Translating pH-sensitive PROgressive saturation for QUantifying Exchange rates using Saturation Times (PRO-QUEST) MRI to a 3T clinical scanner

Purpose: To translate the recently developed PRO-QUEST (Progressive saturation for quantifying exchange rates using saturation times) sequence from preclinical 9.4T to 3T clinical magnetic field strength. Methods: Numerical simulations were performed to define the optimal saturation flip angles for PRO-QUEST saturation pulses at 3T and demonstrate the effect of a ∆T2 error on the exchange rate (kex) estimation at various field strengths. Exchange-dependent relaxation rate (Rex) was measured for glutamate solutions in various pH, healthy volunteers and patients with multiple sclerosis (MS). Additionally, concentration-independent ratiometric Rex maps were produced to evaluate regional signal variations across the brain of human volunteers. Results: The calculated Rex significantly correlates with pH in glutamate samples, however, kex values are underestimated as compared to those previously obtained at 9.4T. In the ratiometric Rex map of healthy volunteers, no significant differences are found between grey matter, white matter, and basal ganglia. In patients with MS, white matter lesions are visible in single saturation power Rex maps whereas only a periventricular lesion is apparent in the ratiometric Rex map. Conclusion: We demonstrate that quantification of pH sensitive indices using PRO-QUEST is feasible at 3T within clinically acceptable acquisition times. Our initial findings in patients with MS show that pH sensitive indices varied with the type of lesion examined whereas no significant difference was found in healthy volunteers between tissue types, suggesting that it would be worthwhile to apply PRO-QUEST in a larger cohort of patients to better understand its distinct imaging features relative to conventional techniques.