased concern about cancer risk from ionizing radiation, but the translation of hyperpolarized gas imaging to the pulmonary clinic has been stunted by limited access to the technology. New developments may open doors to greater access and more translation to clinical studies. Here we briefly review a few translational applications of hyperpolarized gas MRI in the contexts of ventilation, diffusion, and dissolved-phase imaging, as well as comparing and contrasting (3)He and (129)Xe gases for these applications. Simple static ventilation MRI reveals regions of the lung not participating in normal ventilation, and these defects have been observed in many pulmonary diseases. Biomarkers related to airspace size and connectivity can be quantified by apparent diffusion coefficient measurements of hyperpolarized gas, and have been shown to be more sensitive to small changes in lung morphology than standard clinical pulmonary functional tests and have been validated by quantitative histology. Parameters related to gas uptake and exchange and lung tissue density can be determined using (129)Xe dissolved-phase MRI. In most cases functional biomarkers can be determined via MRI of either gas, but for some applications one gas may be preferred, such as (3)He for long-range diffusion measurements and (129)Xe for dissolved-phase imaging. Greater access to hyperpolarized gas imaging coupled with newly developing therapeutics makes pulmonary medicine poised for a potential revolution, further adding to the prospects of personalized medicine already evidenced by advancements in molecular biology. Hyperpolarized gas researchers have the opportunity to contribute to this revolution, particularly if greater clinical application of hyperpolarized gas imaging is realized.

Quantitative Magnetic Resonance Imaging of Bronchopulmonary Dysplasia in the Neonatal Intensive Care Unit Environment

“…In the future, the quantitative and textural differentiation of highintensity pathologies will be explored; we hypothesize that the macromolecular structural differences of these pathologies will give rise to differential relaxation and/ or textural properties, and that information will be used to refine the quantitative threshold analysis. In addition to these efforts, we are adapting other pulmonary imaging methods, including UTE (25,26) and hyperpolarized-gas MRI (30) techniques for neonatal patients. We expect that in the future, UTE MRI will provide higher spatial resolution and some insensitivity to motion artifacts and that hyperpolarized-gas MRI will illuminate regional pulmonary function and airspace size.…”

Molecular hydrogen and catalytic combustion in the production of hyperpolarized83Kr and129Xe MRI contrast agents

“…spin-exchange optical pumping | hyperpolarized noble gas contrast agents | cryogenic separation | chemical looping combustion | pulmonary imaging T he development of hyperpolarized (hp) noble gas MRI has resulted in a number of excellent protocols to probe different structural and functional aspects of lungs in health and disease (1)(2)(3)(4)(5)(6). Technological improvements (6)(7)(8)(9)(10)(11)(12)(13)(14)(15) have enabled pulmonary hp 129 Xe MRI at high spatial resolution, thereby reducing the need for use of the scarcely available 3 He isotope.…”

“…Furthermore, SEOP is currently the only method to provide hp 83 Kr for biomedical MRI applications (24). During SEOP of 83 Kr or 129 Xe, the noble gas is diluted with a buffer gas, usually either a 4 He-N 2 mixture or pure N 2 gas. The buffer gas serves a dual purpose as it prevents destructive radiation trapping, originating from radiative electronic relaxation of rubidium (27,28), but also causes pressure broadening of the Rb D 1 linewidth.…”

Synchronous Spin-Exchange Optical Pumping

“…The ability to produce highly magnetized noble gases via spin-exchange collisions with spin-polarized alkali atoms [1] has greatly impacted scientific studies of magnetic resonance imaging [2], high-energy nuclear physics with spin-polarized targets [3], and chemical physics [4]. Applications in precision measurements began with NMR gyros [5] and have continued with fundamental symmetry tests using multiple cell free induction decay [6], dual-species masers [7,8], selfcompensating co-magnetometers [9], NMR oscillators [10], and free spin-precession co-magnetometers [11][12][13][14].…”