{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:23:44Z","timestamp":1793381024480,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1005392","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T00:00:00Z","timestamp":1487030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005392","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T14:53:35Z","timestamp":1487084015000},"page":"e1005392","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":139,"title":["Depth-dependent flow and pressure characteristics in cortical microvascular networks"],"prefix":"10.1371","volume":"13","author":[{"given":"Franca","family":"Schmid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-5276","authenticated-orcid":true,"given":"Philbert S.","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kleinfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Jenny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,2,14]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"H133","DOI":"10.1152\/ajpheart.1988.254.1.H133","article-title":"Effect of sciatic nerve stimulation on pial arterioles in rats","volume":"254","author":"AC Ngai","year":"1988","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1152\/jn.1997.78.2.651","article-title":"Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex","volume":"78","author":"C Iadecola","year":"1997","journal-title":"Journal of neurophysiology"},{"key":"ref3","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":"ref4","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"},{"key":"ref5","first-page":"0271678X15605851","article-title":"Early capillary flux homogenization in response to neural activation","author":"J Lee","year":"2015","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"34","key":"ref6","doi-asserted-by":"crossref","first-page":"15246","DOI":"10.1073\/pnas.1006735107","article-title":"Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal","volume":"107","author":"P Tian","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"ref7","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1161\/01.HYP.6.3.408","article-title":"Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats","volume":"6","author":"SL Harper","year":"1984","journal-title":"Hypertension"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1161\/01.RES.55.3.286","article-title":"Effects of chronic hypertension and sympathetic nerves on the cerebral microvasculature of stroke-prone spontaneously hypertensive rats","volume":"55","author":"AH Werber","year":"1984","journal-title":"Circulation research"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1152\/ajplegacy.1971.221.1.279","article-title":"Dynamic pressures in the pial arterial microcirculation","volume":"221","author":"HM Shapiro","year":"1971","journal-title":"American Journal of Physiology\u2013Legacy Content"},{"key":"ref10","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":"J Cereb Blood Flow Metab"},{"issue":"26","key":"ref11","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":"ref12","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1364\/BOE.5.001160","article-title":"Statistical intensity variation analysis for rapid volumetric imaging of capillary network flux","volume":"5","author":"J Lee","year":"2014","journal-title":"Biomedical optics express"},{"key":"ref13","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"},{"key":"ref14","first-page":"0271678X16631560","article-title":"Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH)","author":"E Guti\u00e9rrez-Jim\u00e9nez","year":"2016","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/jcbfm.2011.153","article-title":"The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism","volume":"32","author":"SN Jespersen","year":"2012","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"10","key":"ref16","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":"4","key":"ref17","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1523\/JNEUROSCI.2765-10.2011","article-title":"Vascularization of cytochrome oxidase-rich blobs in the primary visual cortex of squirrel and macaque monkeys","volume":"31","author":"AL Keller","year":"2011","journal-title":"The Journal of Neuroscience"},{"issue":"2","key":"ref18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/cercor\/12.2.199","article-title":"Vascularization in the primate visual cortex during development","volume":"12","author":"C Fonta","year":"2002","journal-title":"Cerebral Cortex"},{"issue":"7","key":"ref19","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 Neurosci"},{"issue":"3","key":"ref20","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.neuron.2012.09.019","article-title":"High-resolution fMRI reveals laminar differences in neurovascular coupling between positive and negative BOLD responses","volume":"76","author":"J Goense","year":"2012","journal-title":"Neuron"},{"issue":"4","key":"ref21","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.neuroimage.2005.11.013","article-title":"Cortical layer-dependent BOLD and CBV responses measured by spin-echo and gradient-echo fMRI: insights into hemodynamic regulation","volume":"30","author":"F Zhao","year":"2006","journal-title":"Neuroimage"},{"issue":"46","key":"ref22","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":"The Journal of Neuroscience"},{"issue":"4","key":"ref23","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1161\/01.RES.67.4.826","article-title":"Blood flow in microvascular networks. Experiments and simulation","volume":"67","author":"A Pries","year":"1990","journal-title":"Circulation research"},{"issue":"6","key":"ref24","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.media.2012.06.004","article-title":"Vectorization of optically sectioned brain microvasculature: Learning aids completion of vascular graphs by connecting gaps and deleting open-ended segments","volume":"16","author":"JP Kaufhold","year":"2012","journal-title":"Medical image analysis"},{"key":"ref25","first-page":"0271678X15610340","article-title":"What is a pericyte?","author":"D Attwell","year":"2015","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"ref26","first-page":"3","article-title":"The comparative anatomy and embryology of the capillary bed of the central nervous system","volume":"18","author":"EH Craigie","year":"1938","journal-title":"Res Publ Ass Nerv Ment Dis 1938b"},{"issue":"1","key":"ref27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0006-8993(81)90619-3","article-title":"Quantitative capillary topography and blood flow in the cerebral cortex of cats: an in vivo microscopic study","volume":"208","author":"G Pawlik","year":"1981","journal-title":"Brain research"},{"issue":"1","key":"ref28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0026-2862(74)90059-4","article-title":"On-line measurement of the dynamic velocity of erythrocytes in the cerebral microvessels in the rat","volume":"8","author":"Y Ma","year":"1974","journal-title":"Microvascular research"},{"issue":"1\u20132","key":"ref29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000142435","article-title":"Die Kapillardichte im