{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:09:03Z","timestamp":1788898143513,"version":"build-2803163510"},"reference-count":103,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":214,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41-EB030006"],"award-info":[{"award-number":["P41-EB030006"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01-EB019437"],"award-info":[{"award-number":["R01-EB019437"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01-EB032746"],"award-info":[{"award-number":["R01-EB032746"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01-MH111419"],"award-info":[{"award-number":["R01-MH111419"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["F32-MH125599"],"award-info":[{"award-number":["F32-MH125599"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U19-NS123717"],"award-info":[{"award-number":["U19-NS123717"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MFE-164755"],"award-info":[{"award-number":["MFE-164755"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Functional magnetic resonance imaging (fMRI) is broadly used to measure human brain activity, however, the hemodynamic changes that comprise the fMRI response to neuronal activity are often interpreted using microscopy data in mice. These microscopy data provide ground-truth observations of how individual blood vessels respond to neuronal activity and thus form the basis of our fundamental understanding of neurovascular coupling. Although these invasive experiments provide invaluable insight, there are striking differences in the vascular architecture of mouse and human brains that may influence the hemodynamic response. Motivated by this, we developed a biophysical modeling framework for realistic hemodynamic simulations in both mouse and human cerebral cortex. For this, we utilized Vascular Anatomical Network (VAN) models that explicitly represent the full microvascular tree as a single connected network, originally based on anatomical reconstructions from a given location of mouse cerebral cortex. We extended the VAN modeling framework using synthetic VAN models representing the microvascular network at a single location of the human cerebral cortex. To account for larger size and complexity of the human VAN models, we developed an efficient computational framework to simulate the full hemodynamic responses in this human model and compared the simulated fMRI responses between mice and humans. Our biophysical simulations are based entirely on first principles (e.g., conservation of mass); model parameter values were fixed across all simulations, not tuned to fit data, as they represent meaningful physical constants taken from previous measurements. Only two simple calibrations were tuned for each simulation, to match baseline perfusion rates (blood flow) and oxygen extraction (OEF). Our results show that differences in microvasculature indeed influenced the hemodynamic response and led to observable differences in timing\u2014for example, the simulated fMRI response peak in humans was delayed by ~2 s compared with that of mice, consistent with prior fMRI observations. While there are many known differences in vascular architecture in rodents and humans, we also discovered that, unexpectedly, an asymmetry in the number of branches of the penetrating intracortical arterioles and venules appears to be conserved across species. We demonstrate through further simulations that this anatomical property may also be needed for suitable hemodynamic responses. Our framework thus provides a valuable tool for bridging in-vivo microscopy of microvascular dynamics to human fMRI.<\/jats:p>","DOI":"10.1162\/imag.a.1340","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T20:01:52Z","timestamp":1785787312000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":0,"title":["Biophysical simulations of fMRI responses using realistic microvascular models: Insights into distinct hemodynamics in humans and mice"],"prefix":"10.1162","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7107-3050","authenticated-orcid":false,"given":"Grant","family":"Hartung","sequence":"first","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States"},{"name":"Department of Radiology, Harvard Medical School, Boston, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery J.L.","family":"Berman","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States"},{"name":"Department of Radiology, Harvard Medical School, Boston, MA, United States"},{"name":"Department of Physics, Carleton University, Ottawa, ON, Canada"},{"name":"Institute of Mental Health Research, Royal Ottawa Mental Health Centre, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sava","family":"Sakad\u017ei\u0107","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States"},{"name":"Department of Radiology, Harvard Medical School, Boston, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Linninger","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States"},{"name":"Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Boas","sequence":"additional","affiliation":[{"name":"Neurophotonics Center, Department of