White Matter Changes Caused by Mild Traumatic Brain Injury in Mice Evaluated Using Neurite Orientation Dispersion and Density Imaging
- 15 August 2020
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 37 (16), 1818-1828
- https://doi.org/10.1089/neu.2020.6992
Abstract
Mild traumatic brain injury (mTBI) is common and can lead to persistent cognitive and behavioral symptoms. Although diffusion tensor imaging (DTI) has demonstrated some sensitivity to changes in white matter following mTBI, recent studies have suggested that more complex geometric models of diffusion, including the neurite orientation dispersion and density imaging (NODDI) model, may be more sensitive and specific. Here, we evaluate microstructural changes in white matter following mTBI using DTI and NODDI in a mouse model, and compare the time course of these changes to behavioral impairment and recovery. We also assess volumetric changes for a comprehensive picture of the structural alterations in the brain and histological staining to identify cellular changes that may contribute to the differences detected in the imaging data. Increased orientation dispersion index (ODI) was observed in the optic tracts of mTBI mice compared with shams. Changes in fractional anisotropy (FA) were not statistically significant. Volume deficits were detected in the optic tract as well as in several gray matter regions: the lateral geniculate nuclei of the thalamus, the entorhinal cortex, and the superior colliculi. Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) staining was increased in the optic tracts of mTBI brains, and this staining correlated with ODI values. A transient impairment in working memory was observed, which resolved by 6 weeks, whereas increased ODI, GFAP, and Iba1 persisted to 18 weeks post-injury. We conclude that the optic tracts are particularly vulnerable to damage from the closed-skull impact model used in this study, and that ODI may be a more sensitive metric to this damage than FA. Differences in ODI and in histological measures of astrogliosis, neuroinflammation, and axonal degeneration persist beyond behavioral impairment in this model.Keywords
This publication has 66 references indexed in Scilit:
- Performing label-fusion-based segmentation using multiple automatically generated templatesHuman Brain Mapping, 2012
- Multiple-mouse Neuroanatomical Magnetic Resonance ImagingJournal of Visualized Experiments, 2011
- Mild Fluid Percussion Injury in Mice Produces Evolving Selective Axonal Pathology and Cognitive Deficits Relevant to Human Brain InjuryJournal of Neurotrauma, 2010
- A prospective diffusion tensor imaging study in mild traumatic brain injuryNeurology, 2010
- High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J miceNeuroImage, 2008
- Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brainMedical Image Analysis, 2008
- Neuropsychological results and neuropathological findings at autopsy in a case of mild traumatic brain injuryJournal of the International Neuropsychological Society, 2004
- Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery RateNeuroImage, 2002
- An analytical model of restricted diffusion in bovine optic nerveMagnetic Resonance in Medicine, 1997
- Topography of Axonal Injury as Defined by Amyloid Precursor Protein and the Sector Scoring Method in Mild and Severe Closed Head InjuryJournal of Neurotrauma, 1995