{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T11:02:10Z","timestamp":1781607730300,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011496","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000}}],"reference-count":115,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["166707"],"award-info":[{"award-number":["166707"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["166707"],"award-info":[{"award-number":["166707"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["166707"],"award-info":[{"award-number":["166707"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["202192"],"award-info":[{"award-number":["202192"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_182703"],"award-info":[{"award-number":["310030_182703"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_200703"],"award-info":[{"award-number":["310030_200703"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel <jats:italic>in silico<\/jats:italic> approach that incorporates case-specific <jats:italic>in vivo<\/jats:italic> data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with <jats:italic>in vivo<\/jats:italic> data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011496","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T17:33:46Z","timestamp":1698082426000},"page":"e1011496","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["The role of leptomeningeal collaterals in redistributing blood flow during stroke"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8951-1987","authenticated-orcid":true,"given":"Robert","family":"Epp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaim","family":"Gl\u00fcck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine Felizitas","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"El Amki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Wegener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Jenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0689-9366","authenticated-orcid":true,"given":"Franca","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"issue":"10","key":"pcbi.1011496.ref001","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":"Cerebral cortex"},{"issue":"6","key":"pcbi.1011496.ref002","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":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"7","key":"pcbi.1011496.ref003","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/nn.3426","article-title":"The cortical angiome: an interconnected vascular network with noncolumnar patterns of blood flow","volume":"16","author":"P Blinder","year":"2013","journal-title":"Nature neuroscience"},{"key":"pcbi.1011496.ref004","doi-asserted-by":"crossref","DOI":"10.1515\/9783112360606","volume-title":"\u00dcber den Kreislauf des Blutes im menschlichen Gehirn","author":"A Mosso","year":"1881"},{"issue":"1-2","key":"pcbi.1011496.ref005","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1113\/jphysiol.1890.sp000321","article-title":"On the regulation of the blood-supply of the brain","volume":"11","author":"CS Roy","year":"1890","journal-title":"The Journal of physiology"},{"key":"pcbi.1011496.ref006","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1146\/annurev-neuro-071013-014111","article-title":"Coupling mechanism and significance of the BOLD signal: a status report","volume":"37","author":"EM Hillman","year":"2014","journal-title":"Annual review of neuroscience"},{"issue":"1","key":"pcbi.1011496.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-019-0118-8","article-title":"Ischaemic stroke","volume":"5","author":"BC Campbell","year":"2019","journal-title":"Nature Reviews Disease Primers"},{"issue":"11","key":"pcbi.1011496.ref008","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1161\/01.STR.0000095791.85737.65","article-title":"Anatomy and functionality of leptomeningeal anastomoses: a review","volume":"34","author":"M Brozici","year":"2003","journal-title":"Stroke"},{"issue":"3","key":"pcbi.1011496.ref009","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/jcbfm.1984.57","article-title":"The modular organization of the pial arterial system in phylogeny","volume":"4","author":"G Mchedlishvili","year":"1984","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"pcbi.1011496.ref010","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.yjmcc.2010.03.014","article-title":"Formation and maturation of the native cerebral collateral circulation","volume":"49","author":"D Chalothorn","year":"2010","journal-title":"Journal of molecular and cellular cardiology"},{"issue":"2","key":"pcbi.1011496.ref011","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1152\/physiolgenomics.00047.2007","article-title":"Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains","volume":"30","author":"D Chalothorn","year":"2007","journal-title":"Physiological genomics"},{"issue":"5","key":"pcbi.1011496.ref012","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/jcbfm.2010.10","article-title":"Wide genetic variation in the native pial collateral circulation is a major determinant of variation in severity of stroke","volume":"30","author":"H