Amide proton transfer-weighted MRI in distinguishing high- and low-grade gliomas: a systematic review and meta-analysis
Grading of brain gliomas is of clinical importance, and noninvasive molecular imaging may help differentiate low- and high-grade gliomas. We aimed to evaluate the diagnostic performance of amide proton transfer-weighted (APTw) MRI for differentiating low- and high-grade gliomas on 3-T scanners.
A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to March 28, 2018. Original articles evaluating the diagnostic performance of APTw MRI for differentiating low- and high-grade gliomas were selected. The pooled sensitivity and specificity were calculated using a bivariate random-effects model. A coupled forest plot and a hierarchical summary receiver operating characteristic curve were obtained. Heterogeneity was investigated using Higgins inconsistency index (I2) test. Meta-regression was performed.
Ten original articles with a total of 353 patients were included. High-grade gliomas showed significantly higher APT signal intensity than low-grade gliomas. The pooled sensitivity and specificity for the diagnostic performance of APTw MRI for differentiating low-grade and high-grade gliomas were 88% (95% CI, 77–94%) and 91% (95% CI, 82–96%), respectively. Higgins I2 statistic demonstrated heterogeneity in the sensitivity (I2 = 68.17%), whereas no heterogeneity was noted in the specificity (I2 = 44.84%). In meta-regression, RF saturation power was associated with study heterogeneity. Correlation coefficients between APT signal intensity and Ki-67 cellular proliferation index ranged from 0.430 to 0.597, indicating moderate correlation. All studies showed excellent interobserver agreement.
Although heterogeneous protocols were used, APTw MRI demonstrated excellent diagnostic performance for differentiating low- and high-grade gliomas. APTw MRI could be a reliable technique for glioma grading in clinical practice.
KeywordsGlioma Grading Amide proton transfer Chemical exchange saturation transfer
Chemical exchange saturation transfer
Amide proton transfer
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Quality Assessment of Diagnostic Accuracy Studies-2
Hierarchical summary receiver operating characteristic
Compliance with ethical standards
This study was funded by the National Research Foundation of Korea (NRF) Grant by the Korean government (MSIP) (Grant no. NRF-2017R1A2A2A05001217) and (NRF-2017R1C1B2007258).
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the meta-analysis studies.
- 6.Bai Y, Lin Y, Zhang W, Kong L, Wang L, Zuo P, Vallines I, Schmitt B, Tian J, Song X, Zhou J, Wang M (2017) Noninvasive amide proton transfer magnetic resonance imaging in evaluating the grading and cellularity of gliomas. Oncotarget 8:5834–5842. https://doi.org/10.18632/oncotarget.13970 Google Scholar
- 7.Su C, Liu C, Zhao L, Jiang J, Zhang J, Li S, Zhu W, Wang J (2017) 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 38:1702–1709. https://doi.org/10.3174/ajnr.A5301 CrossRefGoogle Scholar
- 8.Togao O, Yoshiura T, Keupp J, Hiwatashi A, Yamashita K, Kikuchi K, Suzuki Y, Suzuki SO, Iwaki T, Hata N, Mizoguchi M, Yoshimoto K, Sagiyama K, Takahashi M, Honda H (2014) Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro-Oncology 16:441–448. https://doi.org/10.1093/neuonc/not158 CrossRefGoogle Scholar
- 9.Choi YS, Ahn SS, Lee SK, Chang JH, Kang SG, Kim SH, Zhou J (2017) Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. Eur Radiol 27:3181–3189. https://doi.org/10.1007/s00330-017-4732-0 CrossRefPubMedCentralGoogle Scholar
- 10.Jiang S, Eberhart CG, Zhang Y, Heo HY, Wen Z, Blair L, Qin H, Lim M, Quinones-Hinojosa A, Weingart JD, Barker PB, Pomper MG, Laterra J, van Zijl PCM, Blakeley JO, Zhou J (2017) Amide proton transfer-weighted magnetic resonance image-guided stereotactic biopsy in patients with newly diagnosed gliomas. Eur J Cancer 83:9–18. https://doi.org/10.1016/j.ejca.2017.06.009 CrossRefPubMedCentralGoogle Scholar
- 11.Park JE, Kim HS, Park KJ, Choi CG, Kim SJ (2015) Histogram analysis of amide proton transfer imaging to identify contrast-enhancing low-grade brain tumor that mimics high-grade tumor: increased accuracy of MR perfusion. Radiology 277:151–161. https://doi.org/10.1148/radiol.2015142347 CrossRefGoogle Scholar
