When CEST meets diffusion: Multi-echo diffusion-encoded CEST (dCEST) MRI to measure intracellular and extracellular
Sultan Z Mahmud1, Hye-Young Heo1
1Department of Radiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Magnetic Resonance in Medicine
|April 14, 2025
Summary
Diffusion-encoded chemical exchange saturation transfer (dCEST) MRI separates intracellular and extracellular signals. This technique reveals distinct water fractions and diffusion properties, enhancing conventional CEST MRI analysis for potential clinical use.
Area of Science:
- Biomedical Imaging
- Magnetic Resonance Imaging
- Biophysics
Background:
- Conventional Chemical Exchange Saturation Transfer (CEST) MRI provides valuable physiological information but struggles to differentiate intracellular and extracellular/intravascular water compartments.
- Understanding the compartmental origin of CEST signals is crucial for accurate interpretation and clinical application.
Purpose of the Study:
- To develop and validate a multi-echo, diffusion-encoded CEST (dCEST) imaging technique.
- To quantify the intracellular and extracellular/intravascular contributions to the conventional CEST signal.
- To estimate water compartment fractions, transverse relaxation times (T2), and apparent diffusion coefficients (ADC) within the brain.
Main Methods:
- A novel dCEST pulse sequence was implemented to acquire multi-echo images across varying echo times (TE), b-values, and radiofrequency (RF) saturation strengths.
- A two-compartment model with distinct diffusivities and T2 values was employed for data analysis.
- Intracellular and extracellular fractions of Z-spectra and Amide Proton Transfer (APT) signals were estimated from 3T human brain scans of healthy volunteers.
Main Results:
- Multi-echo diffusion analysis revealed significantly higher intracellular water fractions and shorter intracellular T2 values compared to extracellular/intravascular compartments.
- The apparent diffusion coefficient (ADC) was significantly lower in the intracellular compartment than in the extracellular compartment.
- dCEST analysis indicated average intracellular and extracellular Z-spectrum fractions of 85% ± 7% and 15% ± 4%, respectively, with higher intracellular APT-weighted values.
Conclusions:
- The developed dCEST imaging technique successfully differentiates and quantifies intracellular and extracellular water compartments.
- This method provides crucial insights into the origin of signals in conventional CEST MRI.
- The dCEST technique holds significant potential for advancing clinical applications of CEST MRI.