Zhang","year":"2010","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"5","key":"pcbi.1011496.ref013","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/jcbfm.2015.2","article-title":"Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for \u2018collateral failure\u2019and infarct expansion after ischemic stroke","volume":"35","author":"DJ Beard","year":"2015","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"9","key":"pcbi.1011496.ref014","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1177\/0271678X20924107","article-title":"Hypoxia induces de novo formation of cerebral collaterals and lessens the severity of ischemic stroke","volume":"40","author":"H Zhang","year":"2020","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"pcbi.1011496.ref015","doi-asserted-by":"crossref","first-page":"108260","DOI":"10.1016\/j.celrep.2020.108260","article-title":"Neutrophils obstructing brain capillaries are a major cause of no-reflow in ischemic stroke","volume":"33","author":"M El Amki","year":"2020","journal-title":"Cell reports"},{"issue":"12","key":"pcbi.1011496.ref016","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.3390\/ijms18122669","article-title":"Improving cerebral blood flow after arterial recanalization: a novel therapeutic strategy in stroke","volume":"18","author":"M El Amki","year":"2017","journal-title":"International journal of molecular sciences"},{"issue":"5","key":"pcbi.1011496.ref017","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1177\/0271678X221146128","article-title":"A systematic observation of vasodynamics from different segments along the cerebral vasculature in the penumbra zone of awake mice following cerebral ischemia and recanalization","volume":"43","author":"B Qiu","year":"2023","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"1","key":"pcbi.1011496.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-27910-3","article-title":"The pial vasculature of the mouse develops according to a sensory-independent program","volume":"8","author":"MD Adams","year":"2018","journal-title":"Scientific reports"},{"issue":"2","key":"pcbi.1011496.ref019","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10456-018-9655-0","article-title":"Mouse models of Alzheimer\u2019s disease cause rarefaction of pial collaterals and increased severity of ischemic stroke","volume":"22","author":"H Zhang","year":"2019","journal-title":"Angiogenesis"},{"key":"pcbi.1011496.ref020","article-title":"Transient versus permanent MCA occlusion in mice genetically modified to have good versus poor collaterals","volume":"4","author":"H Zhang","year":"2019","journal-title":"Med one"},{"issue":"195","key":"pcbi.1011496.ref021","doi-asserted-by":"crossref","first-page":"20220649","DOI":"10.1098\/rsif.2022.0649","article-title":"Modelling collateral flow and thrombus permeability during acute ischaemic stroke","volume":"19","author":"RM Padmos","year":"2022","journal-title":"Journal of the Royal Society Interface"},{"issue":"6","key":"pcbi.1011496.ref022","doi-asserted-by":"crossref","first-page":"e11270","DOI":"10.1371\/journal.pone.0011270","article-title":"Mild sensory stimulation completely protects the adult rodent cortex from ischemic stroke","volume":"5","author":"CC Lay","year":"2010","journal-title":"PloS one"},{"issue":"5","key":"pcbi.1011496.ref023","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.108696","article-title":"Gamma frequency activation of inhibitory neurons in the acute phase after stroke attenuates vascular and behavioral dysfunction","volume":"34","author":"M Balbi","year":"2021","journal-title":"Cell Reports"},{"issue":"23","key":"pcbi.1011496.ref024","doi-asserted-by":"crossref","first-page":"e2117346119","DOI":"10.1073\/pnas.2117346119","article-title":"Ultrafast two-photon fluorescence imaging of cerebral blood circulation in the mouse brain in vivo","volume":"119","author":"G Meng","year":"2022","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"28","key":"pcbi.1011496.ref025","doi-asserted-by":"crossref","first-page":"e2207474119","DOI":"10.1073\/pnas.2207474119","article-title":"A FACED lift for cerebral blood flow imaging","volume":"119","author":"B Weber","year":"2022","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"2","key":"pcbi.1011496.ref026","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1371\/journal.pbio.0040022","article-title":"Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion","volume":"4","author":"CB Schaffer","year":"2006","journal-title":"PLoS biology"},{"issue":"4","key":"pcbi.1011496.ref027","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/jcbfm.2008.166","article-title":"Active dilation of penetrating arterioles restores red blood cell flux to penumbral neocortex after focal stroke","volume":"29","author":"AY Shih","year":"2009","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"pcbi.1011496.ref028","doi-asserted-by":"crossref","first-page":"025006","DOI":"10.1117\/1.NPh.2.2.025006","article-title":"Vasodynamics of pial and penetrating arterioles in relation to arteriolo-arteriolar anastomosis after focal stroke","volume":"2","author":"U