Biomedical Engineering, Boston University, Boston, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-1179","authenticated-orcid":false,"given":"Jonathan R.","family":"Polimeni","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States"},{"name":"Department of Radiology, Harvard Medical School, Boston, MA, United States"},{"name":"Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"281","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.neuroimage.2011.10.025","article-title":"SPM: A history","volume":"62","author":"Ashburner","year":"2012","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuroimage.2017.09.015","article-title":"The impact of vessel size, orientation and intravascular contribution on the neurovascular fingerprint of BOLD bSSFP fMRI","volume":"163","author":"B\u00e1ez-Y\u00e1\u00f1ez","year":"2017","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/B978-0-443-13480-7.00008-9","article-title":"Biophysical modeling: An approach for understanding the physiological fingerprint of the BOLD fMRI signal","volume-title":"Computational and Network Modeling of Neuroimaging Data","author":"B\u00e1ez-Y\u00e1\u00f1ez","year":"2024"},{"key":"2026090815560393100_IMAG.a.1340-b4","doi-asserted-by":"crossref","DOI":"10.1162\/imag_a_00573","article-title":"Impact of vascular architecture, oxygen saturation, and hematocrit on human cortical depth-dependent GE-and SE-BOLD fMRI signals: A simulation approach using realistic 3D vascular networks","volume":"3","author":"B\u00e1ez-Y\u00e1\u00f1ez","year":"2025","journal-title":"Imaging Neuroscience"},{"issue":"2\u20133","key":"2026090815560393100_IMAG.a.1340-b5","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/ima.1850060203","article-title":"Effects of biophysical and physiologic parameters on brain activation-induced R2* and R2 changes: Simulations using a deterministic diffusion model","volume":"6","author":"Bandettini","year":"1995","journal-title":"International Journal of Imaging Systems and Technology"},{"key":"2026090815560393100_IMAG.a.1340-b6","article-title":"Biophysical simulations of the BOLD fMRI signal using realistic imaging gradients: Understanding macrovascular contamination in spin-echo EPI","volume":"29","author":"Berman","year":"2021","journal-title":"Proceedings of the International Society for Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b7","article-title":"Segmentation of cerebral cortical microvasculature using an enhanced multi-scale Frangi approach","volume":"25","author":"Bernier","year":"2019","journal-title":"Proceedings of the Organization for Human Brain Mapping"},{"key":"2026090815560393100_IMAG.a.1340-b8","doi-asserted-by":"crossref","first-page":"210","DOI":"10.3389\/fnagi.2018.00210","article-title":"Pericyte structural remodeling in cerebrovascular health and homeostasis","volume":"10","author":"Berthiaume","year":"2018","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"7","key":"2026090815560393100_IMAG.a.1340-b9","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":"Blinder","year":"2013","journal-title":"Nature Neuroscience"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b10","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":"Boas","year":"2008","journal-title":"NeuroImage"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b11","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s41467-019-09082-4","article-title":"Mesoscopic and microscopic imaging of sensory responses in the same animal","volume":"10","author":"Boido","year":"2019","journal-title":"Nature Communications"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/mrm.1910340412","article-title":"MR contrast due to intravascular magnetic susceptibility perturbations","volume":"34","author":"Boxerman","year":"1995","journal-title":"Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b13","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511605505","volume-title":"Introduction to functional magnetic resonance imaging: Principles and techniques","author":"Buxton","year":"2009"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b14","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.neuroimage.2012.01.012","article-title":"Dynamic models of BOLD contrast","volume":"62","author":"Buxton","year":"2012","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b15","doi-asserted-by":"crossref","first-page":"S220","DOI":"10.1016\/j.neuroimage.2004.07.013","article-title":"Modeling the hemodynamic response to brain activation","volume":"23","author":"Buxton","year":"2004","journal-title":"NeuroImage"},{"issue":"25","key":"2026090815560393100_IMAG.a.1340-b16","doi-asserted-by":"crossref","first-page":"E5796","DOI":"10.1073\/pnas.1707702115","article-title":"Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses","volume":"115","author":"Cai","year":"2018","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b17","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":"Cassot","year":"2006","journal-title":"Microcirculation"},{"key":"2026090815560393100_IMAG.a.1340-b18","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":"Cassot","year":"2010","journal-title":"Brain