Current radiologic techniques are severely limited in their ability to assess neurologic status in newborns and infants. New methods to noninvasively assess infant brain physiology are required both to better understand normal brain development and to detect and characterize neurologic anomalies. We have recently developed 3D MR spectroscopic imaging techniques to detect metabolite levels throughout the majority of the baby brain. 3D MRSI is a significant advance over the single voxel MRS used in prior studies of the infant brain. With the new technique, hundreds of spectra can be obtained throughout the brain in a single acquisition at spatial resolution of 1cc, which is 5-fold better than typically used in single voxel MRS. The preliminary results have demonstrated the ability of 3D MRSI to detect metabolic variations due to anatomic location, development and brain injury. In these studies we have also applied MR diffusion tensor imaging to provide complementary biologic information by detecting physiologic changes associated with the degree and preferred direction of water diffusion. In this exploratory research project, we will apply these new metabolic and functional imaging techniques to the study of infants between ages 1 month and two years. The main focus will be patients with developmental delay resulting from destructive lesions, inborn errors of metabolism, and developmental brain malformations. Anatomic variation of metabolic and diffusion parameters will be measured and correlated with the type and severity of the neurologic abnormality (motor, visual, cognitive). We will also add these techniques to MR exams of age-matched infants being examined for macrocephaly, microcephaly, suspected mild trauma, or febrile seizures. Only those with normal development and normal neurologic exams will be included. We expect a large percentage (>80%) of this group to develop normally; thus, they will provide normative data, obviating recruitment of volunteer infants. As most of these patients are truly normal, we will avoid the difficulty and ethical concerns of studying and thus sedating normal volunteer infants in this exploratory study. Moreover, the inclusion of patients with normal neurologic development will provide important, currently lacking data on the metabolic and water diffusion changes that occur temporally and anatomically in this 1-24 month age group. Through this project we will develop and evaluate new MR imaging methods to noninvasively monitor infant brain physiology. These exciting new techniques have the potential to greatly enhance future studies (both research and clinical) of pediatric brain disorders.
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