Positron emission tomography methods with potential for increased understanding of mental retardation and developmental disabilities

Abstract

Positron emission tomography (PET) is a technique that enables imaging of the distribution of radiolabeled tracers designed to track biochemical and molecular processes in the body after intravenous injection or inhalation. New strategies for the use of radiolabeled tracers hold potential for imaging gene expression in the brain during development and following interventions. In addition, PET may be key in identifying the physiological consequences of gene mutations associated with mental retardation. The development of high spatial resolution microPET scanners for imaging of rodents provides a means for longitudinal study of transgenic mouse models of genetic disorders associated with mental retardation. In this review, we describe PET methodology, illustrate how PET can be used to delineate biochemical changes during brain development, and provide examples of how PET has been applied to study brain glucose metabolism in Rett syndrome, serotonin synthesis in autism, and GABAA receptors in Angelman's syndrome and Prader-Willi syndrome. Future application of PET scanning in the study of mental retardation might include measurements of brain protein synthesis in fragile X syndrome and tuberous sclerosis complex, two common conditions associated with mental retardation in which cellular mechanisms involve dysregulation of protein synthesis. Mental retardation results in life-long disability, and application of new PET technologies holds promise for a better understanding of the biological underpinnings of mental retardation, with the potential to uncover new treatment options.

Cortical excitability decreases in Lennox‐Gastaut syndrome

“…These authors have found diffuse, bifrontal and/or biparietal or bitemporal decreased fluorine‐18 fluorodeoxyglucose (FDG) uptake (hypometabolism) on positron emission tomography (PET). This was also reported in mentally retarded subjects without epilepsy (Sundaram et al., 2005). Decreased FDG uptake is believed to reflect decreased glucose metabolism within the neuronal cytoplasm and of ATP production by the mitochondria, a process that is mainly mediated by the excitatory neurotransmitter glutamate (Di Lazzaro et al., 1998).…”

Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients

“…PET may be a key technology in identifying the physiological consequences of gene mutations associated with intellectual disabilities [ 23 ]. The utility of PET in elucidating the functional consequences of specific genetic abnormalities was previously reported in the Angelman and Prader-Willi syndromes.…”

Are Incidental Findings on Brain Magnetic Resonance Images in Children Merely Incidental?

“…It is likely that with increasing sensitivity of neuroimaging, more of such incidental findings will be evident. 19,20 For this reason, it is understandable that findings which are revealed ''incidentally,'' may have clinical significance in children with developmental delay without regression of unknown etiology. Such associations may provide evidence-based discussion and understanding in the management of children with developmental delay.…”