Wirbeltiergehirn","volume":"54","author":"W Lierse","year":"1963","journal-title":"Cells Tissues Organs"},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1006\/mvre.1993.1054","article-title":"Imaging system for three-dimensional mapping of cerebrocortical capillary networks in vivo","volume":"46","author":"AG Hudetz","year":"1993","journal-title":"Microvascular research"},{"issue":"4","key":"ref31","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":"20","key":"ref32","doi-asserted-by":"crossref","first-page":"8473","DOI":"10.1073\/pnas.1100428108","article-title":"Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity","volume":"108","author":"PJ Drew","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"7","key":"ref33","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"},{"issue":"6","key":"ref34","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":"A Pries","year":"1992","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1152\/physrev.1929.9.2.241","article-title":"The suspension stability of the blood","volume":"9","author":"R Fahr\u00e6us","year":"1929","journal-title":"Physiol Rev"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/S0026-2862(73)80005-6","article-title":"Stochastic flow in capillary blood vessels","volume":"5","author":"YC Fung","year":"1973","journal-title":"Microvascular research"},{"issue":"2","key":"ref37","first-page":"H251","article-title":"Effect of velocity of distribution on red cell distribution in capillary blood vessels","volume":"235","author":"R Yen","year":"1978","journal-title":"The American journal of physiology"},{"issue":"1","key":"ref38","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/0026-2862(80)90082-5","article-title":"Cell distribution in capillary networks","volume":"19","author":"G Schmid-Sch\u00f6nbein","year":"1980","journal-title":"Microvascular research"},{"issue":"1","key":"ref39","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/btpr.5420010107","article-title":"Unsteady cell distributions in capillary networks","volume":"1","author":"M Furman","year":"1985","journal-title":"Biotechnology progress"},{"issue":"6","key":"ref40","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"},{"key":"ref41","first-page":"1429","article-title":"Vascular graph model to simulate the cerebral blood flow in realistic vascular networks","volume":"29","author":"J Reichold","year":"2009","journal-title":"JCBFM"},{"issue":"2","key":"ref42","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"},{"key":"ref43","first-page":"0271678X16671146","article-title":"The capillary bed offers the largest hemodynamic resistance to the cortical blood supply","author":"IG Gould","year":"2016","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"3","key":"ref44","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/jcbfm.1987.72","article-title":"Pressure distribution in the pial arterial system of rats based on morphometric data and mathematical models","volume":"7","author":"AG Hudetz","year":"1987","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref45","article-title":"ETH Zurich","author":"J Reichold","year":"2011"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"DeFelipe J. The evolution of the brain, the human nature of cortical circuits, and intellectual creativity. Frontiers in neuroanatomy. 2011;5.","DOI":"10.3389\/fnana.2011.00029"},{"key":"ref47","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 research"},{"key":"ref48","first-page":"952","article-title":"Topology and hemodynamics of the cortical cerebrovascular system","volume":"32","author":"S Hirsch","year":"2012","journal-title":"JCBFM"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3109\/10739689709146787","article-title":"Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy","volume":"4","author":"AG Hudetz","year":"1997","journal-title":"Microcirculation"},{"issue":"1","key":"ref50","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"},{"issue":"2","key":"ref51","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.neuroimage.2006.03.033","article-title":"Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia","volume":"32","author":"EB Hutchinson","year":"2006","journal-title":"Neuroimage"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.brainres.2010.01.032","article-title":"RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size","volume":"1320","author":"M Unekawa","year":"2010","journal-title":"Brain research"},{"key":"ref53","first-page":"0271678X16649195","article-title":"Contribution of low-and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice","author":"B Li","year":"2016","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"2","key":"ref54","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 atomically 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":"3","key":"ref55","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/micc.12195","article-title":"Robust and fragile aspects of cortical blood flow in relation to the underlying angioarchitecture","volume":"22","author":"AY Shih","year":"2015","journal-title":"Microcirculation"},{"issue":"1","key":"ref56","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":"51","key":"ref57","doi-asserted-by":"crossref","first-page":"22290","DOI":"10.1073\/pnas.1011321108","article-title":"Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain","volume":"107","author":"F Fern\u00e1ndez-Klett","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Sakad\u017ei\u0107 S, Mandeville ET, Gagnon L, Musacchia JJ, Yaseen MA, Yucel MA, et al. Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nature communications. 2014;5.","DOI":"10.1038\/ncomms6734"},{"issue":"3","key":"ref59","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/jcbfm.2014.213","article-title":"The effects of transit time heterogeneity on brain oxygenation during rest and functional activation","volume":"35","author":"PM Rasmussen","year":"2015","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"ref60","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":"J Cereb Blood Flow Metab"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e12024","DOI":"10.7554\/eLife.12024","article-title":"Mapping oxygen concentration in the awake mouse brain","volume":"5","author":"DG Lyons","year":"2016","journal-title":"eLife"},{"issue":"38","key":"ref62","doi-asserted-by":"crossref","first-page":"13676","DOI":"10.1523\/JNEUROSCI.1968-11.2011","article-title":"Overshoot of O2 is required to maintain baseline tissue oxygenation at locations distal to blood vessels","volume":"31","author":"A Devor","year":"2011","journal-title":"The Journal of Neuroscience"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1005392","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T11:34:17Z","timestamp":1589024057000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005392"}},"subtitle":[],"editor":[{"given":"Jeffrey J.","family":"Saucerman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,2,14]]},"references-count":62,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005392","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,14]]}}}