Research"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b19","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":"Cassot","year":"2009","journal-title":"Microcirculation"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b20","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.neuroimage.2010.09.036","article-title":"High-speed vascular dynamics of the hemodynamic response","volume":"54","author":"Chen","year":"2011","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b21","doi-asserted-by":"crossref","first-page":"118658","DOI":"10.1016\/j.neuroimage.2021.118658","article-title":"Investigating mechanisms of fast BOLD responses: The effects of stimulus intensity and of spatial heterogeneity of hemodynamics","volume":"245","author":"Chen","year":"2021","journal-title":"NeuroImage"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b22","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.neuroimage.2009.03.015","article-title":"Origins of the BOLD post-stimulus undershoot","volume":"46","author":"Chen","year":"2009","journal-title":"NeuroImage"},{"issue":"9","key":"2026090815560393100_IMAG.a.1340-b23","doi-asserted-by":"crossref","first-page":"e3000923","DOI":"10.1371\/journal.pbio.3000923","article-title":"Assessment of single-vessel cerebral blood velocity by phase contrast fMRI","volume":"19","author":"Chen","year":"2021","journal-title":"PLoS Biology"},{"issue":"6","key":"2026090815560393100_IMAG.a.1340-b24","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1002\/mrm.27660","article-title":"Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks","volume":"81","author":"Cheng","year":"2019","journal-title":"Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b25","doi-asserted-by":"crossref","first-page":"118978","DOI":"10.1016\/j.neuroimage.2022.118978","article-title":"Cortical layer-specific differences in stimulus selectivity revealed with high-field fMRI and single-vessel resolution optical imaging of the primary visual cortex","volume":"251","author":"Cho","year":"2022","journal-title":"NeuroImage"},{"issue":"6","key":"2026090815560393100_IMAG.a.1340-b26","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nmeth.2481","article-title":"CLARITY for mapping the nervous system","volume":"10","author":"Chung","year":"2013","journal-title":"Nature Methods"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b27","doi-asserted-by":"crossref","first-page":"14229","DOI":"10.1038\/s41598-021-93503-2","article-title":"A simulation study investigating potential diffusion-based MRI signatures of microstrokes","volume":"11","author":"Damseh","year":"2021","journal-title":"Scientific Reports"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b28","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1073\/pnas.95.4.1834","article-title":"Calibrated functional MRI: Mapping the dynamics of oxidative metabolism","volume":"95","author":"Davis","year":"1998","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b29","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0896-6273(03)00403-3","article-title":"Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex","volume":"39","author":"Devor","year":"2003","journal-title":"Neuron"},{"key":"2026090815560393100_IMAG.a.1340-b30","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.conb.2019.06.004","article-title":"Vascular and neural basis of the BOLD signal","volume":"58","author":"Drew","year":"2019","journal-title":"Current Opinion in Neurobiology"},{"issue":"20","key":"2026090815560393100_IMAG.a.1340-b31","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":"Drew","year":"2011","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"5","key":"2026090815560393100_IMAG.a.1340-b32","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":"Duvernoy","year":"1981","journal-title":"Brain Research Bulletin"},{"key":"2026090815560393100_IMAG.a.1340-b33","doi-asserted-by":"crossref","first-page":"566303","DOI":"10.3389\/fphys.2020.566303","article-title":"Predicting vessel diameter changes to up-regulate biphasic blood flow during activation in realistic microvascular networks","volume":"11","author":"Epp","year":"2020","journal-title":"Frontiers in Physiology"},{"issue":"22","key":"2026090815560393100_IMAG.a.1340-b34","doi-asserted-by":"crossref","first-page":"17530","DOI":"10.1364\/OE.16.017530","article-title":"Oxygen advection and diffusion in a three dimensional vascular anatomical network","volume":"16","author":"Fang","year":"2008","journal-title":"Optics Express"},{"key":"2026090815560393100_IMAG.a.1340-b35","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.neuroimage.2016.06.048","article-title":"Systematic variation of population receptive field properties across cortical depth in human visual cortex","volume":"139","author":"Fracasso","year":"2016","journal-title":"NeuroImage"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b36","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.neuroimage.2010.03.060","article-title":"The effect of different anesthetics on neurovascular