{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:01:21Z","timestamp":1782280881681,"version":"3.54.5"},"posted":{"date-parts":[[2026,2,6]]},"group-title":"Bioengineering","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH NIA","award":["1R01AG079894-01"],"award-info":[{"award-number":["1R01AG079894-01"]}]},{"name":"NIH NINDS","award":["U19NS123717"],"award-info":[{"award-number":["U19NS123717"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mechanistic simulations of blood flow and oxygen exchange showed regions of cortical tissue tolerating substantial increase in local oxygen consumption (CMRO2) before reaching hypoxia (pO2&lt;10 mmHg). The observed robustness in O\n                  <jats:sub>2<\/jats:sub>\n                  supply was attributed to overcapacity in convective oxygen transport in the pial arterial network combined with a surplus in the number of capillary flow paths. Microcirculatory flux analysis suggests that\n                  <jats:italic>network<\/jats:italic>\n                  induced hemodynamic flow patterns impart\n                  <jats:italic>intrinsic reserve<\/jats:italic>\n                  to protect the brain against perfusion variances or metabolic demand surges during activation. Furthermore, oxygen transport in cortical tissue is characterized by two regimes: in the\n                  <jats:italic>transport zone \u2014<\/jats:italic>\n                  centered on\n                  <jats:italic>penetrating arteriole trees<\/jats:italic>\n                  composed of a single penetrating vessel connected to the post-arteriole capillary transition zone \u2014 strong diffusion supports high oxygen tension with only modest contribution from capillaries. This regime transitions into the\n                  <jats:italic>terminal\/reactive zone<\/jats:italic>\n                  where oxygenation is sensitive to capillary density and perfusion. Quasi-dynamic simulations also enabled reconstruction of the BOLD signal underlying functional imaging. Simulations at single micron resolution further show that age-related reductions in arterial saturation and systemic hematocrit were sufficient to induce hypoxic tissue pockets in the terminal zone at nominal perfusion (CBF) and metabolic activity (CMRO\n                  <jats:sub>2<\/jats:sub>\n                  ), and neutrophil adhesion induced capillary flow stalling further exacerbates hypoxia.\n                <\/jats:p>","DOI":"10.64898\/2026.02.03.703617","type":"posted-content","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T21:20:57Z","timestamp":1770412857000},"source":"Crossref","is-referenced-by-count":0,"title":["Microvascular network organization and hemodynamic perfusion protect the brain against hypoxia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9951-0712","authenticated-orcid":false,"given":"Thomas","family":"Ventimiglia","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois, Chicago, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8241-7712","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Lesage","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, Polytechnique Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-630X","authenticated-orcid":false,"given":"Andreas A.","family":"Linninger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Illinois, Chicago, USA"},{"name":"Department of Neurosurgery, University of Illinois, Chicago, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026021010054566000_2026.02.03.703617v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.01.136"},{"key":"2026021010054566000_2026.02.03.703617v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26543-w"},{"key":"2026021010054566000_2026.02.03.703617v1.3","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20914179"},{"key":"2026021010054566000_2026.02.03.703617v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108260"},{"key":"2026021010054566000_2026.02.03.703617v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0329-4"},{"key":"2026021010054566000_2026.02.03.703617v1.6","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1919.sp001839"},{"key":"2026021010054566000_2026.02.03.703617v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1963.tb02652.x"},{"key":"2026021010054566000_2026.02.03.703617v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.153"},{"key":"2026021010054566000_2026.02.03.703617v1.9","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-013-0828-0"},{"key":"2026021010054566000_2026.02.03.703617v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12156"},{"key":"2026021010054566000_2026.02.03.703617v1.11","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16671146"},{"key":"2026021010054566000_2026.02.03.703617v1.12","doi-asserted-by":"crossref","first-page":"7295","DOI":"10.1038\/s41467-021-27534-8","article-title":"Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction","volume":"12","year":"2021","journal-title":"Nat Commun"},{"key":"2026021010054566000_2026.02.03.703617v1.13","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","year":"2021","journal-title":"Elife"},{"key":"2026021010054566000_2026.02.03.703617v1.14","doi-asserted-by":"crossref","first-page":"e1010166","DOI":"10.1371\/journal.pcbi.1010166","article-title":"Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees","volume":"18","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2026021010054566000_2026.02.03.703617v1.15","doi-asserted-by":"crossref","unstructured":"Materne S , Possenti L , Pisani F , et al. 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