pH Mapping of Gliomas Using Quantitative Chemical Exchange Saturation Transfer MRI: Quasi‐Steady‐State, Spillover‐, and MT‐Corrected Omega Plot Analysis

Abstract

BackgroundQuantitative in‐situ pH mapping of gliomas is important for therapeutic interventions, given its significant association with tumor progression, invasion, and metastasis. Although chemical exchange saturation transfer (CEST) offers a noninvasive way for pH imaging based on the pH‐dependent exchange rate (ksw), the reliable quantification of ksw in glioma remains constrained due to technical challenges.PurposeTo quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis.Study TypeProspective.Phantoms/Animal Model/SubjectsCreatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2–4 gliomas.Field Strength/Sequence11.7 T, 7.0 T, CEST imaging, T2‐weighted (T2W) imaging, and T1‐mapping.AssessmentOmega plot analysis, quasi‐steady‐state (QUASS) analysis, multi‐pool Lorentzian fitting, amine and amide concentration‐independent detection, pH enhanced method with the combination of amide and guanidyl (pHenh), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow‐up and histopathological analysis.Statistical TestsMann–Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between ksw and other parameters.ResultsIn vitro experiments reveal that the determined ksw at 2 ppm increases exponentially with pH (creatine phantoms: ksw = 106 + 0.147 × 10(pH‐4.198); lysates: ksw = 185.1 + 0.101 × 10(pH‐3.914)). Omega plot analysis exhibits a linear correlation between 1/MTRRex and 1/ω12 in the glioma xenografts (R2 > 0.98) and glioma patients (R2 > 0.99). The exchange rate in the rat glioma decreases compared to the contralateral normal tissue (349.46 ± 30.40 s−1 vs. 403.54 ± 51.01 s−1, P = 0.025), while keeping independence from changes in concentration (r = 0.5037, P = 0.095). Similar pattern was observed in human data.Data ConclusionUtilizing QUASS‐based, spillover‐, and MT‐corrected omega plot analysis for the measurement of exchange rates, offers a feasible method for quantifying pH within glioma.Level of EvidenceNATechnical EfficacyStage 1