Comparative evaluation of polynomial and Lorentzian lineshape-fitted amine CEST imaging in acute ischemic stroke

Chemical exchange saturation transfer signals from amines are sensitive to pH, and detection of these signals can serve as an alternative pH imaging method to amide proton transfer (APT). However, conflicting results regarding amine CEST imaging at 2 ppm in ischemic stroke have been reported. Here, we correlated amine CEST with APT in animal stroke models to evaluate its specificity to pH, and investigated the reason for the different results through simulations and sample studies.

A three-point quantification method was used to quantify APT. A polynomial fit method and a multiple-pool Lorentzian fit method were used to quantify amine CEST. Samples of creatine and glutamate were prepared to study the different CEST effects from arginine amine and fast exchanging pools. Samples of tissue homogenates with different pH were prepared to study the variation in CEST signals due only to changes in pH.

The polynomial fit of amine CEST at 2 ppm had a significant correlation with APT, whereas the Lorentzian fit did not. Further studies showed that arginine amine contributed to the polynomial fit, whereas both the arginine amine and the fast exchanging pools contributed to the Lorentzian fit with their CEST effects varying in opposite directions after stroke. The CEST signal from the fast exchanging pool decreased, probably due to the reduced pool concentration but not pH.

The variation in opposite directions led to an insignificant correlation of the Lorentzian fit of amine CEST with APT and the different results in different experimental conditions.