Hyperpolarized (hp) 129Xe and hp 83Kr for magnetic resonance imaging (MRI) are typically obtained through spin-exchange optical pumping (SEOP) in gas mixtures with dilute concentrations of the respective noble gas. The usage of dilute noble gases mixtures requires cryogenic gas separation after SEOP, a step that makes clinical and preclinical applications of hp 129Xe MRI cumbersome. For hp 83Kr MRI, cryogenic concentration is not practical due to depolarization that is caused by quadrupolar relaxation in the condensed phase. In this work, the concept of stopped flow SEOP with concentrated noble gas mixtures at low pressures was explored using a laser with 23.3 W of output power and 0.25 nm linewidth. For 129Xe SEOP without cryogenic separation, the highest obtained MR signal intensity from the hp xenon-nitrogen gas mixture was equivalent to that arising from 15.5±1.9% spin polarized 129Xe in pure xenon gas. The production rate of the hp gas mixture, measured at 298 K, was 1.8 cm3/min. For hp 83Kr, the equivalent of 4.4±0.5% spin polarization in pure krypton at a production rate of 2 cm3/min was produced. The general dependency of spin polarization upon gas pressure obtained in stopped flow SEOP is reported for various noble gas concentrations. Aspects of SEOP specific to the two noble gas isotopes are discussed and compared with current theoretical opinions. A non-linear pressure broadening of the Rb D1 transition was observed and taken into account for the qualitative description of the SEOP process.

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Hyperpolarized (hp) 83 Kr is a promising MRI contrast agent for the diagnosis of pulmonary diseases affecting the surface of the respiratory zone. However, the distinct physical properties of 83 Kr that enable unique MRI contrast also complicate the production of hp 83 Kr. This work presents a previously unexplored approach in the generation of hp 83 Kr that can likewise be used for the production of hp 129 Xe. Molecular nitrogen, typically used as buffer gas in spin-exchange optical pumping (SEOP), was replaced by molecular hydrogen without penalty for the achievable hyperpolarization. In this particular study, the highest obtained nuclear spin polarizations were P = 29% for 83 Kr and P = 63% for 129 Xe. The results were reproduced over many SEOP cycles despite the laser-induced on-resonance formation of rubidium hydride (RbH). Following SEOP, the H 2 was reactively removed via catalytic combustion without measurable losses in hyperpolarized spin state of either Xe can be obtained through dynamic nuclear polarization (25) with high spin-polarization levels of up to P = 30% (26) 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. Rubidium line broadening maximizes adsorption of laser light emitted by high-power solid devices, even if those are line narrowed. Following SEOP, hp 129

Ex vivo rodent lung models are explored for physiological measurements of respiratory function with hyperpolarized (hp) 129Xe MRI. It is shown that excised lung models allow for simplification of the technical challenges involved and provide valuable physiological insights that are not feasible using in vivo MRI protocols. A custom designed breathing apparatus enables MR images of gas distribution on increasing ventilation volumes of actively inhaled hp 129Xe. Straightforward hp 129Xe MRI protocols provide residual lung volume (RV) data and permit for spatially resolved tracking of small hp 129Xe probe volumes during the inhalation cycle. Hp 129Xe MRI of lung function in the excised organ demonstrates the persistence of post mortem airway responsiveness to intravenous methacholine challenges. The presented methodology enables physiology of lung function in health and disease without additional regulatory approval requirements and reduces the technical and logistical challenges with hp gas MRI experiments. The post mortem lung functional data can augment histological measurements and should be of interest for drug development studies.

PurposeAsthma is a disease of increasing worldwide importance that calls for new investigative methods. Ex vivo lung tissue is being increasingly used to study functional respiratory parameters independent of confounding systemic considerations but also to reduce animal numbers and associated research costs. In this work, a straightforward laboratory method is advanced to probe dynamic changes in gas inhalation patterns by using an ex vivo small animal ovalbumin (OVA) model of human asthma.MethodsHyperpolarized (hp) 129Xe was actively inhaled by the excised lungs exposed to a constant pressure differential that mimicked negative pleural cavity pressure. The method enabled hp 129Xe MRI of airway responsiveness to intravenous methacholine (MCh) and airway challenge reversal through salbutamol.ResultsSignificant differences were demonstrated between control and OVA challenged animals on global lung hp 129Xe gas inhalation with P < 0.05 at MCh dosages above 460 μg. Spatial mapping of the regional hp gas distribution revealed an approximately three‐fold increase in heterogeneity for the asthma model organs.ConclusionThe experimental results from this proof of concept work suggest that the ex vivo hp noble gas imaging arrangement and the applied image analysis methodology may be useful as an adjunct to current diagnostic techniques. Magn Reson Med 76:1224–1235, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.