The NIH MRI study of normal brain development i Brain Development Cooperative Group 1 Alan C. Evans * Montreal Neurological Institute, McGill University, Department of Neurology and Neurosurgery, 3801 University St., Montreal, H3A 2B4 Canada Received 28 January 2005; revised 8 July 2005; accepted 14 September 2005 Available online 11 January 2006 MRI is increasingly used to study normal and abnormal brain development, but we lack a clear understanding of ‘‘normal’’. Previous studies have been limited by small samples, narrow age ranges and few behavioral measures. This multi-center project conducted epidemio- logically based recruitment of a large, demographically balanced sample across a wide age range, using strict exclusion factors and comprehensive clinical/behavioral measures. A mixed cross-sectional and longitudinal design was used to create a MRI/clinical/behavioral database from approximately 500 children aged 7 days to 18 years to be shared with researchers and the clinical medicine community. Using a uniform acquisition protocol, data were collected at six Pediatric Study Centers and consolidated at a Data Coordinating Center. All data were transferred via a web-network into a MYSQL database that allowed (i) secure data transfer, (ii) automated MRI segmentation, (iii) correlation of neuroanatomical and clinical/ behavioral variables as 3D statistical maps and (iv) remote interroga- tion and 3D viewing of database content. A population-based epidemiologic sampling strategy minimizes bias and enhances generalizability of the results. Target accrual tables reflect the demographics of the U.S. population (2000 Census data). Enrolled subjects underwent a standardized protocol to characterize neurobehavioral and pubertal status. All subjects underwent multi- spectral structural MRI. In a subset, we acquired T1/T2 relaxometry, diffusion tensor imaging, single-voxel proton spectroscopy and spec- troscopic imaging. In the first of three cycles, successful structural MRI data were acquired in 392 subjects aged 4:6 – 18:3 years and in 72 subjects aged 7 days to 4:6 years. We describe the methodologies of MRI data acquisition and analysis, using illustrative results. This database will provide a basis for characterizing healthy brain maturation in relationship to behavior and serve as a source of control data for studies of childhood disorders. All data described here will be available to the scientific community from July, 2006. D 2005 Elsevier Inc. All rights reserved. Keywords: Pediatric; MRI; Database; Brain behavior; Multi-center Introduction Magnetic resonance imaging (MRI) has made it possible to study normal structural and metabolic brain development across age groups. It had been difficult to study infants, children and adolescents with earlier imaging modalities because of safety concerns related to radiation exposure. Hence, relatively little was known about healthy brain development in humans prior to the advent of MRI. Background In the 1990s, several research groups demonstrating age-related changes in gray matter volumes, white matter volumes, myelina- tion and subcortical measures with MRI in samples of healthy children aged 4 – 21 years (Filipek et al., 1994; Jernigan and Tallal, 1990; Jernigan et al., 1991; Pfefferbaum et al., 1994). Subsequent- ly, additional studies have described normal developmental changes in specific brain regions based on samples of children and young adults ranging in size from N = 13 to 176 (Bartzokis et al., 2001; Blanton et al., 2001, 2004; Blatter et al., 1995; Caviness et al., 1996, 1999; Courchesne et al., 2000; DeBellis et al., 2001; Giedd et al., 1996, 1999; Gogtay et al., 2002, 2004; Kennedy et al., 1998, 2003; Lange et al., 1997; Paus et al., 1999; Reiss et al., 1996; Sowell et al., 1999, 2002, 2003, 2004a). Several recent reviews have summarized this research (Durston et al., 2001; Gogtay et al., 2002; Paus et al., 2001; Sowell et al., 2004b) with respect to maturation and correlation with postmortem findings in infancy and childhood. It is clear that during early childhood and adolescence specific regional brain measures vary widely in healthy populations. Cross-sectional studies have therefore been limited in the conclusions they can reach about healthy brain development. Similarly, studies of pediatric brain disorders have been hampered by the lack of control data for healthy develop- ment. Longitudinal studies have noted that individual develop- mental brain growth trajectories are highly variable, regionally specific and may demonstrate gender-specific patterns (Giedd et al., 1996, 1999). They highlight the need for large sample sizes in order to obtain reliable conclusions about the normative range for specific regional volumetric data and maturation patterns (Gogtay et al., 2004). 1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2005.09.068 i Researchers who are interested in using the database resulting from this project are encouraged to request the protocols by e-mailing rozie@bic.mni.mcgill.ca. * Corresponding author. Fax: +1 514 398 8948. E-mail address: alan.evans@mcgill.ca (A.C. Evans). 1 See Appendix A for author list. Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 30 (2006) 184 – 202