Establish the biophysical mapping between diffusivity and cellular microstructure

Establish the definitive biophysical correlations between local water diffusivity values estimated by the intravoxel diffusivity probability distribution (IDPD) model and the complex cellular and subcellular microcompartments that generate them, using an appropriate microstructural ground truth.

Background

The IDPD model interprets different diffusivity regimes as potentially reflecting distinct microstructural environments, including myelin water, intracellular and extracellular water, edema-associated water, necrotic fluid, and cerebrospinal fluid. However, these assignments are inferential because no established third-party technology currently measures water diffusion at a spatial scale directly comparable to the cellular and subcellular structures under investigation.

The paper therefore identifies definitive validation of the diffusivity–microstructure relationship as unresolved. Advanced optical microscopy or histopathology is proposed as a means of establishing a microstructural ground truth and determining whether specific IDPD components correspond to the hypothesized biological compartments.