High resolution pH(e) imaging of rat glioma using pH-dependent relaxivity

Magn Reson Med. 2006 Feb;55(2):309-15. doi: 10.1002/mrm.20773.


Previous studies using MR spectroscopy have shown that the extracellular pH (pH(e)) of tumors is acidic compared to normal tissues. This has a number of important sequelae that favor the emergence of more aggressive and therapy-resistant tumors. New MRI methods based on pH-sensitive T1 relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH-dependent GdDOTA-4AmP5- and a pH-independent analog, GdDOTP5-, were used to image renal pH in mice. The current study has used a similar approach to image pH(e) in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP5- was found to be affected by the higher extracellular protein content of tumors. Second, the pixel-by-pixel analysis of the GdDOTP5- and GdDOTA-4AmP5- pharmacokinetics showed significant dispersion, likely due to the temporal fluctuations in tumor perfusion. However, there was a robust correlation between the maximal enhancements produced by the two boluses. Therefore, to account for the local time-courses differences, pH(e) maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pH(e) and the time to maximal intensity maps revealed an inverse relationship between pH(e) and tumor perfusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Contrast Media / pharmacokinetics
  • Glioma / metabolism*
  • Heterocyclic Compounds / pharmacokinetics
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy / methods*
  • Organometallic Compounds / pharmacokinetics
  • Rats
  • Reproducibility of Results
  • Tumor Cells, Cultured


  • Contrast Media
  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate