Imaging selective vulnerability in the developing nervous system

Abstract

Why do cells in the central nervous system respond differently to different stressors and why is this response so age-dependent? In the immature brain, there are regions of selective vulnerability that are predictable and depend on the age when the insult occurs and the severity of the insult. This damage is both region and cell population specific. Vulnerable cell populations include the subplate neurons and oligodendrocyte precursors early in development and the neurons closer to the end of human gestation. Mechanisms of injury include excitotoxicity, oxidative stress and inflammation as well as accelerated apoptosis. Advanced imaging techniques have shown us particular patterns of injury according to age at insult. These changes seen in the newborn at the time of injury on magnetic resonance imaging correlate well with the neurodevelopmental outcome. New questions about how the injury evolves and how the newborn brain adapts and repairs itself have emerged as we now know that injury in the newborn brain can evolve over days and weeks, rather than hours. The ability to follow these processes has allowed us to investigate the role of repair in attenuating the injury. Neurogenesis and angiogenesis exist in response to ischemic injury and can be enhanced by processes that are known to protect the brain. The injury response in the developing brain is a complex process that evolves over time and is amenable to repair.

Fig. 1

Imaging the subplate and vulnerable white matter regions in the preterm brain. (A) Diffusion-weighted image of a 4-day-old infant born at 28 weeks gestation. The high signal in the periventricular white matter is consistent with periventricular white matter injury that is diffuse. (B) An apparent diffusivity coefficient map of this newborn shows the subplate region in red.

Fig. 2

Injury to the preterm newborn brain. (A) Minimal white matter injury in a premature newborn born at 31 weeks gestational age and scanned at 6 days of life. The spoiled gradient echo volumetric scan shows small foci of T1 hyperintensity (arrow) without cavitation in the periventricular white matter. This newborn also had intraventricular hemorrhage. (B) Moderate white matter injury in a premature newborn born at 29 weeks gestational age and scanned at 2 weeks of life. The spoiled gradient echo volumetric scan shows more numerous foci of T1 hyperintensity (involving less than 5% of the hemisphere involved) without cavitation (arrow) in the posterior periventricular white matter. (C) Severe white matter injuries in a premature newborn born at 29 weeks gestational age and studied at 4 weeks of age. The spoiled gradient echo volumetric scan demonstrates confluent areas of T1 hyperintensity (arrows) without cavitation throughout the periventricular white matter of both cerebral hemispheres.

Fig. 3

The predominant patterns of injury in term newborn with hypoxic–ischemic encephalopathy. (A) Watershed injury pattern: axial T2-weighted image above the body of the lateral ventricles, demonstrating the characteristic T2 hyperintensity of the cortex and white matter in the posterior watershed regions. (B) Basal ganglia injury pattern: axial T1-weighted image demonstrating marked hyperintensity of the caudate, putamen and thalamus.