Oxygen Response Index: A Potential OE-MRI-Derived Non-Invasive Biomarker for Assessing Radiation Treatment Efficacy

The goal of this study was to develop an optimized oxygen-enhanced MRI (OE-MRI) protocol for longitudinal monitoring of tumor oxygenation during radiation therapy in a pre-clinical model and to introduce the Oxygen Response Index (ORI) as a potential early biomarker of treatment efficacy.

A high-throughput mouse imaging protocol was designed for a clinical 3 T MRI system using optimized variable flip angle T₁ mapping for relaxometry. Six male C3H mice bearing SCC7 tumors underwent longitudinal OE-MRI during fractionated radiation therapy (2 Gy/day for 7 days), followed by a single 60 Gy dose. Tumor oxygenation response was quantified as the change in longitudinal relaxation rate (ΔR₁) between normoxic and hyperoxic breathing. ORI was defined as the product of the baseline-normalized longitudinal relaxation rate under normoxia (R₁ ^21%/R_1,0 ^21%) and the baseline-normalized fraction of oxygen-responsive tumor voxels (∆R₁ ⁺/∆R_1,0 ⁺), providing a composite index of oxygenation competence.

During fractionated irradiation, ORI declined progressively, with the change-point analysis identifying treatment response inflection at scan 4 (day 8), one scan interval before tumor volume at scan 5 (day 10). After the 60-Gy dose, conversion of putatively hypoxic tissue to oxygen-responsive tissue was observed. Spatial analysis revealed persistent oxygen-response gradients, with tumor regions adjacent to normoxic tissue demonstrating greater responsiveness than non-adjacent tumor areas.

ORI captured longitudinal changes in tumor oxygenation during both ineffective and effective treatment phases and may provide a useful complementary biomarker for monitoring treatment response.