{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:37:33Z","timestamp":1792132653972,"version":"4.4.0"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deep and periventricular white matter hyperintensities (dWMH\/pvWMH) are bright appearing white matter tissue lesions in T2-weighted fluid attenuated inversion recovery magnetic resonance images and are frequent observations in the aging human brain. While early stages of these white matter lesions are only weakly associated with cognitive impairment, their progressive growth is a strong indicator for long-term functional decline. DWMHs are typically associated with vascular degeneration in diffuse white matter locations; for pvWMHs, however, no unifying theory exists to explain their consistent onset around the horns of the lateral ventricles. We use patient imaging data to create anatomically accurate finite element models of the lateral ventricles, white and gray matter, and cerebrospinal fluid, as well as to reconstruct their WMH volumes. We simulated the mechanical loading of the ependymal cells forming the primary brain-fluid interface, the ventricular wall, and its surrounding tissues at peak ventricular pressure during the hemodynamic cycle. We observe that both the maximum principal tissue strain and the largest ependymal cell stretch consistently localize in the anterior and posterior horns. Our simulations show that ependymal cells experience a loading state that causes the ventricular wall to be <jats:italic>stretched thin<\/jats:italic>. Moreover, we show that maximum wall loading coincides with the pvWMH locations observed in our patient scans. These results warrant further analysis of white matter pathology in the periventricular zone that includes a mechanics-driven deterioration model for the ventricular wall.<\/jats:p>","DOI":"10.1038\/s41598-021-00610-1","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T11:02:38Z","timestamp":1636455758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Peak ependymal cell stretch overlaps with the onset locations of periventricular white matter lesions"],"prefix":"10.1038","volume":"11","author":[{"given":"Valery L.","family":"Visser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Rusinek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Weickenmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"issue":"2","key":"610_CR1","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2214\/ajr.149.2.351","volume":"149","author":"F Franz","year":"1987","unstructured":"Franz, F., Chawluk, J. B., Alavi, A., Hurtig, H. I. & Zimmerman, R. A. Mr signal abnormalities at 1.5 t in alzheimer\u2018s dementia and normal aging. Am. J. Roentgenol. 149(2), 351\u2013356 (1987).","journal-title":"Am. J. Roentgenol."},{"issue":"8","key":"610_CR2","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","volume":"12","author":"JM Wardlaw","year":"2013","unstructured":"Wardlaw, J. M. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12(8), 822\u2013838 (2013).","journal-title":"Lancet Neurol."},{"issue":"6","key":"610_CR3","doi-asserted-by":"publisher","first-page":"e001140","DOI":"10.1161\/JAHA.114.001140","volume":"4","author":"JM Wardlaw","year":"2015","unstructured":"Wardlaw, J. M., Vald\u00e9s\u00a0Hern\u00e1ndez, M. C. & Mu\u00f1oz-Maniega, S. What are white matter hyperintensities made of? relevance to vascular cognitive impairment. J. Am. Heart Assoc. 4(6), e001140 (2015).","journal-title":"J. Am. Heart Assoc."},{"issue":"1","key":"610_CR4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/jnnp.70.1.9","volume":"70","author":"FE De Leeuw","year":"2001","unstructured":"De Leeuw, F. E. et al. Prevalence of cerebral white matter lesions in elderly people: A population based magnetic resonance imaging study. The rotterdam scan study. J. Neurol. Neurosurg. Psychiatry 70(1), 9\u201314 (2001).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"610_CR5","doi-asserted-by":"crossref","unstructured":"J Alber, S Alladi, H-J Bae, DA Barton, LA Beckett, JM Bell, SE Berman, GJ Biessels, SE Black, I Bos, et al. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (vcid): Knowledge gaps and opportunities. Alzheimer\u2018s Dementia Transl. Res. Clin. Interv. 