Through your participation in the Premature MRI study, we have examined more than 170 premature newborns with serial neonatal magnetic resonance (MR) exams and are now following these infants through childhood to determine the impact of brain injury on neurodevelopmental outcome. To date, the key findings of our research of brain injury in the premature newborn are:

• Brain injury in premature newborns is safely detected with MRI before term equivalent age. We have demonstrated that brain abnormalities in premature newborns are safely and reliably detected with serial MRI from well before term age (approximately 40 weeks).
• Focal Non-Cystic White Matter Injury is the Characteristic Pattern of Injury in the Premature Newborn on MRI. The incidence of cystic periventricular leukomalacia (PVL), the most severe form of white matter injury, has declined dramatically over the last decade. This decline is most closely related to a decrease in the use of mechanical ventilation. We also find that most children with abnormal outcome do not have PVL on ultrasound. Yet, in contrast we are finding focal non-cystic white matter injury is seen in more than half of premature newborns on MRI, consistent with our observation that ultrasound has limited sensitivity for diagnosing focal non-cystic white matter injury.
• Early brain injury is associated with adverse early neurodevelopmental outcome. We have recently found that abnormal neurodevelopmental outcome was strongly associated with increasing severity of focal non-cystic white matter injury, ventriculomegaly and intraventricular hemorrhage on MRI1. In fact, abnormalities on the early MRI scan were as or more strongly associated with adverse neurodevelopmental outcome than the near term age MRI. In this study, both postnatal infection and white matter injury were independently associated with adverse outcome. This suggests that a neonatal inflammatory state may lead to poor outcome by pathways distinct from white matter injury, such as by specific impairments in cerebral development. In another preliminary study of newborns delivered before 28 weeks gestation we found that longer duration indomethacin exposure was associated with a reduction in white matter injury (Submitted).
• Brain injury in the immature brain impairs subsequent brain development. Using serial diffusion tensor imaging (DTI), we have demonstrated that in premature newborns, focal non-cystic white matter lesions are associated with widespread abnormalities of white matter development as these newborns approach term equivalent age. These abnormalities are found in all brain regions, even those that were normal on conventional MRI. This was the first report of premature newborns studied serially with MR techniques from shortly after birth.
• MR Technique Development for Studying the Newborn Brain. We are continually refining our techniques of "region of interest" analyses of microscopic water motion, using a technique known as diffusion tensor imaging (DTI). We are also able to quantify and compare water diffusion in multiple directions from specific white matter tracts and to map out white matter tracts using a technique called DTI tractography. This allows us to determine whether the large connecting pathways in the brain are forming properly. Further advances in the analysis of diffusion tensor imaging allow, for the first time, the segmentation of developing brain into multiple layers that are developmentally regulated. These include a transient area of cerebral cortex, known as the subplate zone, which is believed to be extremely important in normal brain development. Using DTI we have also demonstrated striking maturational changes in the microstructure of the developing cerebral cortex. These maturational changes show remarkable regional heterogeneity of cerebral cortical development.

back to top