Amide proton transfer imaging allows detection of glioma grades and tumor proliferation: Comparison with Ki-67 expression and proton MR spectroscopy imaging

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,weinvestigated 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.