coupling","volume":"51","author":"Franceschini","year":"2010","journal-title":"NeuroImage"},{"issue":"1815","key":"2026090815560393100_IMAG.a.1340-b37","doi-asserted-by":"crossref","first-page":"20190623","DOI":"10.1098\/rstb.2019.0623","article-title":"Time-dependent spatial specificity of high-resolution fMRI: Insights into mesoscopic neurovascular coupling","volume":"376","author":"Fukuda","year":"2021","journal-title":"Philosophical Transactions of the Royal Society B"},{"issue":"8","key":"2026090815560393100_IMAG.a.1340-b38","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1523\/JNEUROSCI.3555-14.2015","article-title":"Quantifying the microvascular origin of BOLD-fMRI from first principles with two-photon microscopy and an oxygen-sensitive nanoprobe","volume":"35","author":"Gagnon","year":"2015","journal-title":"Journal of Neuroscience"},{"key":"2026090815560393100_IMAG.a.1340-b39","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.neuroimage.2016.11.069","article-title":"Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal","volume":"153","author":"Gao","year":"2017","journal-title":"NeuroImage"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b40","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/mrm.28429","article-title":"Modeling of vascular space occupancy and BOLD functional MRI from first principles using real microvascular angiograms","volume":"85","author":"Genois","year":"2021","journal-title":"Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b41","doi-asserted-by":"crossref","DOI":"10.1162\/imag_a_00399","article-title":"The temporal specificity of BOLD fMRI is systematically related to anatomical and vascular features of the human brain","volume":"2","author":"Gomez","year":"2024","journal-title":"Imaging Neuroscience"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/micc.12156","article-title":"Hematocrit distribution and tissue oxygenation in large microcirculatory networks","volume":"22","author":"Gould","year":"2015","journal-title":"Microcirculation"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b43","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":"Gould","year":"2017","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b44","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neuroimage.2011.05.077","article-title":"A theoretical framework for estimating cerebral oxygen metabolism changes using the calibrated-BOLD method: Modeling the effects of blood volume distribution, hematocrit, oxygen extraction fraction, and tissue signal properties on the BOLD signal","volume":"58","author":"Griffeth","year":"2011","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b45","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1146\/annurev-physiol-061121-040127","article-title":"Pericyte control of blood flow across microvascular zones in the central nervous system","volume":"84","author":"Hartmann","year":"2022","journal-title":"Annual Review of Physiology"},{"issue":"5","key":"2026090815560393100_IMAG.a.1340-b46","doi-asserted-by":"crossref","first-page":"e12687","DOI":"10.1111\/micc.12687","article-title":"Mathematical synthesis of the cortical circulation for the whole mouse brain-Part II: Microcirculatory closure","volume":"28","author":"Hartung","year":"2021","journal-title":"Microcirculation"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b47","doi-asserted-by":"crossref","first-page":"e1008584","DOI":"10.1371\/journal.pcbi.1008584","article-title":"Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex","volume":"17","author":"Hartung","year":"2021","journal-title":"PLoS Computational Biology"},{"key":"2026090815560393100_IMAG.a.1340-b48","article-title":"Estimating cortical laminar specificity of blood flow from precapillary arterioles using biophysical simulations","volume":"28","author":"Hartung","year":"2022","journal-title":"Proceedings of the Organization for Human Brain Mapping"},{"issue":"11","key":"2026090815560393100_IMAG.a.1340-b49","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":"Hartung","year":"2018","journal-title":"PLoS Computational Biology"},{"key":"2026090815560393100_IMAG.a.1340-b50","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.neuroimage.2017.07.034","article-title":"Echo-time dependence of the BOLD response transients\u2013a window into brain functional physiology","volume":"159","author":"Havlicek","year":"2017","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b51","doi-asserted-by":"crossref","first-page":"116209","DOI":"10.1016\/j.neuroimage.2019.116209","article-title":"A dynamical model of the laminar BOLD response","volume":"204","author":"Havlicek","year":"2020","journal-title":"NeuroImage"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.neuroimage.2006.11.032","article-title":"Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation","volume":"35","author":"Hillman","year":"2007","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b53","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.neuroimage.2017.07.041","article-title":"Non-BOLD contrast for laminar fMRI in humans: CBF, CBV, and