Biophysical Approaches to the Study of Traumatic Brain Injury

Abstract

We applied biophysical methods to study the anatomical origins of diffuse axonal injury (DAI), a common pathological finding in closed_head traumatic brain injury. The only method capable of detecting DAI non-invasively is diffusion tensor imaging (DTI), which is sensitive to the anisotropic movement of water along axons. Regions in the white matter of the brain exhibiting abnormally low fractional anisotropy are indicative of axonal disruption and are clinically interpreted as evidence of DAI. However, a direct relationship between reduced fractional anisotropy and anatomic axonal injury has not been firmly established. In this study, regions in the corpus callosum with reduced fractional anisotropy were identified in DTI maps of post-mortem brains imaged on a 9.4-Tesla magnetic resonance microscope. The anatomic structures of the corpus callosum in regions with normal and reduced fractional anisotropy were subsequently examined by Coherent Anti-Stokes Raman Scattering (CARS) microscopy using the symmetric C-H stretching band at 2845 wavenumbers to highlight the myelin membrane. Regions of the corpus callosum with normal fractional anisotropy revealed intact axons running in orderly parallel tracks. In contrast, regions with low fractional anisotropy exhibited bisected axons, axonal fragments, regions devoid of myelin lipid, and a loss of parallel axonal orientation. The results of this study establish an anatomical link between DTI and DAI that may result in improved methods to detect, study, and treat traumatic brain injury.