title: In vivo detection of reduced Purkinje cell fibers with diffusion MRI tractography in children with autistic spectrum disorders.
abstract: Postmortem neuropathology studies report reduced number and size of Purkinje cells (PC) in a majority of cerebellar specimens from persons diagnosed with autism spectrum disorders (ASD). We used diffusion weighted MRI tractography to investigate whether structural changes associated with reduced number and size of PC, could be detected in vivo by measuring streamlines connecting the posterior-lateral region of the cerebellar cortex to the dentate nucleus using an independent component analysis with a ball and stick model. Seed regions were identified in the cerebellar cortex, and streamlines were identified to two sorting regions, the dorsal dentate nucleus (DDN) and the ventral dentate nucleus (VDN), and probability of connection and measures of directional coherence for these streamlines were calculated. Tractography was performed in 14 typically developing children (TD) and 15 children with diagnoses of ASD. Decreased numbers of streamlines were found in the children with ASD in the pathway connecting cerebellar cortex to the right VDN (p-value = 0.015). Reduced fractional anisotropy (FA) values were observed in pathways connecting the cerebellar cortex to the right DDN (p-value = 0.008), the right VDN (p-value = 0.010) and left VDN (p-value = 0.020) in children with ASD compared to the TD group. In an analysis of single subjects, reduced FA in the pathway connecting cerebellar cortex to the right VDN was found in 73% of the children in the ASD group using a threshold of 3 standard errors of the TD group. The detection of diffusion changes in cerebellum may provide an in vivo biomarker of Purkinje cell pathology in children with ASD.
authors.affiliation: Department of Pediatrics and Neurology, Wayne State University Detroit, MI, USA ; Translational Imaging Laboratory, PET center, Children's Hospital of Michigan Detroit, MI, USA.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Pediatrics and Neurology, Wayne State University Detroit, MI, USA ; Translational Imaging Laboratory, PET center, Children's Hospital of Michigan Detroit, MI, USA.
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Tiwari
authors.affiliation: Department of Pediatrics and Neurology, Wayne State University Detroit, MI, USA ; Translational Imaging Laboratory, PET center, Children's Hospital of Michigan Detroit, MI, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Behen
authors.affiliation: Department of Pediatrics and Neurology, Wayne State University Detroit, MI, USA ; Translational Imaging Laboratory, PET center, Children's Hospital of Michigan Detroit, MI, USA.
authors.forename: Harry T
authors.initials: HT
authors.lastname: Chugani
authors.affiliation: Department of Pediatrics and Neurology, Wayne State University Detroit, MI, USA ; Translational Imaging Laboratory, PET center, Children's Hospital of Michigan Detroit, MI, USA.
authors.forename: Diane C
authors.initials: DC
authors.lastname: Chugani
keywords: Purkinje cell; autism spectrum disorders; dentate nucleus; diffusion weighted MRI; independent component analysis tractography with a ball and stick model