CMRO2","volume":"197","author":"Huber","year":"2019","journal-title":"NeuroImage"},{"issue":"6","key":"2026090815560393100_IMAG.a.1340-b54","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/sj.jcbfm.9600435","article-title":"A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation","volume":"27","author":"Huppert","year":"2007","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026090815560393100_IMAG.a.1340-b55","doi-asserted-by":"crossref","first-page":"117807","DOI":"10.1016\/j.neuroimage.2021.117807","article-title":"Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging","volume":"230","author":"Juttukonda","year":"2021","journal-title":"NeuroImage"},{"issue":"5","key":"2026090815560393100_IMAG.a.1340-b56","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1114\/1.290","article-title":"Staged growth of optimized arterial model trees","volume":"28","author":"Karch","year":"2000","journal-title":"Annals of Biomedical Engineering"},{"issue":"24","key":"2026090815560393100_IMAG.a.1340-b57","doi-asserted-by":"crossref","first-page":"6381","DOI":"10.1088\/0031-9155\/51\/24\/007","article-title":"Rapid calculations of susceptibility-induced magnetostatic field perturbations for in vivo magnetic resonance","volume":"51","author":"Koch","year":"2006","journal-title":"Physics in Medicine & Biology"},{"issue":"8","key":"2026090815560393100_IMAG.a.1340-b58","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1038\/jcbfm.2012.63","article-title":"Cerebral blood volume changes during brain activation","volume":"32","author":"Krieger","year":"2012","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b59","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1137\/20M1329664","article-title":"Analysis and approximation of mixed-dimensional PDEs on 3D-1D domains coupled with Lagrange multipliers","volume":"59","author":"Kuchta","year":"2021","journal-title":"SIAM Journal on Numerical Analysis"},{"key":"2026090815560393100_IMAG.a.1340-b60","doi-asserted-by":"crossref","first-page":"116446","DOI":"10.1016\/j.neuroimage.2019.116446","article-title":"A cortical rat hemodynamic response function for improved detection of BOLD activation under common experimental conditions","volume":"208","author":"Lambers","year":"2020","journal-title":"NeuroImage"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b61","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":"Lauwers","year":"2008","journal-title":"NeuroImage"},{"issue":"9","key":"2026090815560393100_IMAG.a.1340-b62","doi-asserted-by":"crossref","first-page":"eadm7605","DOI":"10.1126\/sciadv.adm7605","article-title":"Mapping cerebral perfusion in mice under various anesthesia levels using highly sensitive BOLD MRI with transient hypoxia","volume":"10","author":"Le","year":"2024","journal-title":"Science Advances"},{"key":"2026090815560393100_IMAG.a.1340-b63","doi-asserted-by":"crossref","first-page":"e42299","DOI":"10.7554\/eLife.42299","article-title":"More homogeneous capillary flow and oxygenation in deeper cortical layers correlate with increased oxygen extraction","volume":"8","author":"Li","year":"2019","journal-title":"Elife"},{"key":"2026090815560393100_IMAG.a.1340-b64","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":"Linninger","year":"2019","journal-title":"Computers in Biology and Medicine"},{"issue":"11","key":"2026090815560393100_IMAG.a.1340-b65","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":"Linninger","year":"2013","journal-title":"Annals of Biomedical Engineering"},{"issue":"5","key":"2026090815560393100_IMAG.a.1340-b66","doi-asserted-by":"crossref","first-page":"801","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":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b67","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1017\/S1355617707070646","article-title":"Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods","volume":"13","author":"Liu","year":"2007","journal-title":"Journal of the International Neuropsychological Society"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b68","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":"Lorthois","year":"2011","journal-title":"NeuroImage"},{"issue":"10","key":"2026090815560393100_IMAG.a.1340-b69","doi-asserted-by":"crossref","first-page":"e3001440","DOI":"10.1371\/journal.pbio.3001440","article-title":"Baseline oxygen consumption decreases with cortical depth","volume":"20","author":"M\u00e4chler","year":"2022","journal-title":"PLoS Biology"},{"issue":"6","key":"2026090815560393100_IMAG.a.1340-b70","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/00004647-199906000-00012","article-title":"Evidence of a cerebrovascular postarteriole windkessel with delayed compliance","volume":"19","author":"Mandeville","year":"1999","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026090815560393100_IMAG.a.1340-b71","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.neuroimage.2016.02.073","article-title":"A cortical vascular model for examining the specificity of the laminar BOLD signal","volume":"132","author":"Markuerkiaga","year":"2016","journal-title":"NeuroImage"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b72","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1460-9568.2009.06812.x","article-title":"Dose-dependent effect of isoflurane on neurovascular