Quantifying amide proton exchange rate and concentration in chemical exchange saturation transfer imaging of the human brain

ABSTRACT Current chemical exchange saturation transfer (CEST) neuroimaging protocols typically acquire CEST‐weighted images, and, as such, do not essentially provide quantitative proton‐specific exchange rates (or brain pH) and concentrations. We developed a dictionary‐free MR fingerprinting (MRF) technique to allow CEST parameter quantification with a reduced data set. This was accomplished by subgrouping proton exchange models (SPEM), taking amide proton transfer (APT) as an example, into two‐pool (water and semisolid macromolecules) and three‐pool (water, semisolid macromolecules, and amide protons) models. A variable radiofrequency saturation scheme was used to generate unique signal evolutions for different tissues, reflecting their CEST parameters. The proposed MRF‐SPEM method was validated using Bloch‐McConnell equation‐based digital phantoms with known ground‐truth, which showed that MRF‐SPEM can achieve a high degree of accuracy and precision for absolute CEST parameter quantification and CEST phantoms. For in‐vivo studies at 3T, using the same model as in the simulations, synthetic Z‐spectra were generated using rates and concentrations estimated from the MRF‐SPEM reconstruction and compared with experimentally measured Z‐spectra as the standard for optimization. The MRF‐SPEM technique can provide rapid and quantitative human brain CEST mapping. HIGHLIGHTSA new MR fingerprinting concept was proposed to allow CEST quantification.A varied RF saturation was designed to generate CEST signal evolutions.Synthetic CEST MRI was used for validation of in‐vivo CEST quantification.The MRF‐SPEM technique can provide rapid and quantitative human brain CEST mapping.