Positron emission tomography in mitochondrial diseases.

Abstract

1. Ontogeny of glucose utilization rates in brain Studies of cerebral glucose metabolism with positron emission tomography (PET) and 2-deoxy2-[ 18 F]fluoro-D-glucose (FDG) in infants and children can provide important information on human brain functional development relevant to the study of mitochondrial disorders. The pattern of glucose metabolism in the human neonatal brain is markedly different from that of adults; typically, four brain regions are metabolically prominent: sensorimotor cortex, thalamus, brainstem and cerebellar vermis [1,2]. Phylogenetically, these are relatively old structures which dominate the behavior and mediate primitive intrinsic reflexes of newborns. During the first year, the ontogeny of cerebral glucose metabolism proceeds in phylogenetic order, correlating well with behavioral maturation of the infant. By 1 year, cerebral glucose metabolic patterns qualitatively resemble that of normal young adults [2,3]. Quantitative analysis of local cerebral metabolic rates for glucose (LCMRglc) shows that the brain follows a protracted glucose metabolic maturational course. Neonatal LCMRglc values, which are about 30% lower than adult rates, rapidly increase to exceed adult values by 2‐3 years in the cerebral cortex and remain at these high levels until about 8‐10 years, when LCMRglc decline to reach adult rates by 16‐18 years [2,3]. Correlation of these cerebral glucose metabolic trends with other neurodevelopmental events suggests that the ascending portion of rapid LCMRglc increase corresponds to the period of rapid overproduction of synapses and nerve terminals known to occur in the human brain. The ‘plateau’ period during which LCMRglc exceeds adult values corresponds to the period of increased cerebral energy demand as a result of transient exuberant connectivity. That segment of the metabolic maturational curve describing the LCMRglc decline corresponds to the period of selective elimination or ‘pruning’ of excessive connectivity, and marks the time when developmental plasticity markedly dimishes in humans [3]. This interpretation is supported by studies in animal models. For example, the kitten brain also goes through a protracted period of metabolic maturation, including a phase when LCMRglc exceeds values for the adult cat [4]. Furthermore, the ascending portion of the LCMRglc maturational curve for the kitten visual cortex, seen between 3 weeks and 3 months, corresponds to the ‘critical period’ and period of rapid synaptogenesis for this structure in the cat. Similarly, there is a correspondence