Unbiased average age-appropriate atlases for pediatric studies

Spatial normalization, registration, and segmentation techniques for Magnetic Resonance Imaging (MRI) often use a target or template volume to facilitate processing, take advantage of prior information, and define a common coordinate system for analysis. In the neuroimaging literature, the MNI305 Talairach-like coordinate system is often used as a standard template. However, when studying pediatric populations, variation from the adult brain makes the MNI305 suboptimal for processing brain images of children. Morphological changes occurring during development render the use of age-appropriate templates desirable to reduce potential errors and minimize bias during processing of pediatric data. This paper presents the methods used to create unbiased, age-appropriate MRI atlas templates for pediatric studies that represent the average anatomy for the age range of 4.5-18.5 years, while maintaining a high level of anatomical detail and contrast. The creation of anatomical T1-weighted, T2-weighted, and proton density-weighted templates for specific developmentally important age-ranges, used data derived from the largest epidemiological, representative (healthy and normal) sample of the U.S. population, where each subject was carefully screened for medical and psychiatric factors and characterized using established neuropsychological and behavioral assessments. Use of these age-specific templates was evaluated by computing average tissue maps for gray matter, white matter, and cerebrospinal fluid for each specific age range, and by conducting an exemplar voxel-wise deformation-based morphometry study using 66 young (4.5-6.9 years) participants to demonstrate the benefits of using the age-appropriate templates. The public availability of these atlases/templates will facilitate analysis of pediatric MRI data and enable comparison of results between studies in a common standardized space specific to pediatric research.