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

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Amide proton transfer–weighted imaging (APTWI) is a novel molecular MR imaging technique developed to detect and quantitatively visualize endogenous proteins and peptides. APTWI is usually reported in terms of asymmetry in the magnetization transfer ratio at 3.5 ppm. 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. 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, 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 may serve as a potential biomarker not only for assessing proliferation, but also for predicting histopathologic grades in gliomas.

Abstract

Figure 2 from paper
Top row, left to right: Transverse T2-FLAIR MR image (left), postgadolinium T1-weighted MR image, APT image, and the location of MR spectroscopy voxel of a 45-year-old woman with diffuse astrocytoma (grade II). Bottom row, left to right: MRSI indicating peaks for choline (Cho), creatine (Cr) and N-acetylaspartate (NAA); Ki-67 immunohistochemical stain for the same patient. The MTRasym(3.5ppm) value for this patient was 2.83%; the choline peak was slightly increased and the NAA peak slightly decreased; and the Ki-67 labeling index was 5%.

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.

 

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Amide Proton Transfer Imaging Allows Detection of Glioma Grades and Tumor Proliferation: Comparison with Ki-67 Expression and Proton MR Spectroscopy Imaging
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jross
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.

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