Influence of phosphate concentration on amine, amide, and hydroxyl CEST contrast

Purpose To evaluate the influence of phosphate on amine, amide, and hydroxyl CEST contrast using Bloch-McConnell simulations applied to physical phantom data. Methods Phantom solutions of 4 representative metabolites with exchangeable protons-glycine (alpha-amine protons), Cr (eta-amine protons), egg white protein (amide protons), and glucose (hydroxyl protons)-were prepared at different pH levels (5.6 to 8.9) and phosphate concentrations (5 to 80 mM). CEST images of the phantom were collected with CEST-EPI sequence at 3 tesla. The CEST data were then fitted to full Bloch-McConnell equation simulations to estimate the exchange rate constants. With the fitted parameters, simulations were performed to evaluate the intracellular and extracellular contributions of CEST signals in normal brain tissue and brain tumors, as well as in dynamic glucose-enhanced experiments. Results The exchange rates of alpha-amine and hydroxyl protons were found to be highly dependent on both pH and phosphate concentrations, whereas the exchange rates of eta-amine and amide protons were pH-dependent, albeit not catalyzed by phosphate. With phosphate being predominantly intracellular, CEST contrast of alpha-amine exhibited a higher sensitivity to changes in the extracellular microenvironment. Simulations of dynamic glucose-enhanced signals demonstrated that the contrast between normal and tumor tissue was mostly due to the extracellular CEST effect. Conclusion The proton exchange rates in some metabolites can be greatly catalyzed by the presence of phosphate at physiological concentrations, which substantially alters the CEST contrast. Catalytic agents should be considered as confounding factors in future CEST-MRI research. This new dimension may also benefit the development of novel phosphate-sensitive imaging methods.

Automated summary

The study found that the exchange rates of alpha-amine and hydroxyl protons are highly dependent on pH and phosphate concentrations, while the exchange rates of eta-amine and amide protons depend on pH but are not catalyzed by phosphate. Phosphate, predominantly intracellular, affects the CEST contrast of alpha-amine, showing higher sensitivity to changes in the extracellular microenvironment.