Baran","year":"2015","journal-title":"Neurophotonics"},{"issue":"24","key":"pcbi.1011496.ref029","doi-asserted-by":"crossref","first-page":"9868","DOI":"10.1073\/pnas.87.24.9868","article-title":"Brain magnetic resonance imaging with contrast dependent on blood oxygenation","volume":"87","author":"S Ogawa","year":"1990","journal-title":"proceedings of the National Academy of Sciences"},{"issue":"12","key":"pcbi.1011496.ref030","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1073\/pnas.89.12.5675","article-title":"Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation","volume":"89","author":"KK Kwong","year":"1992","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"16","key":"pcbi.1011496.ref031","doi-asserted-by":"crossref","first-page":"13904","DOI":"10.1364\/OE.17.013904","article-title":"Dynamic laser speckle imaging of cerebral blood flow","volume":"17","author":"P Zakharov","year":"2009","journal-title":"Optics express"},{"issue":"7579","key":"pcbi.1011496.ref032","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature16066","article-title":"Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging","volume":"527","author":"C Errico","year":"2015","journal-title":"Nature"},{"issue":"5","key":"pcbi.1011496.ref033","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1021\/cr9002566","article-title":"Molecular imaging by means of multispectral optoacoustic tomography (MSOT)","volume":"110","author":"V Ntziachristos","year":"2010","journal-title":"Chemical reviews"},{"issue":"1","key":"pcbi.1011496.ref034","first-page":"1","article-title":"High-speed volumetric two-photon fluorescence imaging of neurovascular dynamics","volume":"11","author":"JL Fan","year":"2020","journal-title":"Nature communications"},{"issue":"8","key":"pcbi.1011496.ref035","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1038\/s41592-022-01549-5","article-title":"Functional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale","volume":"19","author":"N Renaudin","year":"2022","journal-title":"Nature methods"},{"issue":"8","key":"pcbi.1011496.ref036","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":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"pcbi.1011496.ref037","doi-asserted-by":"crossref","first-page":"e1005392","DOI":"10.1371\/journal.pcbi.1005392","article-title":"Depth-dependent flow and pressure characteristics in cortical microvascular networks","volume":"13","author":"F Schmid","year":"2017","journal-title":"PLoS computational biology"},{"issue":"8","key":"pcbi.1011496.ref038","doi-asserted-by":"crossref","first-page":"e1007231","DOI":"10.1371\/journal.pcbi.1007231","article-title":"Red blood cells stabilize flow in brain microvascular networks","volume":"15","author":"F Schmid","year":"2019","journal-title":"PLoS computational biology"},{"issue":"2","key":"pcbi.1011496.ref039","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.neuroimage.2010.09.032","article-title":"Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: Methodology and baseline flow","volume":"54","author":"S Lorthois","year":"2011","journal-title":"NeuroImage"},{"issue":"4","key":"pcbi.1011496.ref040","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1016\/j.neuroimage.2010.10.040","article-title":"Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters","volume":"54","author":"S Lorthois","year":"2011","journal-title":"Neuroimage"},{"issue":"sup1","key":"pcbi.1011496.ref041","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1080\/10255842.2012.713680","article-title":"Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network","volume":"15","author":"S Lorthois","year":"2012","journal-title":"Computer methods in biomechanics and biomedical engineering"},{"issue":"7","key":"pcbi.1011496.ref042","doi-asserted-by":"crossref","first-page":"H733","DOI":"10.1152\/ajpheart.00335.2014","article-title":"The impact of capillary dilation on the distribution of red blood cells in artificial networks","volume":"308","author":"F Schmid","year":"2015","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"pcbi.1011496.ref043","first-page":"1132","article-title":"Predicting vessel diameter changes to up-regulate biphasic blood flow during activation in realistic microvascular networks","volume":"11","author":"R Epp","year":"2020","journal-title":"Frontiers in physiology"},{"key":"pcbi.1011496.ref044","doi-asserted-by":"crossref","first-page":"e60208","DOI":"10.7554\/eLife.60208","article-title":"The severity of microstrokes depends on local vascular topology and baseline perfusion","volume":"10","author":"F Schmid","year":"2021","journal-title":"Elife"},{"issue":"10","key":"pcbi.1011496.ref045","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1177\/0271678X17698970","article-title":"3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy","volume":"37","author":"E Lugo-Hernandez","year":"2017","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"4","key":"pcbi.1011496.ref046","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cell.2020.01.028","article-title":"Mapping the fine-scale organization and plasticity of the brain vasculature","volume":"180","author":"C