DEW-MEGA-PRESS of Phosphorylethanolamine and Glutathione: Reproducibility and Feasibility in Individuals with Autism

To demonstrate double-editing (DEW) MEGA-PRESS editing of phosphorylethanolamine (PE) and glutathione (GSH) in vivo, estimate measurement variability, and conduct a feasibility study on individuals with autism.

13 participants with autism spectrum disorder (ASD), with an average age of 28.00±4.81 years, and 14 typically developing (TD) participants, with an average age of 29.33±5.36 years, were enrolled in the study. DEW-MEGA-PRESS at a Siemens 3T MRI scanner was used to edit both PE and GSH (ON_PE/ON_GSH = 3.98/4.56 ppm). Within-subject variability was examined in 15 participants (11 TD and 4 ASD) using repeated scans conducted at 4 and/or 12 weeks after baseline. Finally, differences in PE and GSH between the two groups were assessed using linear mixed-effects models.

In vivo experiments show excellent separation between the PE (3.22 ppm) and GSH (2.95 ppm) signals. Within- and between-subject reproducibility assessments revealed coefficients of variation (CV) of 9.0/18.5% for PE and 7.4/10.3% for GSH. Although GSH showed no statistically significant differences, PE levels were significantly higher in ASD than in TD (p<0.05), and only TD showed a decrease in PE with aging (p<0.05).

In vivo experiments demonstrate excellent separation between PE and GSH, and good within-subject reproducibility, supporting the stability of the approach. Between-subject variability exceeded within-subject variability for both chemicals, suggesting that biological differences between individuals dominate over measurement noise and supporting the feasibility study assessing differences between TD and ASD.