When CEST meets diffusion: Multi-echo diffusion-encoded CEST (dCEST) MRI to measure intracellular and extracellular CEST signal distributions.

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To develop a multi-echo, diffusion-encoded chemical exchange saturation transfer (dCEST) imaging technique for estimating the intracellular and extracellular/intravascular contributions to the conventional CEST signal. A dCEST pulse sequence was developed to quantify the signal fractions, transverse relaxation times (T2), and apparent diffusion coefficient (ADC) of the intracellular and extracellular/intravascular water compartments. dCEST images were acquired across a wide range of TE, b-values, RF saturation strengths, and frequency offsets. The data were analyzed using a two-compartment model with distinct diffusivities and T2 values. Intracellular and extracellular fractions of conventional water-saturation spectra (Z-spectra) and corresponding amide proton transfer (APT) signals were estimated from human brain scans of healthy volunteers at 3 T. The multi-echo diffusion results showed that the intracellular water fractions were significantly higher than the extracellular water fractions, whereas the intracellular T2 values were shorter than those of the extracellular/intravascular compartments. The ADC for the intracellular compartment was significantly lower than that of the extracellular compartment. The dCEST analysis showed that the average intracellular and extracellular fractions of the Z-spectra were 85 ± 7% and 15 ± 4%, respectively. The overall intracellular APT-weighted values were higher than the total (i.e., intracellular + extracellular) APT-weighted values. The dCEST imaging technique provides valuable insight into the source of signals in conventional CEST MRI, offering potential utility for clinical applications.