6) [65]. The longitudinal relaxation of the peaks associated with the dissolved phase was MG-132 mouse found to be on the order of seconds thus allowing for the possibility to image xenon incorporated into the tissue components separately from the gas phase [66]. Chemical shift selective MRI of dissolved xenon in lungs is facilitated by the significant frequency shift between 129Xe in the gas phase (around 0 ppm) and in the dissolved phase (191–213 ppm) [67]. Unfortunately, xenon in the dissolved phase constitutes only about 1–2% of the total inhaled xenon. Therefore, the associated hp 129Xe signal intensity arising from the dissolved phase is fairly weak. Therefore,

Fig. 6 does not reflect the true intensity of the gas phase peak because the excitation frequency was selected for the 200 ppm region. If full broadband excitation would be applied, the gas phase peak should be about 50–100 times stronger than the dissolved signal. However, the dissolved phase xenon is constantly replenished from the alveolar gas phase through rapid diffusive exchange. Thus, chemical shift selective excitation of the dissolved phase (i.e. that does not depolarized the hp 129Xe in the gas phase) allows for signal averaging with very short delay times in the millisecond regime. Fujiwara

and coworkers have demonstrated the use of continuous delivery of hp ALK inhibitor gas in the mouse lung as a method to enhance the dissolved phases signal [68] and [69]. Single breath-hold and chemical shift selective three-dimensional MRI of the dissolved phases in

human volunteers with reasonable spatial resolution have also been reported [70] and [71]. This concept can be used for new physiological measurements that probe gas transfer in lungs using xenon as a surrogate for oxygen and may be helpful for early diagnosis of interstitial lung diseases such as idiopathic pulmonary fibrosis (IPF). Due to a thickening of the lung parenchyma Cell press that separates the alveolar space from the blood, gas exchange is reduced in these diseases and gas transport requires longer time periods. Driehuys et al. explored the exchange between the alveolar membrane and capillary blood using a technique called xenon alveolar capillary transfer imaging (XACT) [72]. The technique uses chemical shift selective separation between tissue and blood dissolved hp 129Xe utilizing the 14 ppm difference between the two dissolved states. The slowed gas transfer from the alveoli to the blood can be visualized with hp 129Xe if short recycle delays are used as shown in Fig. 7. The underlying concept of XACT is chemical shift selected recovery of the hp 129Xe signal. This method has been explored by Butler and co-workers to measure surface area to volume ratios (SA/Vgas) in a variety of porous media and has been applied later in a non-spatially resolved manner to study morphometry of healthy human lungs in vivo [73] and [74].