Does neurite density as measured by diffusion-weighted MR imaging relate to neuronal density as measured by MR spectroscopy?

Capturing the earliest signs of dementia with MR imaging relies on techniques that are sensitive to the subtle loss or disconnection of neurons before atrophy occurs. Models of multi-shell HARDI such as NODDI claim to quantify neurite density in vivo and non-invasively, but the specificity of these HARDI-based metrics remain unvalidated. This study aims to determine the sensitivity of NODDI’s neurite density and orientation dispersion index to regional variation of MRS markers of neuronal and glial cell density. We find that caution must be exercised when interpreting NODDI’s neurite density as related to neuronal density. Orientation dispersion instead appears to be a closer marker of neuronal density and may be a more sensitive marker of disease-related change.