Vasodynamic changes significantly impact the interpretation of TOLD MRI

Motivation: Although TOLD MRI shows potential in evaluating tumor hypoxia by identifying hypoxic regions through T1 or R1 changes after a hyperoxic gas challenge, studies have shown inconsistent correlations between TOLD MRI results and hypoxia markers or radiosensitivity. Goal(s): This study used EPR oximetry to measure pO₂ distribution in MC38 murine colon tumors, examining the correlation between pO₂ changes and ΔR1 in TOLD MRI. Approach: A pixel-by-pixel comparison between the pO₂ map from EPR oximetry and the ΔR1 map was conducted. Results: The effects of 100% oxygen and carbogen on tumor oxygenation differed, and both hyperoxic challenges triggered significant vasodynamic responses, complicating data interpretation. Impact: In this study, hypoxic regions showed improved pO₂ without a corresponding R1 increase, indicating that factors beyond pO₂ —such as blood perfusion, volume, and interstitial exchanges —also influence R1 values and may obscure isolated pO₂ effects.