{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:19:55Z","timestamp":1792030795607,"version":"4.4.0"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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. Mol. Biosci."],"abstract":"<jats:p>Early detection and accurate assessment of ischemic stroke (IS) are essential for timely treatment and prognosis evaluation. Conventional bedside and imaging-based approaches, including the National Institutes of Health Stroke Scale (NIHSS), computed tomography (CT), and magnetic resonance imaging (MRI), remain central to acute stroke assessment, but they have important limitations in the hyperacute stage, when neurological deficits may be subtle and structural imaging changes may not yet be fully apparent. Among the metabolic alterations triggered by ischemia, tissue acidosis is particularly informative because pH declines rapidly after cerebral hypoperfusion and may reveal ischemic injury before conventional imaging abnormalities become obvious. In this review, we summarize recent advances in pH-based detection of IS, with emphasis on its potential for early diagnosis and physiologically informed stroke grading. We discuss current clinical and imaging assessment methods, the pathophysiological basis of ischemia-associated acidosis, emerging pH-detection technologies, and the major barriers to clinical translation. Finally, we outline a future perspective in which pH-related information is integrated with perfusion imaging, complementary biomarkers, and artificial intelligence to support a more comprehensive framework for ischemic stroke assessment.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1821099","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:35:08Z","timestamp":1777437308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["pH-sensitive probes for ischemic stroke: advancing early detection and accurate grading"],"prefix":"10.3389","volume":"13","author":[{"given":"Chen","family":"Zou","sequence":"first","affiliation":[{"name":"School of Health Science and Engineering, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Health Science and Engineering, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Yang","sequence":"additional","affiliation":[{"name":"Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfu","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Changhai Hospital, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Navy Medical University","place":["Shanghai, China"]},{"name":"Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Academy for Engineering and Technology, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Oriental Pan-Vascular Devices Innovation College, University of Shanghai for Science and Technology","place":["Shanghai, China"]},{"name":"Neurovascular Center, Changhai Hospital, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1038\/s41582-021-00542-4","article-title":"Stroke in Africa: profile, progress, prospects and priorities","volume":"17","author":"Akinyemi","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.63278\/jicrcr.vi.364","article-title":"Comparison of CT and MRI for brain imaging","volume":"7","author":"Al Murdef","year":"2024","journal-title":"J. Int. Crisis Risk Commun. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.clinimag.2021.09.015","article-title":"Applications of artificial intelligence for DWI and PWI data processing in acute ischemic stroke: current practices and future directions","volume":"81","author":"Alaya","year":"2022","journal-title":"Clin. Imaging"},{"key":"B4","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1111\/j.1747-4949.2009.00387.x","article-title":"Oxidative stress and its role in the pathogenesis of ischaemic stroke","volume":"4","author":"Allen","year":"2009","journal-title":"Int. Journal Stroke"},{"key":"B5","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1097\/00004647-199806000-00001","article-title":"Magnetic resonance imaging of acute stroke","volume":"18","author":"Baird","year":"1998","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3528","DOI":"10.1093\/brain\/awt201","article-title":"The exact science of stroke thrombolysis and the quiet art of patient selection","volume":"136","author":"Balami","year":"2013","journal-title":"Brain"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1021\/nl060865w","article-title":"All-optical nanoscale pH meter","volume":"6","author":"Bishnoi","year":"2006","journal-title":"Nano Letters"},{"key":"B8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.5772\/28300","article-title":"Excitotoxicity and oxidative stress in acute ischemic stroke","volume":"200","author":"Bret\u00f3N","year":"2012","journal-title":"Acute Ischemic Stroke"},{"key":"B9","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1159\/000321965","article-title":"Biochemical markers for blood-brain barrier dysfunction in acute ischemic stroke correlate with evolution and outcome","volume":"65","author":"Brouns","year":"2011","journal-title":"Eur. Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1002\/jmri.28994","article-title":"Environmental sustainability and MRI: challenges, opportunities, and a call for action","volume":"59","author":"Chaban","year":"2024","journal-title":"J. Magnetic Reson. Imaging"},{"key":"B11","doi-asserted-by":"publisher","first-page":"113900","DOI":"10.1016\/j.ab.2020.113900","article-title":"Recent advances in fluorescent probes for extracellular pH detection and imaging","volume":"612","author":"Chen","year":"2021","journal-title":"Anal. Biochemistry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3390\/s5040209","article-title":"On calibration of pH meters","volume":"5","author":"Cheng","year":"2005","journal-title":"Sensors"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1378\/chest.114.5.1368","article-title":"Comparison of pleural fluid pH values obtained using blood gas machine, pH meter, and pH indicator strip","volume":"114","author":"Cheng","year":"1998","journal-title":"Chest"},{"key":"B14","doi-asserted-by":"publisher","first-page":"56909","DOI":"10.1021\/acsami.1c16530","article-title":"pH-Responsive multifunctional theranostic rapamycin-loaded nanoparticles for imaging and treatment of acute ischemic stroke","volume":"13","author":"Cheng","year":"2021","journal-title":"ACS Appl. Mater. and Interfaces"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1152\/physrev.00010.2003","article-title":"Regulation and modulation of pH in the brain","volume":"83","author":"Chesler","year":"2003","journal-title":"Physiol. Reviews"},{"key":"B16","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1007\/s12975-020-00868-z","article-title":"Refined ischemic penumbra imaging with tissue pH and diffusion kurtosis magnetic resonance imaging","volume":"12","author":"Cheung","year":"2021","journal-title":"Transl. Stroke Research"},{"key":"B17","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-05299-1","volume-title":"Magnetic resonance and its applications","author":"Chizhik","year":"2014"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1523\/JNEUROSCI.10-08-02493.1990","article-title":"Cerebral hypoxia: some new approaches and unanswered questions","volume":"10","author":"Choi","year":"1990","journal-title":"J. Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/0006-8993(83)90037-9","article-title":"A topographic quantitative method for measuring brain tissue pH under physiological and pathophysiological conditions","volume":"289","author":"Csiba","year":"1983","journal-title":"Brain Research"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2456550","DOI":"10.1155\/2022\/2456550","article-title":"Deep learning in ischemic stroke imaging analysis: a comprehensive review","volume":"2022","author":"Cui","year":"2022","journal-title":"BioMed Res. Int."},{"key":"B21","volume-title":"Cost effective EC and pH measurements","author":"Dankwa","year":"2020"},{"key":"B22","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1159\/000519730","article-title":"Ischemic penumbra: a personal view","volume":"50","author":"Davis","year":"2021","journal-title":"Cerebrovasc. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.5958\/0974-360x.2017.00342.0","article-title":"Evaluation the sensitivity of diffusion and perfusion weighted imaging in therapeutic timing of stroke","volume":"10","author":"Dayani","year":"2017","journal-title":"Res. J. Pharm. Technol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1161\/STROKEAHA.119.028337","article-title":"Review of perfusion imaging in acute ischemic stroke: from time to tissue","volume":"51","author":"Demeestere","year":"2020","journal-title":"Stroke"},{"key":"B25","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1002\/glia.20157","article-title":"Astrocytic contributions to bioenergetics of cerebral ischemia","volume":"50","author":"Dienel","year":"2005","journal-title":"Glia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1161\/01.str.29.3.695","article-title":"Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region-specific sensitivity and delayed