Estimation of Superoxide Relaxivity at 0.35T MR-Linac
Abstract
Purpose
Conventional radiotherapy dose (Gy) quantifies deposited energy, but response is influenced by the local radiochemical environment driving indirect DNA damage. Superoxide is a comparatively long-lived paramagnetic radical species showing potential as a marker for radiation-produced chemistry, measurable with quantitative T1 mapping on 0.35T MR-Linac. Determination of T1 changes due to paramagnetic species requires both accurate concentration and relaxivity at 0.35T. Previous work utilized a superoxide relaxivity (10,346 M-1s-1) estimated with a least-squares fit across multiple experimental conditions (Warner 2023). Here, we estimate the effective relaxivity of superoxide at 0.35T using calibration phantoms and simulation-derived concentrations.
Methods
Double-deionized water and 10 mM Coumarin phantoms were irradiated on an 0.35T MR-Linac. Dissolved oxygen was measured pre- and post-irradiation to account for its paramagnetic contribution. Measured T1 was converted into R1 (=1/T1) and dissolved-oxygen contribution was removed using an empirical relaxivity (320 M-1s-1) at 0.35T (Bluemke 2022), modeled as a monotonic linear decline across irradiation based on simulation-derived oxygen concentrations. Matched radiation chemistry simulations produced time-resolved superoxide concentrations. Effective superoxide relaxivity was estimated by linear regression of oxygen-corrected R1 and simulated superoxide concentration, with its slope yielding the effective relaxivity at 0.35T, and the coefficient of determination (R2) to quantify agreement.
Results
Oxygen-corrected R1 vs. simulated superoxide concentration resulted in a superoxide relaxivity of 3,788 M-1s-1 (R2=0.550) in water and 5,153 M-1s-1 (R2=0.916) in Coumarin, with a mean effective r1 of 4,471 M-1s-1. While minor variations indicate sensitivity to chemical environment, this value provides an approximate, order-of-magnitude effective relaxivity for estimating superoxide in similar aqueous-based phantom conditions at 0.35T.
Conclusion
We report an updated effective superoxide relaxivity at 0.35T for quantitative T1 estimation of radiation-produced superoxide on a clinical 0.35T MR-Linac. This reduces reliance on previously assumed constants derived under global conditions, supporting the development of real-time superoxide monitoring during MR-guided radiotherapy.