  Purpose: Biophysical models of diffusion MRI have been developed to
characterize microstructure in various tissues, but existing models are not
suitable for tissue composed of permeable spherical cells. In this study we
introduce Cellular Exchange Imaging (CEXI), a model tailored for permeable
spherical cells, and compares its performance to a related Ball \& Sphere (BS)
model that neglects permeability. Methods: We generated DW-MRI signals using
Monte-Carlo simulations with a PGSE sequence in numerical substrates made of
spherical cells and their extracellular space for a range of membrane
permeability. From these signals, the properties of the substrates were
inferred using both BS and CEXI models. Results: CEXI outperformed the
impermeable model by providing more stable estimates cell size and
intracellular volume fraction that were diffusion time-independent. Notably,
CEXI accurately estimated the exchange time for low to moderate permeability
levels previously reported in other studies ($\kappa<25\mu m/s$). However, in
highly permeable substrates ($\kappa=50\mu m/s$), the estimated parameters were
less stable, particularly the diffusion coefficients. Conclusion: This study
highlights the importance of modeling the exchange time to accurately quantify
microstructure properties in permeable cellular substrates. Future studies
should evaluate CEXI in clinical applications such as lymph nodes, investigate
exchange time as a potential biomarker of tumor severity, and develop more
appropriate tissue models that account for anisotropic diffusion and highly
permeable membranes.
