High resolution pH_e imaging of rat glioma using pH‐dependent relaxivity

<jats:title>Abstract</jats:title><jats:p>Previous studies using MR spectroscopy have shown that the extracellular pH (pH<jats:sub>e</jats:sub>) 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 T<jats:sub>1</jats:sub> relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH‐dependent GdDOTA‐4AmP<jats:sup>5‐</jats:sup> and a pH‐independent analog, GdDOTP<jats:sup>5‐</jats:sup>, were used to image renal pH in mice. The current study has used a similar approach to image pH<jats:sub>e</jats:sub> in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP<jats:sup>5‐</jats:sup> was found to be affected by the higher extracellular protein content of tumors. Second, the pixel‐by‐pixel analysis of the GdDOTP<jats:sup>5‐</jats:sup> and GdDOTA‐4AmP<jats:sup>5‐</jats:sup> 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<jats:sub>e</jats:sub> maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pH<jats:sub>e</jats:sub> and the time to maximal intensity maps revealed an inverse relationship between pH<jats:sub>e</jats:sub> and tumor perfusion. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.</jats:p>