Gray Matter Growth Is Accompanied by Increasing Blood Flow and Decreasing Apparent Diffusion Coefficient during Childhood

BACKGROUND AND PURPOSE:Normal values of gray matter volume, cerebral blood flow, and water diffusion have not been established for healthy children. We sought to determine reference values for age-dependent changes of these parameters in healthy children.MATERIALS AND METHODS:We retrospectively reviewed MR imaging data from 100 healthy children. Using an atlas-based approach, age-related normal values for regional CBF, apparent diffusion coefficient, and volume were determined for the cerebral cortex, hippocampus, thalamus, caudate, putamen, globus pallidus, amygdala, and nucleus accumbens.RESULTS:All gray matter structures grew rapidly before the age of 10 years and then plateaued or slightly declined thereafter. The ADC of all structures decreased with age, with the most rapid changes occurring prior to the age of 5 years. With the exception of the globus pallidus, CBF increased rather linearly with age.CONCLUSIONS:Normal brain gray matter is characterized by rapid early volume growth and increasing CBF with concomitantly decreasing ADC. The extracted reference data that combine CBF and ADC parameters during brain growth may provide a useful resource when assessing pathologic changes in children.

At birth, brain volume is approximately one-third that of a healthy adult brain and undergoes rapid growth during the first 3 months.¹ By the age of 1 year, brain volume has already doubled in size.² Initially, most hemispheric growth relates to an increase in gray matter volume,³ thought to reflect synapse formation occurring earliest in the primary motor and sensory cortices and later in the prefrontal cortex,⁴ directing a posterior-to-anterior pattern of hemispheric white matter maturation.⁵ After the first few years, white matter volume increases at a higher rate during the rest of the childhood,⁶ while synaptic pruning occurs concurrently in the gray matter.⁴Compared with macrostructural analysis using image-based volume extraction, diffusion-weighted MR imaging can be used to probe microstructural changes, including myelination patterns^7,8 and white matter connectivity,⁹ and has also shown utility for brain tumor characterization¹⁰ and metabolic diseases.¹¹ Various studies have examined apparent diffusion coefficient changes of white matter in children.^12–14 However, at present, the ADC of the gray matter, notably at the cortical level, is not well-documented.While volumetric and diffusion analysis can be used to probe macro- and microstructural changes, respectively, arterial spin-labeling (ASL) cerebral blood flow is increasingly used clinically to obtain advanced physiologic information.^15–18 ASL may be particularly useful in the pediatric population because it does not require intravenous contrast or ionizing radiation. However, only a few studies have examined ASL CBF changes in children.^19,20These few studies have included ASL CBF of unsedated healthy term and preterm neonates²¹ or infants 3–5 months of age.²² Apart from these 2 studies, normal values have also been assessed as part of studies investigating CBF changes across the whole life span with only limited data from children²⁰ or for feasibility analysis of ASL imaging, also using only a limited number of healthy children.¹⁹At present, no study has examined the CBF of a healthy pediatric cohort across the age spectrum. Therefore, the goal of this study was to extract and establish age-related CBF values in gray matter along with corresponding volume and diffusion metrics.