{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:13:41Z","timestamp":1789456421675,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The mechanism by which idiopathic normal pressure hydrocephalus (iNPH) causes cognitive impairment, gait dysfunction and urinary incontinence is unclear. The key radiological feature is ventriculomegaly, and symptoms can be treated with surgery. We hypothesise that ventricular expansion causes clinical effects by stretching and\/or compressing white matter tracts. We define disease-specific white matter abnormalities, explore their relationship to clinical features and test whether they can be explained by a computational model of ventricular expansion in iNPH.<\/jats:p>\n                  <jats:p>In this observational study, diffusion tensor imaging with Tract-Based Spatial Statistics analysis was used to investigate white matter abnormalities in 22 patients with iNPH (14 males, mean age=71.91, SD=7.06), 28 with Alzheimer\u2019s disease (AD) (18 males, mean age=74.80), 23 with moderate-severe traumatic brain injury (TBI) (15 males, mean age=69.87) and 30 healthy controls (16 males, mean age=73.80). We developed a finite-element biomechanical model of hydrocephalus, which predicts patterns of white matter stretch and compression generated to deform from healthy to iNPH brain, and studied their effect on the extracted diffusion properties.<\/jats:p>\n                  <jats:p>Increased ventricular size relative to controls was found in both iNPH, AD and TBI. However, iNPH showed a unique pattern of increased and decreased fractional anisotropy (FA) in distinct sections of the corticospinal tract and corona radiata compared to AD, TBI and controls. Biomechanical modelling revealed that stretch in these tracts was associated with increased FA, driven by increased axial diffusivity (AxD) with little change or a reduction in radial diffusivity (RD). In contrast, compression was associated with reduced FA, resulting from increases in both AxD and RD. Parcel-based correlation analysis showed that strain predicted by the biomechanical model in these tracts was strongly and positively correlated with FA and negatively correlated with RD. The corpus callosum experienced greater stretch along its entire length than the corona radiata and corticospinal tract, yet it demonstrated the largest reduction in FA, driven by increases in both AxD and RD. In iNPH, processing speed impairments were associated with increased AxD in the corpus callosum and AxD and RD in the corona radiata. Higher urinary incontinence correlated with reduced FA in the corona radiata and corticospinal tract.<\/jats:p>\n                  <jats:p>iNPH is characterised by a distinct biomechanical substrate, in which predictable patterns of stretch and compression associated with ventricular expansion lead to clinically relevant white matter damage. These diffusion abnormalities distinguish iNPH from AD and TBI and may serve as potential biomarkers. Longitudinal studies of patients undergoing CSF drainage are warranted.<\/jats:p>","DOI":"10.1093\/brain\/awag312","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:52:45Z","timestamp":1789127565000},"source":"Crossref","is-referenced-by-count":0,"title":["Modelling the effect of ventricular expansion on white matter in normal pressure hydrocephalus"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3476-8494","authenticated-orcid":false,"given":"Martina","family":"Del Giovane","sequence":"first","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Darvishi","sequence":"additional","affiliation":[{"name":"Imperial College London, Dyson School of Design Engineering , 1st Floor, Royal College of Science, South Kensington Campus, London SW7 2DB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C B","family":"David","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena A","family":"Kolanko","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Scott","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl A","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]},{"name":"Imperial College London, Dyson School of Design Engineering , 1st Floor, Royal College of Science, South Kensington Campus, London SW7 2DB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2165-7840","authenticated-orcid":false,"given":"Valentina","family":"Giunchiglia","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"King\u2019s College London, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience , London, SE5 8AF ,","place":["UK"]},{"name":"Harvard Medical School, Department of Biomedical Informatics , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Gontsarova","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust, Department of Neuroradiology, Charing Cross Hospital , London W6 8RF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Hampshire","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience , London, SE5 8AF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-0780","authenticated-orcid":false,"given":"Paresh A","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]},{"name":"Imperial College Healthcare NHS Trust, Department of Neurology, Charing Cross Hospital , London W6 8RF, London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5678-5124","authenticated-orcid":false,"given":"Mazdak","family":"Ghajari","sequence":"additional","affiliation":[{"name":"Imperial College London, Dyson School of Design Engineering , 1st Floor, Royal College of Science, South Kensington Campus, London SW7 2DB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Carswell","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College Healthcare NHS Trust, Department of Neurology, Charing Cross Hospital , London W6 8RF, London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Sharp","sequence":"additional","affiliation":[{"name":"Imperial College London, Department of Brain Sciences. Burlington Danes , the Hammersmith Campus, London, W12 0NN ,","place":["UK"]},{"name":"Imperial College London, the UK Dementia Research Institute Care Research and Technology Centre , 9th Floor, Sir Michael Uren Hub, London, W12 0BZ ,","place":["UK"]},{"name":"Imperial College Healthcare NHS Trust, Department of Neurology, Charing Cross Hospital , London W6 8RF, London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,15]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag312\/71082901\/awag312.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag312\/71082901\/awag312.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:54:08Z","timestamp":1789455248000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag312\/8795203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag312","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"article-number":"awag312"}}