Improving the detection specificity of endogenous MRI for reactive oxygen species (ROS)

Background The detection of tissue reactive oxygen species (ROS) using endogenous MRI methods has great potential applications in research and the clinic. We recently demonstrated that ROS produce a significant T-1-shortening effect. However, T-1 or T-1-weighted contrast is not specific, as there are many other factors that alter tissue T-1. Purpose To investigate whether the presence of ROS alters tissue environmental conditions such as the proton exchange rate (K-ex) to improve the detection specificity of endogenous ROS MRI. Study Type Prospective. Subjects/Phantom The ROS-producing phantoms consisted of fresh egg white treated with H2O2 and healthy mice injected with pro-oxidative rotenone. Field Strength/Sequence T-1 mapping was performed based on fast spin-echo sequence and K-ex was evaluated using chemical exchange saturation transfer (CEST) MRI with varied saturation power (QUESP) on a 9.4 T animal scanner. Assessment Phantom experiments were conducted to evaluate the overall K-ex of CEST-expressing metabolites in fresh egg white treated with H2O2 of various concentrations (0, 0.025, 0.05, 0.1, and 0.25 v/v%). The egg white phantom continuously produced ROS for more than 3 hours. Various experiments were performed to rule out potential contributing factors to the observed K-ex changes. In addition, in vivo MRI study was conducted with a well-established rotenone-exposed mouse model. Statistical Tests Student's t-test. Results Egg white phantoms treated with H2O2 of various concentrations showed a 26-85% increase in K-ex compared with controls. In addition, the K-ex of egg white is negligibly affected by other potential confounding factors, including paramagnetic contrast agents (<11%), oxygen (2.3%), and iron oxidation (<10%). Changes in temperature (<1 degrees C) and pH (Delta pH <0.1) in H2O2-treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T-1 relaxation time (6%) and increased K-ex (9%) in rotenone-treated mice. Data Conclusion We demonstrate that the specificity of endogenous ROS MRI can be improved with the aid of proton exchange rate mapping. Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.