Multi-echo length and offset VARied saturation (MeLOVARS) method for improved CEST imaging

Purpose: The aim of this study was to develop a technique for rapid collection of chemical exchange saturation transfer images with the saturation varied to modulate signal loss transfer and enhance contrast. Methods: Multi-echo Length and Offset VARied Saturation (MeLOVARS) divides the saturation pulse of length T_sat into N = 3-8 submodules, each consisting of a saturation pulse with length of T_sat/N (∼0.3-1 s), one or more low flip-angle gradient-echo readout(s) and a flip back pulse. This results in N readouts with increasing saturation time from T_sat/N to T_sat without extra scan time. Results: For phantoms, eight images with T_sat incremented every 0.5 s from 0.5-4 s were collected simultaneously using MeLOVARS, which allows rapid determination of exchange rates for agent protons. For live mice bearing glioblastomas, the Z-spectra for five different T_sat values from 0.5 to 2.5 s were acquired in a time normally used for one T_sat. With the additional T_sat-dependence information, LOVARS phase maps were produced with a more clearly defined tumor boundary and an estimated 4.3-fold enhanced contrast-to-noise ratio (CNR). We also show that enhancing CNR is achievable by simply averaging the collected images or transforming them using the principal component analysis. Conclusions: MeLOVARS enables collection of multiple saturation-time-weighted images without extra time, producing a LOVARS phase map with increased CNR.