title: Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury.
abstract: Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression.
authors.affiliation: Cell, Molecular and Developmental Biology Program, University of California, Riverside, 1140 Bachelor Hall, Riverside, CA 92521, USA ; Center for Glial-Neuronal Interactions, University of California, Riverside, School of Medicine Research Building, CA 92521, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Donovan
authors.forename: Anthony
authors.initials: A
authors.lastname: Bianchi
authors.forename: Richard
authors.initials: R
authors.lastname: Hartman
authors.forename: Bir
authors.initials: B
authors.lastname: Bhanu
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Carson
authors.forename: Andre
authors.initials: A
authors.lastname: Obenaus
keywords: DTI, diffusion tensor imaging; Edema; FA, fractional anisotropy; HPC, hemorrhagic progression of the contusion; Hemorrhagic progression; Histogram; MD, mean diffusivity; Quantitative magnetic resonance imaging; T2