Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging

Purpose: To evaluate the reliability of four CEST imaging metrics for brain tumors, at varied saturation power levels and magnetic field strengths (3−9.4 Tesla (T)). Methods: A five-pool proton exchange model (free water, semisolid, amide, amine, and NOE-related protons) was used for the simulations. For the in vivo study, eight glioma-bearing rats were scanned at 4.7 T. The CEST ratio (CESTR), CESTR normalized with the reference value (CESTR^nr), inverse Z-spectrum-based (MTR_Rex), and apparent exchange-related relaxation (AREX) were compared. Results: The simulated CEST signal intensities using MTR_Rex and AREX were substantially increased at relatively high radiofrequency (RF) saturation powers at 3 T and 4.7 T, whereas CESTR and CESTR^nr metrics remained relatively stable. There were tremendously high MTR_Rex and AREX signals around the water frequency at all field strengths because of the small denominators. In the rat tumor study at 4.7 T, both CESTR and CESTR^nr showed clear contrasts in the tumor with respect to the normal tissue across all saturation power levels (0.5−3 μT), whereas the AREX showed negligible to negative insignificant contrasts. Conclusions: CEST metrics must be carefully selected based on the different experimental settings. CESTR and CESTR^nr are more reliable at 3 T (a clinical field strength) and 4.7 T. Magn Reson Med 77:1853–1865, 2017.