Quantitative Consistency of Amide Proton Transfer-Weighted MRI for Brain Tumor Differentiation: Systematic Review of Clinical Evidence

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Abstract
Background/Objectives: Accurate grading of brain gliomas is important, and amide proton transfer-weighted (APTw) MRI shows promise for non-invasive tumor differentiation. This study aimed to perform a comprehensive review and meta-analyses to demonstrate heterogeneity in both the diagnostic accuracy and quantitative consistency of APTw MRI in distinguishing high-grade gliomas (HGGs) from low-grade gliomas (LGGs), highlight issues with reporting standards and identify sources of heterogeneity through meta-regression. Methods: A systematic literature search was conducted between 1 January 2013 and 18 January 2026, following PRISMA guidelines. Peer-reviewed articles in English reporting diagnostic accuracy/contrast values of APTw MRI and study parameters were included. Principal component analysis (PCA) was used to extract the principal components (PCs) of the chemical exchange saturation transfer (CEST) contrast mechanism. Random-effects meta-analyses and univariate meta-regression models using individual CEST parameters and three PCs were performed. Forest plots with pooled estimates were generated. Leave-one-out meta-analysis (LOOMA) and complete case analysis were performed to examine the effects of outliers and missing data, respectively. Results: A total of 31 studies were included. Meta-analyses of the AUC and mean difference demonstrated significant heterogeneity across the studies (I2 = 73.9% & 78.2%, p < 0.001). The mean difference was moderated by one SD within the mean of the readout PC (p = 0.034) and the total PC (p = 0.02). The heterogeneity for the AUC and group mean difference was not substantially reduced by moderating nor LOOMA. The results of the meta-regression using all the data were similar to those using only data with no missing parameters. Conclusions: While APTw MRI shows promise for non-invasively distinguishing glioma grades, substantial heterogeneity in the study parameters limits generalizability. To improve consistency and comparability across studies, full reports of imaging parameters and standardization of APTw protocols are essential.
Funding Information
  • Emory University (I3 Medical Technology Research Award)
  • Georgia Clinical and Translational Award, National Center for Advancing Translational Sciences (NCATS, UL1–TR002378)
  • National Institutes of Health (2R01NS083654)
  • Georgia Tech/Emory (Biolocity Program Support)

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