Quantitative microstructural imaging based on diffusion MRI provides a non-invasive means to measure microstructural parameters, e.g., cell size. However, due to the remarkable complexity of incorporating transcytolemmal water exchange into diffusion biophysical models, water exchange is usually ignored. This leads to biased estimation of microstructural parameters, particularly intracellular volume fraction. Here, we propose a new approach to incorporate water exchange naturally in diffusion biophysical models with arbitrary gradient waveforms, making it possible to fit cell size, density, and intracellular water lifetime simultaneously. This establishes a general framework to incorporate transcytolemmal water exchange in any diffusion MRI-based microstructural imaging models.
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