coupling in rat cerebral cortex","volume":"30","author":"Masamoto","year":"2009","journal-title":"European Journal of Neuroscience"},{"key":"2026090815560393100_IMAG.a.1340-b73","doi-asserted-by":"crossref","first-page":"120512","DOI":"10.1016\/j.neuroimage.2024.120512","article-title":"Network response of brain microvasculature to neuronal stimulation","volume":"287","author":"Mester","year":"2024","journal-title":"NeuroImage"},{"issue":"5","key":"2026090815560393100_IMAG.a.1340-b74","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1113\/JP282246","article-title":"The post-arteriole transitional zone: A specialized capillary region that regulates blood flow within the CNS microvasculature","volume":"601","author":"Mughal","year":"2023","journal-title":"The Journal of Physiology"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b75","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":"Murray","year":"1926","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"19","key":"2026090815560393100_IMAG.a.1340-b76","doi-asserted-by":"crossref","first-page":"8411","DOI":"10.1523\/JNEUROSCI.3285-12.2013","article-title":"In vivo stimulus-induced vasodilation occurs without IP3 receptor activation and may precede astrocytic calcium increase","volume":"33","author":"Nizar","year":"2013","journal-title":"Journal of Neuroscience"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b77","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/S0006-3495(93)81441-3","article-title":"Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model","volume":"64","author":"Ogawa","year":"1993","journal-title":"Biophysical Journal"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b78","doi-asserted-by":"crossref","first-page":"e3288","DOI":"10.1002\/cnm.3288","article-title":"Quantification of blood flow patterns in the cerebral arterial circulation of individual (human) subjects","volume":"36","author":"Park","year":"2020","journal-title":"International Journal for Numerical Methods in Biomedical Engineering"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b79","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.medengphy.2015.09.004","article-title":"Modelling the effects of cerebral microvasculature morphology on oxygen transport","volume":"38","author":"Park","year":"2016","journal-title":"Medical Engineering & Physics"},{"issue":"3","key":"2026090815560393100_IMAG.a.1340-b80","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.neuroimage.2008.01.022","article-title":"A novel technique for modeling susceptibility-based contrast mechanisms for arbitrary microvascular geometries: The finite perturber method","volume":"40","author":"Pathak","year":"2008","journal-title":"NeuroImage"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b81","doi-asserted-by":"crossref","first-page":"e12428","DOI":"10.1111\/micc.12428","article-title":"Oxygen delivery from the cerebral microvasculature to tissue is governed by a single time constant of approximately 6 seconds","volume":"25","author":"Payne","year":"2018","journal-title":"Microcirculation"},{"key":"2026090815560393100_IMAG.a.1340-b82","article-title":"The role of rapid capillary resistance decreases in the BOLD response assessed through simulations in a realistic vascular network","volume":"28","author":"Pfannmoeller","year":"2020","journal-title":"Proceedings of the International Society for Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b83","article-title":"Simulations of the BOLD non-linearity based on a viscoelastic model for capillary and vein compliance","volume":"29","author":"Pfannmoeller","year":"2021","journal-title":"Proceedings of the International Society for Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b84","doi-asserted-by":"crossref","first-page":"102174","DOI":"10.1016\/j.pneurobio.2021.102174","article-title":"Imaging faster neural dynamics with fast fMRI: A need for updated models of the hemodynamic response","volume":"207","author":"Polimeni","year":"2021","journal-title":"Progress in Neurobiology"},{"key":"2026090815560393100_IMAG.a.1340-b85","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.conb.2018.04.026","article-title":"Magnetic resonance imaging technology\u2014Bridging the gap between noninvasive human imaging and optical microscopy","volume":"50","author":"Polimeni","year":"2018","journal-title":"Current Opinion in Neurobiology"},{"issue":"46","key":"2026090815560393100_IMAG.a.1340-b86","doi-asserted-by":"crossref","first-page":"15263","DOI":"10.1523\/JNEUROSCI.1015-15.2015","article-title":"Layer-specific fMRI responses to excitatory and inhibitory neuronal activities in the olfactory bulb","volume":"35","author":"Poplawsky","year":"2015","journal-title":"Journal of Neuroscience"},{"issue":"8","key":"2026090815560393100_IMAG.a.1340-b87","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":"Reichold","year":"2009","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"key":"2026090815560393100_IMAG.a.1340-b88","doi-asserted-by":"crossref","first-page":"5734","DOI":"10.1038\/ncomms6734","article-title":"Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue","volume":"5","author":"Sakad\u017ei\u0107","year":"2014","journal-title":"Nature