Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI
Rong-Wen Tain1,2, Alessandro M Scotti1,2,3, Weiguo Li4,5
1Department of Radiology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
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 (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).
Results:
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).
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.
Insights
This study characterizes reactive oxygen species (ROS) relaxation properties for endogenous ROS MRI. Results show ROS MRI is sensitive for in vitro and in vivo applications, enabling new diagnostic capabilities.
Area of Science:
- Biomedical Imaging
- Magnetic Resonance Imaging
- Reactive Oxygen Species Biology
Background:
- Reactive oxygen species (ROS) play crucial roles in cellular signaling and disease pathogenesis.
- Accurate detection and quantification of endogenous ROS are vital for understanding physiological and pathological processes.
- Current methods for ROS detection have limitations in sensitivity and specificity, necessitating advanced imaging techniques.
Purpose of the Study:
- To characterize the relaxation properties of reactive oxygen species (ROS) for developing endogenous ROS contrast magnetic resonance imaging (MRI).
- To establish a foundation for quantitative ROS imaging using MRI by determining T1 and T2 relaxation parameters.
- To assess the sensitivity and feasibility of ROS-specific MRI in both in vitro and in vivo models.
Main Methods:
- Utilized 9.4T MRI to acquire T1 and T2 maps of ROS-producing phantoms and animal models.
- Investigated the effects of hydrogen peroxide (H2O2) on T1 and T2 relaxation times in egg white and bovine serum albumin (BSA) solutions.
- Monitored pH and temperature changes and evaluated the influence of H2O2 and molecular oxygen on relaxation properties.
- Assessed dynamic temporal changes in T1 to estimate ROS concentration and detection sensitivity.
- Demonstrated in vivo feasibility using a rotenone-induced mouse model of oxidative stress.
Main Results:
- Significant T1 relaxation time reduction was observed in H2O2-treated egg white (P < 0.05), with minimal pH/temperature changes.
- H2O2 itself caused minor T1 changes in BSA, while molecular oxygen induced small T1 and T2 reductions.
- A significant T2-shortening effect was noted in H2O2-treated BSA (>10%, P < 0.05).
- Estimated ROS MRI detection sensitivity at approximately 10 pM.
- ROS exhibited a substantially higher T1 relaxivity (3.4 × 10^7 s⁻¹·mM⁻¹) compared to Gd-DTPA (0.9 s⁻¹·mM⁻¹).
- Significantly reduced T1 was observed in the brains of rotenone-treated mice (5.1 ± 2.5%, P < 0.05).
Conclusions:
- Endogenous ROS MRI, leveraging the paramagnetic effect, demonstrates significant sensitivity for both in vitro and in vivo applications.
- This technique provides a promising non-invasive method for detecting and quantifying oxidative stress.
- The findings support the development of ROS-specific MRI as a valuable tool in diagnostics and research.
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