Kirst","year":"2020","journal-title":"Cell"},{"issue":"4","key":"pcbi.1011496.ref047","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41592-020-0792-1","article-title":"Machine learning analysis of whole mouse brain vasculature","volume":"17","author":"MI Todorov","year":"2020","journal-title":"Nature methods"},{"issue":"7","key":"pcbi.1011496.ref048","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.neuron.2021.02.006","article-title":"Brain microvasculature has a common topology with local differences in geometry that match metabolic load","volume":"109","author":"X Ji","year":"2021","journal-title":"Neuron"},{"issue":"11","key":"pcbi.1011496.ref049","doi-asserted-by":"crossref","first-page":"e1006549","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 computational biology"},{"key":"pcbi.1011496.ref050","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fphys.2019.00233","article-title":"Brain capillary networks across species: a few simple organizational requirements are sufficient to reproduce both structure and function","volume":"10","author":"AF Smith","year":"2019","journal-title":"Frontiers in physiology"},{"issue":"26","key":"pcbi.1011496.ref051","doi-asserted-by":"crossref","first-page":"15741","DOI":"10.1073\/pnas.95.26.15741","article-title":"Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex","volume":"95","author":"D Kleinfeld","year":"1998","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"4","key":"pcbi.1011496.ref052","doi-asserted-by":"crossref","first-page":"e12343","DOI":"10.1111\/micc.12343","article-title":"Model-based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach","volume":"24","author":"PM Rasmussen","year":"2017","journal-title":"Microcirculation"},{"issue":"3","key":"pcbi.1011496.ref053","doi-asserted-by":"crossref","first-page":"e12445","DOI":"10.1111\/micc.12445","article-title":"Modeling the hematocrit distribution in microcirculatory networks: a quantitative evaluation of a phase separation model","volume":"25","author":"PM Rasmussen","year":"2018","journal-title":"Microcirculation"},{"key":"pcbi.1011496.ref054","doi-asserted-by":"crossref","unstructured":"Sunwoo J, Cornelius NR, Doerschuk PC, Schaffer CB. Estimating brain microvascular blood flows from partial two-photon microscopy data by computation with a circuit model. In: 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE; 2011. p. 174\u2013177.","DOI":"10.1109\/IEMBS.2011.6089922"},{"issue":"1","key":"pcbi.1011496.ref055","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1177\/0271678X17741086","article-title":"Experimentally constrained circuit model of cortical arteriole networks for understanding flow redistribution due to occlusion and neural activation","volume":"38","author":"T Bollu","year":"2018","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"6","key":"pcbi.1011496.ref056","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1549-8719.2012.00184.x","article-title":"Estimation of blood flow rates in large microvascular networks","volume":"19","author":"BC Fry","year":"2012","journal-title":"Microcirculation"},{"issue":"1","key":"pcbi.1011496.ref057","doi-asserted-by":"crossref","first-page":"015008","DOI":"10.1117\/1.NPh.2.1.015008","article-title":"Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography","volume":"2","author":"L Gagnon","year":"2015","journal-title":"Neurophotonics"},{"issue":"5","key":"pcbi.1011496.ref058","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":"Circulation research"},{"key":"pcbi.1011496.ref059","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s12021-017-9344-y","article-title":"CHIPS: an extensible toolbox for cellular and hemodynamic two-photon image analysis","volume":"16","author":"MJ Barrett","year":"2018","journal-title":"Neuroinform"},{"issue":"1","key":"pcbi.1011496.ref060","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10827-009-0159-1","article-title":"Rapid determination of particle velocity from space-time images using the Radon transform","volume":"29","author":"PJ Drew","year":"2010","journal-title":"Journal of computational neuroscience"},{"key":"pcbi.1011496.ref061","first-page":"2023","article-title":"Leptomeningeal collaterals regulate reperfusion in ischemic stroke","author":"N Binder","year":"2023","journal-title":"Preprint at bioRxiv"},{"key":"pcbi.1011496.ref062","unstructured":"Reichold J. Cerebral blood flow modeling in realistic cortical microvascular networks; 2011."