Quantitative Assessment of Hyperbaric Effects on Tumor Reoxygenation Using Oxygen-Enhanced MRI
Abstract
Purpose
To evaluate tumor oxygenation response to hyperbaric oxygen therapy using oxygen-enhanced MRI (OE-MRI) and assess whether elevated oxygen partial pressure can convert hypoxic, radiation-resistant tumor regions to a more radiosensitive state.
Methods
A custom MRI-compatible hyperbaric chamber was designed to accommodate multiple mice for pre-clinical imaging at varying oxygen concentrations and pressures. SCC7 tumor-bearing mice were imaged under four breathing conditions: 21% O2 at 1 ATM (NormOx), 21% O2 at 2 ATM (NormOxHyp), 100% O2 at 1 ATM (HyperOx), and 100% O2 at 2 ATM (HyperOxHyp). T1-weighted images were acquired to generate R1 maps, and ΔR1 values were calculated relative to baseline NormOx conditions. Tumor tissue was categorized by ΔR1 response: negative (less than -0.01 s-1, severely hypoxic), near-zero (-0.01 to 0.01 s-1, unresponsive/potentially necrotic), and positive (greater than 0.01 s-1, oxygen-responsive). Pixel-by-pixel analysis compared R1 values across breathing conditions.
Results
Brain and heart tissues demonstrated uniform increases in R1 with increasing pO2. Tumors exhibited heterogeneous responses, with peripheral regions showing oxygen responsiveness while central regions remained refractory. The fraction of severely hypoxic tissue (negative ΔR1) decreased significantly from NormOxHyp to HyperOx to HyperOxHyp conditions, while oxygen-responsive tissue (positive ΔR1) increased correspondingly. Near-zero ΔR1 tissue fractions, representing unresponsive regions, remained relatively stable across all breathing conditions, indicating that these regions are likely necrotic tumor subregions. Average ΔR1 increases of 100-200 ms-1 were observed between baseline and hyperbaric hyperoxic conditions.
Conclusion
Hyperbaric oxygen therapy combined with hyperoxic breathing can impact and convert severely hypoxic tumor tissue to an oxygenated, responsive state as measured by OE-MRI. However, potentially necrotic tissue regions remain unresponsive regardless of oxygenation conditions, suggesting that hyperbaric therapy alone may be insufficient to eliminate all hypoxic tumor fractions.