Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI

Purpose

To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI).

Materials and Methods

ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T₁ and T₂ maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H₂O₂) were used to evaluate the effect of produced ROS in T₁ and T₂ for up to 4 hours. pH and temperature changes due to H₂O₂ treatment in egg white were also monitored. The influences from H₂O₂ itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T₁ in H₂O₂-treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T₁ mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n = 6).

Results

pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T₁ relaxation time in the H₂O₂-treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T₂ (<10%). In the H₂O₂-treated BSA solution that produce no ROS, there was a small change in T₁ due to H₂O₂ itself (±1%), although a significant T₂-shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T₁ (13 ± 1%) and T₂ (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T₁ relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 × 10⁷ vs. 0.9 s⁻¹·mM⁻¹). Finally, significantly reduced T₁ was observed in rotenone-treated mouse brain (5.1 ± 2.5%, P < 0.05).

Conclusion

We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications.

Level of Evidence: 2

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2017.

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