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

Abstract

To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). 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 (H2 O2 ) were used to evaluate the effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes due to H2 O2 treatment in egg white were also monitored. The influences from H2 O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -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). pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T1 relaxation time in the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that produce no ROS, there was a small change in T1 due to H2 O2 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). We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.