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Positron emission tomography study of human brain functional development
H T Chugani1, M E Phelps, J C Mazziotta
1Department of Neurology, UCLA School of Medicine 90024.
Insights
This study tracked brain glucose metabolism in 29 children, revealing how local cerebral metabolic rates for glucose (lCMRGlc) change from infancy to adolescence, mirroring normal brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Normal brain development involves dynamic changes in neural activity and metabolism.
- Positron emission tomography (PET) with 2-deoxy-2[18F]fluoro-D-glucose (FDG) is a powerful tool for assessing cerebral glucose metabolism.
Purpose of the Study:
- To characterize developmental changes in local cerebral metabolic rates for glucose (lCMRGlc) in healthy children.
- To establish a normative dataset for lCMRGlc across different brain regions and age groups.
Main Methods:
- Utilized PET imaging with FDG to measure lCMRGlc in 29 children (5 days to 15.1 years).
- Selected children with transient neurological events that did not impact neurodevelopment to represent a normal cohort.
- Analyzed metabolic patterns in sensorimotor cortex, thalamus, brainstem, cerebellum, basal ganglia, and various cortical regions.
Main Results:
- Infants showed highest lCMRGlc in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis.
- Metabolic rates increased in cortical and subcortical regions by 3 months, with frontal and occipital regions maturing by 6-8 months.
- Absolute lCMRGlc values rose rapidly from birth, peaked between 3-4 years, and declined to adult levels by late adolescence.
Conclusions:
- The observed changes in lCMRGlc correlate with known processes of synaptic overproduction and elimination during brain maturation.
- Establishing normative metabolic patterns is crucial for identifying and understanding abnormal brain development using PET imaging.
Abstract:
From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.