Stephen R. Dager, M.D.
SUMMARY: Magnetic resonance spectroscopy (MRS) can detect and quantify various brain tissue-based chemicals and brain levels of certain psychotropic medications increasingly being prescribed to pediatric populations. Dr. Stephen Dager explained the usefulness of MRS in the noninvasive investigation of brain pharmacokinetics, including measurement of brain uptake, steady-state, brain binding and brain half-life, and for the study of pediatric neuropsychiatric disorders, such as factors that underlie abnormal brain maturation processes in autism. MRS is an ideal modality for use with pediatric populations, as it is noninvasive, does not involve ionizing radiation and, for some applications such as studying brain pharmakokinetics, is less sensitive to movement than other magnetic resonance techniques.
Dager’s group used MRS to investigate the brain pharmacokinetics of selective serotonin re-uptake inhibitors (SSRIs) prescribed to pediatric patients being treated for pervasive developmental disorders. Data were compared to similar data from adults prescribed the same drugs. A significant relationship was shown between dose and drug concentration in the brain for fluvoxamine or fluoxetine across the age range studied. It was concluded that a reasonable target dose range for prescribing these drugs in pediatric populations could be determined by scaling adult doses in relationship to body mass.
Dager also covered results from an ongoing longitudinal MRS imaging study of preschool-aged children with autism spectrum disorder (ASD). Regional brain chemistry was evaluated for evidence of increased neuronal packing density or decreased synaptic pruning, postulated by some as an explanation for manifestations of autism. In the context of characteristic brain structural abnormalities, Dager found brain chemical abnormalities that were detectable in autistic children at 3–4 years of age, but the findings do not support hypotheses of diffuse increased neuronal packing density in ASD.