ABSTRACT:The swine brain is emerging as a potentially valuable translational animal model of neurodevelopment and offers the ability to assess the impact of experimentally induced neurological disorders. The goal for this study was to characterize swine brain development using noninvasive MRI measures of microstructural and cerebrovascular changes. Thirteen pigs at various postnatal ages (2.3-43.5 kg) were imaged on a 1.5-Tesla MRI system. Microstructural changes were assessed using diffusion tensor imaging measures of mean diffusivity and fractional anisotropy. Cerebrovascular changes were assessed using arterial spin labeling measures of baseline cerebral blood flow (CBF) and the cerebrovascular reactivity (CVR) of the blood-oxygen level dependent (BOLD) MRI signal to CO 2 . We found a positive logarithmic relationship for regional tissue volumes and fractional anisotropy with body weight, which is similar to the pattern reported in the developing human brain. Unlike in the maturing human brain, no consistent changes in mean diffusivity or baseline CBF with development were observed. Changes in BOLD CVR exhibited a positive logarithmic relationship with body weight, which may impact the interpretation of functional MRI results at different stages of development. This animal model can be validated by applying the same noninvasive measures in humans. (Pediatr Res 69: 418-424, 2011) P rocesses of human brain development are integral to the understanding of the long-term impact of neurological disorders afflicting the immature brain. Animal models provide a means to investigate developmental processes in a controlled manner and to model the effects of disease and injury on the immature brain. Dobbing and Sands (1) proposed that the swine brain may represent an appropriate model for the immature human brain based on the timing of the brain growth spurt (rapid stages of brain growth), which is recognized as a period of increased vulnerability to injury. Additional benefits of the swine model for developmental neuroscience include similar histology, cortical folding, and gray-matter (GM)-to-white-matter (WM) ratio to humans (1). Moreover, recent advances in transgenic neural gene manipulations and the ability to model brain injury and neurologic disorders have also supported the increasing use of swine as a model for neuroscience and neurosurgical research (2,3).Ontogeny of the brain typically focuses on structural changes during development; however, these changes may also be linked to cerebrovascular development based on the observed association between rapid stages of brain growth and increased cerebral perfusion that is believed to be required to match increased metabolic needs (4). Given that many pathologies of the immature brain involve compromised cerebral perfusion (e.g., neonatal encephalopathy and intraventricular hemorrhage), there is a need to characterize both cerebrovascular and structural changes occurring in animal models of early human brain development.MRI is emerging as the prominent modality for ...

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