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Characterizing microstructural alterations in a mTBI ratmodel: a multi-shell diffusion MRI analysis

2017; Frontiers Media; Volume: 11; Linguagem: Inglês

10.3389/conf.fnins.2017.94.00029

1662-4548

Kim Braeckman, Benedicte Descamps, Karen Caeyenberghs, Christian Vanhove,

Traumatic Brain Injury Research

Event Abstract Back to Event Characterizing microstructural alterations in a mTBI ratmodel: a multi-shell diffusion MRI analysis Kim Braeckman1*, Benedicte Descamps1, Karen Caeyenberghs2 and Christian Vanhove1 1 Ghent University, Belgium 2 Australian Catholic University, Australia Introduction Traumatic brain injury (TBI) is the leading cause of acquired disability in young adults, often caused by traffic accidents or sport injuries (Thurman, 2016). Mild TBI (mTBI) is the most common type of TBI. While conventional scans (CT or anatomical MRI) show no evidence of injury due to the diffuse and subtle nature of mTBI, the patients can suffer from chronic cognitive defects evens years after their injury. Due to the lack of specificity of FA for histological features (Jones et al, 2013), the aim of this study is to better characterize white matter changes with advanced diffusion MRI analysis in a rat model of mTBI. Methods Animal model: 20 female Wistar rats weighing 265±16.9g were used in this study. 13 sustained mTBI utilizing the Marmarou weight drop model (Marmarou et al, 1994) and 7 received a sham injury. In brief, in anesthetized rats a steel helmet was fixed on the skull 1/3 before and 2/3 behind bregma. The rat was positioned under a 450g brass weight on a foam bed. The weight was dropped from a height of 1m guided through a plexiglass column. The foam bed together with the rat was rapidly removed from the column to prevent a second impact. For the sham animals, the procedure was the same except for the impact. Imaging and data analysis: MRI data were acquired on a 7T MR scanner (PharmaScan, Bruker, Ettlingen) before, 1 day, 1 week and 3 months after injury. T2-weighted images were acquired for anatomical reference. Multi-shell diffusion data were acquired with multiple directions/b-values, i.e. b=800, 1500 and 2000 s/mm2; 32, 46 and 64 directions. DWI images were corrected for EPI, motion and eddy current distortions in ExploreDTI version 4.8.6. (Leemans et al, 2009). Moreover diffusion kurtosis tensor estimation was performed using weighted linear least squares method (Veraart et al, 2013). Maps for the diffusion and kurtosis metrics (FA, MD, AD, RD, MK, AK and RK) were calculated based on the diffusion kurtosis imaging model (Veraart et al, 2011) and maps for the white matter metrics (AWF, AxEAD, RadEAD, tortuosity) were calculated based on a white matter diffusion model (Fieremans et al, 2011). The maps were then co-registered in SPM12 on an anatomical template based on the local population, using the T2-weighted images. Next, a volume-of-interest analysis was performed in the hippocampus, cingulum, cortex and corpus callosum using Amide toolbox (Loening et al, 2003). Low quality scans were left out of the analysis. The Wilcoxon signed rank test was performed on each map to investigate changes in white matter between time points in SPSS. Subsequently, the Mann-Whitney U test was carried out to test for differences between the sham and TBI group at each timepoint. P<0.05 was considered significant. Histological analysis: Rats were sacrificed for histological analysis and perfused with 4% paraformaldehyde 1 day (n=1), 1 week (n=6) and 3 months (n=10) after impact. Sections of the brain were stained for the following markers: synapses (with anti-synaptophysin); myelin (with Luxol Fast Blue staining); astrocytes (with anti-glial fibrillary acidic protein); and neurons (with anti-neurofilament, NF). Results As can be seen from Table 1, we found increased values for AK and AWF, 1 week post injury compared to baseline in the TBI group for the corpus callosum. The increase in AWF was also seen in the cingulum. When comparing the TBI and sham group, a significant difference was found between the two groups for the AWF, 1 week post injury in the cingulum. No significant differences were found 1 day and 6 months post injury, nor in the sham group. Staining for NF might suggest that several neurons are undergoing Walerian degeneration (1 week after impact)(Figure 1). Discussion and conclusion An increase in AWF could be explained by axonal swelling, consistent with an increased AK. Because AWF values were significantly different between the TBI and sham group as well, we can conclude that this metric is very sensitive for changes in microstructure due to mTBI (1 week post injury). Since there were too few subjects 1 day and 6 months post injury in each group (n=3) and the variability of the measurements was too high, we could not find significant results at these time points. More subjects will be added in future research. Walerian degeneration in the cortex might indicate injured and swollen axons. Further histological analysis is needed in order to provide a biological basis to support this hypothesis. Figure 1 Figure 2 References Fieremans, et al. (2011) White matter characterization with diffusional kurtosis imaging, NeuroImage, 58(1):177-188. Jones, et al (2013) White matter integrity, fiber count, and other fallacies: The do's and don'ts of diffusion MRI. NeuroImage, 73:239–254 Leemans, et al. (2009) ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. 17th Annual Meeting of Intl Soc Mag Reson Med, p. 3537, Hawaii, USA. Loening, et al. (2003) AMIDE: A Free Software Tool for Multimodality Medical Image Analysis. Molecular Imaging, 2(3):131-137. Marmarou, et al. (1994) A new model of diffuse brain injury in rats: Part I. J Neuroscience, 80:291-300. Thurman (2016) The Epidemiology of Traumatic Brain Injury in Children and Youths: A Review of Research Since 1990. J Child Neurol, 31(1):20-27. Veraart, et al. (2011) More Accurate Estimation of Diffusion Tensor Parameters Using Diffusion Kurtosis Imaging. MRM, 65:138-145. Veraart, et al. (2013) Weighted linear least squares estimation of diffusion MRI parameters: strengths, limitations, and pitfalls. NeuroImage, 81:335-346. Keywords: Diffusion tensor imaging (DTI), diffusion kurtosis imaging, Mild Traumatic Brain Injury (mTBI), Wistar rat, white matter microstructure Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017. Presentation Type: Poster Presentation Topic: Disorders of the Nervous System Citation: Braeckman K, Descamps B, Caeyenberghs K and Vanhove C (2019). Characterizing microstructural alterations in a mTBI ratmodel: a multi-shell diffusion MRI analysis. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00029 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 01 May 2017; Published Online: 25 Jan 2019. * Correspondence: Miss. Kim Braeckman, Ghent University, Ghent, Belgium, kim.braeckman@ugent.be Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kim Braeckman Benedicte Descamps Karen Caeyenberghs Christian Vanhove Google Kim Braeckman Benedicte Descamps Karen Caeyenberghs Christian Vanhove Google Scholar Kim Braeckman Benedicte Descamps Karen Caeyenberghs Christian Vanhove PubMed Kim Braeckman Benedicte Descamps Karen Caeyenberghs Christian Vanhove Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.