Measurement of restricted and hindered anisotropic di삨煍usion tissue compartments in a rat model of Wallerian degeneration

Synopsis The DIAMOND model has been recently proposed to model the heterogeneity of tissue compartments in di삨煍usion compartment imaging. However, it did not enable the characterization of the intra-axonal volume fraction (IAVF), a critical measure to more accurately characterizing axonal loss in abnormal tissues. In this work we investigated mathematical extensions to DIAMOND that model both the IAVF and the heterogeneous nature of in-vivo tissue. We validated our approach using both Monte-Carlo simulations and histological microscopy with an animal model of Wallerian degeneration. We show that our novel model better predicts the signal and provides additional parameters to further describe tissues. Purpose In a recent work, Scherrer et al proposed a novel di삨煍usion compartment imaging (DCI) model that describes the statistical distribution of 3-D di삨煍usivities arising from each compartment in each voxel (DIAMOND), allowing for the characterization of both compartment-speci䃏듣c di삨煍usion parameters (cFA, cMD, cAD, cRD) and the overall compartment microstructural heterogeneity. DIAMOND was shown to better predict the DW signal compared to NODDI . However, it did not enable characterization of the intra-axonal volume fraction (IAVF), a critical measure to more accurately characterizing axonal loss in abnormal tissues. In this work, we investigated mathematical extensions to DIAMOND that model both the IAVF and the heterogeneous nature of in-vivo tissue. We 䃏듣rst used Monte-Carlo simulations to identify the best candidate model to estimate IAVF. Then, we validated our novel approach using an animal model of Wallerian degeneration and histological observations. Method Mathematical modeling. In the original DIAMOND formulation, the combined contribution of intra-axonal (IA) restricted and extra-axonal (EA) hindered di삨煍usion was modeled by a single statistical distribution of di삨煍usivities . In this work, we instead considered models that separately represent IA and EA di삨煍usion arising from a fascicle , by considering: (with : signal arising from a fascicle; , : signal arising from IA/EA space, respectively; : IAVF). was modeled using the analytic expression of the di삨煍usion in cylinders. was modeled using a matrix-variate Gamma distribution of di삨煍usivities to capture the intracompartment heterogeneity. We evaluated three di삨煍erent estimation strategies: 1) DIAMOND+H1: a model in which the radial di삨煍usivities of IA/EA compartments ( / ) are freely estimated; 2) DIAMOND+H2: models in which is 䃏듣xed and is estimated; and 3) DIAMOND+H3: a model