{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:04:56Z","timestamp":1789697096762,"version":"4.0.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2024.1238533","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:56:37Z","timestamp":1714006597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study"],"prefix":"10.3389","volume":"15","author":[{"given":"Vittorio","family":"Stumpo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ece Su","family":"Sayin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Bellomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Sobczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan Hendrik Bas","family":"van Niftrik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Seb\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Weller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Regli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Kulcs\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Pangalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Duffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Mikulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorn","family":"Fierstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e5360375","DOI":"10.1155\/2018\/5360375","article-title":"Overview and critical appraisal of arterial spin labelling technique in brain perfusion imaging","volume":"2018","author":"Alsaedi","year":"2018","journal-title":"Contrast Media and Mol. Imaging"},{"key":"B2","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1002\/mrm.25197","article-title":"Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia","volume":"73","author":"Alsop","year":"2015","journal-title":"Magnetic Reson. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","article-title":"The blood\u2013brain barrier and blood\u2013tumour barrier in brain tumours and metastases","volume":"20","author":"Arvanitis","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/mrm.10468","article-title":"Cluster analysis of BOLD fMRI time series in tumors to study the heterogeneity of hemodynamic response to treatment","volume":"49","author":"Baudelet","year":"2003","journal-title":"Magnetic Reson. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"119523","DOI":"10.1016\/j.neuroimage.2022.119523","article-title":"Quantifying cerebral blood arrival times using hypoxia-mediated arterial BOLD contrast","volume":"261","author":"Bhogal","year":"2022","journal-title":"NeuroImage"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1093\/neuonc\/noaa141","article-title":"Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas","volume":"22","author":"Boxerman","year":"2020","journal-title":"Neuro Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"096601","DOI":"10.1088\/0034-4885\/76\/9\/096601","article-title":"The physics of functional magnetic resonance imaging (fMRI)","volume":"76","author":"Buxton","year":"2013","journal-title":"Rep. Prog. Phys."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pnmrs.2013.04.002","article-title":"Arterial input function in perfusion MRI: a comprehensive review","volume":"74","author":"Calamante","year":"2013","journal-title":"Prog. Nucl. Magnetic Reson. Spectrosc."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1016\/j.ejrad.2014.07.002","article-title":"Assesment of perfusion in glial tumors with arterial spin labeling; comparison with dynamic susceptibility contrast method","volume":"83","author":"Cebeci","year":"2014","journal-title":"Eur. J. Radiology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1006\/cbmr.1996.0014","article-title":"AFNI: software for analysis and visualization of functional magnetic resonance neuroimages","volume":"29","author":"Cox","year":"1996","journal-title":"Comput. Biomed. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/(SICI)1099-1492(199706\/08)10:4\/5<171::AID-NBM453>3.0.CO;2-L","article-title":"Software tools for analysis and visualization of fMRI data","volume":"10","author":"Cox","year":"1997","journal-title":"NMR Biomed."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5809","DOI":"10.1113\/jphysiol.2013.259150","article-title":"Measuring cerebrovascular reactivity: what stimulus to use?","volume":"591","author":"Fierstra","year":"2013","journal-title":"J. Physiology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.mri.2016.02.003","article-title":"Altered intraoperative cerebrovascular reactivity in brain areas of high-grade glioma recurrence","volume":"34","author":"Fierstra","year":"2016","journal-title":"Magn. Reson. Imaging"},{"key":"B14","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.mri.2017.09.017","article-title":"Diffuse gliomas exhibit whole brain impaired cerebrovascular reactivity","volume":"45","author":"Fierstra","year":"2018","journal-title":"Magn. Reson. Imaging"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1161\/STROKEAHA.118.021012","article-title":"Magnetic resonance imaging\u2013based cerebrovascular reactivity and hemodynamic reserve","volume":"49","author":"Fisher","year":"2018","journal-title":"Stroke"},{"key":"B16","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.neuroimage.2018.03.018","article-title":"BOLD signal physiology: models and applications","volume":"187","author":"Gauthier","year":"2019","journal-title":"NeuroImage"},{"key":"B17","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.nec.2010.11.001","article-title":"Overview of functional magnetic resonance imaging","volume":"22","author":"Glover","year":"2011","journal-title":"Neurosurg. Clin. N. Am."},{"key":"B18","doi-asserted-by":"publisher","first-page":"813927","DOI":"10.3389\/falgy.2022.813927","article-title":"Hypersensitivity to gadolinium-based contrast media","volume":"3","author":"Gracia Bara","year":"2022","journal-title":"Front. Allergy"},{"key":"B19","doi-asserted-by":"publisher","first-page":"722917","DOI":"10.3389\/fcell.2021.722917","article-title":"Blood\u2013brain barrier, cell junctions, and tumor microenvironment in brain metastases, the biological prospects and dilemma in therapies","author":"Guan","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.3390\/cancers14061432","article-title":"Hemodynamic imaging in cerebral diffuse glioma - Part A: concept, differential diagnosis and tumor grading","volume":"14","author":"Guida","year":"2022","journal-title":"Cancers"},{"key":"B21","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/S1474-4422(17)30158-8","article-title":"Gadolinium deposition in the brain: summary of evidence and recommendations","volume":"16","author":"Gulani","year":"2017","journal-title":"Lancet Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1148\/radiol.2016150789","article-title":"Arterial