Abstract
Objective: To establish the magnitude and time course of the changes in water diffusion coefficient (Dav) following newborn infant brain injury.
Methods: Ten newborn infants at high risk for perinatal brain injury were recruited from the neonatal intensive care unit. Conventional and diffusion tensor MRI was performed on three occasions during the first week of life. Regions of injury were determined by evaluating conventional MR images (T1, T2, fluid-attenuated inversion recovery) at 1 week after injury. Dav values were determined for these regions for all three scans.
Results: Dav values were decreased in most infants 1 day after injury, but injury was not evident or underestimated in 4 of 10 infants despite the presence of injury on conventional imaging at 1 week. By the third day, Dav values were decreased in injured areas in all infants, reaching a nadir of approximately 35% less than normal values. By the seventh day after injury, Dav values were returning to normal (pseudonormalization).
Conclusions: MR diffusion images (for which contrast is determined by changes in Dav) obtained on the first day after injury do not necessarily show the full extent of ultimate injury in newborn infants. Images obtained between the second and fourth days of life reliably indicate the extent of injury. By the seventh day, diffusion MR is less sensitive to perinatal brain injury than conventional MR because of transient pseudonormalization of Dav. Overall, diffusion MR may not be suitable as a gold standard for detection of brain injury during the first day after injury in newborn infants.
The neurologic examination often falls short as a definitive test of CNS integrity, particularly cerebral cortical integrity, in newborn infants. Whereas the likelihood of significant brain injury increases with signs of perinatal distress (e.g., low umbilical cord blood pH, low Apgar scores, hepatic or renal dysfunction, seizures), the positive predictive value of history, physical examination, and routine testing remains suboptimal.1 Complicating matters further, many newborn infants suspected of having injury may not have injury. The challenge of evaluating newborn infants for brain injury will become more relevant if neuroprotective agents become available for treatment of brain injury.
Imaging methods that are currently used to augment the clinical evaluation of newborn infants include cranial sonography, CT, and conventional MRI (T1- and T2-weighted and fluid-attenuated inversion recovery [FLAIR] images). These modalities fall short as the definitive evaluation of the earliest signs of brain injury in the newborn infant because they may miss injury for up to 3 days after its occurrence.2,3⇓ Diffusion-weighted imaging (DWI; for which contrast is based on water apparent diffusion coefficient [ADC], T2 relaxation, and spin density) is promising because it has been shown to be a sensitive and early indicator of brain injury in both animal models4 and adult humans.5 Hence, DWI may provide the means by which to establish the presence or absence of injury in newborn infants within the critical, early hours following possible injury. Thus far, the application of these techniques to the study of brain injury in newborn infants has shown great promise.6-9⇓⇓⇓ In the study described below, we determine the characteristics of changes in the water isotropic apparent diffusion coefficient (Dav) following brain injury in newborn infants.
The primary goal of this study is to establish the time course of the diffusion abnormality following a well-defined episode of perinatal brain injury. Such information is useful in assessing the reliability of Dav measurements for early detection of injury and indicates the optimal time for using Dav measurements to assess injury. It is also the first step in addressing the utility of diffusion imaging in the management of perinatal hypoxic–ischemic injury. If diffusion imaging is to play a significant role in patient management, it should be sensitive for detecting injury in the time shortly after the inciting event, which would allow for early therapeutic intervention and, potentially, reduced morbidity.
Acknowledgments
Supported by NIH grant NS37357 and a Child Neurology Society grant (J.J.N.).
The authors thank Drs. Pratik Mukherjee and Bill Powers for thoughtful discussion and Drs. Erbil Akbudak and Tom Conturo for technical support.
Footnotes
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See also page 798
- Received November 20, 2001.
- Accepted March 30, 2002.
References
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