23Na chemical shift imaging in the living rat brain using a chemical shift agent, Tm[DOTP]5–

Abstract

ObjectiveIt is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood–brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP]5−.Materials and methodsHyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP]5− containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the 23Na resonance spectrum were followed in a 9.4T small animal scanner.ResultsBased on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the 23Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion.ConclusionOur novel protocol showed bulk accumulation of Tm[DOTP]5− thus enabling separation of the extra-/intracellular 23Na signal components in the living rat brain while maintaining physiological homeostasis.