},{"key":"pcbi.1011496.ref063","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fnana.2011.00029","article-title":"The evolution of the brain, the human nature of cortical circuits, and intellectual creativity","volume":"5","author":"J DeFelipe","year":"2011","journal-title":"Frontiers in neuroanatomy"},{"key":"pcbi.1011496.ref064","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"},{"issue":"4","key":"pcbi.1011496.ref065","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.neuroimage.2007.10.054","article-title":"Novel three-dimensional analysis tool for vascular trees indicates complete micro-networks, not single capillaries, as the angiogenic endpoint in mice overexpressing human VEGF165 in the brain","volume":"39","author":"S Heinzer","year":"2008","journal-title":"Neuroimage"},{"issue":"3","key":"pcbi.1011496.ref066","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuroimage.2007.12.061","article-title":"A vascular anatomical network model of the spatio-temporal response to brain activation","volume":"40","author":"DA Boas","year":"2008","journal-title":"Neuroimage"},{"key":"pcbi.1011496.ref067","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-fluid-010816-060302","article-title":"Blood flow in the microcirculation","volume":"49","author":"TW Secomb","year":"2017","journal-title":"Annual Review of Fluid Mechanics"},{"issue":"11","key":"pcbi.1011496.ref068","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1038\/jcbfm.2010.105","article-title":"Cerebral blood flow modeling in primate cortex","volume":"30","author":"R Guibert","year":"2010","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"6","key":"pcbi.1011496.ref069","doi-asserted-by":"crossref","first-page":"H2657","DOI":"10.1152\/ajpheart.00297.2005","article-title":"Microvascular blood viscosity in vivo and the endothelial surface layer","volume":"289","author":"AR Pries","year":"2005","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"6","key":"pcbi.1011496.ref070","doi-asserted-by":"crossref","first-page":"H1770","DOI":"10.1152\/ajpheart.1992.263.6.H1770","article-title":"Blood viscosity in tube flow: dependence on diameter and hematocrit","volume":"263","author":"AR Pries","year":"1992","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"1","key":"pcbi.1011496.ref071","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nn.3278","article-title":"The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit","volume":"16","author":"AY Shih","year":"2013","journal-title":"Nature neuroscience"},{"key":"pcbi.1011496.ref072","first-page":"100105","article-title":"Hierarchical regularization of solution ambiguity in underdetermined inverse and optimization problems","author":"R Epp","year":"2022","journal-title":"Journal of Computational Physics: X"},{"key":"pcbi.1011496.ref073","doi-asserted-by":"crossref","first-page":"112264","DOI":"10.1016\/j.jcp.2023.112264","article-title":"Fast convergence strategy for ambiguous inverse problems based on hierarchical regularization","author":"R Epp","year":"2023","journal-title":"Journal of Computational Physics"},{"issue":"5","key":"pcbi.1011496.ref074","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/sj.jcbfm.9600590","article-title":"Functional reactivity of cerebral capillaries","volume":"28","author":"B Stefanovic","year":"2008","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"pcbi.1011496.ref075","doi-asserted-by":"crossref","unstructured":"Moeini M, Tabatabaei MS, B\u00e9langer S, Avti P, Castonguay A, Pouliot P, et al. Effects of anesthesia on the cerebral capillary blood flow in young and old mice. In: Multiphoton Microscopy in the Biomedical Sciences XV. vol. 9329. SPIE; 2015. p. 199\u2013204.","DOI":"10.1117\/12.2079803"},{"issue":"6","key":"pcbi.1011496.ref076","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1097\/HJH.0000000000002033","article-title":"Effects of vasodilating medications on cerebral haemodynamics in health and disease: systematic review and meta-analysis","volume":"37","author":"AJ Webb","year":"2019","journal-title":"Journal of hypertension"},{"issue":"2","key":"pcbi.1011496.ref077","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1161\/01.STR.32.2.461","article-title":"Very early nimodipine use in Stroke (VENUS) A randomized, double-blind, placebo-controlled Trial","volume":"32","author":"J Horn","year":"2001","journal-title":"Stroke"},{"key":"pcbi.1011496.ref078","article-title":"A Dynamic Multiscale Model of Cerebral Blood Flow and Autoregulation in the Microvasculature","author":"A Daher","year":"2023","journal-title":"Applied Mathematical Modelling"},{"key":"pcbi.1011496.ref079","doi-asserted-by":"crossref","first-page":"104503","DOI":"10.1016\/j.mvr.2023.104503","article-title":"A network-based model of dynamic cerebral autoregulation","volume":"147","author":"A Daher","year":"2023","journal-title":"Microvascular Research"},{"issue":"11","key":"pcbi.1011496.ref080","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1161\/STROKEAHA.110.594168","article-title":"Cerebral autoregulation in stroke: a review of transcranial Doppler studies","volume":"41","author":"MJ Aries","year":"2010","journal-title":"Stroke"},{"key":"pcbi.1011496.ref081","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1023\/B:ENGI.0000007979.32871.e2","article-title":"One-dimensional modelling of a vascular network in space-time variables","volume":"47","author":"S Sherwin","year":"2003","journal-title":"Journal of engineering mathematics"},{"issue":"4","key":"pcbi.1011496.ref082","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/00004647-200404000-00003","article-title":"Capillary flow and diameter changes during reperfusion after global cerebral ischemia studied by intravital video microscopy","volume":"24","author":"EF