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

Abstract

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.

Microglia trigger astrocyte-mediated neuroprotection via purinergic gliotransmission

“…Furthermore, it has been demonstrated that human microglia are activated in the absence of significant neuronal loss in the presence of a low concentration of MeHg (i.e., <300 ppb)19, indicating potential neuroprotective roles of microglia. In fact, recent reports have shown microglia-mediated neuroprotective actions including neurotrophic support during brain development23, neuroprotection against NMDA-induced neurotoxicity24 and global brain ischemia25. Here we report that microglia can detect MeHg low , but their neuroprotective action against MeHg low requires astrocytes.…”

Nanoparticle-Based Contrast Agents for129Xe HyperCEST NMR and MRI Applications

“…While chemical engineering continued introducing novel Xe host and sensing concepts, particularly for an expanding palette of molecular targets [42] and for improved CEST detection, hardware and pulse sequence development delivered significant progress for Xe MRI in human applications. The combination of (a) modern polarizers including high-performance laser diodes for a wider user community [43], (b) optimized RF antenna systems [44, 45], and (c) adapted readout protocols enabled novel studies of dissolved Xe in different tissues [46–48]. Imaging of the human brain has been demonstrated in the meantime [49–51] as well as Xe MRI of kidney perfusion [52].…”

Oxygen‐dependent hyperpolarized 129Xe brain MR

“…Hyperpolarized 129 Xe MRI has great potential for the study of brain function due to: (i) the absence of a background MR signal for xenon in the biological tissues; (ii) the high sensitivity of the 129 Xe chemical shift to different chemical environments in various tissues; and (iii) the high lipid solubility of xenon in biological tissue and Ostwald solubility in red blood cells and plasma (0.2 and 0.1, respectively) . As a result of these benefits, hyperpolarized 129 Xe has been successfully used for brain MRI by research groups . Recently, Zhou and co‐workers successfully detected the stroke area in a rat brain using hyperpolarized 129 Xe ; Mazzanti and co‐workers applied hyperpolarized xenon for brain functional imaging (fMRI) and demonstrated the feasibility of detecting brain function changes using hyperpolarized 129 Xe .…”

“…Moreover, the amount of hyperpolarized xenon available is limited by the allowed volume of injectable solution and the solution‐tissue partition coefficient. The second method, which is non‐invasive and widely used, involves inhaling hyperpolarized 129 Xe gas through the lung . The inhaled hyperpolarized xenon first enters the lung while in the gas phase, and then diffuses across the alveolar walls and enters the pulmonary capillaries.…”