Patient-informed biomechanical modelling reveals mechanical mechanism of brain damage in idiopathic normal pressure hydrocephalus

Vahid Darvishi, Martina Del Giovane, Michael David, Magdalena A. Kolanko, Anastasia Gontsarova, Paresh Malhotra, C. Melody Carswell, David J Sharp, Mazdak Ghajari

bioRxiv (Cold Spring Harbor Laboratory), 2026

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a globally growing neurological disorder in older adults, radiologically characterised by enlargement of ventricles. However, it remains unknown whether ventricular enlargement can produce biomechanical loading large enough to drive brain morphological changes and tissue damage. Here, we develop an anatomically detailed biomechanical model of ageing human brain and apply ventricular enlargement using a three-dimensional displacement field derived from MRI of iNPH patients and age-matched controls. The model accurately reproduces radiological markers of iNPH, including Evans index, callosal angle and high-convexity sulcal narrowing. It further predicts large mechanical strains in periventricular white matter, particularly within the corpus callosum and anterior thalamic radiations, tracts consistently implicated in iNPH imaging abnormalities. These findings provide strong evidence that ventricular enlargement induces mechanical strain that contributes to iNPH brain abnormalities, which can potentially be reversed by reducing strain following shunting surgery. The biomechanical brain model forms the foundation of a predictive…

Cite as (BibTeX)

@article{darvishi-2026-patient-informed-biomechanical-modelling,
  title={Patient-informed biomechanical modelling reveals mechanical mechanism of brain damage in idiopathic normal pressure hydrocephalus},
  author={Vahid Darvishi and Martina Del Giovane and Michael David and Magdalena A. Kolanko and Anastasia Gontsarova and Paresh Malhotra and C. Melody Carswell and David J Sharp and Mazdak Ghajari},
  journal={bioRxiv (Cold Spring Harbor Laboratory)},
  year={2026},
  doi={10.64898/2026.04.27.721128}
}