A common goal of research on various developmental brain disorders is to understand how an insult to the system affects the subsequent development of the brain. Toward this objective, we have studied cognitive and brain development in children with unilateral pre- or perinatal brain lesions (PL) for over a decade. Our longitudinal, behavioral studies have shown that children with PL have milder deficits than adult patients, and in the domain of language, the mapping between lesion site and ensuing deficits differs from adults. The mildness of children's impairments and the mismatch in functional mapping suggests an alteration in the structure and organization in the neural substrate. To examine the macroanatomic structure of the intact brain, we previously used noninvasive magnetic resonance imaging (MRI) techniques. The MRI analysis of neuroanatomical brain development revealed reduced cerebral white matter (WM) volume in both the ipsilesional and contralesional hemispheres. The WM attenuation was region-specific and occurred in sites that would typically maintain projections to or through the site of injury. Heretofore the opportunity to examine WM tracts noninyasively has been limited by standard MRI techniques. In order to examine structural changes in intact WM fiber tracts following early disruption, this study will use diffusion weighted imaging (DWI) and quantitative analysis techniques. DWI is sensitive to the movement of water molecules. In the brain, cell membranes and myelin sheaths restrict the movement of water such that molecules moves more readily parallel to axon fibers than perpendicular to them. Thus DWI methods can be used to measure water movement (diffusion) and directionality (anisotropy) as indices to assess white matter integrity. To determine the extent and degree of WM alteration following early injury, we will image the brains of 20 children with unilateral PL (11-18 years old) and 40 sex- and age-matched control children. From the DWI datasets we will derive measures of diffusivity and anisotropy in regions of previously identified WM attenuation and in the major cerebral pathways. In addition, standard MRI methods will be used to measure longitudinal relaxation time (T1) and proton density (MO) to begin to differentiate types of WM disorder that may underlie abnormal anisotropy. ? ?
