Oxygen Response Index As an OE-MRI Biomarker for Early Detection of Radiation Treatment Response
Abstract
Purpose
To evaluate the Oxygen Response Index (ORI) as a new oxygen-enhanced MRI (OE-MRI) metric for quantifying tumor radiation therapy efficacy that accounts for tissue oxygen response and tumor size, and to compare its sensitivity for detecting treatment response against conventional metrics, including tumor growth rate and change in spin-lattice relaxation rate (ΔR1).
Methods
Six male C3H mice with SCC7 tumors on the right hind leg underwent longitudinal OE-MRI at 3T using custom MRI-compatible 3D-printed housing. The OE-MRI protocol included B1 field corrections and variable-flip-angle T1 mapping under both 21% and 100% oxygen breathing conditions, with 1.5% isoflurane anesthesia. Mice received a 7-day low-dose fractionated regimen (2Gy daily, 320kV, 3Gy/min) with OE-MRI performed every other day, followed by a single large dose of 60Gy (TCD95) and two additional imaging sessions. ORI was defined as ΔR1 divided by tumor volume. Higher ORI values reflect a greater tissue oxygen response and/or smaller tumor volumes, suggesting a positive treatment response, while lower ORI values indicate a diminished oxygen response and/or larger tumor volumes, suggesting disease progression.
Results
The low-dose fractionated regimen was found to be insufficient for tumor control, as the ORI steadily declined throughout treatment, indicating progressive hypoxia and tumor growth. Following the 60Gy dose, ORI increased at the 2-day follow-up scan, demonstrating early detection of treatment response before tumor volume decreased at 4 days post-treatment. Analysis of ΔR1 tissue fractions revealed decreased negative and near-zero components only after the 60Gy dose, while control tissue remained stable throughout.
Conclusion
The Oxygen Response Index enables longitudinal monitoring of the tissue oxygen response before, during, and after radiation therapy, providing earlier detection of treatment response than tumor volume measurements alone. ORI accurately captures physiological changes reflecting treatment efficacy, suggesting it could be a promising non-invasive biomarker for radiation therapy monitoring.