Compartment-specific 129Xe HyperCEST z spectroscopy and chemical shift imaging of cucurbit[6]uril in spontaneously breathing rats

Abstract

129Xe hyperpolarized gas chemical exchange saturation transfer (HyperCEST) MRI has been suggested as molecular imaging modality but translation to in vivo imaging has been slow, likely due to difficulties of synthesizing suitable molecules. Cucurbit[6]uril–either in readily available non-functionalized or potentially in functionalized form–may, combined with 129Xe HyperCEST MRI, prove useful as a switchable 129Xe MR contrast agent but the likely differential properties of contrast generation in individual chemical compartments as well as the influence of 129Xe signal drifts encountered in vivo on HyperCEST MRI are unknown. Here, HyperCEST z spectroscopy and chemical shift imaging with compartment-specific analysis are performed in a total of 10 rats using cucurbit[6]uril injected i.v. and under a protocol employing spontaneous respiration. Differences in intensity of the HyperCEST effect between chemical compartments and anatomical regions are investigated. Strategies to mitigate influence of signal instabilities associated with drifts in physiological parameters are developed. It is shown that presence of cucurbit[6]uril can be readily detected under spontaneous 129Xe inhalation mostly in aqueous tissues further away from the lung. Differences of effect intensity in individual regions and compartments must be considered in HyperCEST data interpretation. In particular, there seems to be almost no effect in lipids. 129Xe HyperCEST MR measurements utilizing spontaneous respiration protocols and extended measurement times are feasible. HyperCEST MRI of non-functionalized cucurbit[6]uril may create contrast between anatomical structures in vivo.