Detecting Changes in Reactive Oxygen Species in the Brain by GSH-Thiol-Weighted Imaging via Variable Delay Multipulse Chemical-Exchange Saturation Transfer.

Purpose: Detecting changes in reactive oxygen species (ROS) is critical for understanding its role in brain health and diseases. We assumed that GSH-thiol-weighted imaging could potentially reflect subtle changes in the ROS in the microenvironment. In this study, we aimed to investigate the capability of GSH-thiol-weighted imaging via VDMP-CEST in detecting alterations of ROS within the brain. Methods: To develop a new technique to image GSH-thiol, phantoms of different GSH concentrations under acidic and weakly alkaline conditions were performed using MRI CEST scanning. To explore the ability of GSH-thiol-weighted VDMP-CEST imaging to detect changes in ROS, experiments were conducted in vitro and in vivo. Phantom imaging in different concentrations of GSH and H₂O₂ was performed. Eight normal rats underwent rat brain imaging, followed by in vitro ROS detection. Another four rats underwent rat brain imaging before and after sleep deprivation. Results: We found that VDMP-CEST could achieve GSH-thiol-weighted imaging under both acid and weakly alkaline conditions. This signal decreased with the mixing time. We also demonstrated that GSH-thiol-weighted VDMP-CEST imaging can reflect alterations in ROS in vitro and in vivo. In vitro, the GSH-thiol-weighted VDMP-CEST signal was sensitive to changes in H₂O₂ concentration. In vivo, the GSH-thiol-weighted VDMP-CEST signal has regional heterogeneity, which is positively correlated with ROS content in vitro (r = 0.7404, P < 0.0001). Furthermore, this signal significantly increased after sleep deprivation (whole brain: P < 0.05, hippocampus: P < 0.01). Conclusions: This study demonstrates that GSH-thiol-weighted imaging via VDMP-CEST can serve as a new method for detecting changes in ROS in the brain.