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

Abstract

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 T 1 and T 2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H 2 O 2 ) were used to evaluate the effect of produced ROS in T 1 and T 2 for up to 4 hours. pH and temperature changes due to H 2 O 2 treatment in egg white were also monitored. The influences from H 2 O 2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T 1 in H 2 O 2 ‐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 T 1 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). T 1 relaxation time in the H 2 O 2 ‐treated egg white was reduced significantly ( P < 0.05), while there was only small reduction in T 2 (<10%). In the H 2 O 2 ‐treated BSA solution that produce no ROS, there was a small change in T 1 due to H 2 O 2 itself (±1%), although a significant T 2 ‐shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T 1 (13 ± 1%) and T 2 (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T 1 relaxivity of ROS was found to be much higher than that of Gd‐DTPA (3.4 × 10 7 vs. 0.9 s −1 ·mM −1 ). Finally, significantly reduced T 1 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 2018;47:222–229.