Measurements of regional partial pressure of oxygen in rodents

Non-invasive, regional assessment of lung function has the potential to markedly enhance the monitoring of progression of pulmonary diseases, as well as response therapeutic procedures. Over the last decade, quantitative Hyperpolarized (HP) gas MRI techniques have been developed to address crucial aspects of both lung structure and function. Alveolar partial pressure of oxygen is one of the important pulmonary markers with high sensitivity to alterations of regional lung physiology. The characteristic depolarization of HP ³He in presence of oxygen has been utilized by many researchers in quantitative measurement of alveolar oxygen tension. Current techniques are, however, mostly tailored towards large animals and humans, and are not easily implemented on small animals, and specifically rodents. These techniques rely on acquiring a series of images during a relatively long breath-hold followed by inhaling HP helium breaths. The signal decay history is then fit to a model of helium-oxygen interaction model to yield partial pressure of oxygen. This approach is impractical in rodents, and is limited by small animals’ higher respiratory rate, higher oxygen uptake rate, and inability to tolerate the necessary long breath-hold. the characteristic time scale of O₂-induced depolarization (16 seconds at physiological O₂ tension) is incompatible with several aspects of the rat physiology. The maximum tolerable breath hold (~5 seconds, if undesirable physiological responses are to be avoided) does not allow adequate depolarization to accurately measure the O₂ tension. Additionally, the faster oxygen uptake rate produces a measurement environment in which gas redistribution during the initial 1-2 seconds of the breath hold is not easily separated from O₂-induced depolarization. Finally, the small lung size causes regional information to be washed out by gas diffusion unless special care is taken to keep delays between images short. The errors associated with gas diffusion in large-animal PO₂measurements are commonly avoided by limiting regional measurements to relatively large-size bins. This approach leads to unacceptable loss of regional information in smaller animals. However, the small animals present a compensatory opportunity for signalaveraging because of the small amount of gas used per breath and great controllability on the ventilation patterns achievable by programmable small animal ventilators. Ability to perform these measurements with high accuracy in rodents, apart from availability of numerous interesting disease models, enables us to tailor ventilation parameters under full control and repeat measurements with an unprecedented reproducibility level that is difficult or impossible in larger species.