Emphysema is a pulmonary disease characterized by alveolar wall destruction, resulting in enlargement of gas exchange spaces without fibrosis. This condition is a part of chronic obstructive pulmonary disease (COPD), which causes 3.5% of deaths worldwide [Anonymous (

A new strategy designed to provide functional magnetic resonance images of the lung in small animals at microscopic resolution using hyperpolarized 3 He is described. The pulse sequence is based on a combination of radial acquisition (RA) and CINE techniques, referred to as RA-CINE, and is designed for use with hyperpolarized 3 He to explore lung ventilation with high temporal and spatial resolution in small animal models. Ventilation of the live guinea pig is demonstrated with effective temporal resolution of 50 msec and in-plane spatial resolution of F100 m using hyperpolarized 3 He. The RA-CINE sequence allows one to follow gas inflow and outflow in the airways as well as in the distal part of the lungs. Regional analysis of signal intensity variations can be performed and can help assess functional lung parameters such as residual gas volume and lung compliance to gas inflow. Magn Reson Med 41:787-792, 1999. 1999 Wiley-Liss, Inc. Key words: functional imaging; lung airways; MR microscopy; hyperpolarized gasThe extraordinary signal gain afforded by MRI with hyperpolarized (HP) gas has been exploited in a number of recent studies (1-7) to demonstrate lung anatomy and pathology. One key application of HP gas MRI that has not yet been reported is the demonstration of lung function. Techniques developed for prior in vivo MR microscopy studies are extended in this study to implement functional lung imaging in the guinea pig at microscopic resolution.The applications of such techniques are many. As production of large quantities of HP gas is challenging, it is feasible to develop functional imaging techniques in small animal models. One can be more frugal with the limited supply of gas and can employ carefully controlled models of obstructive and/or restrictive disease to validate developed techniques. The understanding of the temporal and spatial dynamics of the polarization can then be easily extended to human studies. Development of these techniques for small animal studies is in itself intrinsically useful because it allows a quantitative understanding of lung function in these animal models. This, in turn, has direct application in the basic physiology of lung disease and the development of new therapies.To date, HP gas ventilatory studies have gated the projection acquisition for a specific period during inspiration and/or held breath. Typically, a delay is set in the ventilatory trigger, followed by an acquisition window (AW) during which data are acquired as rapidly as possible, yielding, for example, N views for each breath. The sequence is repeated for M breaths to yield M · N views required for a single image. For example, in work by Chen et al (7), 20 views were acquired over 40 breaths to yield 800 views for a high-resolution image. The first problem with this technique is that the HP gas is literally being thrown away during that part of the cycle not covered by the acquisition. The second disadvantage of this study is that it does not provide continuous dynamic information.We describe here a strategy ...

Optical pumping methods can be used to achieve nonequilibrium nuclear spin polarizations of 10-50% in the noble gases 3 He and 129 Xe. The dramatically enhanced signal of such hyperpolarized (HP) gases in NMR (1-3) has been utilized in biomedical imaging of void spaces, including investigation of healthy and diseased human lungs (4-7) and magnetic resonance microscopy in small animals in vivo (8-10). In such experiments, introduction of HP noble gas into the organism is performed through the trachea. After inhalation, noble gas is taken up in the alveoli by the pulmonary blood and transported throughout the body by the circulatory system. Consequently, HP gases have a potential for imaging other organs and perfusion studies. If gas delivery is performed by inhalation, xenon may have an inherent advantage for such investigations because it is approximately 15-20 times more soluble in blood than helium (11). Tissue-dissolved HP 129 Xe NMR signals from the thorax (7,12,13) and from brain (7) have already been observed in both rodents and humans, and 129 Xe images were recorded from rat brain using twodimensional (2D) chemical shift imaging (14).Simulations considering the well-established pharmacokinetics of xenon and experimental NMR parameters have been utilized to investigate the time-dependent blood and tissue concentrations of inhaled HP 129 Xe theoretically (15,16). Assuming continuous breathing of pure xenon, Martin et al (16) estimated maximum signals of 6% of the pulmonary gas space signal in the cerebral arteries and 0.5% in the veins. Such low signal intensities suggest that angiography of the veins would be difficult. An alternative method to obtain higher local xenon concentrations in blood or tissues may involve pre-dissolving HP gas in a liquid with subsequent injection into the organism, as suggested by Bifone et al (17). Injection delivery of radioactive 133 Xe has been used in nuclear medicine to study regional blood flow for more than 30 years (18). The feasibility of this technique for MRI was shown in a recent study reporting 129 Xe images from a rat hind-leg, which were obtained after intramuscular injection of a xenon/ saline solution (19). More recently, vascular HP 3 He images of high signal-to-noise ratio (SNR) were recorded in vivo after injection of microbubble suspensions (20).In the present work, we demonstrate the feasibility of HP 129 Xe magnetic resonance angiography (MRA) in the rat using intravenous injection of a suitable biocompatible carrier. Additionally, quantitative information about venous blood flow is obtained. The known high xenon solubility of lipids (21) suggests the use of fat emulsions for this purpose. Commercially available fat emulsions, which are approved by the U.S. Food and Drug Administration (FDA) for intravenous infusion, are oil-in-water emulsions containing soybean or safflower oils, egg phosphatides as an emulsifier, and glycerin to adjust tonicity. Clinically, they are used as a source of calories and essential fatty acids for patients requiring parenter...

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