- 13.Sakata A, Fushimi Y, Okada T, Arakawa Y, Kunieda T, Minamiguchi S, Kido A, Sakashita N, Miyamoto S, Togashi K (2017) Diagnostic performance between contrast enhancement, proton MR spectroscopy, and amide proton transfer imaging in patients with brain tumors. J Magn Reson Imaging 46:732–739. https://doi.org/10.1002/jmri.25597 CrossRefGoogle Scholar
- 14.Zhou J, Zhu H, Lim M, Blair L, Quinones-Hinojosa A, Messina SA, Eberhart CG, Pomper MG, Laterra J, Barker PB, van Zijl PCM, Blakeley JO (2013) Three-dimensional amide proton transfer MR imaging of gliomas: initial experience and comparison with gadolinium enhancement. J Magn Reson Imaging 38:1119–1128. https://doi.org/10.1002/jmri.24067 CrossRefGoogle Scholar
- 17.Zhang L, Min Z, Tang M, Chen S, Lei X, Zhang X (2017) The utility of diffusion MRI with quantitative ADC measurements for differentiating high-grade from low-grade cerebral gliomas: evidence from a meta-analysis. J Neurol Sci 373:9–15. https://doi.org/10.1016/j.jns.2016.12.008 CrossRefGoogle Scholar
- 19.Wang Q, Zhang H, Zhang J, Wu C, Zhu WJ, Li FY, Chen XL, Xu BN (2016) The diagnostic performance of magnetic resonance spectroscopy in differentiating high-from low-grade gliomas: a systematic review and meta-analysis. Eur Radiol 26:2670–2684. https://doi.org/10.1007/s00330-015-4046-z CrossRefGoogle Scholar
- 21.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65–W94CrossRefGoogle Scholar
- 22.Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM, QUADAS-2 Group (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536. https://doi.org/10.7326/0003-4819-155-8-201110180-00009 CrossRefGoogle Scholar
- 24.Kim KW, Lee J, Choi SH, Huh J, Park SH (2015) Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: a practical review for clinical researchers-part I. general guidance and tips. Korean J Radiol 16:1175–1187. https://doi.org/10.3348/kjr.2015.16.6.1175 CrossRefPubMedCentralGoogle Scholar
- 25.Lee J, Kim KW, Choi SH, Huh J, Park SH (2015) Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: a practical review for clinical researchers-part II. Statistical methods of meta-analysis. Korean J Radiol 16:1188–1196. https://doi.org/10.3348/kjr.2015.16.6.1188 CrossRefPubMedCentralGoogle Scholar
- 32.Sakata A, Okada T, Yamamoto A, Kanagaki M, Fushimi Y, Okada T, Dodo T, Arakawa Y, Schmitt B, Miyamoto S, Togashi K (2015) Grading glial tumors with amide proton transfer MR imaging: different analytical approaches. J Neuro-Oncol 122:339–348. https://doi.org/10.1007/s11060-014-1715-8 CrossRefGoogle Scholar
- 33.Park KJ, Kim HS, Park JE, Shim WH, Kim SJ, Smith SA (2016) Added value of amide proton transfer imaging to conventional and perfusion MR imaging for evaluating the treatment response of newly diagnosed glioblastoma. Eur Radiol 26:4390–4403. https://doi.org/10.1007/s00330-016-4261-2 CrossRefGoogle Scholar
- 34.Park JE, Lee JY, Kim HS, Oh JY, Jung SC, Kim SJ, Keupp J, Oh M, Kim JS (2018) Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography. Eur Radiol 28:3285–3295. https://doi.org/10.1007/s00330-018-5341-2 CrossRefGoogle Scholar
- 35.Yu H, Lou H, Zou T, Wang X, Jiang S, Huang Z, du Y, Jiang C, Ma L, Zhu J, He W, Rui Q, Zhou J, Wen Z (2017) Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma. Eur Radiol 27:4516–4524. https://doi.org/10.1007/s00330-017-4867-z CrossRefPubMedCentralGoogle Scholar
- 36.Jiang S, Yu H, Wang X, Lu S, Li Y, Feng L, Zhang Y, Heo HY, Lee DH, Zhou J, Wen Z (2016) Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 tesla. Eur Radiol 26:64–71. https://doi.org/10.1007/s00330-015-3805-1 CrossRefGoogle Scholar
- 37.Keupp J, Baltes C, Harvey P, Van den Brink J (2011) Parallel RF transmission based MRI technique for highly sensitive detection of amide proton transfer in the human brain at 3T. In: Proc Int Soc Magn Reson Med, p 710Google Scholar
- 38.Togao O, Hiwatashi A, Keupp J, Yamashita K, Kikuchi K, Yoshiura T, Yoneyama M, Kruiskamp MJ, Sagiyama K, Takahashi M, Honda H (2016) Amide proton transfer imaging of diffuse gliomas: effect of saturation pulse length in parallel transmission-based technique. PLoS One 11:e0155925. https://doi.org/10.1371/journal.pone.0155925 CrossRefPubMedCentralGoogle Scholar