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Published

Patient-Informed Biomechanical Modeling Reveals Mechanical Mechanism of Brain Damage in Idiopathic Normal Pressure Hydrocephalus

Authors

Vahid Darvishi, Martina Del Giovane, Michael C B David, Balvinder K Dhillon, Magdalena A Kolanko, Anastasia Gontsarova, Paresh A Malhotra, Christopher Carswell, David J Sharp, Mazdak Ghajari

Abstract

Smart Med. 2026 Oct 30;5(5):e70060. doi: 10.1002/smmd.70060. eCollection 2026 Oct.

ABSTRACT

Idiopathic normal pressure hydrocephalus (iNPH) is a globally growing neurological disorder in older adults that is radiologically characterized 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 aging 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 the periventricular white matter, particularly within the corona radiata, 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 digital platform and future "digital twin" technology to support diagnosis, patient stratification, and treatment planning in iNPH.

PMID:42964987 | PMC:PMC13720981 | DOI:10.1002/smmd.70060