zzzzzzzzzzzzzz Microstructural Brain Development After Perinatal Cerebral White Matter Injury Assessed by Diffusion Tensor Magnetic Resonance Imaging

Objective. Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. Methods. Twenty premature infants (gestational age: 29.1 6 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. Results. At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. Conclusions. Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development. Pediatrics 2001;107:455–460; diffusion tensor magnetic resonance imaging, brain development, premature infant, white matter injury. ABBREVIATIONS. WM, white matter; MRI, magnetic resonance imaging; ADC, apparent diffusion coefficient; RA, relative anisotropy. Periventricular leukomalacia, or cerebral white matter (WM) injury, is the major form of brain injury in the premature infant.1 Although the exact time of occurrence of the WM injury is not known, the bulk of available data implicates the periods shortly before birth and shortly after birth to varying extents.1 Although the adverse neurologic impact of the tissue loss caused directly by this perinatal WM injury is recognized,1 the impact of such WM injury on subsequent brain development is largely unknown. Previous studies of the brain of seemingly normal premature infants by quantitative volumetric magnetic resonance imaging (MRI) and by diffusion tensor MRI documented dramatic developmental changes from approximately 28 weeks From the *Division of Newborn Medicine, Harvard Medical School, Boston, Massachusetts; ‡Department of Radiology and MRI Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; §Department of Radiology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts; iDepartment of Neurology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts. Received for publication Mar 8, 2000; accepted Jul 26, 2000. Reprint requests to (J.J.V.) Department of Neurology, Children’s Hospital, Fegan 1103, 300 Longwood Ave, Boston, MA 02115. PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Acad-