Communications"},{"issue":"9","key":"2026090815560393100_IMAG.a.1340-b89","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nmeth.1490","article-title":"Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue","volume":"7","author":"Sakad\u017ei\u0107","year":"2010","journal-title":"Nature Methods"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b90","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1002\/mrm.28871","article-title":"BOLD sensitivity and vessel size specificity along CPMG and GRASE echo trains","volume":"86","author":"Scheffler","year":"2021","journal-title":"Magnetic Resonance in Medicine"},{"key":"2026090815560393100_IMAG.a.1340-b91","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":"Schmid","year":"2019","journal-title":"NeuroImage"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b92","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":"Schmid","year":"2017","journal-title":"PLoS Computational Biology"},{"issue":"34","key":"2026090815560393100_IMAG.a.1340-b93","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":"Tian","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"46","key":"2026090815560393100_IMAG.a.1340-b94","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":"Tsai","year":"2009","journal-title":"Journal of Neuroscience"},{"key":"2026090815560393100_IMAG.a.1340-b95","doi-asserted-by":"crossref","first-page":"e14315","DOI":"10.7554\/eLife.14315","article-title":"Cell type specificity of neurovascular coupling in cerebral cortex","volume":"5","author":"Uhlirova","year":"2016","journal-title":"Elife"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b96","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.neuroimage.2009.05.051","article-title":"An integrative model for neuronal activity-induced signal changes for gradient and spin echo functional imaging","volume":"48","author":"Uluda\u011f","year":"2009","journal-title":"NeuroImage"},{"key":"2026090815560393100_IMAG.a.1340-b97","article-title":"Measuring individual vein and artery BOLD responses to visual stimuli in humans with multi-echo single-vessel functional MRI at 7T","volume":"31","author":"Varadarajan","year":"2023","journal-title":"Proceedings of the International Society for Magnetic Resonance in Medicine"},{"issue":"2","key":"2026090815560393100_IMAG.a.1340-b98","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/jcbfm.2009.213","article-title":"Changes in cerebral arterial, tissue and venous oxygenation with evoked neural stimulation: Implications for hemoglobin-based functional neuroimaging","volume":"30","author":"Vazquez","year":"2010","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"8","key":"2026090815560393100_IMAG.a.1340-b99","doi-asserted-by":"crossref","first-page":"e3735","DOI":"10.1002\/cnm.3735","article-title":"Mesh-free high-resolution simulation of cerebrocortical oxygen supply with fast Fourier preconditioning","volume":"39","author":"Ventimiglia","year":"2023","journal-title":"International Journal for Numerical Methods in Biomedical Engineering"},{"key":"2026090815560393100_IMAG.a.1340-b100","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuroimage.2019.04.036","article-title":"Dependence of resting-state fMRI fluctuation amplitudes on cerebral cortical orientation relative to the direction of B0 and anatomical axes","volume":"196","author":"Viessmann","year":"2019","journal-title":"NeuroImage"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b101","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/jcbfm.2010.227","article-title":"Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation","volume":"31","author":"Yaseen","year":"2011","journal-title":"Journal of Cerebral Blood Flow & Metabolism"},{"issue":"4","key":"2026090815560393100_IMAG.a.1340-b102","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nmeth.3765","article-title":"Sensory and optogenetically driven single-vessel fMRI","volume":"13","author":"Yu","year":"2016","journal-title":"Nature Methods"},{"issue":"1","key":"2026090815560393100_IMAG.a.1340-b103","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nmeth.2730","article-title":"Deciphering laminar-specific neural inputs with line-scanning fMRI","volume":"11","author":"Yu","year":"2014","journal-title":"Nature Methods"}],"container-title":["Imaging Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/direct.mit.edu\/imag\/article-pdf\/doi\/10.1162\/IMAG.a.1340\/2618540\/imag.a.1340.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/direct.mit.edu\/imag\/article-pdf\/doi\/10.1162\/IMAG.a.1340\/2618540\/imag.a.1340.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:56:25Z","timestamp":1788897385000},"score":1,"resource":{"primary":{"URL":"https:\/\/direct.mit.edu\/imag\/article\/doi\/10.1162\/IMAG.a.1340\/138024\/Biophysical-simulations-of-fMRI-responses-using"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":103,"URL":"https:\/\/doi.org\/10.1162\/imag.a.1340","relation":{},"ISSN":["2837-6056"],"issn-type":[{"value":"2837-6056","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"IMAG.a.1340"}}