Novel ¹H NMR approach to quantitative tissue oximetry using hexamethyldisiloxane

¹⁹F NMR spin-lattice relaxometry of hexafluorobenzene (HFB) has been shown to be a highly sensitive indicator of tumor oxygenation. In this study hexamethyldisiloxane (HMDSO) was identified as a proton NMR analog, and its potential as a probe for investigating dynamic changes in tissue oxygen tension (pO₂) was evaluated. HMDSO has a single proton resonance (δ= -0.3 ppm) and the spin-lattice relaxation rate, R₁ (= 1/T₁) exhibits a linear dependence on pO₂: R₁ (s^-1) = 0.1126 + 0.0013* pO₂ (torr) at 37°C. To demonstrate application in vivo, HMDSO was administered into healthy rat thigh muscle (100 μl) and tumors (50 μl). Local pO₂ was determined by using pulse-burst saturation recovery (PBSR) ¹H NMR spectroscopy to assess R₁. Water and fat signals were effectively suppressed by frequency-selective excitation of the HMDSO resonance. Rat thigh muscle had a mean baseline pO₂ of 35 ± 11 torr, with a typical stability of ±3 torr over 20 min, when the rats breathed air. Altering the inhaled gas to oxygen produced a significant increase in pO₂ to 100-200 torr. In tumors, altering the inspired gas also produced significant (albeit generally smaller) changes. This new pO₂ reporter molecule offers a potentially valuable new tool for investigating pO₂ in vivo.