In vivo imaging of extracellular pH using ¹H MRSI

Tumor pH is physiologically important since it influences a number of processes relevant to tumorigenesis and therapy. Hence, knowledge of localized pH within tumors would contribute to understanding these processes. The destructiveness, poor spatial resolution, and poor signal-to-noise ratio (SNR) of current technologies (e.g., microelectrodes, ³¹p magnetic resonance spectroscopy) have limited such studies. An extrinsic chemical extracellular pH (pH(e)) probe is described that is used in combination with ¹H magnetic resonance spectroscopic imaging to yield pH(e) maps with a spatial resolution of 1 x 1 x 4 mm³. The principle of the technique is demonstrated on a phantom. Further data are shown to demonstrate its application in vivo, and results agree with previously reported pH values. The accuracy of the reported pH measurements is <0.1 pH units, as derived from a detailed analysis of the errors associated with the technique, the description of which is included.