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 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.
['Tain|Rong-Wen|RW|', 'Scotti|Alessandro M|AM|', 'Cai|Kejia|K|']
D000818:Animals D001921:Brain D007091:Image Processing, Computer-Assisted D008279:Magnetic Resonance Imaging D051379:Mice D023421:Models, Animal D019047:Phantoms, Imaging D011446:Prospective Studies D011522:Protons D017382:Reactive Oxygen Species D012680:Sensitivity and Specificity
reactive oxygen species proton exchange rate T1 relaxation time CEST MRI free radicals oxidative stress