IRUS Total

From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury.

File Description SizeFormat 
CKDonat_etal_Biomechanics_to_pathology_spiral.pdfAccepted version911.85 kBAdobe PDFView/Open
Title: From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury.
Authors: Donat, C
Yanez Lopez, M
Sastre, M
Baxan, N
Goldfinger, M
Seeamber, R
Mueller, F
Davies, P
Hellyer, P
Siegkas, P
Gentleman, S
Sharp, D
Ghajari, M
Item Type: Journal Article
Abstract: The relationship between biomechanical forces and neuropathology is key to understanding traumatic brain injury. White matter tracts are damaged by high shear forces during impact, resulting in axonal injury, a key determinant of long-term clinical outcomes. However, the relationship between biomechanical forces and patterns of white matter injuries, associated with persistent diffusion MRI abnormalities, is poorly understood. This limits the ability to predict the severity of head injuries and the design of appropriate protection. Our previously developed human finite element model of head injury predicted the location of post-traumatic neurodegeneration. A similar rat model now allows us to experimentally test whether strain patterns calculated by the model predicts in vivo MRI and histology changes. Using a Controlled Cortical Impact, mild and moderate injuries(1 and 2 mm) were performed. Focal and axonal injuries were quantified withvolumetric and diffusion 9.4T MRI two weeks post injury. Detailed analysis of the corpus callosum was conducted using multi-shell diffusion MRI and histopathology. Microglia and astrocyte density, including process parameters,along with white matter structural integrity and neurofilament expression were determined by quantitative immunohistochemistry. Linear mixed effects regression analyses for strain and strain rate with the employed outcome measures were used to ascertain how well immediate biomechanics could explain MRI and histology changes.The spatial pattern of mechanical strain and strain rate in the injured cortex shows good agreement with the probability maps of focal lesions derived from volumetric MRI. Diffusion metrics showed abnormalities in segments of the corpus callosum predicted to have a high strain, indicating white matter changes. The same segments also exhibited a severity-dependent increase in glia cell density, white matter thinning and reduced neurofilament expression. Linear mixed-effects regression analyses showed that mechanical strain and strain rate were significant predictors of in vivoMRI and histology changes. Specifically, strain and strain rate respectively explained 33% and 28% of the reduction in fractional anisotropy, 51% and 29% of the change in neurofilament expression and 51% and 30% of microglia density changes. The work provides evidence that strain and strain rate in the first milliseconds after injury are important factors in determining patterns of glial and axonal injury and serve as experimental validators of our computational model of TBI. Our results provide support for the use of this model in understanding the relationship of biomechanics and neuropathology and can guide the development of head protection systems, such as airbags and helmets.
Issue Date: Jan-2021
Date of Acceptance: 14-Sep-2020
URI: http://hdl.handle.net/10044/1/83596
DOI: 10.1093/brain/awaa336
ISSN: 0006-8950
Publisher: Oxford University Press (OUP)
Start Page: 70
End Page: 91
Journal / Book Title: Brain: a journal of neurology
Volume: 144
Issue: 1
Copyright Statement: © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model). This is a pre-copy-editing, author-produced version of an article accepted for publication in Brain following peer review. The definitive publisher-authenticated version Cornelius K Donat, Maria Yanez Lopez, Magdalena Sastre, Nicoleta Baxan, Marc Goldfinger, Reneira Seeamber, Franziska Müller, Polly Davies, Peter Hellyer, Petros Siegkas, Steve Gentleman, David J Sharp, Mazdak Ghajari, From biomechanics to pathology: predicting axonal injury from patterns of strain after traumatic brain injury, Brain, Volume 144, Issue 1, January 2021, Pages 70–91 is available online at: https://doi.org/10.1093/brain/awaa336
Sponsor/Funder: Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 105603/Z/14/Z
'CR & T IMP'
Keywords: controlled cortical impact
diffusion tensor imaging
finite element modelling
quantitative histology
traumatic brain injury
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Online Publication Date: 2021-01-17
Appears in Collections:Computing
Faculty of Medicine
Dyson School of Design Engineering
Department of Brain Sciences
Faculty of Engineering