Functional magnetic resonance imaging of the primary somatosensory cortex in piglets.

OBJECT: The piglet is an excellent model for the developing human brain, and has been used increasingly in various centers for studies of traumatic brain injury and other insults. Unlike rodent or primate models, however, there are few behavioral scales for the piglet, and the available ones are used to test general responsiveness rather than specific functional outcome. The differing behavioral repertoires of animals of different ages provide an additional challenge when age-dependent injury responses are compared. To overcome these experimental limitations of piglets in brain injury research, the authors developed a functional magnetic resonance (fMR) imaging paradigm that can be used to track recovery in the somatosensory cortex over time in anesthetized animals of different ages. METHODS: Fifteen fMR imaging studies in eight piglets were performed before and after scaled cortical impact injury to the primary somatosensory cortex subserving snout sensation. Specific anesthetic and imaging protocols enabled visualization of cortical activation, and comparison with somatosensory evoked potentials obtained before and after injury was obtained. A piglet brain template for group-level analysis of these data was constructed, similar to the fMR imaging techniques used in humans, to allow for group comparisons and longitudinal change analysis over time. CONCLUSIONS: Loss of function in a specifically traumatized cortical region and its subsequent recovery over time can now be demonstrated visually by fMR imaging in the piglet. Besides its value in understanding intrinsic recovery mechanisms and plasticity at different ages, this functional outcome measure will enable the use of the piglet model in treatment trials specifically designed for the immature brain.

Magnetic resonance imaging studies of age-dependent responses to scaled focal brain injury in the piglet.

OBJECT: Whether the brain differs in its response to traumatic injury as a function of age remains unclear. To further investigate the age-dependent response of the brain to mechanical trauma, a cortical contusion model scaled for brain growth during maturation was used to study the evolution of injury over time as demonstrated on serial magnetic resonance (MR) imaging studies in piglets of different ages. METHODS: Sixteen Yorkshire piglets received scaled cortical contusions. Animals were either 5 days (six animals), 1 month (five animals), or 4 months (five animals) of age at injury. These ages correspond developmentally to human infants, toddlers, and early adolescents, respectively. Serial MR imaging examinations, including fluid-attenuated inversion-recovery and T1-, T2-, and diffusion-weighted sequences were performed at 24 hours, 1 week, and 1 month after injury. Lesions were quantified and expressed as a ratio of the lesion volume divided by the volume of the uninjured hemisphere for each animal and each MR sequencing. Differences in relative lesion volume among the varied ages at a single time point and in lesion volume over time at each age were compared. In addition, the relationship between age and evolution of injury were analyzed using a two-compartment mathematical model. Histological features were examined at 1 month postinjury. Despite comparable injury inputs, the youngest animals had lesions whose volumes peaked earlier and resolved more quickly than those in older animals. The intermediate-age piglets (toddler) had the most pronounced swelling of any age group, and the oldest piglets (adolescent) had the latest peak in lesion volume. CONCLUSIONS: Scaled cortical contusions in piglets demonstrated age-dependent differences in injury response, both in magnitude and time course. These observations may shed light on development-related trauma response in the gyrencephalic brain.

Traumatic brain injury in piglets of different ages: techniques for lesion analysis using histology and magnetic resonance imaging.

Quantitation of lesions in large gyrencephalic brains presents a variety of technical challenges. Specific techniques are required when comparing lesions in subjects of different ages in order to assess maturational effects. We have modified existing techniques to attain reliable, consistent and reproducible paraffin-embedded histological sections for volumetric lesion analysis and correlation with magnetic resonance imaging (MRI) in piglets of different ages following focal traumatic brain injury. Twenty-four Yorkshire domestic piglets at three different ages (5 days, 1 month, and 4 months old) underwent scaled cortical impact injury to the fronto-parietal cortex. This contusion model utilizes a rapid volume of indentation scaled proportionally to the growth of the brain, allowing for examination of maturational influences on the brain's response to focal mechanical trauma. To overcome problems with differential processing and embedding of brains ranging from 43 to 107 g, we developed a piglet parallel brain slicing apparatus. Along with specific methods for processing, embedding, mounting, and slide preparation, these techniques enabled excellent quality 10-microm serial coronal sections to be obtained for histology and immunohistochemical analysis. Accurate co-registration of histologic, immunohistochemical and radiologic images at different ages was possible, which may enhance understanding of developmental aspects of brain injury pathophysiology.