Following validation in healthy C57BL/6 J animals, we evaluate its performance to quantify brain volumetric changes in longitudinal studies corresponding to models of cuprizone-induced demyelination in C57BL/6 J mice, transactive response DNA binding protein 43 (TDP43) mice modeling amyotrophic lateral sclerosis, and in C57BL/6 J mice within an EAE model. Here, TARDBP is linked to amyotrophic lateral sclerosis.