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

Background: Quantitative 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 (k _sw ), the reliable quantification of k _sw in glioma remains constrained due to technical challenges.
Purpose: To quantify the pH of gliomas by measuring the proton exchange rate through optimized omega plot analysis.
Study Type: Prospective.
Phantoms/animal Model/subjects: Creatine and murine brain lysates phantoms, six rats with glioma xenograft model, and three patients with World Health Organization grade 2-4 gliomas.
Field Strength/sequence: 11.7 T, 7.0 T, CEST imaging, T ₂ -weighted (T ₂ W) imaging, and T ₁ -mapping.
Assessment: Omega 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 (pH _enh ), and magnetization transfer ratio (MTR) were utilized for pH metric quantification. The clinical outcomes were determined through radiologic follow-up and histopathological analysis.
Statistical Tests: Mann-Whitney U test was performed to compare glioma with normal tissue, and Pearson's correlation analysis was used to assess the relationship between k _sw and other parameters.
Results: In vitro experiments reveal that the determined k _sw at 2 ppm increases exponentially with pH (creatine phantoms: k _sw  = 106 + 0.147 × 10 ^(pH-4.198) ; lysates: k _sw  = 185.1 + 0.101 × 10 ^(pH-3.914) ). Omega plot analysis exhibits a linear correlation between 1/MTR _Rex and 1/ω ₁ ² in the glioma xenografts (R ²  > 0.98) and glioma patients (R ²  > 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 Conclusion: Utilizing 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 Evidence: NA TECHNICAL EFFICACY: Stage 1.
(© 2024 International Society for Magnetic Resonance in Medicine.)