High Resolution Diffusion Tensor Imaging to Assess Brain Microstructural Abnormalities in a Neuroligin-3 Knockin Mouse Model Associated with Autism Spectrum Disorders

Manoj Kumar¹, Jeffrey T. Duda¹, Ranjit Ittyerah¹, Adler Daniel¹, Stephen B. Pickup¹, Edward S. Brodkin², Ted Abel³, James C. Gee¹, Harish Poptani¹

Ex-vivo high resolution diffusion tensor imaging (DTI) and behavioral tests were performed at 3 different time points on NL-3 (n=41) and wild-type littermates (n=42) to assess microstructural brain abnormalities in NL-3 mice. DTI data was processed and brain was segmented in to 40 different gray and white matter regions including ventricles. Along with DTI indices, volumetric measurement was performed in different segmented regions of the brain. We did not observe any significant differences in DTI indices in segmented gray or white matter regions in NL-3 compared to wild type mice. However, we observed significantly reduced volume in 16 different gray and white matter regions out of 40 segmented brain regions in NL-3 compared to wild type mice. The volume changes in different white matter regions suggests that changes in volume in these regions are not due to abnormal myelination or breakdown of the white matter microstructure but may be because of immature or smaller number of axons in these regions due to abnormal neurodevelopment in this mouse model.