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

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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.

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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.