A Proton 7T MR Spectroscopy Study of ASD: Altered Creatine Levels

Background:  Magnetic Resonance Spectroscopy (MRS) can be a useful method to study pathophysiological changes in ASD. Several studies have reported reductions in NAA, Cr, Cho and GABA in many brain regions of individuals with ASD, suggesting abnormalities in the excitatory and inhibitory balance in the brain, as well as neuronal and glial densities. However, depending on factors like participant age and brain region, these results tend to vary. Moreover, the vast majority of these studies have been carried out on 3T and 1.5T MRI scanners. Higher magnetic fields can help increase the signal-to-noise ratio and help resolve some of the overlapping peaks of the metabolites

Objectives:  The goal of our study was to look at metabolite levels in an area of primary visual cortex (VC) representing BA17, as well as medial prefrontal cortex (PFC), representing BA32, using 7T MRS. We were mainly interested in group differences in the following metabolites: NAA, Cr, Cho, GABA and Glu.

Methods:  We scanned 8 ASD individuals and 6 typically developing (TD) individuals matched for age, gender and IQ, at the Oxford Centre for functional MRI of the Brain (FMRIB). Both the VC and PFC MRS voxels were placed in a region that centres on the midsaggital plane. For the VC, we placed the MRS voxel in a region that includes the anterior part of the calcarine sulcus. For PFC, we included the region anterior to the cingulated gyrus that represents BA32. We collected data using a semi-LASER sequence, and used LCModel to fit our spectra.

Results:  We found that Cr levels were significantly increased in VC compared to PFC for both groups (p < 0.05), and that Cr levels were significantly increased in PFC for ASD compared to TD individuals (p < 0.05). When we controlled for age differences, we found no regional differences, but the group difference remained. There were no other group differences. NAA values were significantly higher in PFC than in VC.  The other metabolites showed no regional differences.

Conclusions:  Elevated Cr levels may be related to abnormal glial function in the medial PFC, which is consistent with some of our postmortem work in other brain regions. Our preliminary results also suggest that altered markers of neuronal metabolism may not always be detected using MRS. Further work will involve trying to correlate measures from spectroscopy with diffusion data and MEG data collected from these same individuals.