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

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 T1 -shortening effect. However, T1 or T1 -weighted contrast is not specific, as there are many other factors that alter tissue T1 . 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 H2 O2 and healthy mice injected with pro-oxidative rotenone. FIELD STRENGTH/SEQUENCE: T1 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 H2 O2 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 H2 O2 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°C) and pH (ΔpH <0.1) in H2 O2 -treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T1 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. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.