High resolution pHe imaging of rat glioma using pH-dependent relaxivity

Maria L. Garcia-Martin, Gary V. Martinez, Natarajan Raghunand, A. Dean Sherry, Shanrong Zhang, Robert J. Gillies

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127 Scopus citations

Abstract

Previous studies using MR spectroscopy have shown that the extracellular pH (pHe) 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, GdDOTP 5-, were used to image renal pH in mice. The current study has used a similar approach to image pHe 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 GdDOTP 5- 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, pHe maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pHe and the time to maximal intensity maps revealed an inverse relationship between pHe and tumor perfusion.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalMagnetic Resonance in Medicine
Volume55
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Keywords

  • Acid-base
  • Gadolinium
  • MRI
  • Relaxivity
  • Tumor, pH

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Garcia-Martin, M. L., Martinez, G. V., Raghunand, N., Sherry, A. D., Zhang, S., & Gillies, R. J. (2006). High resolution pHe imaging of rat glioma using pH-dependent relaxivity. Magnetic Resonance in Medicine, 55(2), 309-315. https://doi.org/10.1002/mrm.20773