The NIH MRI study of normal brain development (Objective-2): Newborns, infants, toddlers, and preschoolers

Abstract

The Magn. Reson. Imaging (MRI) study of normal brain development currently conducted by the Brain Development Cooperative Group represents the most extensive MRI study of brain and behavioral development from birth through young adulthood ever conducted. This multi-center project, sponsored by four Institutes of the National Institutes of Health, uses a combined longitudinal and cross-sectional design to characterize normal, healthy brain and behavioral development. Children, ages newborn through 18-plus years of age, receive comprehensive behavioral, neurological and multimodal MRI evaluations via Objective-2 (birth through 4-years 5-months of age) and Objective-1 (4-years 6-months through 18 years of age and older). This report presents methods (e.g., neurobehavioral assessment, brain scan) and representative preliminary results (e.g., growth, behavior, brain development) for children from newborn through 4-years 5-months of age. To date, 75 participants from birth through 4-years 5-months have been successfully brain scanned during natural sleep (i.e., without sedation); most with multiple longitudinal scans (i.e., 45 children completing at least three scans, 22 completing four or more scans). Results from this younger age range will increase our knowledge and understanding of healthy brain and neurobehavioral development throughout an important, dynamic, and rapid growth period within the human life span; determine developmental associations among measures of brain, other physical characteristics, and behavior; and facilitate the development of automated, quantitative MR image analyses for neonates, infants and young children. The correlated brain MRI and neurobehavioral database will be released for use by the research and clinical communities at a future date.

Introduction

Knowledge of structural and functional development of the human brain is advancing through evolution of magnetic resonance (MR) technology, and the development and refinement of analytical methods for anatomical MR imaging (aMRI and Diffusion Tensor Imaging [DTI]), MR Spectroscopy (MRS), and functional MR imaging (fMRI) (e.g., Ball, 2000, Barkovich, 2000, Giedd, 2004, Huisman et al., 2002, Huppi, 2001, Martin and Marcar, 2001, Neil et al., 1998, Poldrack et al., 2002, Rivkin, 2000, Sowell et al., 2004). Reports using MR to describe and characterize ‘typical’ brain development of children from school and adolescence ages have been increasing at a relatively rapid rate since the early 1990s (e.g., Blanton et al., 2001, Blatter et al., 1995, Courchesne et al., 2000, Giedd et al., 1996, Gogtay et al., 2004, Jernigan et al., 1991, Kanemura et al., 2003, Lange et al., 1997, Mukherjee et al., 2001, Paus et al., 1999, Pfefferbaum et al., 1994, Schaefer et al., 1990, Schmithorst et al., 2002, Sowell and Jernigan, 1998).

Fewer MR studies of brain development from newborn through preschool ages are available (e.g., Ashikaga et al., 1999, Barkovich, 1998, Barkovich et al., 1988, Holland et al., 1986, Martin et al., 1991, McGraw et al., 2002, Mukherjee et al., 2001, Neil et al., 1998), and many of those studies have used clinical populations of sedated infants and young children. Consequently, the currently available studies do not provide MR data for this young age range that can confidently be accepted as representative of truly healthy brain development. This gap in our knowledge of early, healthy brain development is not limited to MR imaging studies. Indeed, the anatomical brain data derived from autopsy specimens of young children (which are few in number for the < 5 year old age range) are not strictly representative of ‘normal or healthy,’ since death was generally caused by, or related to, some type of pathology (e.g., Benes et al., 1994, Brody et al., 1987, Dekaban and Sadowsky, 1978, Dobbing and Sands, 1973, Huttenlocher and Dabholkar, 1997, Yakovlev and Lecours, 1967).

MRI has become the premier tool for the quantitative, noninvasive study of childhood brain development. Developmentally accurate MR data are critically needed to determine the actual ranges of variation in brain structure and function that can be expected for healthy infants and young children. Achievement of such an MR data resource would provide standards to permit clinicians and researchers to better identify and define brain pathology that is associated with behavioral, neurological, and/or psychiatric disorders for infants, children, and adolescents.

The NIH has recognized that the scientific and clinical communities have a need for a developmental neuroimaging and behavioral database for normal, healthy children ranging in age from birth through adolescence. In 1999, NIH funded the current, ongoing multi-center project to provide research and clinical communities with a correlated MRI and behavior database that would be demographically diverse and generally representative of gender, race, ethnicity, and income level established by the United States Census Bureau (2000) and United States Department of Housing and Urban Development’s Office of Policy Development and Research (2003). Six Pediatric Study Centers (PSCs) serve as principal recruitment and data acquisition sites and are located at Children’s Hospital Boston, Children’s Hospital Medical Center of Cincinnati, University of Texas Health Science Center at Houston, University of California-Los Angeles, Children’s Hospital of Philadelphia, and Washington University Medical Center in Saint Louis. A Data Coordinating Center (DCC; Montreal Neurological Institute, McGill University) coordinates the imaging and database aspects of the project. A Clinical Coordinating Center (CCC; Washington University Medical Center in Saint Louis) coordinates and maintains quality control for the sampling plan, screening and recruitment, and neurobehavioral measures. Centralized data analysis of DTI data is provided by a Diffusion Tensor Imaging Data Processing Center (DTI-DPC; NIH, NICHD, Intramural Program). Spectroscopy data is processed at the University of California-Los Angeles by the Magnetic Resonance Spectroscopy Data Processing Center (MRS-DPC). All of the Centers listed above participate as full scientific partners in this research endeavor.

The overall project comprises two objectives which span the entire period of childhood development from birth through early adulthood. Objective-1 recruits children between the ages of 4-years 6-months through 18 years, while Objective-2 recruits from birth through 4-years 5-months of age. Notably, children advancing to 4-years 6-months of age and older are transferred to Objective-1 for their further participation in the project. Similarly, children who enter Objective-1 in late adolescence (e.g., 18 years of age) continue to participate in the project through their early twenties. As a result, the entire developmental epoch from birth through early adulthood is represented in the combined Objective 1 and 2 samples of participants. This project will yield a correlated brain MRI and neurobehavioral database for healthy brain and behavioral development from birth through young adulthood that will be made accessible to the scientific and clinical communities for use in research studies and clinical practice. It is anticipated that the process of releasing brain and behavioral data to the public will begin in the near future.

The remainder of this report describes the methodology and preliminary results for Objective-2, which is being conducted by the Boston and Saint Louis sites only. An overview report, generally describing the sample and methods of the entire project, is available (see Brain Development Cooperative Group, 2006).