Project Summary/Abstract
Autism spectrum disorder (ASD) is a group of complex neurodevelopment disorders affecting nearly 1.5
percent of American children. The underlying and contributing mechanisms of ASD are largely undetermined
and there are no FDA-approved medications to treat the core social-communicative symptoms of the disorder.
Unlike other brain disorders such as Alzheimer’s disease (AD), there is a gross disparity between the high
prevalence of ASD and the small number of PET research studies; this condition should be addressed since
the opportunities for PET imaging to have an impact in ASD research are substantial.
Synapses allow for the transmission of electrochemical information, which is the essential means of
communication in the brain. Synaptic pathology has been associated with brain disorders including AD,
epilepsy, autism, depression, and schizophrenia. Our recent development of 11C-UCB-J, a PET radioligand
that binds to synaptic vesicle glycoprotein 2A (SV2A), provides the ability to quantify synaptic density in the
living human brain. 11C-UCB-J for SV2A PET imaging has the potential to make game-changing contributions
to ASD research and potential diagnosis. However, because of the current imaging dose, the technique cannot
be applied regularly in autism research of children due to the requirement of low radiation exposure especially
for longitudinal studies in the same individuals at different developmental stages.
The goal of this proposal is to reduce the clinical 11C-UCB-J PET imaging dose to be lower than the
radiation one receives from a round-trip cross-country flight. To accomplish this goal, we will develop artificial
neural network-based dose-reduction techniques. We hypothesize that 1) the proposed techniques will
enhance (parametric) images from 1/10 of the dose so that they are comparable to the full-dose (parametric)
images in terms of noise and resolution and 2) with the reduced dose, the test-retest reproducibility and the
ability to differentiate patients from controls will not be diminished.
The proposed research will be the first study to demonstrate that PET imaging dose can be reduced to a point
of acceptability for ASD research in children and other diseases of adolescence. This effort is in line with the
NIBIB I/START program to develop clinical technologies for imaging development in children and synergizes
with the NIH supported large scale ABCD (Adolescent Brain Cognitive Development) longitudinal study for brain
development in children, where MRI has been widely used but PET has not. If successful, we will apply for a
larger grant to use SV2A PET to characterize the mechanisms of ASD neuropathology toward more effective
diagnosis and personalized treatment.