damage","volume":"29","author":"Dijkhuizen","year":"1998","journal-title":"Stroke"},{"key":"B27","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/s0166-2236(99)01401-0","article-title":"Pathobiology of ischaemic stroke: an integrated view","volume":"22","author":"Dirnagl","year":"1999","journal-title":"Trends Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1177\/1747493020975229","article-title":"The ischemic penumbra: from concept to reality","volume":"16","author":"Ermine","year":"2021","journal-title":"Int. J. Stroke"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1212\/WNL.0000000000207387","article-title":"Global burden, risk factor analysis, and prediction study of ischemic stroke, 1990\u20132030","volume":"101","author":"Fan","year":"2023","journal-title":"Neurology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1177\/0271678X241289756","article-title":"A dangerous liaison: spreading depolarization and tissue acidification in cerebral ischemia","volume":"45","author":"Farkas","year":"2024","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1056\/NEJMoa1804492","article-title":"Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016","volume":"379","author":"Feigin","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.21037\/qims-20-1339","article-title":"Clinical translation of amide proton transfer (APT) MRI for ischemic stroke: a systematic review (2003\u20132020)","volume":"11","author":"Foo","year":"2021","journal-title":"Quantitative Imaging Med. Surg."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/s0140-6736(01)33228-2","article-title":"Modern ideas respecting acidity and alkalinity","volume":"199","author":"Gamble","year":"1922","journal-title":"Lancet"},{"key":"B35","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jconrel.2010.09.012","article-title":"pH-responsive polymeric micelle based on PEG-poly (\u03b2-amino ester)\/(amido amine) as intelligent vehicle for magnetic resonance imaging in detection of cerebral ischemic area","volume":"155","author":"Gao","year":"2011","journal-title":"J. Controlled Release"},{"key":"B36","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/s0749-0704(01)00012-4","article-title":"Metabolic acidosis in the intensive care unit","volume":"18","author":"Gauthier","year":"2002","journal-title":"Crit. Care Clinics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.nic.2023.12.001","article-title":"Dual-energy computed tomography in the evaluation and management of subarachnoid hemorrhage, intracranial hemorrhage, and acute ischemic stroke","volume":"34","author":"Gemmete","year":"2024","journal-title":"Neuroimaging Clin."},{"key":"B38","first-page":"1","article-title":"Planning and advance cancellation of MRI examinations of stroke patients","author":"Geng","year":"2010"},{"key":"B39","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/jcbfm.1988.4","article-title":"High energy phosphate metabolism in experimental permanent focal cerebral ischemia: an in vivo 31P magnetic resonance spectroscopy study","volume":"8","author":"Germano","year":"1988","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.3171\/2009.3.JNS081040","article-title":"Edema formation in the hyperacute phase of ischemic stroke","volume":"111","author":"Gerriets","year":"2009","journal-title":"J. Neurosurgery"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5248","DOI":"10.1021\/acs.chemrev.8b00655","article-title":"Recent progress in electrochemical pH-sensing materials and configurations for biomedical applications","volume":"119","author":"Ghoneim","year":"2019","journal-title":"Chem. Reviews"},{"key":"B42","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2967\/jnmt.106.037846","article-title":"Principles of CT: radiation dose and image quality","volume":"35","author":"Goldman","year":"2007","journal-title":"J. Nuclear Medicine Technology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"AB127","DOI":"10.1016\/j.gie.2024.04.908","article-title":"Correlation between histological staging of atrophic gastritis by the olga system and gastric ph measured with paper litmus","volume":"99","author":"Gomez","year":"2024","journal-title":"Gastrointest. Endosc."