Assuming that one dimensional diffusion drives signal growth of the dissolved phase one can deduce the SA/Vgas in lungs from the dissolved phase to gas phase signal ratio. Recently, this model was refined with lung blood flow corrections and was used to determine additional parameters including alveolar septal thickness (h) [75]. The surface area to volume ratio was

found to decrease in healthy subjects with increasing inhalation volumes as expected and was noted to be lower in patients with COPD, indicating airspace destruction. The septal thickness was seen to be significantly raised in patients with mild interstitial lung disease. Xenon transfer contrast GDC 0199 (XTC) is an alternative approach to fight the relatively weak hp 129Xe signal originating from the dissolved

phase through the usage of indirect detection of the dissolved phase in the gas phase [76]. The underlying principle is that hp 129Xe exchanges not only from the gas phase to the dissolved phase but also vice versa from the tissue into the alveolar space. Therefore, chemical shift selective destruction of the hp 129Xe magnetization (i.e. saturation) in the dissolved phase by 90° pulses can be observed indirectly through a reduction of alveolar hp 129Xe gas phase signal. The advantage is that the alveolar signal GSK-3 assay is much stronger and hence easier to detect. The reduction of the signal is measured in comparison with experiments without chemical shift selective saturation. Since the concept is based on gas exchange, it allows for regional

measurement of gas diffusion into the parenchyma. To obtain spatial information the XTC preparatory sequences are usually combined with FLASH imaging protocol. To further maximize the image contrast the signal associated with the dissolved phase can be inverted rather than suppressed [77] and [78]. Information is obtained from the decrease of the gas phase signal after multiple exchange Rebamipide times during the XTC sequence as it is proportional to the surface to volume ratio between the lung parenchyma and airspaces. Consequently, the increase of the gas phase signal is indicative of alveolar membrane thickening. With this in mind regional gas exchange has been probed in healthy humans and subjects with COPD [78]. Reduced surface area that corresponded to destruction of the airspaces and septal wall thickening resulted in distinctive contrast in XTC images. As 129Xe is reasonably soluble in saline solution, it can also be added to physiological solutions and then injected into the blood stream [79]. The T1 relaxation time of hp 129Xe is in excess of 60 s in saline solution, reduces to 13 s in oxygenated blood, and is further shortened in deoxygenated blood [80] and [81]. After intravenous injections, the hp 129Xe is delivered through the blood stream (i.e. via perfusion) and subsequent diffusion through the lung parenchyma into the alveolar gas phase.