Development of a fast method for quantitative measurement of hyperpolarized 129Xe dynamics in mouse brain

A fast method has been established for the precise measurement and quantification of the dynamics of hyperpolarized (HP) xenon-129 ((129)Xe) in the mouse brain. The key technique is based on repeatedly applying radio frequency (RF) pulses and measuring the decrease of HP (129)Xe magnetization after the brain Xe concentration has reached a steady state due to continuous HP (129)Xe ventilation. The signal decrease of the (129)Xe nuclear magnetic resonance (NMR) signal was well described by a simple theoretical model. The technique made it possible to rapidly evaluate the rate constant α, which is composed of cerebral blood flow (CBF), the partition coefficient of Xe between the tissue and blood (λ(i)), and the longitudinal relaxation time (T(1i)) of HP (129)Xe in the brain tissue, without any effect of depolarization by RF pulses and the dynamics in the lung. The technique enabled the precise determination of α as 0.103 ± 0.018  s(-1) (± SD, n = 5) on healthy mice. To investigate the potential of this method for detecting physiological changes in the brain of a kainic acid (KA) -induced mouse model of epilepsy, an attempt was made to follow the time course of α after KA injection. It was found that the α value changes characteristically with time, reflecting the change in the physiological state of the brain induced by KA injection. By measuring CBF using (1)H MRI and (129)Xe dynamics simultaneously and comparing these results, it was suggested that the reduction of T(1i), in addition to the increase of CBF due to KA-induced epilepsy, are possible causes of the change in (129)Xe dynamics. Thus, the present method would be useful to detect a pathophysiological state in the brain and provide a novel tool for future brain study.