spin labeling perfusion of the brain: emerging clinical applications","volume":"281","author":"Haller","year":"2016","journal-title":"Radiology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1148\/radiol.2017170845","article-title":"Glioblastoma: vascular habitats detected at preoperative dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging predict survival","volume":"287","author":"Juan-Albarrac\u00edn","year":"2018","journal-title":"Radiology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.3174\/ajnr.A3263","article-title":"Resting-state fMRI: a review of methods and clinical applications","volume":"34","author":"Lee","year":"2013","journal-title":"Am. J. Neuroradiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3174\/ajnr.A5027","article-title":"Effects of MRI protocol parameters, preload injection dose, fractionation strategies, and leakage correction algorithms on the fidelity of dynamic-susceptibility contrast MRI estimates of relative cerebral blood volume in gliomas","volume":"38","author":"Leu","year":"2017","journal-title":"Am. J. Neuroradiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.mri.2020.03.012","article-title":"Hemodynamic investigation of peritumoral impaired blood oxygenation-level dependent cerebrovascular reactivity in patients with diffuse glioma","volume":"70","author":"Muscas","year":"2020","journal-title":"Magn. Reson. Imaging"},{"key":"B28","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1002\/jmri.20460","article-title":"Principles of cerebral perfusion imaging by bolus tracking","volume":"22","author":"\u00d8stergaard","year":"2005","journal-title":"J. Magnetic Reson. Imaging"},{"key":"B29","doi-asserted-by":"publisher","first-page":"3012","DOI":"10.1002\/mrm.28974","article-title":"Perfusion MRI using endogenous deoxyhemoglobin as a contrast agent: preliminary data","volume":"86","author":"Poublanc","year":"2021","journal-title":"Magnetic Reson. Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3174\/ajnr.A8068","article-title":"Assessing perfusion in steno-occlusive cerebrovascular disease using transient hypoxia-induced deoxyhemoglobin as a dynamic susceptibility contrast agent","volume":"45","author":"Sayin","year":"","journal-title":"Am. J. Neuroradiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1002\/hbm.26131","article-title":"Investigations of hypoxia-induced deoxyhemoglobin as a contrast agent for cerebral perfusion imaging","volume":"44","author":"Sayin","year":"2022","journal-title":"Hum. Brain Mapp."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1167857","DOI":"10.3389\/fphys.2023.1167857","article-title":"Transfer function analysis assesses resting cerebral perfusion metrics using hypoxia-induced deoxyhemoglobin as a contrast agent","volume":"14","author":"Sayin","year":"","journal-title":"Front. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1007\/s12311-020-01174-y","article-title":"Crossed cerebellar diaschisis in patients with diffuse glioma is associated with impaired supratentorial cerebrovascular reactivity and worse clinical outcome","volume":"19","author":"Seb\u00f6k","year":"2020","journal-title":"Cerebellum"},{"key":"B34","doi-asserted-by":"publisher","first-page":"vdab048","DOI":"10.1093\/noajnl\/vdab048","article-title":"Hypermetabolism and impaired cerebrovascular reactivity beyond the standard MRI-identified tumor border indicate diffuse glioma extended tissue infiltration","volume":"3","author":"Seb\u00f6k","year":"2021","journal-title":"Neuro-Oncology Adv."},{"key":"B35","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1002\/jmri.24648","article-title":"Principles of T2*-weighted dynamic susceptibility contrast MRI technique in brain tumor imaging","volume":"41","author":"Shiroishi","year":"2015","journal-title":"J. Magnetic Reson. Imaging"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1113\/jphysiol.2007.129395","article-title":"Prospective targeting and control of end-tidal CO2 and O2 concentrations","volume":"581","author":"Slessarev","year":"2007","journal-title":"J. Physiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1093\/neuonc\/noaa044","article-title":"Resting-state fMRI detects alterations in whole brain connectivity related to tumor biology in glioma patients","volume":"22","author":"Stoecklein","year":"2020","journal-title":"Neuro-Oncology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.3390\/cancers14051342","article-title":"Hemodynamic imaging in cerebral diffuse glioma - Part B: molecular correlates, treatment effect monitoring, prognosis, and future directions","volume":"14","author":"Stumpo","year":"2022","journal-title":"Cancers"},{"key":"B39","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10334-021-00980-7","article-title":"Feasibility of glioblastoma tissue response mapping with physiologic BOLD imaging using precise oxygen and carbon dioxide challenge","volume":"35","author":"Stumpo","year":"2021","journal-title":"Magn. Reson Mater Phy"},{"key":"B40","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.nec.2015.11.004","article-title":"Advanced imaging of intracranial meningiomas","volume":"27","author":"Tamrazi","year":"2016","journal-title":"Neurosurg. Clin. N. Am."},{"key":"B41","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/mrm.28422","article-title":"Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI","volume":"85","author":"Vu","year":"2021","journal-title":"Magnetic Reson. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1148\/radiol.2020202903","article-title":"Use of intravenous gadolinium-based contrast media in patients with kidney disease: consensus statements from the American College of radiology and the national kidney foundation","volume":"298","author":"Weinreb","year":"2021","journal-title":"Radiology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1002\/jmri.24406","article-title":"Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI","volume":"40","author":"Zac\u00e0","year":"2014","journal-title":"J. Magnetic Reson. Imaging"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2024.1238533\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:56:40Z","timestamp":1714006600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2024.1238533\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,25]]},"references-count":43,"alternative-id":["10.3389\/fphys.2024.1238533"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2024.1238533","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,25]]},"article-number":"1238533"}}