Hauck","year":"2004","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"9","key":"pcbi.1011496.ref083","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/nm.2022","article-title":"Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery","volume":"15","author":"M Yemisci","year":"2009","journal-title":"Nature medicine"},{"issue":"7494","key":"pcbi.1011496.ref084","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature13165","article-title":"Capillary pericytes regulate cerebral blood flow in health and disease","volume":"508","author":"CN Hall","year":"2014","journal-title":"Nature"},{"issue":"1","key":"pcbi.1011496.ref085","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/jcbfm.2013.162","article-title":"Augmenting collateral blood flow during ischemic stroke via transient aortic occlusion","volume":"34","author":"IR Winship","year":"2014","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"pcbi.1011496.ref086","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s12975-019-00710-1","article-title":"Impaired collateral flow in pial arterioles of aged rats during ischemic stroke","volume":"11","author":"J Ma","year":"2020","journal-title":"Translational stroke research"},{"issue":"6","key":"pcbi.1011496.ref087","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1109\/TMI.2019.2895779","article-title":"Monitoring acute stroke progression: multi-parametric OCT imaging of cortical perfusion, flow, and tissue scattering in a mouse model of permanent focal ischemia","volume":"38","author":"WJ Choi","year":"2019","journal-title":"IEEE transactions on medical imaging"},{"issue":"12","key":"pcbi.1011496.ref088","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1177\/0271678X16631560","article-title":"Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH)","volume":"36","author":"E Guti\u00e9rrez-Jim\u00e9nez","year":"2016","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"1","key":"pcbi.1011496.ref089","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1161\/01.RES.75.1.55","article-title":"Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study","volume":"75","author":"A Villringer","year":"1994","journal-title":"Circulation research"},{"issue":"1-2","key":"pcbi.1011496.ref090","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0006-8993(02)03848-9","article-title":"Cortical electrical stimulation alters erythrocyte perfusion pattern in the cerebral capillary network of the rat","volume":"963","author":"M Schulte","year":"2003","journal-title":"Brain research"},{"issue":"11","key":"pcbi.1011496.ref091","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1038\/jcbfm.2013.158","article-title":"Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography","volume":"33","author":"J Lee","year":"2013","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"28","key":"pcbi.1011496.ref092","doi-asserted-by":"crossref","first-page":"12670","DOI":"10.1073\/pnas.1007239107","article-title":"Topological basis for the robust distribution of blood to rodent neocortex","volume":"107","author":"P Blinder","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"11","key":"pcbi.1011496.ref093","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41592-019-0554-0","article-title":"The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue","volume":"16","author":"FF Voigt","year":"2019","journal-title":"Nature methods"},{"issue":"4","key":"pcbi.1011496.ref094","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.cell.2014.10.010","article-title":"iDISCO: a simple, rapid method to immunolabel large tissue samples for volume imaging","volume":"159","author":"N Renier","year":"2014","journal-title":"Cell"},{"key":"pcbi.1011496.ref095","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.3389\/fphys.2019.01329","article-title":"Blood rheology: key parameters, impact on blood flow, role in sickle cell disease and effects of exercise","volume":"10","author":"E Nader","year":"2019","journal-title":"Frontiers in physiology"},{"issue":"3","key":"pcbi.1011496.ref096","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/0026-2862(80)90064-3","article-title":"The distensibility of single capillaries and venules in the cat mesentery","volume":"20","author":"L Smaje","year":"1980","journal-title":"Microvascular research"},{"issue":"2","key":"pcbi.1011496.ref097","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0026-2862(86)90051-8","article-title":"Pressure pulse transmission into vascular beds","volume":"32","author":"AG Salotto","year":"1986","journal-title":"Microvascular research"},{"issue":"2","key":"pcbi.1011496.ref098","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.neuroimage.2006.03.043","article-title":"Hierarchical microimaging for multiscale analysis of large vascular networks","volume":"32","author":"S Heinzer","year":"2006","journal-title":"Neuroimage"},{"issue":"46","key":"pcbi.1011496.ref099","doi-asserted-by":"crossref","first-page":"14553","DOI":"10.1523\/JNEUROSCI.3287-09.2009","article-title":"Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels","volume":"29","author":"PS Tsai","year":"2009","journal-title":"Journal of