A system and method are provided for non-invasively assessing neuro-inflammation in a subject. The method includes acquiring neurite orientation dispersion and density imaging (NODDI) data of the subject and processing the NODDI data to determine an orientation dispersion index (ODI) component of the NODDI data. The method also includes assessing the ODI component against one of a reference of neuro-inflammation or a prior ODI component acquired from the subject to determine one of an acute assessment or a chronic assessment of neuro-inflammation in the subject. The method further includes generating a report indicating the one of an acute assessment or a chronic assessment of neuro-inflammation in the subject.