},{"key":"B44","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/brain\/awu374","article-title":"Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging","volume":"138","author":"Harston","year":"2015","journal-title":"Brain"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1161\/STROKEAHA.111.000604","article-title":"National institutes of health stroke scale score and vessel occlusion in 2152 patients with acute ischemic stroke","volume":"44","author":"Heldner","year":"2013","journal-title":"Stroke"},{"key":"B46","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1002\/mrm.26799","article-title":"Improving the detection sensitivity of p h-weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals","volume":"78","author":"Heo","year":"2017","journal-title":"Magnetic Resonance Medicine"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e4734","DOI":"10.1002\/nbm.4734","article-title":"Amide proton transfer imaging in stroke","volume":"36","author":"Heo","year":"2023","journal-title":"NMR Biomed."},{"key":"B48","doi-asserted-by":"publisher","first-page":"W258","DOI":"10.2214\/AJR.11.8081","article-title":"Cerebral edema","volume":"199","author":"Ho","year":"2012","journal-title":"Am. J. Roentgenol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.09.011","article-title":"Disrupted ionic homeostasis in ischemic stroke and new therapeutic targets","volume":"26","author":"Hu","year":"2017","journal-title":"J. Stroke Cerebrovascular Diseases"},{"key":"B50","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.3892\/mmr.2015.3165","article-title":"Novel gradient echo sequence-based amide proton transfer magnetic resonance imaging in hyperacute cerebral infarction","volume":"11","author":"Huang","year":"2015","journal-title":"Mol. Medicine Reports"},{"key":"B51","first-page":"53","volume-title":"Acute ischemic stroke. Seminars in thrombosis and hemostasis","author":"Huber","year":"1996"},{"key":"B52","doi-asserted-by":"crossref","DOI":"10.1201\/9780203758731","volume-title":"Electromagnetic analysis and design in magnetic resonance imaging","author":"Jin","year":"2018"},{"key":"B53","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1002\/mrm.30194","article-title":"Amide proton transfer MRI at 9.4 T for differentiating tissue acidosis in a rodent model of ischemic stroke","volume":"92","author":"Jin","year":"2024","journal-title":"Magnetic Reson. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/S1474-4422(06)70495-1","article-title":"Clinical interpretation and use of stroke scales","volume":"5","author":"Kasner","year":"2006","journal-title":"Lancet Neurology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1007\/s00542-017-3495-5","article-title":"A review on pH sensitive materials for sensors and detection methods","volume":"23","author":"Khan","year":"2017","journal-title":"Microsyst. Technol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/0006-8993(80)90869-0","article-title":"A topographic measurement of brain pH","volume":"195","author":"Kogure","year":"1980","journal-title":"Brain Research"},{"key":"B57","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1097\/RMR.0000000000000129","article-title":"CT-based techniques for brain perfusion","volume":"26","author":"Krishnan","year":"2017","journal-title":"Top. Magnetic Reson. Imaging"},{"key":"B58","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1161\/01.str.29.3.705","article-title":"Calcium in ischemic cell death","volume":"29","author":"Kristi\u00e1N","year":"1998","journal-title":"Stroke"},{"key":"B59","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jphys.2013.12.012","article-title":"National institutes of health stroke scale (NIHSS)","volume":"60","author":"Kwah","year":"2014","journal-title":"J. Physiotherapy"},{"key":"B60","doi-asserted-by":"publisher","first-page":"793741","DOI":"10.3389\/fphys.2021.793741","article-title":"Magnetic resonance pH imaging in stroke - combining the old with the new","volume":"12","author":"Larkin","year":"2021","journal-title":"Front. Physiol."},{"key":"B61","first-page":"80","article-title":"Application of SERS nanoparticles for intracellular pH measurements. Plasmonics: Metallic nanostructures and their optical properties II","author":"Laurence","year":"2004"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1177\/0271678X17700913","article-title":"Imaging the physiological evolution of the ischemic penumbra in acute ischemic stroke","volume":"38","author":"Leigh","year":"2018","journal-title":"J. Cereb. Blood Flow and Metabolism"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.14336\/AD.2020.0119","article-title":"Serum occludin as a biomarker to predict the severity of acute ischemic stroke, hemorrhagic transformation, and patient prognosis","volume":"11","author":"Li","year":"2020","journal-title":"Aging Disease"},{"key":"B64","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3390\/biology10050424","article-title":"Metabolic reprogramming: strategy for ischemic stroke treatment by ischemic