Varun Shandal MBBS, Presenter: Nothing to Disclose

Senthil K Sundaram, Abstract Co-Author: Nothing to Disclose

Diane C Chugani PhD, Abstract Co-Author: Research Consultant, Shire plc

Ajay Kumar MD, PhD, Abstract Co-Author: Nothing to Disclose

Michael E Behen, Abstract Co-Author: Nothing to Disclose

Harry T. Chugani MD, Abstract Co-Author: Nothing to Disclose

To evaluate the rate of cerebral protein synthesis (rCPS) in language areas of children with developmental delay (DD) with and without symptoms of pervasive developmental disorder (PDD) using L-[1-11C]-leucine positron emission tomography (LeuPET).

We performed LeuPET on 16 children with DD. These children were further classified based on neuropsychological evaluation as DD with PDD (n=8; M/F = 7/1; mean age = 76.25 ± 20.59 months) and DD without PDD (n=8; M/F = 5/3; mean age = 77.63 ± 13.8 months). Regions of interest (ROI) were marked bilaterally on middle and inferior frontal, inferior parietal, superior and middle posterior inferior temporal regions of PET scans after co-registration with magnetic resonance imaging (MRI) scans. The unidirectional uptake rate constant (K), an indirect measure of rCPS, for these regions was obtained using Patlak graphical analysis. Regional K values were normalized to whole brain K (nK).

We found a statistically significant difference in the nK obtained from the left posterior middle temporal region (higher in DD with PDD; p=0.014). There was a significant correlation of GARS autism index score with nK of left posterior middle temporal region (r=0.496, p=0.05). In addition, significant asymmetric protein synthesis (right > left) is observed in DD children without PDD in middle frontal and posterior middle temporal regions (p=0.03 and p=0.04 respectively).

We found higher protein synthesis in the left posterior middle temporal region in DD children with PDD that correlated with severity of autism. Thus, DD children with PDD have abnormal protein synthesis in perisylvian language areas that may be related to the pervasive symptoms. In DD children without PDD, significant asymmetry in protein synthesis was observed in middle frontal and posterior middle temporal regions. It is possible that these atypical patterns of protein synthesis in language regions represent one manifestation of aberrant connections between language areas previously identified in DD children.

Abnormal protein synthesis of perisylvian language regions identified by C-11 leucine PET scan can be used as an imaging biomarker to assess the severity of autism.

Shandal, V, Sundaram, S, Chugani, D, Kumar, A, Behen, M, Chugani, H, Abnormal Brain Protein Synthesis in Language Areas of Children with Pervasive Developmental Disorder: A L-[1-11C]-Leucine PET Study.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11002004.html