Combining Oxygen-Enhanced MRI and Electron Paramagnetic Resonance Oximetry for Quantitative OE-MRI (qOE-MRI) as a...

Tumor hypoxia remains a major barrier to effective radiation therapy, yet no current imaging technique can generate spatially resolved, absolute pO₂ maps with sufficient depth penetration and spatial resolution for clinical use. This study introduces quantitative oxygen-enhanced MRI (qOE-MRI), a multimodal approach integrating electron paramagnetic resonance (EPR) oximetry using the OxyChip with oxygen-enhanced MRI to enable high-resolution mapping of absolute tumor pO₂.

Phantom studies at 9.4 T validated the linearity of the R₁-pO₂ relationship using saturation-recovery T₁ mapping across known oxygen concentrations. OxyChip sensors coated with gold nanoparticles were used for EPR oximetry. In vivo qOE-MRI was evaluated and tested in an SCC7 mouse tumor model by combining L-band EPR oximetry under normoxic and hyperoxic breathing with quantitative T₁ mapping at 9.4 T. Tissue-specific R₁ versus pO₂ calibration was established using EPR-derived pO₂ measurements at implanted OxyChip locations and applied voxel-wise to generate spatial pO₂ maps.

Phantom validation demonstrated excellent R₁-pO₂ linearity (R² = 0.999) with predictive precision of 2.6 mmHg. OxyChip characterization confirmed robust oxygen sensitivity (12.6 mG/mmHg) and MRI visibility with gold coating. In vivo calibration showed a strong R₁-pO₂ correlation (R² = 0.9737). Resulting pO₂ maps revealed marked intratumoral heterogeneity: the hypoxic core on average showed no increase in oxygenation due to hyperoxygenation, whereas peripheral and muscle-adjacent regions exhibited increased oxygenation.

qOE-MRI enables repeatable and spatially resolved absolute tumor pO₂ mapping. By combining OxyChip technology, clinical EPR systems, and standard MRI platforms, this approach holds promise for translation into hypoxia-guided radiation therapy planning.