preconditioning","volume":"10","author":"Liang","year":"2021","journal-title":"Biology"},{"key":"B65","first-page":"282","article-title":"Nanoplasmonic resonance energy transfer spectroscopic pH imaging. Plasmonics: nanoimaging, nanofabrication, and their applications V","author":"Liu","year":"2009"},{"key":"B66","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2174\/1871527320666210212141232","article-title":"Role of calcium homeostasis in ischemic stroke: a review","volume":"21","author":"Ludhiadch","year":"2022","journal-title":"CNS and Neurological Disorders-Drug Targets"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1007\/s10072-018-3324-3","article-title":"Susceptibility-weighted imaging predicts infarct size and early-stage clinical prognosis in acute ischemic stroke","volume":"39","author":"Luo","year":"2018","journal-title":"Neurol. Sciences"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1161\/01.str.30.11.2347","article-title":"Underlying structure of the national institutes of health stroke scale: results of a factor analysis","volume":"30","author":"Lyden","year":"1999","journal-title":"Stroke"},{"key":"B69","doi-asserted-by":"publisher","first-page":"158","DOI":"10.4103\/2045-9912.318862","article-title":"Effects of lactate and carbon monoxide interactions on neuroprotection and neuropreservation","volume":"11","author":"Mahan","year":"2021","journal-title":"Med. Gas Research"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1177\/02841851221130612","article-title":"Virtual monoenergetic images by spectral detector computed tomography May improve image quality and diagnostic ability for ischemic lesions in acute ischemic stroke","volume":"64","author":"Mellander","year":"2023","journal-title":"Acta Radiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/nrneurol.2010.129","article-title":"Imaging of acute stroke","volume":"6","author":"Merino","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainresbull.2015.02.006","article-title":"Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models","volume":"114","author":"Nathaniel","year":"2015","journal-title":"Brain Res. Bull."},{"key":"B73","doi-asserted-by":"publisher","first-page":"381","DOI":"10.12968\/jowc.2017.26.7.381","article-title":"Measurement of pH, exudate composition and temperature in wound healing: a systematic review","volume":"26","author":"Power","year":"2017","journal-title":"J. Wound Care"},{"key":"B74","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1177\/0003319713506516","article-title":"Link between oxidative stress and acute brain ischemia","volume":"65","author":"Radak","year":"2014","journal-title":"Angiology"},{"key":"B75","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/ana.410130103","article-title":"The pathophysiology of brain ischemia","volume":"13","author":"Raichle","year":"1983","journal-title":"Ann. Neurology Official J. Am. Neurological Assoc. Child Neurology Soc."},{"key":"B76","volume-title":"Measurement of pH using chemical exchange saturation transfer magnetic resonance imaging","author":"Ray","year":"2017"},{"key":"B77","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/s0196-0644(85)80055-x","article-title":"Brain acidosis","volume":"14","author":"Rehncrona","year":"1985","journal-title":"Ann. Emerg. Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1161\/01.str.29.5.939","article-title":"Regional ischemia and ischemic injury in patients with acute middle cerebral artery stroke as defined by early diffusion-weighted and perfusion-weighted MRI","volume":"29","author":"Rordorf","year":"1998","journal-title":"Stroke"},{"key":"B79","doi-asserted-by":"publisher","first-page":"107368","DOI":"10.1016\/j.clineuro.2022.107368","article-title":"Application of susceptibility weighted imaging (SWI) in diagnostic imaging of brain pathologies\u2013a practical approach","volume":"221","author":"Rubin","year":"2022","journal-title":"Clin. Neurology Neurosurg."},{"key":"B80","doi-asserted-by":"publisher","first-page":"101967","DOI":"10.1016\/j.bspc.2020.101967","article-title":"Phosphorus magnetic resonance spectroscopy and imaging (31P-MRS\/MRSI) as a window to brain and muscle metabolism: a review of the methods","volume":"60","author":"Santos-D\u00edAZ","year":"2020","journal-title":"Biomed. Signal Process. Control"},{"key":"B81","doi-asserted-by":"publisher","first-page":"415","DOI":"10.2741\/4727","article-title":"Cerebral ischemic stroke: cellular fate and therapeutic opportunities","volume":"24","author":"Sarkar","year":"2019","journal-title":"Front. Bioscience-Landmark"},{"key":"B82","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1093\/oxfordjournals.jbchem.a134413","article-title":"Intracellular pH determination by a 31P-NMR technique. The second dissociation constant of phosphoric acid in a biological system","volume":"94","author":"Seo","year":"1983","journal-title":"J. Biochem."