Amide Proton Transfer Imaging Allows Detection of Glioma Grades and Tumor Proliferation: Comparison with Ki-67 Expression and Proton MR Spectroscopy Imaging

AJNR Am J Neuroradiol. 2017 Sep;38(9):1702-1709. doi: 10.3174/ajnr.A5301. Epub 2017 Jul 20.

Abstract

Background and purpose: Prognosis in glioma depends strongly on tumor grade and proliferation. In this prospective study of patients with untreated primary cerebral gliomas, we investigated whether amide proton transfer-weighted imaging could reveal tumor proliferation and reliably distinguish low-grade from high-grade gliomas compared with Ki-67 expression and proton MR spectroscopy imaging.

Materials and methods: This study included 42 patients with low-grade (n = 28) or high-grade (n = 14) glioma, all of whom underwent conventional MR imaging, proton MR spectroscopy imaging, and amide proton transfer-weighted imaging on the same 3T scanner within 2 weeks before surgery. We assessed metabolites of choline and N-acetylaspartate from proton MR spectroscopy imaging and the asymmetric magnetization transfer ratio at 3.5 ppm from amide proton transfer-weighted imaging and compared them with histopathologic grade and immunohistochemical expression of the proliferation marker Ki-67 in the resected specimens.

Results: The asymmetric magnetization transfer ratio at 3.5 ppm values measured by different readers showed good concordance and were significantly higher in high-grade gliomas than in low-grade gliomas (3.61% ± 0.155 versus 2.64% ± 0.185, P = .0016), with sensitivity and specificity values of 92.9% and 71.4%, respectively, at a cutoff value of 2.93%. The asymmetric magnetization transfer ratio at 3.5 ppm values correlated with tumor grade (r = 0.506, P = .0006) and Ki-67 labeling index (r = 0.502, P = .002). For all patients, the asymmetric magnetization transfer ratio at 3.5 ppm correlated positively with choline (r = 0.43, P = .009) and choline/N-acetylaspartate ratio (r = 0.42, P = .01) and negatively with N-acetylaspartate (r = -0.455, P = .005). These correlations held for patients with low-grade gliomas versus those with high-grade gliomas, but the correlation coefficients were higher in high-grade gliomas (choline: r = 0.547, P = .053; N-acetylaspartate: r = -0.644, P = .017; choline/N-acetylaspartate: r = 0.583, P = .036).

Conclusions: The asymmetric magnetization transfer ratio at 3.5 ppm may serve as a potential biomarker not only for assessing proliferation, but also for predicting histopathologic grades in gliomas.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Amides / chemistry*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / surgery
  • Choline / metabolism
  • Female
  • Glioma / diagnostic imaging*
  • Glioma / pathology*
  • Glioma / surgery
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prospective Studies
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Protons*
  • Sensitivity and Specificity
  • Treatment Outcome

Substances

  • Amides
  • Ki-67 Antigen
  • Protons
  • Aspartic Acid
  • N-acetylaspartate
  • Choline