An assessment of the sensitivity of in vivo 31P nuclear magnetic resonance spectroscopy as a means of detecting pH heterogeneity in tumours: a simulation study.

The presence of hypoxia and low pH in tumours is known to influence several treatment modalities including radiotherapy, chemotherapy and hyperthermia. Hypoxic and acidic regions have been demonstrated in tumours using pH and pO2 microelectrodes. The technique has shown marked heterogeneity within individual tumours. A non-invasive measure of intracellular pH is provided by 31P nuclear magnetic resonance (NMR) spectroscopy from determination of the chemical shift of inorganic phosphate, and is being increasingly applied to the study of human tumours in vivo. Based upon the assumption that hypoxic cells are also acidic, we have assessed the ability of a whole-body NMR spectrometer to detect acidic subpopulations within a tumour using simulated tumour spectra. In these simulations the size of the acidic subpopulation, assigned pH values from 5.0 to 7.0, was varied between 5% and 50% of the neutral "control" population. Gaussian noise was added to the simulated spectra giving signal-to-noise ratios for the neutral control inorganic phosphate peak of 3, 5 and 7, which are typical of values encountered in human tumour measurements. From the results of the simulations it seems unlikely that human hypoxic, and presumably acidic, cell fractions, typically 1-15%, will be detected by this method in the presence of signal-to-noise levels characteristic of current equipment. Therefore, whole-body in vivo 31P NMR spectroscopy may fail to identify significant pH heterogeneity within human tumours. Improvements in signal-to-noise and line separation owing to improvements in technique and higher field strength instruments may improve sensitivity to heterogeneous populations.