Neuroscience"},{"issue":"4","key":"pcbi.1011496.ref100","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1152\/jappl.1999.86.4.1211","article-title":"Increased brain capillaries in chronic hypoxia","volume":"86","author":"JA Boero","year":"1999","journal-title":"Journal of applied physiology"},{"issue":"2","key":"pcbi.1011496.ref101","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.neuron.2018.06.012","article-title":"Vascular compartmentalization of functional hyperemia from the synapse to the pia","volume":"99","author":"RL Rungta","year":"2018","journal-title":"Neuron"},{"issue":"3","key":"pcbi.1011496.ref102","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nn.4489","article-title":"Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain","volume":"20","author":"K Kisler","year":"2017","journal-title":"Nature neuroscience"},{"issue":"5","key":"pcbi.1011496.ref103","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41593-020-00793-2","article-title":"Brain capillary pericytes exert a substantial but slow influence on blood flow","volume":"24","author":"DA Hartmann","year":"2021","journal-title":"Nature Neuroscience"},{"issue":"1","key":"pcbi.1011496.ref104","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":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pcbi.1011496.ref105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-14330-z","article-title":"Precapillary sphincters maintain perfusion in the cerebral cortex","volume":"11","author":"S Grubb","year":"2020","journal-title":"Nature communications"},{"key":"pcbi.1011496.ref106","article-title":"IT\u2019IS Database for thermal and electromagnetic parameters of biological tissues","author":"P Hasgall","year":"2018","journal-title":"Version 40"},{"issue":"5","key":"pcbi.1011496.ref107","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.7150\/thno.18509","article-title":"Hypertension, cerebrovascular impairment, and cognitive decline in aged A\u03b2PP\/PS1 mice","volume":"7","author":"M Wiesmann","year":"2017","journal-title":"Theranostics"},{"issue":"1","key":"pcbi.1011496.ref108","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/2394-8108.178544","article-title":"Magnetic resonance imaging of cerebral blood flow in animal stroke models","volume":"2","author":"Q Shen","year":"2016","journal-title":"Brain circulation"},{"issue":"1","key":"pcbi.1011496.ref109","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1006\/nbdi.2001.0460","article-title":"Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein","volume":"9","author":"K Niwa","year":"2002","journal-title":"Neurobiology of disease"},{"issue":"4","key":"pcbi.1011496.ref110","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1177\/0271678X211062274","article-title":"Arterial spin labeling demonstrates preserved regional cerebral blood flow in the P301L mouse model of tauopathy","volume":"42","author":"D Kindler","year":"2022","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"pcbi.1011496.ref111","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.brainres.2018.08.001","article-title":"Multifaceted assessment of the APP\/PS1 mouse model for Alzheimer\u2019s disease: Applying MRS, DTI, and ASL","volume":"1698","author":"Z Shen","year":"2018","journal-title":"Brain research"},{"issue":"5","key":"pcbi.1011496.ref112","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1161\/01.RES.77.5.1017","article-title":"Design principles of vascular beds","volume":"77","author":"AR Pries","year":"1995","journal-title":"Circulation research"},{"issue":"1","key":"pcbi.1011496.ref113","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/10739680590894966","article-title":"Microvascular rheology and hemodynamics","volume":"12","author":"HH Lipowsky","year":"2005","journal-title":"Microcirculation"},{"issue":"3","key":"pcbi.1011496.ref114","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/0026-2862(77)90030-9","article-title":"Methods for the simultaneous measurement of pressure differentials and flow in single unbranched vessels of the microcirculation for rheological studies","volume":"14","author":"HH Lipowsky","year":"1977","journal-title":"Microvascular research"},{"issue":"9","key":"pcbi.1011496.ref115","doi-asserted-by":"crossref","first-page":"e14067","DOI":"10.14814\/phy2.14067","article-title":"Three-dimensional distribution of wall shear stress and its gradient in red cell-resolved computational modeling of blood flow in in vivo-like microvascular networks","volume":"7","author":"P Balogh","year":"2019","journal-title":"Physiological reports"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011496","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011496","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T18:23:49Z","timestamp":1698949429000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011496"}},"subtitle":[],"editor":[{"given":"Timothy W.","family":"Secomb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":115,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011496","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1011496","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}