Whole-Body Oxygen-Enhanced MRI of Tumor-Bearing Mice Under Hyperbaric Oxygenation

Oxygen-enhanced MRI (OE-MRI) enables noninvasive assessment of tissue oxygenation by exploiting the paramagnetic effect of molecular oxygen on longitudinal relaxation. The purpose of this study was to evaluate whether whole-body oxygen-enhanced MRI (OE-MRI) can be performed under hyperbaric oxygen (HBO) conditions and to assess its utility for detecting oxygenation changes in a small-animal tumor model using a clinical 3 T scanner.

A fully MRI-compatible HBO chamber was built for imaging mice and installed in a 3 T clinical scanner. SCC7-tumor-bearing C3H mice underwent whole-body OE-MRI with variable flip-angle T₁ mapping. Longitudinal relaxation-rates (R₁) and ΔR₁ were measured while the animals breathed 21% O₂ at 1 ATA, 21% O₂ at 2 ATA, 100% O₂ at 1 ATA, and 100% O₂ at 2 ATA. ΔR₁ was quantified in tumor, brain, and heart regions.

High-quality OE-MRI was obtained under all hyperbaric conditions. Normal tissues (brain, heart) showed uniform, pressure-dependent increases in ΔR₁ with higher inspired oxygen fractions. Tumors displayed pronounced spatial heterogeneity: many voxels responded robustly, while others showed little or no ΔR₁ change even at 2 ATA 100% O₂. The proportion of oxygen-responsive tumor voxels rose with increasing pressure, yet non-responsive regions persisted.

Whole-body pre-clinical OE-MRI on a clinical 3 T system is feasible and sensitive under hyperbaric oxygenation, capturing both tissue-level pressure effects and heterogeneous tumor oxygen responses. This non-invasive HBO-OE-MRI platform provides a valuable pre-clinical tool for assessing oxygen delivery and identifying oxygen-refractory tumor zones, supporting oxygen-guided therapeutic strategies.