RESUMEN
Characterizing neural tissue microstructure is a critical goal for future neuroimaging. Diffusion MRI (dMRI) provides contrasts that reflect diffusing spins' interactions with myriad microstructural features of biological systems. However, the specificity of dMRI remains limited due to the ambiguity of its signals vis-à-vis the underlying microstructure. To improve specificity, biophysical models of white matter (WM) typically express dMRI signals according to the Standard Model (SM) and have more recently in gray matter (GM) taken spherical compartments into account (the SANDI model) in attempts to represent cell soma. The validity of the assumptions underlying these models, however, remains largely undetermined, especially in GM. To validate these assumptions experimentally, observing their unique, functional properties, such as the b-1/2 power-law associated with one-dimensional diffusion, has emerged as a fruitful strategy. The absence of this signature in GM, in turn, has been explained by neurite water exchange, non-linear morphology, and/or by obscuring soma signal contributions. Here, we present diffusion simulations in realistic neurons demonstrating that curvature and branching does not destroy the stick power-law behavior in impermeable neurites, but also that their signal is drowned by the soma signal under typical experimental conditions. Nevertheless, by studying the GM dMRI signal's behavior as a function of diffusion weighting as well as time, we identify an attainable experimental regime in which the neurite signal dominates. Furthermore, we find that exchange-driven time dependence produces a signal behavior opposite to that which would be expected from restricted diffusion, thereby providing a functional signature that disambiguates the two effects. We present data from dMRI experiments in ex vivo rat brain at ultrahigh field of 16.4T and observe a time dependence that is consistent with substantial exchange but also with a GM stick power-law. The first finding suggests significant water exchange between neurites and the extracellular space while the second suggests a small sub-population of impermeable neurites. To quantify these observations, we harness the Kärger exchange model and incorporate the corresponding signal time dependence in the SM and SANDI models.
Asunto(s)
Sustancia Gris , Sustancia Blanca , Encéfalo/fisiología , Corteza Cerebral , Imagen de Difusión por Resonancia Magnética/métodos , Sustancia Gris/diagnóstico por imagen , Humanos , Neuroimagen/métodos , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: Soma and neurite density imaging (SANDI) is a new biophysical model that incorporates soma in addition to neurite density, thus possibly providing more specific information about the complex pathological processes of multiple sclerosis (MS). PURPOSE: To discriminate the pathological abnormalities of MS white matter (WM) lesions, normal-appearing (NA) WM and cortex and to evaluate the associations among SANDI-derived measures, clinical disability, and conventional MRI variables. METHODS: Twenty healthy controls (HC) and 23 MS underwent a 3 T brain MRI. Using SANDI on diffusion-weighted sequence, the fractions of neurite (fneurite) and soma (fsoma) were assessed in WM lesions, NAWM, and cortex. RESULTS: Compared to HC WM, MS NAWM showed lower fneurite (false discovery rate [FDR]-p = 0.011). In MS patients, WM lesions showed lower fneurite and fsoma compared to both HC and MS NAWM (FDR-p < 0.001 for all). In the cortex, MS patients had lower fneurite and fsoma compared to HC (FDR-p ≤ 0.009). Compared to both HC and RRMS, PMS patients had lower fneurite in NAWM (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.003) and cortex (vs HC: FDR-p < 0.001; vs RRMS: p = 0.031, not surviving FDR correction), and lower cortical fsoma (vs HC: FDR-p < 0.001; vs RRMS: FDR-p = 0.009). Compared to HC, PMS also showed a higher fsoma in NAWM (FDR-p = 0.015). Fneurite and fsoma in the different brain compartments were correlated with age, phenotype, disease duration, disability, WM lesion volumes, normalized brain, cortical, and WM volumes (r from - 0.761 to 0.821, FDR-p ≤ 0.4). CONCLUSIONS: SANDI may represent a clinically relevant model to discriminate different neurodegenerative phenomena that gradually accumulate through MS disease course.