PET/MRI investigation of neuroinflammation in autism spectrum disorders
Zurcher Wimmer, Nicole
Massachusetts General Hospital
Meixner Translational Postdoctoral Fellowship
The large majority of cases of autism are idiopathic and likely result from gene-environment interactions. One of these interactions could be adverse environmental exposure early in life leading to abnormal immune reactions. Neuroinflammation, evidenced by high levels of microglia activation, may play a role in the development of autism. Evidence supporting involvement of the immune system in the etiology of autism is the higher prevalence of autoimmune disorders in first- and second-degree relatives of individuals with autism. The aim of this project is to investigate the potential link between neuroinflammation and autism spectrum disorders (ASD). Neuroinflammation can be assessed using [11C]PBR-28, a ligand binding with high affinity and selectivity to a glial translocator protein over-expressed on mitochondrial membranes of microglia during inflammatory processes as well as in astrocytes. In the current study innovative combined magnetic resonance imaging (MRI)/ positron emission tomography (PET) technology will be used to assess the presence of activated microglia and astrocytes in autism and investigate correlations between neuroinflammation and brain connectivity. If signs of neuroinflammation are identified in individuals with ASD, this could serve as a biomarker for at least one subtype of autism. In addition, increased activation of neuroimmune cells could be linked with abnormalities in structural connectivity between fiber tracts, measurable by anatomical diffusion imaging, and/or correlated with measures of functional connectivity assessed using resting state functional MR (fMRI)I. This project may potentially lead to direct clinical applications, which could lead to novel treatments aimed at modifying the glial response in individuals with ASD.
Neuroscience, Biomarkers, Immune Systems, Gene-Environment Interaction, Functional Neuroimaging, FCMRI, Structural Neuroimaging, DTI, Positron Emission Tomography, Screening/ Diagnosis/ Phenotyping, Etiology/ Risk Factors, Treatment/ Prevention, Adolescents/ Young Adults (13-25 Years), Adults (>25 Years), Autism Spectrum Disorder