TY - JOUR
T1 - Mechanical loading of the ventricular wall as a spatial indicator for periventricular white matter degeneration
AU - Visser, Valery L.
AU - Caçoilo, Andreia
AU - Rusinek, Henry
AU - Weickenmeier, Johannes
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/7
Y1 - 2023/7
N2 - Progressive white matter degeneration in periventricular and deep white matter regions appears as white matter hyperintensities (WMH) on MRI scans. To date, periventricular WMHs are often associated with vascular dysfunction. Here, we demonstrate that ventricular inflation resulting from cerebral atrophy and hemodynamic pulsation with every heartbeat leads to a mechanical loading state of periventricular tissues that significantly affects the ventricular wall. Specifically, we present a physics-based modeling approach that provides a rationale for ependymal cell involvement in periventricular WMH formation. Building on eight previously created 2D finite element brain models, we introduce novel mechanomarkers for ependymal cell loading and geometric measures that characterize lateral ventricular shape. We show that our novel mechanomarkers, such as maximum ependymal cell deformations and maximum curvature of the ventricular wall, spatially overlap with periventricular WMH locations and are sensitive predictors for WMH formation. We also explore the role of the septum pellucidum in mitigating mechanical loading of the ventricular wall by constraining the radial expansion of the lateral ventricles during loading. Our models consistently show that ependymal cells are stretched thin only in the horns of the ventricles irrespective of ventricular shape. We therefore pose that periventricular WMH etiology is strongly linked to the deterioration of the over-stretched ventricular wall resulting in CSF leakage into periventricular white matter. Subsequent secondary damage mechanisms, including vascular degeneration, exacerbate lesion formation and lead to progressive growth into deep white matter regions.
AB - Progressive white matter degeneration in periventricular and deep white matter regions appears as white matter hyperintensities (WMH) on MRI scans. To date, periventricular WMHs are often associated with vascular dysfunction. Here, we demonstrate that ventricular inflation resulting from cerebral atrophy and hemodynamic pulsation with every heartbeat leads to a mechanical loading state of periventricular tissues that significantly affects the ventricular wall. Specifically, we present a physics-based modeling approach that provides a rationale for ependymal cell involvement in periventricular WMH formation. Building on eight previously created 2D finite element brain models, we introduce novel mechanomarkers for ependymal cell loading and geometric measures that characterize lateral ventricular shape. We show that our novel mechanomarkers, such as maximum ependymal cell deformations and maximum curvature of the ventricular wall, spatially overlap with periventricular WMH locations and are sensitive predictors for WMH formation. We also explore the role of the septum pellucidum in mitigating mechanical loading of the ventricular wall by constraining the radial expansion of the lateral ventricles during loading. Our models consistently show that ependymal cells are stretched thin only in the horns of the ventricles irrespective of ventricular shape. We therefore pose that periventricular WMH etiology is strongly linked to the deterioration of the over-stretched ventricular wall resulting in CSF leakage into periventricular white matter. Subsequent secondary damage mechanisms, including vascular degeneration, exacerbate lesion formation and lead to progressive growth into deep white matter regions.
KW - Ependymal cells
KW - Finite element simulations
KW - Lateral ventricles
KW - Tissue damage
KW - White matter hyperintensities
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U2 - 10.1016/j.jmbbm.2023.105921
DO - 10.1016/j.jmbbm.2023.105921
M3 - Article
C2 - 37269602
AN - SCOPUS:85160858891
SN - 1751-6161
VL - 143
JO - Journal of the Mechanical Behavior of Biomedical Materials
JF - Journal of the Mechanical Behavior of Biomedical Materials
M1 - 105921
ER -