5, 107\u2013117 (2019).","DOI":"10.1016\/j.trci.2019.02.001"},{"issue":"3","key":"610_CR6","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/01.STR.0000058480.77236.B3","volume":"34","author":"JM Wardlaw","year":"2003","unstructured":"Wardlaw, J. M., Sandercock, P. A. G., Dennis, M. S. & Starr, J. Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia?. Stroke 34(3), 806\u2013812 (2003).","journal-title":"Stroke"},{"issue":"4","key":"610_CR7","doi-asserted-by":"publisher","first-page":"3774","DOI":"10.1016\/j.neuroimage.2011.11.032","volume":"59","author":"P Schmidt","year":"2012","unstructured":"Schmidt, P. et al. An automated tool for detection of flair-hyperintense white-matter lesions in multiple sclerosis. Neuroimage 59(4), 3774\u20133783 (2012).","journal-title":"Neuroimage"},{"issue":"10","key":"610_CR8","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1002\/hbm.20951","volume":"31","author":"K Bendfeldt","year":"2010","unstructured":"Bendfeldt, K. et al. Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional grey matter volume reductions in relapsing-remitting multiple sclerosis. Hum. Brain Map. 31(10), 1542\u20131555 (2010).","journal-title":"Hum. Brain Map."},{"issue":"7","key":"610_CR9","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1177\/0333102417728751","volume":"38","author":"CY Cheng","year":"2018","unstructured":"Cheng, C. Y. et al. White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates. Cephalalgia 38(7), 1225\u20131236 (2018).","journal-title":"Cephalalgia"},{"key":"610_CR10","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1161\/STROKEAHA.107.498535","volume":"39","author":"AA Gouw","year":"2008","unstructured":"Gouw, A. A. et al. Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period the leukoaraiosis and disability study. Stroke 39, 1414\u20131420 (2008).","journal-title":"Stroke"},{"issue":"4","key":"610_CR11","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1161\/01.STR.27.4.645","volume":"27","author":"H Fukuda","year":"1996","unstructured":"Fukuda, H. & Kitani, M. Cigarette smoking is correlated with the periventricular hyperintensity grade on brain magnetic resonance imaging. Stroke 27(4), 645\u2013649 (1996).","journal-title":"Stroke"},{"issue":"1","key":"610_CR12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s10072-011-0617-1","volume":"33","author":"SH Kim","year":"2012","unstructured":"Kim, S. H. et al. Age-dependent association between cigarette smoking on white matter hyperintensities. Neurol. Sci. 33(1), 45\u201351 (2012).","journal-title":"Neurol. Sci."},{"key":"610_CR13","first-page":"1","volume":"4","author":"HSN Al-Anbari","year":"2020","unstructured":"Al-Anbari, H. S. N. et al. High blood lead levels: An increased risk for development of brain hyperintensities among type 2 diabetes mellitus patients. Biol. Trace Element Res. 4, 1\u20139 (2020).","journal-title":"Biol. Trace Element Res."},{"issue":"20","key":"610_CR14","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1212\/WNL.0000000000001582","volume":"84","author":"KA Nunley","year":"2015","unstructured":"Nunley, K. A. et al. White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes. Neurology 84(20), 2062\u20132069 (2015).","journal-title":"Neurology"},{"issue":"1","key":"610_CR15","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1001\/jamaneurol.2017.2853","volume":"75","author":"W-J Lee","year":"2018","unstructured":"Lee, W.-J. et al. Association of cardiac hemodynamic factors with severity of white matter hyperintensities in chronic valvular heart disease. JAMA Neurol. 75(1), 80\u201387, 01 (2018).","journal-title":"JAMA Neurol."},{"issue":"1","key":"610_CR16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1161\/01.STR.0000150668.58689.f2","volume":"36","author":"C DeCarli","year":"2005","unstructured":"DeCarli, C., Fletcher, E., Ramey, V., Harvey, D. & Jagust, W. J. Anatomical mapping of white matter hyperintensities (wmh). Stroke 36(1), 50\u201355 (2005).","journal-title":"Stroke"},{"issue":"4","key":"610_CR17","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1093\/brain\/aww009","volume":"139","author":"C Lambert","year":"2016","unstructured":"Lambert, C. et al. Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease. Brain 139(4), 1136\u20131151 (2016).","journal-title":"Brain"},{"issue":"6","key":"610_CR18","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1161\/01.STR.0000221308.94473.14","volume":"37","author":"MS Fernando","year":"2006","unstructured":"Fernando, M. S. et al. White matter lesions in an unselected cohort of the elderly: Molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 37(6), 1391\u20131398 (2006).","journal-title":"Stroke"},{"issue":"4","key":"610_CR19","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1093\/brain\/aww008","volume":"139","author":"M Habes","year":"2016","unstructured":"Habes, M. et al. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain 139(4), 1164\u20131179 (2016).","journal-title":"Brain"},{"issue":"7","key":"610_CR20","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1161\/01.STR.26.7.1171","volume":"26","author":"A Ylikoski","year":"1995","unstructured":"Ylikoski, A. et al. White matter hyperintensities on mri in the neurologically nondiseased elderly: Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. Stroke 26(7), 1171\u20131177 (1995).","journal-title":"Stroke"},{"issue":"12","key":"610_CR21","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1093\/brain\/awh567","volume":"128","author":"F Fazekas","year":"2005","unstructured":"Fazekas, F. et al. Mti of white matter hyperintensities. Brain 128(12), 2926\u20132932 (2005).","journal-title":"Brain"},{"issue":"4","key":"610_CR22","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/hbm.20586","volume":"30","author":"W Wen","year":"2009","unstructured":"Wen, W., Sachdev, P. S., Li, J. J., Chen, X. & Anstey, K. J. White matter hyperintensities in the forties: Their prevalence and topography in an epidemiological sample aged 44\u201348. Hum. Brain Map. 30(4), 1155\u20131167 (2009).","journal-title":"Hum. Brain Map."},{"issue":"1","key":"610_CR23","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.neuroimage.2003.12.027","volume":"22","author":"W Wen","year":"2004","unstructured":"Wen, W. & Sachdev, P. The topography of white matter hyperintensities on brain mri in healthy 60-to 64-year-old individuals. Neuroimage 22(1), 144\u2013154 (2004).","journal-title":"Neuroimage"},{"issue":"4\u20135","key":"610_CR24","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1016\/S0010-9452(08)70879-7","volume":"39","author":"H S\u00f6derlund","year":"2003","unstructured":"S\u00f6derlund, H., Nyberg, L., Adolfsson, R., Nilsson, L.-G. & Launer, L. J. High prevalence of white matter hyperintensities in normal aging: Relation to blood pressure and cognition. Cortex 39(4\u20135), 1093\u20131105 (2003).","journal-title":"Cortex"},{"issue":"3","key":"610_CR25","doi-asserted-by":"publisher","first-page":"667","DOI":"10.2214\/AJR.18.20888","volume":"213","author":"M-L Wang","year":"2019","unstructured":"Wang, M.-L., Zhang, X.-X., Meng-Meng, Yu., Li, W.-B. & Li, Y.-H. Prevalence of white matter hyperintensity in young clinical patients. Am. J. Roentgenol. 213(3), 667\u2013671 (2019).","journal-title":"Am. J. Roentgenol."},{"issue":"3","key":"610_CR26","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1002\/ana.10294","volume":"52","author":"JC De Groot","year":"2002","unstructured":"De Groot, J. C. et al. Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann. Neurol. 52(3), 335\u2013341 (2002).","journal-title":"Ann. Neurol."},{"issue":"4","key":"610_CR27","first-page":"610","volume":"58","author":"R Schmidt","year":"2005","unstructured":"Schmidt, R. et al. White matter lesion progression, brain atrophy, and cognitive decline: The austrian stroke prevention study. Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc. 58(4), 610\u2013616 (2005).","journal-title":"Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"issue":"1","key":"610_CR28","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/jgs.15149","volume":"66","author":"MS Dhamoon","year":"2018","unstructured":"Dhamoon, M. S. et al. Periventricular white matter hyperintensities and functional decline. J. Am. Geriatrics Soc. 66(1), 113\u2013119 (2018).","journal-title":"J. Am. Geriatrics Soc."},{"issue":"9","key":"610_CR29","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1093\/brain\/awt184","volume":"136","author":"M Duering","year":"2013","unstructured":"Duering, M. et al. Incident lacunes preferentially localize to the edge of white matter hyperintensities: Insights into the pathophysiology of cerebral small vessel disease. Brain 136(9), 2717\u20132726 (2013).","journal-title":"Brain"},{"key":"610_CR30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nrneurol.2015.10","volume":"11","author":"ND Prins","year":"2015","unstructured":"Prins, N. D. & Scheltens, P. White matter hyperintensities, cognitive impairment and dementia: An update. Nat. Rev. Neurol. 11, 157\u2013165 (2015).","journal-title":"Nat. Rev. Neurol."},{"issue":"4","key":"610_CR31","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.biopsych.2008.03.024","volume":"64","author":"KW Kim","year":"2008","unstructured":"Kim, K. W., MacFall, J. R. & Payne, M. E. Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol. Psychiatry 64(4), 273\u2013280 (2008).","journal-title":"Biol. Psychiatry"},{"key":"610_CR32","doi-asserted-by":"crossref","unstructured":"Jim\u00e9nez, A. J., Dom\u00ednguez-Pinos, M. D., Guerra, M. M., Fern\u00e1ndez-Llebrez, P. & P\u00e9rez-F\u00edgares, J. Structure and function of the ependymal barrier and diseases associated with ependyma disruption (2014).","DOI":"10.4161\/tisb.28426"},{"issue":"9","key":"610_CR33","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1097\/NEN.0b013e3182a2d5fe","volume":"72","author":"C Oliver","year":"2013","unstructured":"Oliver, C. et al. Disruption of cdh2\/n-cadherin-based adherens junctions leads to apoptosis of ependymal cells and denudation of brain ventricular walls. J. Neuropathol. Exp. Neurol. 72(9), 846\u2013860 (2013).","journal-title":"J. Neuropathol. Exp. Neurol."},{"issue":"2","key":"610_CR34","doi-asserted-by":"publisher","first-page":"263","DOI":"10.4103\/1673-5374.265551","volume":"15","author":"D Hatrock","year":"2020","unstructured":"Hatrock, D., Caporicci-Dinucci, N. & Stratton, J. A. Ependymal cells and multiple sclerosis: Proposing a relationship. Neural Regen. Res. 15(2), 263 (2020).","journal-title":"Neural Regen. Res."},{"issue":"9","key":"610_CR35","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1212\/WNL.43.9.1683","volume":"43","author":"F Fazekas","year":"1993","unstructured":"Fazekas, F., Kleinert, R. & Offenbacher, H. Pathologic correlates of incidental mri white matter signal hyperintensities. Neurology 43(9), 1683\u20131683 (1993).","journal-title":"Neurology"},{"issue":"3","key":"610_CR36","first-page":"S48","volume":"40","author":"Sandra Black","year":"2009","unstructured":"Black, Sandra, Gao, FuQiang & Bilbao, Juan. Understanding white matter disease. Stroke 40(3), S48\u2013S52 (2009).","journal-title":"Stroke"},{"issue":"4","key":"610_CR37","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/j.1365-2990.2007.00828.x","volume":"33","author":"JE Simpson","year":"2007","unstructured":"Simpson, J. E. et al. White matter lesions in an unselected cohort of the elderly: Astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol. Appl. Neurobiol. 33(4), 410\u2013419 (2007).","journal-title":"Neuropathol. Appl. Neurobiol."},{"issue":"4","key":"610_CR38","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00401-012-0992-6","volume":"124","author":"R Roales-Buj\u00e1n","year":"2012","unstructured":"Roales-Buj\u00e1n, R. et al. Astrocytes acquire morphological and functional characteristics of ependymal cells following disruption of ependyma in hydrocephalus. Acta Neuropathologica 124(4), 531\u2013546 (2012).","journal-title":"Acta Neuropathologica"},{"issue":"3","key":"610_CR39","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1212\/01.wnl.0000251302.55202.73","volume":"68","author":"P Sachdev","year":"2007","unstructured":"Sachdev, P., Wen, W., Chen, X. & Brodaty, H. Progression of white matter hyperintensities in elderly individuals over 3 years. Neurology 68(3), 214\u2013222 (2007).","journal-title":"Neurology"},{"issue":"3","key":"610_CR40","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/cne.20798","volume":"494","author":"A Qui\u00f1ones-Hinojosa","year":"2006","unstructured":"Qui\u00f1ones-Hinojosa, A. et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: A niche of neural stem cells. J. Comp. Neurol. 494(3), 415\u2013434 (2006).","journal-title":"J. Comp. Neurol."},{"issue":"3","key":"610_CR41","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S0301-0082(00)00035-6","volume":"63","author":"JL Venero","year":"2001","unstructured":"Venero, J. L., Vizuete, M. L., Machado, A. & Cano, J. Aquaporins in the central nervous system. Prog. Neurobiol. 63(3), 321\u2013336 (2001).","journal-title":"Prog. Neurobiol."},{"issue":"12","key":"610_CR42","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1038\/sj.jcbfm.9600306","volume":"26","author":"O Bloch","year":"2006","unstructured":"Bloch, O., Auguste, K. I., Manley, G. T. & Verkman, A. S. Accelerated progression of kaolin-induced hydrocephalus in aquaporin-4-deficient mice. J. Cereb. Blood Flow Metab. 26(12), 1527\u20131537 (2006).","journal-title":"J. Cereb. Blood Flow Metab."},{"issue":"5","key":"610_CR43","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1001\/archneur.1970.00480230015002","volume":"22","author":"TH Milhorat","year":"1970","unstructured":"Milhorat, T. H., Clark, R. G., Hammock, M. K. & McGrath, P. P. Structural, ultrastructural, and permeability changes in the ependyma and surrounding brain favoring equilibration in progressive hydrocephalus. Arch. Neurol. 22(5), 397\u2013407 (1970).","journal-title":"Arch. Neurol."},{"issue":"6","key":"610_CR44","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1227\/00006123-198712000-00019","volume":"21","author":"T Nagashima","year":"1987","unstructured":"Nagashima, T., Tamaki, N., Matsumoto, S., Horwitz, B. & Seguchi, Y. Biomechanics of hydrocephalus: A new theoretical model. Neurosurgery 21(6), 898\u2013904 (1987).","journal-title":"Neurosurgery"},{"issue":"1","key":"610_CR45","first-page":"107","volume":"45","author":"A Pena","year":"1999","unstructured":"Pena, A., Bolton, M. D., Whitehouse, H. & Pickard, J. D. Effects of brain ventricular shape on periventricular biomechanics: A finite-element analysis. Neurosurgery 45(1), 107\u2013118 (1999).","journal-title":"Neurosurgery"},{"issue":"8","key":"610_CR46","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.jbiomech.2003.11.027","volume":"37","author":"Z Taylor","year":"2004","unstructured":"Taylor, Z. & Miller, K. Reassessment of brain elasticity for analysis of biomechanisms of hydrocephalus. J. Biomech. 37(8), 1263\u20131269 (2004).","journal-title":"J. Biomech."},{"issue":"1","key":"610_CR47","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3171\/2010.12.JNS10926","volume":"115","author":"RD Penn","year":"2011","unstructured":"Penn, R. D., Basati, S., Sweetman, B., Guo, X. & Linninger, A. Ventricle wall movements and cerebrospinal fluid flow in hydrocephalus. J. Neurosurg. 115(1), 159\u2013164 (2011).","journal-title":"J. Neurosurg."},{"key":"610_CR48","doi-asserted-by":"crossref","unstructured":"Cheng, S. & Bilston, L. E. Computational model of the cerebral ventricles in hydrocephalus. J. Biomech. Eng. 132(5), (2010).","DOI":"10.1115\/1.4001025"},{"issue":"8","key":"610_CR49","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1089\/neu.2019.6634","volume":"37","author":"Z Zhou","year":"2020","unstructured":"Zhou, Z., Li, X. & Kleiven, S. Biomechanics of periventricular injury. J. Neurotrauma 37(8), 1074\u20131090 (2020).","journal-title":"J. Neurotrauma"},{"key":"610_CR50","first-page":"661","volume":"24","author":"B Reisberg","year":"1988","unstructured":"Reisberg, B. Global deterioration scale (gds). Psychopharmacol. Bull. 24, 661\u2013663 (1988).","journal-title":"Psychopharmacol. Bull."},{"key":"610_CR51","doi-asserted-by":"crossref","unstructured":"Morriss, R. et al. THREAD\u00a0Study Group. Inter-rater reliability of the hamilton depression rating scale as a diagnostic and outcome measure of depression in primary care. J. Aff. Disorders 111(2\u20133), 204\u2013213 (2008).","DOI":"10.1016\/j.jad.2008.02.013"},{"issue":"9","key":"610_CR52","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/j.1532-5415.1992.tb01992.x","volume":"40","author":"TN Tombaugh","year":"1992","unstructured":"Tombaugh, T. N. & McIntyre, N. J. The mini-mental state examination: A comprehensive review. J. Am. Geriatrics Soc. 40(9), 922\u2013935 (1992).","journal-title":"J. Am. Geriatrics Soc."},{"key":"610_CR53","unstructured":"Penny, W. D., Friston, K. J., Ashburner, J. T., Kiebel, S. J. & Nichols, T. E. Statistical Parametric Mapping: The Analysis of Functional Brain Images (Elsevier, 2011)."},{"issue":"1","key":"610_CR54","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1148\/radiol.2017161216","volume":"285","author":"N Miskin","year":"2017","unstructured":"Miskin, N. et al. Diagnosis of normal-pressure hydrocephalus: Use of traditional measures in the era of volumetric MR imaging. Radiology 285(1), 197\u2013205 (2017).","journal-title":"Radiology"},{"issue":"1","key":"610_CR55","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1109\/42.668698","volume":"7","author":"JG Sled","year":"1998","unstructured":"Sled, J. G., Zijdenbos, A. P. & Evans, A. C. A nonparametric method for automatic correction of intensity nonuniformity in mri data. IEEE Trans. Med. Imaging 7(1), 87\u201397 (1998).","journal-title":"IEEE Trans. Med. Imaging"},{"issue":"5","key":"610_CR56","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/cnm.2618","volume":"30","author":"J Weickenmeier","year":"2014","unstructured":"Weickenmeier, J., Itskov, M., Mazza, E. & Jabareen, M. A physically motivated constitutive model for 3d numerical simulation of skeletal muscles. Int. J. Numer. Methods Biomed. Eng. 30(5), 545\u2013562 (2014).","journal-title":"Int. J. Numer. Methods Biomed. Eng."},{"key":"610_CR57","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.cma.2016.08.011","volume":"314","author":"J Weickenmeier","year":"2017","unstructured":"Weickenmeier, J., Butler, C. A. M., Young, P. G., Goriely, A. & Kuhl, E. The mechanics of decompressive craniectomy: Personalized simulations. Comput. Methods Appl. Mech. Eng. 314, 180\u2013195 (2017).","journal-title":"Comput. Methods Appl. Mech. Eng."},{"issue":"15","key":"610_CR58","doi-asserted-by":"publisher","first-page":"158101","DOI":"10.1103\/PhysRevLett.121.158101","volume":"121","author":"J Weickenmeier","year":"2018","unstructured":"Weickenmeier, J., Kuhl, E. & Goriely, A. Multiphysics of prionlike diseases: Progression and atrophy. Phys. Rev. Lett. 121(15), 158101 (2018).","journal-title":"Phys. Rev. Lett."},{"key":"610_CR59","doi-asserted-by":"crossref","unstructured":"Abderezaei, J. et al. Amplified flow imaging (aflow): A novel mri-based tool to unravel the coupled dynamics between the human brain and cerebrovasculature. IEEE Trans. Med. Imaging 39 (2020).","DOI":"10.1109\/TMI.2020.3012932"},{"issue":"6","key":"610_CR60","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1002\/mrm.26142","volume":"75","author":"SJ Holdsworth","year":"2016","unstructured":"Holdsworth, S. J., Rahimi, M. S., Ni, W. W., Zaharchuk, G. & Moseley, M. E. Amplified magnetic resonance imaging (amri). Magn. Reson. Med. 75(6), 2245\u20132254 (2016).","journal-title":"Magn. Reson. Med."},{"issue":"4","key":"610_CR61","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1109\/TBME.2005.844021","volume":"52","author":"AA Linninger","year":"2005","unstructured":"Linninger, A. A. et al. Pulsatile cerebrospinal fluid dynamics in the human brain. IEEE Trans. Biomed. Eng. 52(4), 557\u2013565 (2005).","journal-title":"IEEE Trans. Biomed. Eng."},{"issue":"4","key":"610_CR62","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1002\/jmri.20679","volume":"24","author":"DC Zhu","year":"2006","unstructured":"Zhu, D. C., Xenos, M., Linninger, A. A. & Penn, R. D. Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic brains. J. Magn. Reson. Imaging 24(4), 756\u2013770 (2006).","journal-title":"J. Magn. Reson. Imaging"},{"key":"610_CR63","doi-asserted-by":"crossref","unstructured":"Butler, W. E., Agarwalla, P. K. & Codd, P. CSF in the ventricles of the brain behaves as a relay medium for arteriovenous pulse wave phase coupling. PLoS ONE 12 (2017).","DOI":"10.1371\/journal.pone.0181025"},{"issue":"8","key":"610_CR64","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1118\/1.3157109","volume":"36","author":"X Zhong","year":"2009","unstructured":"Zhong, X. et al. Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI. Med. Phys. 36(8), 3413\u20133419 (2009).","journal-title":"Med. Phys."},{"key":"610_CR65","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.actbio.2016.07.040","volume":"42","author":"J Weickenmeier","year":"2016","unstructured":"Weickenmeier, J. et al. Brain stiffness increases with myelin content. Acta Biomaterialia 42, 265\u2013272 (2016).","journal-title":"Acta Biomaterialia"},{"issue":"5","key":"610_CR66","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/s00466-019-01707-1","volume":"64","author":"SJ Connolly","year":"2019","unstructured":"Connolly, S. J., Mackenzie, D. & Gorash, Y. Isotropic hyperelasticity in principal stretches: Explicit elasticity tensors and numerical implementation. Comput. Mech. 64(5), 1273\u20131288 (2019).","journal-title":"Comput. Mech."},{"issue":"2","key":"610_CR67","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jmbbm.2009.09.001","volume":"3","author":"JAW van Dommelen","year":"2010","unstructured":"van Dommelen, J. A. W., van der Sande, T. P. J., Hrapko, M. & Peters, G. W. M. Mechanical properties of brain tissue by indentation: Interregional variation. J. Mech. Behav. Biomed. Mater. 3(2), 158\u2013166 (2010).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"610_CR68","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.jmbbm.2015.02.024","volume":"46","author":"S Budday","year":"2015","unstructured":"Budday, S. et al. Mechanical properties of gray and white matter brain tissue by indentation. J. Mech. Behav. Biomed. Mater. 46, 318\u2013330 (2015).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"issue":"6","key":"610_CR69","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/j.jbiomech.2011.01.019","volume":"44","author":"T Kaster","year":"2011","unstructured":"Kaster, T., Sack, I. & Samani, A. Measurement of the hyperelastic properties of ex vivo brain tissue slices. J. Biomech. 44(6), 1158\u20131163 (2011).","journal-title":"J. Biomech."},{"key":"610_CR70","unstructured":"Chen, J. et al. Bilateral distance partition of periventricular and deep white matter hyperintensities: Performance of the method in the aging brain. Acad. Radiol. 29 (2020)."},{"issue":"3","key":"610_CR71","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.bbadis.2011.08.007","volume":"1822","author":"N Raz","year":"2012","unstructured":"Raz, N., Yang, Y., Dahle, C. L. & Land, S. Volume of white matter hyperintensities in healthy adults: Contribution of age, vascular risk factors, and inflammation-related genetic variants. Biochimica et Biophysica Acta - Molecular Basis of Disease 1822(3), 361\u2013369 (2012).","journal-title":"Biochimica et Biophysica Acta - Molecular Basis of Disease"},{"key":"610_CR72","doi-asserted-by":"publisher","first-page":"111575","DOI":"10.1016\/j.mad.2021.111575","volume":"200","author":"Y Blinkouskaya","year":"2021","unstructured":"Blinkouskaya, Y. et al. Brain aging mechanisms with mechanical manifestations. Mech. Ageing Dev. 200, 111575 (2021).","journal-title":"Mech. Ageing Dev"},{"key":"610_CR73","doi-asserted-by":"publisher","DOI":"10.3389\/fmech.2021.705653","author":"Y Blinkouskaya","year":"2021","unstructured":"Blinkouskaya, Y. & Johannes, W. Brain shape changes associated with cerebral atrophy in healthy aging and alzheimer\u2019s disease. Front. Mech. Eng. https:\/\/doi.org\/10.3389\/fmech.2021.705653 (2021).","journal-title":"Front. Mech. Eng."},{"issue":"2","key":"610_CR74","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.ncl.2008.02.003","volume":"26","author":"L Rangel-Castillo","year":"2008","unstructured":"Rangel-Castillo, L., Gopinath, S. & Robertson, C. S. Management of intracranial hypertension. Neurol. Clin. 26(2), 521\u2013541 (2008).","journal-title":"Neurol. Clin."},{"key":"610_CR75","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1469-8749.1968.tb04841.x","volume":"10","author":"KENNETH SHULMAN","year":"1968","unstructured":"SHULMAN, K. E. N. N. E. T. H. & MARMAROU, A. N. T. H. O. N. Y. Analysis of intracranial pressure in hydrocephalus. Dev. Med. Child Neurol. 10, 11\u201316 (1968).","journal-title":"Dev. Med. Child Neurol."},{"issue":"6","key":"610_CR76","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s00285-009-0250-2","volume":"59","author":"AA Linninger","year":"2009","unstructured":"Linninger, A. A. et al. A mathematical model of blood, cerebrospinal fluid and brain dynamics. J. Math. Biol. 59(6), 729\u2013759 (2009).","journal-title":"J. Math. Biol."},{"key":"610_CR77","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.actbio.2016.10.036","volume":"48","author":"S Budday","year":"2017","unstructured":"Budday, S. et al. Mechanical characterization of human brain tissue. Acta Biomaterialia 48, 319\u2013340 (2017).","journal-title":"Acta Biomaterialia"},{"key":"610_CR78","doi-asserted-by":"crossref","unstructured":"Hooper, R. Hydrocephalus and obstruction of the superior vena cava in infancy. Pediatrics 28(5), (1961).","DOI":"10.1542\/peds.28.5.792"},{"key":"610_CR79","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1111\/j.1469-8749.1968.tb04841.x","volume":"10","author":"K Shulman","year":"2008","unstructured":"Shulman, K. & Marmarou, A. Analysis of Intracranial Pressure in Hydrocephalus. Dev. Med. Child Neurol. 10, 11\u201316 (2008).","journal-title":"Dev. Med. Child Neurol."},{"issue":"12","key":"610_CR80","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/S1474-4422(12)70241-7","volume":"11","author":"P Maillard","year":"2012","unstructured":"Maillard, P. et al. Effects of systolic blood pressure on white-matter integrity in young adults in the framingham heart study: A cross-sectional study. Lancet Neurol. 11(12), 1039\u20131047 (2012).","journal-title":"Lancet Neurol."},{"issue":"2","key":"610_CR81","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/acel.12184","volume":"13","author":"BA Shook","year":"2014","unstructured":"Shook, B. A. et al. Ventriculomegaly associated with ependymal gliosis and declines in barrier integrity in the aging human and mouse brain. Aging Cell 13(2), 340\u2013350 (2014).","journal-title":"Aging Cell"},{"key":"610_CR82","doi-asserted-by":"publisher","first-page":"445","DOI":"10.3389\/fnagi.2017.00445","volume":"9","author":"KL Todd","year":"2018","unstructured":"Todd, K. L. et al. Ventricular and periventricular anomalies in the aging and cognitively impaired brain. Front. Aging Neurosci. 9, 445 (2018).","journal-title":"Front. Aging Neurosci."},{"issue":"5","key":"610_CR83","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1007\/s00466-019-01717-z","volume":"64","author":"L No\u00ebl","year":"2019","unstructured":"No\u00ebl, L. & Kuhl, E. Modeling neurodegeneration in chronic traumatic encephalopathy using gradient damage models. Comput. Mech. 64(5), 1375\u20131387 (2019).","journal-title":"Comput. Mech."},{"issue":"42","key":"610_CR84","doi-asserted-by":"publisher","first-page":"21213","DOI":"10.1073\/pnas.1902376116","volume":"116","author":"J Wang","year":"2019","unstructured":"Wang, J. et al. Gray matter age prediction as a biomarker for risk of dementia. Proc. Natl. Acad. Sci. 116(42), 21213\u201321218 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"610_CR85","unstructured":"Holland, D. et al. Alzheimer\u2019s Disease\u00a0Neuroimaging Initiative. Subregional neuroanatomical change as a biomarker for alzheimer\u2018disease. Proc. Natl. Acad. Sci. 106(49), 20954\u201320959 (2009)."},{"issue":"50","key":"610_CR86","doi-asserted-by":"publisher","first-page":"25243","DOI":"10.1073\/pnas.1907730116","volume":"116","author":"J Chiappelli","year":"2019","unstructured":"Chiappelli, J. et al. Cardiovascular risks impact human brain n-acetylaspartate in regionally specific patterns. Proc. Natl. Acad. Sci. 116(50), 25243\u201325249 (2019).","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"11","key":"610_CR87","doi-asserted-by":"publisher","first-page":"e038971","DOI":"10.1136\/bmjopen-2020-038971","volume":"10","author":"A Gupta","year":"2020","unstructured":"Gupta, A. et al. Treatment of hypertension reduces cognitive decline in older adults: A systematic review and meta-analysis. BMJ Open 10(11), e038971 (2020).","journal-title":"BMJ Open"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00610-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00610-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00610-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T17:13:34Z","timestamp":1670087614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00610-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,9]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["610"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-00610-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,9]]},"assertion":[{"value":"18 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"21956"}}