},{"key":"B83","doi-asserted-by":"publisher","first-page":"443","DOI":"10.2147\/JMDH.S90554","article-title":"Stroke subtype, age, and baseline NIHSS score predict ischemic stroke outcomes at 3 months: a preliminary study from central Nepal","volume":"8","author":"Shrestha","year":"2015","journal-title":"J. Multidisciplinary Healthcare"},{"key":"B84","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3171\/jns.1984.60.5.0883","article-title":"Cerebral circulation and metabolism","volume":"60","author":"Siesj\u00f6","year":"1984","journal-title":"J. Neurosurgery"},{"key":"B85","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/s0197-0186(01)00122-x","article-title":"Mitochondrial contributions to tissue damage in stroke","volume":"40","author":"Sims","year":"2002","journal-title":"Neurochem. International"},{"key":"B86","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3389\/fneur.2017.00067","article-title":"Evolution of cerebral ischemia assessed by amide proton transfer-weighted MRI","volume":"8","author":"Song","year":"2017","journal-title":"Front. Neurol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.bbrc.2022.04.143","article-title":"MnCO3@ BSA-ICG nanoparticles as a magnetic resonance\/photoacoustic dual-modal contrast agent for functional imaging of acute ischemic stroke","volume":"614","author":"Song","year":"2022","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B88","doi-asserted-by":"publisher","first-page":"12357","DOI":"10.1021\/acs.chemrev.0c00451","article-title":"Optical sensing and imaging of pH values: spectroscopies, materials, and applications","volume":"120","author":"Steinegger","year":"2020","journal-title":"Chem. Reviews"},{"key":"B89","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.2174\/138161208786848748","article-title":"Ischemic neuronal damage","volume":"14","author":"Taoufik","year":"2008","journal-title":"Curr. Pharmaceutical Design"},{"key":"B90","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/nbm.3048","article-title":"Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI","volume":"27","author":"Tietze","year":"2014","journal-title":"NMR Biomed."},{"key":"B91","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1148\/rg.233025036","article-title":"Comprehensive imaging of ischemic stroke with multisection CT","volume":"23","author":"Tomandl","year":"2003","journal-title":"Radiographics"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.14232\/phd.10876","article-title":"Tissue acidosis associated with ischemic stroke to guide nimodipine delivery","author":"T\u00f3th","year":"2021","journal-title":"Szegedi Tudomanyegyetem Hung"},{"key":"B93","doi-asserted-by":"publisher","first-page":"460","DOI":"10.3390\/biology9120460","article-title":"Tissue acidosis associated with ischemic stroke to guide neuroprotective drug delivery","volume":"9","author":"T\u00f3th","year":"2020","journal-title":"Biology"},{"key":"B94","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1212\/WNL.0000000000008481","article-title":"Automated CT perfusion imaging for acute ischemic stroke: pearls and pitfalls for real-world use","volume":"93","author":"Vagal","year":"2019","journal-title":"Neurology"},{"key":"B95","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.nic.2024.01.002","article-title":"Metabolic imaging of acute ischemic stroke (PET, 1Hydrogen spectroscopy, 17Oxygen imaging, 23Sodium MRI, pH imaging)","volume":"34","author":"Vasireddi","year":"2024","journal-title":"Neuroimaging Clin."},{"key":"B96","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.mri.2004.01.036","article-title":"A newborn piglet study of moderate hypoxic-ischemic brain injury by 1H-MRS and MRI","volume":"22","author":"Vial","year":"2004","journal-title":"Magn. Resonance Imaging"},{"key":"B97","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1042\/bj0070260","article-title":"The use of litmus paper as a quantitative indicator of reaction","volume":"7","author":"Walpole","year":"1913","journal-title":"Biochem. J."