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 +/- 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.
Division of Newborn Medicine, Harvard Medical School, Boston, Massachusetts, USA.
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PS
Hüppi
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B
Murphy
S E
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Maier
G P
GP
Zientara
T E
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Inder
P D
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Barnes
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Kikinis
F A
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Jolesz
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Volpe
D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007969:Leukomalacia, Periventricular / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D013687:Telencephalon / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure