{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T17:39:18Z","timestamp":1782668358481,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013459","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","award":["88887.001789\/2024-00"],"award-info":[{"award-number":["88887.001789\/2024-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","award":["E26\/203.082\/2023"],"award-info":[{"award-number":["E26\/203.082\/2023"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","award":["E-26\/200.364\/2023"],"award-info":[{"award-number":["E-26\/200.364\/2023"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","award":["304347\/2023-0"],"award-info":[{"award-number":["304347\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["24\/016\/A"],"award-info":[{"award-number":["24\/016\/A"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"Understanding cerebral circulation is crucial for early diagnosis and patient-oriented therapies for brain conditions. However, blood flow simulations at the organ scale have been limited. This work introduces a framework for modeling extensive vascular networks in the human cerebral cortex and conducting pulsatile blood flow simulations. Using a patient-specific cerebral geometry, we applied a parallelized adaptive constrained constructive optimization algorithm to create a comprehensive pial vascular network in the left hemisphere, starting from the main cerebral arteries. The resulting network included over 75\u00a0000, 103\u00a0000, and 55\u00a0000 vessels for the anterior, middle, and posterior territories, respectively. Pial vessel diameters featured a median [interquartile range, IQR] value of 62.8<\/mml:mn>[<\/mml:mo>49.3<\/mml:mn>,<\/mml:mo>89.3<\/mml:mn>]<\/mml:mo>\u03bc<\/mml:mi>m<\/mml:mi><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>. We integrated the pial vascular network model with the Anatomically-Detailed Arterial Network (ADAN) model to conduct one-dimensional (1D) blood flow simulations under normotensive and hypertensive conditions. Viscoelastic dissipation proved to be a key ingredient in the characterization of the hemodynamic environments in the pial circulation. In the normotensive scenario, mean blood pressure in the pial vessels resulted in a median [IQR] value of 56.7<\/mml:mn>[<\/mml:mo>49.8<\/mml:mn>,<\/mml:mo>63.5<\/mml:mn>]<\/mml:mo>m<\/mml:mi>m<\/mml:mi>H<\/mml:mi>g<\/mml:mi><\/mml:mrow><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>. The flow pulsatility index and its corresponding damping factor were effective descriptors of the hypertensive state. The median [IQR] pulsatility index in the normotensive state was 0.39<\/mml:mn>[<\/mml:mo>0.38<\/mml:mn>,<\/mml:mo>0.40<\/mml:mn>]<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>, and in hypertension it increased up to 0.84<\/mml:mn>[<\/mml:mo>0.83<\/mml:mn>,<\/mml:mo>0.85<\/mml:mn>]<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>, while its corresponding damping factor in the normotensive state was 2.07<\/mml:mn>[<\/mml:mo>1.78<\/mml:mn>,<\/mml:mo>2.48<\/mml:mn>]<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>, and in the hypertensive state it was reduced to 1.20<\/mml:mn>[<\/mml:mo>1.16<\/mml:mn>,<\/mml:mo>1.39<\/mml:mn>]<\/mml:mo><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula>. We observed large regional pressure gradients in terminal vessels, with pressure levels ranging from 50<\/mml:mn>m<\/mml:mi>m<\/mml:mi>H<\/mml:mi>g<\/mml:mi><\/mml:mrow><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula> in normotension to 70<\/mml:mn>m<\/mml:mi>m<\/mml:mi>H<\/mml:mi>g<\/mml:mi><\/mml:mrow><\/mml:mrow><\/mml:math><\/jats:alternatives><\/jats:inline-formula> in hypertension. Additionally, the pulsatility index at terminal vessels increased with distance from the Circle of Willis in the hypertensive case, contrasting with the decreasing pattern seen in normotension. This approach provides a unique characterization of hemodynamics in the pial vascular network of the human cerebral cortex, paving the way for research into microcirculatory environments, the link between hemodynamics and neural function, and their roles in conditions like stroke and dementia.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013459","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T18:09:30Z","timestamp":1757354970000},"page":"e1013459","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Blood flow in the human cerebral cortex: Large-scale pial vascularization and 1D simulation"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-2271","authenticated-orcid":true,"given":"Eduardo G.","family":"Zilves","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas O.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-992X","authenticated-orcid":true,"given":"Gonzalo D. M.","family":"Talou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Hachinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7478-1098","authenticated-orcid":true,"given":"J. David","family":"Spence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-619X","authenticated-orcid":true,"given":"Pablo J.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"10","key":"pcbi.1013459.ref001","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional,, National Burden of Stroke and Its risk factors 1990 \u20132019: a systematic analysis for the global burden of disease study 2019","volume":"20","author":"VL Feigin","year":"2021","journal-title":"The Lancet Neurology"},{"key":"pcbi.1013459.ref002","first-page":"14","article-title":"Global, regional,, national burden of Alzheimer\u2019s disease and other dementias 1990 -2019","author":"X Li","year":"2022","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"9558","key":"pcbi.1013459.ref003","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(07)60151-2","article-title":"Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison","volume":"369","author":"JA Chalela","year":"2007","journal-title":"Lancet"},{"issue":"1","key":"pcbi.1013459.ref004","doi-asserted-by":"crossref","DOI":"10.1007\/s11033-024-09708-x","article-title":"Advances in development of biomarkers for brain damage and ischemia","volume":"51","author":"D Karimova","year":"2024","journal-title":"Molecular Biology Reports"},{"issue":"1668","key":"pcbi.1013459.ref005","doi-asserted-by":"crossref","first-page":"20140172","DOI":"10.1098\/rstb.2014.0172","article-title":"The restless brain: how intrinsic activity organizes brain function","volume":"370","author":"ME Raichle","year":"2015","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"3","key":"pcbi.1013459.ref006","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nrn2575","article-title":"Complex brain networks: graph theoretical analysis of structural and functional systems","volume":"10","author":"E Bullmore","year":"2009","journal-title":"Nat Rev Neurosci"},{"issue":"5","key":"pcbi.1013459.ref007","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1073\/pnas.1214900110","article-title":"Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain","volume":"110","author":"X Liang","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pcbi.1013459.ref008","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease","volume":"96","author":"C Iadecola","year":"2017","journal-title":"Neuron"},{"issue":"6","key":"pcbi.1013459.ref009","doi-asserted-by":"crossref","DOI":"10.1161\/STR.0000000000000431","article-title":"The neurovasculome: key roles in brain health and cognitive impairment: a scientific statement from the American Heart Association\/American Stroke Association","volume":"54","author":"C Iadecola","year":"2023","journal-title":"Stroke"},{"issue":"4","key":"pcbi.1013459.ref010","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1109\/TMI.2005.844159","article-title":"Efficient pipeline for image-based patient-specific analysis of cerebral aneurysm hemodynamics: technique and sensitivity","volume":"24","author":"JR Cebral","year":"2005","journal-title":"IEEE Trans Med Imaging"},{"key":"pcbi.1013459.ref011","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1146\/annurev.bioeng.10.061807.160521","article-title":"Patient-specific modeling of cardiovascular mechanics","volume":"11","author":"CA Taylor","year":"2009","journal-title":"Annu Rev Biomed Eng"},{"issue":"10","key":"pcbi.1013459.ref012","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1007\/s10439-010-0083-6","article-title":"Patient-specific modeling of blood flow and pressure in human coronary arteries","volume":"38","author":"HJ Kim","year":"2010","journal-title":"Ann Biomed Eng"},{"issue":"2","key":"pcbi.1013459.ref013","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s10439-006-9224-3","article-title":"Effects of exercise and respiration on hemodynamic efficiency in CFD simulations of the total cavopulmonary connection","volume":"35","author":"AL Marsden","year":"2007","journal-title":"Ann Biomed Eng"},{"issue":"1","key":"pcbi.1013459.ref014","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1109\/TBME.2010.2065229","article-title":"From vascular corrosion cast to electrical analog model for the study of human liver hemodynamics and perfusion","volume":"58","author":"C Debbaut","year":"2011","journal-title":"IEEE Trans Biomed Eng"},{"issue":"9","key":"pcbi.1013459.ref015","doi-asserted-by":"crossref","DOI":"10.1152\/ajpregu.00039.2013","article-title":"A model-based approach to investigating the pathophysiological mechanisms of hypertension and response to antihypertensive therapies: extending the Guyton model","volume":"306","author":"KM Hallow","year":"2014","journal-title":"American Journal of Physiology - Regulatory Integrative and Comparative Physiology"},{"issue":"8","key":"pcbi.1013459.ref016","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1016\/j.jbiomech.2006.07.008","article-title":"Modelling the circle of Willis to assess the effects of anatomical variations and occlusions on cerebral flows","volume":"40","author":"J Alastruey","year":"2007","journal-title":"J Biomech"},{"key":"pcbi.1013459.ref017","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1475-925X-10-84","article-title":"A computational model study of the influence of the anatomy of the circle of Willis on cerebral hyperperfusion following carotid artery surgery","volume":"10","author":"F Liang","year":"2011","journal-title":"Biomed Eng Online"},{"key":"pcbi.1013459.ref018","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1016\/j.cma.2009.04.015","article-title":"Patient-specific isogeometric fluid-structure interaction analysis of thoracic aortic blood flow due to implantation of the Jarvik 2000 left ventricular assist device","volume":"198","author":"Y Bazilevs","year":"2009","journal-title":"Computer Methods in Applied Mechanics and Engineering"},{"issue":"10","key":"pcbi.1013459.ref019","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3174\/ajnr.A3080","article-title":"Effects of flow-diverting device oversizing on hemodynamics alteration in cerebral aneurysms","volume":"33","author":"F Mut","year":"2012","journal-title":"AJNR Am J Neuroradiol"},{"issue":"1","key":"pcbi.1013459.ref020","doi-asserted-by":"crossref","first-page":"20170021","DOI":"10.1098\/rsfs.2017.0021","article-title":"Patient-specific simulations for planning treatment in congenital heart disease","volume":"8","author":"C Capelli","year":"2018","journal-title":"Interface Focus"},{"issue":"8","key":"pcbi.1013459.ref021","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1038\/jcbfm.2009.58","article-title":"Vascular graph model to simulate the cerebral blood flow in realistic vascular networks","volume":"29","author":"J Reichold","year":"2009","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"pcbi.1013459.ref022","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1177\/0271678X16671146","article-title":"The capillary bed offers the largest hemodynamic resistance to the cortical blood supply","volume":"37","author":"IG Gould","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"pcbi.1013459.ref023","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.compbiomed.2019.05.004","article-title":"Mathematical synthesis of the cortical circulation for the whole mouse brain-part I. theory and image integration","volume":"110","author":"A Linninger","year":"2019","journal-title":"Comput Biol Med"},{"issue":"5","key":"pcbi.1013459.ref024","doi-asserted-by":"crossref","DOI":"10.1111\/micc.12687","article-title":"Mathematical synthesis of the cortical circulation for the whole mouse brain\u2014part II: microcirculatory closure","volume":"28","author":"G Hartung","year":"2021","journal-title":"Microcirculation"},{"issue":"1","key":"pcbi.1013459.ref025","doi-asserted-by":"crossref","first-page":"20190125","DOI":"10.1098\/rsfs.2019.0125","article-title":"Coupling one-dimensional arterial blood flow to three-dimensional tissue perfusion models for in silico trials of acute ischaemic stroke","volume":"11","author":"RM Padmos","year":"2021","journal-title":"Interface Focus"},{"issue":"10","key":"pcbi.1013459.ref026","doi-asserted-by":"crossref","DOI":"10.1002\/cnm.3386","article-title":"A 3D-1D coupled blood flow and oxygen transport model to generate microvascular networks","volume":"36","author":"T Koppl","year":"2020","journal-title":"International Journal for Numerical Methods in Biomedical Engineering"},{"issue":"1","key":"pcbi.1013459.ref027","doi-asserted-by":"crossref","first-page":"20190127","DOI":"10.1098\/rsfs.2019.0127","article-title":"A porous circulation model of the human brain for in silico clinical trials in ischaemic stroke","volume":"11","author":"TI J\u00f3zsa","year":"2021","journal-title":"Interface Focus"},{"issue":"9","key":"pcbi.1013459.ref028","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1011452","article-title":"Computational modeling of multiscale collateral blood supply in a whole-brain-scale arterial network","volume":"19","author":"T Otani","year":"2023","journal-title":"PLoS Comput Biol"},{"issue":"5","key":"pcbi.1013459.ref029","doi-asserted-by":"crossref","DOI":"10.1177\/0271678X231214840","article-title":"Vascular synthesis based on hemodynamic efficiency principle recapitulates measured cerebral circulation properties in the human brain","volume":"44","author":"Linninger","year":"2024","journal-title":"J Cereb Blood Flow Metab"},{"key":"pcbi.1013459.ref030","unstructured":"Hachinski V, Norris JW. The Acute Stroke. Philadelphia: F A Davis Co; 1985."},{"issue":"6","key":"pcbi.1013459.ref031","doi-asserted-by":"crossref","DOI":"10.1161\/STROKEAHA.120.033492","article-title":"The ambibaric brain: pathophysiological and clinical implications","volume":"52","author":"V Hachinski","year":"2021","journal-title":"Stroke"},{"issue":"3","key":"pcbi.1013459.ref032","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1136\/svn-2017-000087","article-title":"Blood pressure gradients in cerebral arteries: a clue to pathogenesis of cerebral small vessel disease","volume":"2","author":"PJ Blanco","year":"2017","journal-title":"Stroke Vasc Neurol"},{"issue":"2","key":"pcbi.1013459.ref033","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1109\/TBME.2014.2364522","article-title":"An anatomically detailed arterial network model for one-dimensional computational hemodynamics","volume":"62","author":"PJ Blanco","year":"2015","journal-title":"IEEE Trans Biomed Eng"},{"issue":"2","key":"pcbi.1013459.ref034","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0141-5425(93)90046-2","article-title":"Computer generation of complex arterial tree models","volume":"15","author":"W Schreiner","year":"1993","journal-title":"J Biomed Eng"},{"issue":"5","key":"pcbi.1013459.ref035","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1109\/10.243413","article-title":"Computer-optimization of vascular trees","volume":"40","author":"W Schreiner","year":"1993","journal-title":"IEEE Transactions on Biomedical Engineering"},{"key":"pcbi.1013459.ref036","article-title":"Three-dimensional optimization of arterial tree models","volume":"4","author":"R Karch","year":"1997","journal-title":"Transactions on Biomedicine and Health"},{"issue":"1","key":"pcbi.1013459.ref037","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0010-4825(98)00045-6","article-title":"A three-dimensional model for arterial tree representation, generated by constrained constructive optimization","volume":"29","author":"R Karch","year":"1999","journal-title":"Comput Biol Med"},{"issue":"12","key":"pcbi.1013459.ref038","doi-asserted-by":"crossref","first-page":"210973","DOI":"10.1098\/rsos.210973","article-title":"Parallel generation of extensive vascular networks with application to an archetypal human kidney model","volume":"8","author":"LFM Cury","year":"2021","journal-title":"R Soc Open Sci"},{"issue":"1","key":"pcbi.1013459.ref039","doi-asserted-by":"crossref","first-page":"6180","DOI":"10.1038\/s41598-021-85434-9","article-title":"Adaptive constrained constructive optimisation for complex vascularisation processes","volume":"11","author":"GDM Talou","year":"2021","journal-title":"Sci Rep"},{"key":"pcbi.1013459.ref040","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.neuroimage.2017.06.046","article-title":"Vascular density and distribution in neocortex","volume":"197","author":"F Schmid","year":"2019","journal-title":"NeuroImage"},{"key":"pcbi.1013459.ref041","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0025-5564(73)90027-8","article-title":"On the one-dimensional theory of blood flow in the larger vessels","volume":"18","author":"TJR Hughes","year":"1973","journal-title":"Mathematical Biosciences"},{"issue":"4","key":"pcbi.1013459.ref042","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.neuroimage.2012.02.084","article-title":"Within-subject template estimation for unbiased longitudinal image analysis","volume":"61","author":"M Reuter","year":"2012","journal-title":"Neuroimage"},{"key":"pcbi.1013459.ref043","unstructured":"Zilves EG. Automatic vascularization of massive arterial networks in the human cerebral cortex: a computational modeling approach. Petr\u00f3polis, Brazil: National Laboratory for Scientific Computing LNCC\/MCTI; 2024."},{"key":"pcbi.1013459.ref044","unstructured":"Schunke M, Schulte E, Schumacher U. Head and neuroanatomy. Stuttgart: Thieme; 2010."},{"issue":"5","key":"pcbi.1013459.ref045","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.medengphy.2005.07.019","article-title":"Optimized arterial trees supplying hollow organs","volume":"28","author":"W Schreiner","year":"2006","journal-title":"Med Eng Phys"},{"issue":"3","key":"pcbi.1013459.ref046","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1073\/pnas.12.3.207","article-title":"The physiological principle of minimum work: I. The vascular system and the cost of blood volume","volume":"12","author":"CD Murray","year":"1926","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pcbi.1013459.ref047","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1161\/01.RES.75.5.904","article-title":"Resistance to blood flow in microvessels in vivo","volume":"75","author":"AR Pries","year":"1994","journal-title":"Circ Res"},{"issue":"3","key":"pcbi.1013459.ref048","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.neuroimage.2007.09.024","article-title":"Morphometry of the human cerebral cortex microcirculation: general characteristics and space-related profiles","volume":"39","author":"F Lauwers","year":"2008","journal-title":"Neuroimage"},{"key":"pcbi.1013459.ref049","doi-asserted-by":"crossref","unstructured":"Murray CD. The physiological principle of minimum work: II. Oxygen exchange in capillaries. Proceedings of the National Academy of Sciences. 1926;12(5):299\u2013304.","DOI":"10.1073\/pnas.12.5.299"},{"key":"pcbi.1013459.ref050","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.jbiomech.2016.03.044","article-title":"Computational modeling of blood flow steal phenomena caused by subclavian stenoses","volume":"49","author":"PJ Blanco","year":"2016","journal-title":"Journal of Biomechanics"},{"key":"pcbi.1013459.ref051","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jcp.2014.06.018","article-title":"Reformulations for general advection-diffusion-reaction equations and locally implicit ADER schemes","volume":"275","author":"GI Montecinos","year":"2014","journal-title":"Journal of Computational Physics"},{"key":"pcbi.1013459.ref052","doi-asserted-by":"crossref","DOI":"10.1137\/130937469","article-title":"Advection-diffusion-reaction equations: hyperbolisation and high-order ader discretizations","volume":"36","author":"E Toro","year":"2014","journal-title":"SIAM Journal of Scientific Computing"},{"issue":"10","key":"pcbi.1013459.ref053","doi-asserted-by":"crossref","DOI":"10.1002\/cnm.2761","article-title":"A high-order local time stepping finite volume solver for one-dimensional blood flow simulations: application to the ADAN model","volume":"32","author":"LO M\u00fcller","year":"2016","journal-title":"Int J Numer Method Biomed Eng"},{"key":"pcbi.1013459.ref054","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jcp.2015.07.056","article-title":"A high order approximation of hyperbolic conservation laws in networks: application to one-dimensional blood flow","volume":"300","author":"LO Muller","year":"2015","journal-title":"Journal of Computational Physics"},{"key":"pcbi.1013459.ref055","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jcp.2016.03.012","article-title":"Consistent treatment of viscoelastic effects at junctions in one-dimensional blood flow models","volume":"314","author":"LO Muller","year":"2016","journal-title":"Journal of Computational Physics"},{"issue":"5","key":"pcbi.1013459.ref056","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1007\/s10237-020-01298-4","article-title":"On the anatomical definition of arterial networks in blood flow simulations: comparison of detailed and simplified models","volume":"19","author":"PJ Blanco","year":"2020","journal-title":"Biomech Model Mechanobiol"},{"issue":"6","key":"pcbi.1013459.ref057","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1007\/s10237-014-0574-8","article-title":"Blood flow distribution in an anatomically detailed arterial network model: criteria and algorithms","volume":"13","author":"PJ Blanco","year":"2014","journal-title":"Biomechanics and Modeling in Mechanobiology"},{"issue":"6","key":"pcbi.1013459.ref058","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/BF02441895","article-title":"Multi-branched model of the human arterial system","volume":"18","author":"AP Avolio","year":"1980","journal-title":"Med Biol Eng Comput"},{"issue":"11","key":"pcbi.1013459.ref059","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1007\/s10439-013-0828-0","article-title":"Cerebral microcirculation and oxygen tension in the human secondary cortex","volume":"41","author":"AA Linninger","year":"2013","journal-title":"Ann Biomed Eng"},{"issue":"11","key":"pcbi.1013459.ref060","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1006549","article-title":"Simulations of blood as a suspension predicts a depth dependent hematocrit in the circulation throughout the cerebral cortex","volume":"14","author":"G Hartung","year":"2018","journal-title":"PLoS Comput Biol"},{"issue":"5","key":"pcbi.1013459.ref061","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0361-9230(81)90007-1","article-title":"Cortical blood vessels of the human brain","volume":"7","author":"HM Duvernoy","year":"1981","journal-title":"Brain Res Bull"},{"issue":"9","key":"pcbi.1013459.ref062","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/s41593-021-00904-7","article-title":"Revisiting the neurovascular unit","volume":"24","author":"S Schaeffer","year":"2021","journal-title":"Nature Neuroscience"},{"issue":"1","key":"pcbi.1013459.ref063","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/(SICI)1097-0185(199805)251:1<87::AID-AR14>3.0.CO;2-7","article-title":"Morphological characteristics and distribution pattern of the arterial vessels in human cerebral cortex: a scanning electron microscope study","volume":"251","author":"F Reina-De La Torre","year":"1998","journal-title":"Anat Rec"},{"issue":"1","key":"pcbi.1013459.ref064","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1073\/pnas.0609551104","article-title":"Penetrating arterioles are a bottleneck in the perfusion of neocortex","volume":"104","author":"N Nishimura","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pcbi.1013459.ref065","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/jcbfm.2012.39","article-title":"Topology and hemodynamics of the cortical cerebrovascular system","volume":"32","author":"S Hirsch","year":"2012","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1","key":"pcbi.1013459.ref066","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10739680500383407","article-title":"A novel three-dimensional computer-assisted method for a quantitative study of microvascular networks of the human cerebral cortex","volume":"13","author":"F Cassot","year":"2006","journal-title":"Microcirculation"},{"issue":"10","key":"pcbi.1013459.ref067","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1093\/cercor\/bhm259","article-title":"The microvascular system of the striate and extrastriate visual cortex of the macaque","volume":"18","author":"B Weber","year":"2008","journal-title":"Cereb Cortex"},{"key":"pcbi.1013459.ref068","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.brainres.2009.12.007","article-title":"Branching patterns for arterioles and venules of the human cerebral cortex","volume":"1313","author":"F Cassot","year":"2010","journal-title":"Brain Res"},{"issue":"4","key":"pcbi.1013459.ref069","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/10739680802662607","article-title":"Scaling laws for branching vessels of human cerebral cortex","volume":"16","author":"F Cassot","year":"2009","journal-title":"Microcirculation"},{"issue":"6","key":"pcbi.1013459.ref070","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1159\/000515829","article-title":"Stroke prevention: little-known and neglected aspects","volume":"50","author":"MR Azarpazhooh","year":"2021","journal-title":"Cerebrovasc Dis"},{"issue":"6","key":"pcbi.1013459.ref071","doi-asserted-by":"crossref","DOI":"10.1093\/ageing\/afaa084","article-title":"Risk from low blood pressure in frail older adults: diastolic pressure and pulse pressure are important","volume":"50","author":"JD Spence","year":"2021","journal-title":"Age Ageing"},{"issue":"6","key":"pcbi.1013459.ref072","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/eurheartj\/ehab552","article-title":"How to identify which patients should not have a systolic blood pressure target of <120 mmHg","volume":"43","author":"JD Spence","year":"2022","journal-title":"Eur Heart J"},{"issue":"2","key":"pcbi.1013459.ref073","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1177\/17474930221127179","article-title":"Vertebrobasilar ischemia: some less recognized aspects","volume":"18","author":"JD Spence","year":"2023","journal-title":"Int J Stroke"},{"issue":"5","key":"pcbi.1013459.ref074","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/ajh\/hpaa195","article-title":"Mechanisms of vascular remodeling in hypertension","volume":"34","author":"JD Humphrey","year":"2021","journal-title":"Am J Hypertens"},{"issue":"1","key":"pcbi.1013459.ref075","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ajh\/hpac093","article-title":"State of the art review: vascular remodeling in hypertension","volume":"36","author":"D Rizzoni","year":"2023","journal-title":"Am J Hypertens"},{"issue":"6","key":"pcbi.1013459.ref076","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1161\/CIRCRESAHA.116.303596","article-title":"The structural factor of hypertension: large and small artery alterations","volume":"116","author":"S Laurent","year":"2015","journal-title":"Circ Res"},{"key":"pcbi.1013459.ref077","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3389\/fcvm.2019.00169","article-title":"Measuring the interaction between the macro- and micro-vasculature","volume":"6","author":"RE Climie","year":"2019","journal-title":"Front Cardiovasc Med"},{"issue":"9","key":"pcbi.1013459.ref078","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1001\/2012.jama.10503","article-title":"Aortic stiffness, blood pressure progression, and incident hypertension","volume":"308","author":"BM Kaess","year":"2012","journal-title":"JAMA"},{"issue":"1","key":"pcbi.1013459.ref079","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1161\/01.CIR.96.1.308","article-title":"Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study","volume":"96","author":"SS Franklin","year":"1997","journal-title":"Circulation"},{"issue":"3","key":"pcbi.1013459.ref080","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1552-6569.2001.tb00039.x","article-title":"Transcranial Doppler pulsatility indices as a measure of diffuse small-vessel disease","volume":"11","author":"CS Kidwell","year":"2001","journal-title":"J Neuroimaging"},{"issue":"1","key":"pcbi.1013459.ref081","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0022-510X(97)05391-4","article-title":"Blood flow velocity changes in the middle cerebral artery as an index of the chronicity of hypertension","volume":"150","author":"SJ Cho","year":"1997","journal-title":"J Neurol Sci"},{"issue":"6","key":"pcbi.1013459.ref082","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1002\/jmri.27989","article-title":"Non-invasive assessment of damping of blood flow velocity pulsatility in cerebral arteries with MRI","volume":"55","author":"T Arts","year":"2022","journal-title":"Journal of Magnetic Resonance Imaging"},{"issue":"4","key":"pcbi.1013459.ref083","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1161\/HYPERTENSIONAHA.122.19866","article-title":"Hypertension correlates with stronger blood flow pulsatility in small perforating cerebral arteries assessed with 7 tesla magnetic resonance imaging","volume":"80","author":"M van den Kerkhof","year":"2023","journal-title":"Hypertension"},{"issue":"6","key":"pcbi.1013459.ref084","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1177\/0271678X231153374","article-title":"Impaired damping of cerebral blood flow velocity pulsatility is associated with the number of perivascular spaces as measured with 7T MRI","volume":"43","author":"M van den Kerkhof","year":"2023","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"pcbi.1013459.ref085","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1161\/STROKEAHA.109.564914","article-title":"Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease","volume":"41","author":"FN Doubal","year":"2010","journal-title":"Stroke"},{"issue":"9","key":"pcbi.1013459.ref086","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1177\/0271678X16629486","article-title":"Aging alters the dampening of pulsatile blood flow in cerebral arteries","volume":"36","author":"L Zarrinkoob","year":"2016","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"2","key":"pcbi.1013459.ref087","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0306-9877(03)00330-X","article-title":"Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer\u2019s disease, vascular dementia and normal pressure hydrocephalus","volume":"62","author":"GA Bateman","year":"2004","journal-title":"Med Hypotheses"},{"issue":"1","key":"pcbi.1013459.ref088","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-63312-4","article-title":"Measuring global cerebrovascular pulsatility transmission using 4D flow MRI","volume":"14","author":"S Dempsey","year":"2024","journal-title":"Scientific Reports"},{"issue":"10","key":"pcbi.1013459.ref089","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1097\/HJH.0b013e32832e8dc8","article-title":"Importance of pulsatility in hypertensive carotid artery growth and remodeling","volume":"27","author":"JF Eberth","year":"2009","journal-title":"J Hypertens"},{"issue":"1","key":"pcbi.1013459.ref090","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1115\/1.2895465","article-title":"Elementary mechanics of the endothelium of blood vessels","volume":"115","author":"YC Fung","year":"1993","journal-title":"J Biomech Eng"},{"issue":"130","key":"pcbi.1013459.ref091","doi-asserted-by":"crossref","first-page":"20170185","DOI":"10.1098\/rsif.2017.0185","article-title":"Mechanotransmission in endothelial cells subjected to oscillatory and multi-directional shear flow","volume":"14","author":"M Dabagh","year":"2017","journal-title":"J R Soc Interface"},{"issue":"6","key":"pcbi.1013459.ref092","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/alz.12340","article-title":"Stroke and dementia, leading causes of neurological disability and death, potential for prevention","volume":"17","author":"A Avan","year":"2021","journal-title":"Alzheimer\u2019s and Dementia"},{"issue":"1","key":"pcbi.1013459.ref093","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/ana.25380","article-title":"Attributable risk of Alzheimer\u2019s dementia attributed to age-related neuropathologies","volume":"85","author":"PA Boyle","year":"2019","journal-title":"Ann Neurol"},{"key":"pcbi.1013459.ref094","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1093\/brain\/awt188","article-title":"Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer\u2019s Coordinating Centre","volume":"136","author":"JB Toledo","year":"2013","journal-title":"Brain"},{"issue":"7","key":"pcbi.1013459.ref095","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.jalz.2019.06.001","article-title":"Preventing dementia by preventing stroke: the Berlin Manifesto","volume":"15","author":"V Hachinski","year":"2019","journal-title":"Alzheimers Dement"},{"issue":"9","key":"pcbi.1013459.ref096","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1002\/alz.12637","article-title":"The apathy, gait impairment, and executive dysfunction (AGED) triad vascular variant","volume":"18","author":"V Hachinski","year":"2022","journal-title":"Alzheimers Dement"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013459","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013459","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T21:52:04Z","timestamp":1758318724000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013459"}},"subtitle":[],"editor":[{"given":"Lyle J.","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":96,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013459","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}