},{"key":"B98","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.neuroimage.2019.02.022","article-title":"Mapping tissue pH in an experimental model of acute stroke - determination of graded regional tissue pH changes with non-invasive quantitative amide proton transfer MRI","volume":"191","author":"Wang","year":"2019","journal-title":"Neuroimage"},{"key":"B99","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S0025-6196(11)64847-7","article-title":"Glucose modulation of ischemic brain injury: review and clinical recommendations","volume":"71","author":"Wass","year":"1996","journal-title":"Mayo Clin Proc."},{"key":"B100","volume-title":"Aspects of brain energy metabolism and cerebral ischemia","author":"Whittingham","year":"1990"},{"key":"B101","doi-asserted-by":"publisher","first-page":"e4850","DOI":"10.1002\/nbm.4850","article-title":"Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2 ppm","volume":"36","author":"Wu","year":"2023","journal-title":"NMR Biomed."},{"key":"B102","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1021\/cbmi.3c00019","article-title":"Label-free chemically and molecularly selective magnetic resonance imaging","volume":"1","author":"Wu","year":"2023","journal-title":"Chem. Biomed. Imaging"},{"key":"B103","doi-asserted-by":"publisher","first-page":"12588","DOI":"10.1039\/c5nr06542a","article-title":"pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area","volume":"8","author":"Yang","year":"2016","journal-title":"Nanoscale"},{"key":"B104","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.colsurfb.2017.04.054","article-title":"CdSe@ ZnS\/ZnS quantum dots loaded in polymeric micelles as a pH-triggerable targeting fluorescence imaging probe for detecting cerebral ischemic area","volume":"155","author":"Yang","year":"2017","journal-title":"Colloids Surfaces B Biointerfaces"},{"key":"B105","doi-asserted-by":"publisher","first-page":"2001544","DOI":"10.1002\/adhm.202001544","article-title":"A targeted activatable NIR\u2010IIb nanoprobe for highly sensitive detection of ischemic stroke in a photothrombotic stroke model","volume":"10","author":"Yang","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"B106","doi-asserted-by":"publisher","first-page":"2201981","DOI":"10.1002\/adhm.202201981","article-title":"Real\u2010time objective evaluation of the ischemic stroke through ph-responsive fluorescence imaging","volume":"12","author":"Yao","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"B107","doi-asserted-by":"publisher","first-page":"81","DOI":"10.13104\/imri.2021.25.2.81","article-title":"Fast MRI in acute ischemic stroke: applications of MRI acceleration techniques for MR-based comprehensive stroke imaging","volume":"25","author":"You","year":"2021","journal-title":"Investig. Magn. Reson. Imaging"},{"key":"B108","doi-asserted-by":"publisher","first-page":"714171","DOI":"10.3389\/fncel.2021.714171","article-title":"Serum occludin level combined with NIHSS score predicts hemorrhage transformation in ischemic stroke patients with reperfusion","volume":"15","author":"Yuan","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1097\/00006123-200208000-00003","article-title":"Brain oxygenation and energy metabolism: part I\u2014Biological function and pathophysiology","volume":"51","author":"Zauner","year":"2002","journal-title":"Neurosurgery"},{"key":"B110","doi-asserted-by":"publisher","first-page":"e422","DOI":"10.1212\/WNL.0000000000201467","article-title":"Global burden of ischemic stroke in young adults in 204 countries and territories","volume":"100","author":"Zhang","year":"2023","journal-title":"Neurology"},{"key":"B111","doi-asserted-by":"publisher","first-page":"4408","DOI":"10.21037\/qims-21-250","article-title":"Amide proton transfer (APT) imaging-based study on the correlation between brain pH and voltage-gated proton channels in piglets after hypoxic-ischemic brain injury","volume":"11","author":"Zheng","year":"2021","journal-title":"Quant. Imaging Med. Surg."},{"key":"B112","doi-asserted-by":"publisher","first-page":"721428","DOI":"10.3389\/fnagi.2021.721428","article-title":"Mitochondrial dynamics: a potential therapeutic target for ischemic stroke","volume":"13","author":"Zhou","year":"2021","journal-title":"Front. Aging Neurosci."}],"updated-by":[{"DOI":"10.3389\/fmolb.2026.1906875","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000}}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1821099\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:01:35Z","timestamp":1783605695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1821099\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":111,"alternative-id":["10.3389\/fmolb.2026.1821099"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1821099","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"article-number":"1821099"}}