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 H₂O₂ 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 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°C) and pH (ΔpH <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 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.

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