Reactive oxygen species (ROS) enhance proton exchange rate (k) in a small-metabolite CEST system

Reactive oxygen species (ROS) serve as key biomarkers of oxidative stress implicated in diverse diseases, including neurodegeneration and cancer. Noninvasive imaging of ROS remains a technical challenge due to their low concentration and transient nature. In previous studies, we demonstrated that ROS, particularly the hydroxyl radicals, enhance proton exchange rate (kex) in chemical exchange saturation transfer (CEST) MRI experiments using egg white tissues, a complex system containing varied proteins and other metabolites. This study is to further validate and confirm this using a simple small-metabolite system, creatine solutions with ROS-producing Fenton reactions. By combining the 9.4 T CEST Z-spectral MRI experiments with Bloch-McConnell modeling, we show that ROS-induced creatine CEST linewidth broadening is primarily linked to increased proton exchange rates rather than relaxation changes. These findings further support endogenous kex mapping as a promising MRI biomarker for in vivo ROS detection, facilitating research and clinical management of oxidative stress-related pathologies.