Journal article
3D finite-element brain modeling of lateral ventricular wall loading to rationalize periventricular white matter hyperintensity locations
- Abstract:
- Aging-related periventricular white matter hyperintensities (pvWMHs) are a common observation in medical images of the aging brain. The underlying tissue damage is part of the complex pathophysiology associated with age-related microstructural changes and cognitive decline. PvWMH formation is linked to blood–brain barrier dysfunction from cerebral small vessel disease as well as the accumulation of cerebrospinal fluid in periventricular tissue due to progressive denudation of the ventricular wall. In need of a unifying theory for pvWMH etiology, image-based finite-element modeling is used to demonstrate that ventricular expansion from age-related cerebral atrophy and hemodynamic loading leads to maximum mechanical loading of the ventricular wall in the same locations that show pvWMHs. Ventricular inflation, induced via pressurization of the ventricular wall, creates significant ventricular wall stretch and stress on the ependymal cells lining the wall, that are linked to cerebrospinal fluid leaking from the lateral ventricles into periventricular white matter tissue. Eight anatomically accurate 3D brain models of cognitively healthy subjects with a wide range of ventricular shapes are created. For all models, our simulations show that mechanomarkers of mechanical wall loading are consistently highest in pvWMHs locations (p < 0.05). Maximum principal strain, the ependymal cell thinning ratio, and wall curvature are on average 14%, 8%, and 24% higher in pvWMH regions compared to the remaining ventricular wall, respectively. Computational modeling provides a powerful framework to systematically study pvWMH formation and growth with the goal to develop pharmacological interventions in the future.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Version of record, pdf, 2.1MB, Terms of use)
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- Publisher copy:
- 10.1007/s00366-022-01700-y
Authors
+ National Institute on Aging
More from this funder
- Funder identifier:
- https://ror.org/049v75w11
- Grant:
- P30AG066512
- Publisher:
- Springer Nature
- Journal:
- Engineering with Computers More from this journal
- Volume:
- 38
- Issue:
- 5
- Pages:
- 3939-3955
- Place of publication:
- United States
- Publication date:
- 2022-07-19
- Acceptance date:
- 2022-06-19
- DOI:
- EISSN:
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1435-5663
- ISSN:
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0177-0667
- Pmid:
-
37485473
- Language:
-
English
- Keywords:
- Pubs id:
-
2036308
- Local pid:
-
pubs:2036308
- Deposit date:
-
2024-10-09
Terms of use
- Copyright holder:
- Caçoilo et al
- Copyright date:
- 2022
- Rights statement:
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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