When CEST meets diffusion: Multi-echo diffusion-encoded CEST MRI to measure intracellular and extracellular CEST signal distribution

Motivation: CEST signals from a voxel are affected by various processes, including flow, diffusion, molecular exchange, etc. Goal(s): To develop a novel diffusion-encoded-CEST (dCEST) imaging technique for evaluating the intracellular and extracellular contributions to the CEST signal. Approach: A multi-echo dCEST pulse sequence was developed to measure the signal fractions, relaxation times, and ADCs from the intracellular and extracellular water compartments. The intracellular Z-spectra and APTw signal were estimated. Results: The intracellular fraction for the Z-spectra was found to be slightly higher at -3.5 ppm than at 3.5 ppm. The overall intracellular APTw signal was higher than the conventional total (i.e., intra+extracellular) APTw signal. Impact: The multi-echo dCEST imaging technique could isolate flow and blood-related bias and especially measure extracellular acidosis and intracellular alkalization in tumors.