Purpose: The aim of this work was to test the hypothesis that decreases in the linewidth of magnetic resonance (MR) water signals in tumors caused by oxygenating treatments are due to increases in capillary and venous oxygen saturation of hemoglobin, which are tightly coupled to increases in extravascular oxygen tension (pO2). To establish this link, changes measured by MR were compared to changes in tissue pO2 measured directly by oxygen microelectrodes during carbogen (95% O2/5% CO2) inhalation.
Methods and materials: Mammary adenocarcinomas (R3230AC) in nine rats were imaged at 4.7 Tesla. T1-weighted (TR = 200 ms, flip angle = 45 degrees) spectroscopic images of the water resonance in a single slice through each tumor were acquired with spectral resolution of 3.9 Hz and bandwidth of +/-1000 Hz. In the same slices in these tumors, microelectrode measurements were made using a non-Clark style oxygen electrode with a 350-micron tip. MR and microelectrode measurements were made during alternating periods of air and carbogen inhalation.
Results: Water resonance linewidth decreased significantly during carbogen-induced hyperoxia. Paired Student's t-test analysis of microelectrode data indicated that pO2 was significantly (p < 0.05) increased as a result of carbogen inhalation. MR and microelectrode data averaged over each tumor demonstrated that decreased MR water signal linewidth is strongly correlated (r = 0.92, p < 0.05) with increased tumor pO2 levels.
Conclusion: Although tumor oxygenating agents increase response to radiation in rodent tumors, clinical studies have shown only marginal effects on the radiosensitivity of human tumors. This may be, in part, because the effects of tumor oxygenating treatments are highly heterogeneous both within each tumor and among a population of tumors. The noninvasive, high-resolution MR methods that are validated by the present work could guide the design of new and more effective tumor oxygenating agents and optimize treatments for individual patients.