{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:14:59Z","timestamp":1784304899428,"version":"3.55.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R43NS103596-01"],"award-info":[{"award-number":["1R43NS103596-01"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Harnessing the maximum diagnostic potential of magnetic resonance imaging (MRI) by including stroke lesion location in relation to specific structures that are associated with particular functions will likely increase the potential to predict functional deficit type, severity, and recovery in stroke patients. This exploratory study aims to identify key structures lesioned by a middle cerebral artery occlusion (MCAO) that impact stroke recovery and to strengthen the predictive capacity of neuroimaging techniques that characterize stroke outcomes in a translational porcine model. Clinically relevant MRI measures showed significant lesion volumes, midline shifts, and decreased white matter integrity post-MCAO. Using a pig brain atlas, damaged brain structures included the insular cortex, somatosensory cortices, temporal gyri, claustrum, and visual cortices, among others. MCAO resulted in severely impaired spatiotemporal gait parameters, decreased voluntary movement in open field testing, and higher modified Rankin Scale scores at acute timepoints. Pearson correlation analyses at acute timepoints between standard MRI metrics (e.g., lesion volume) and functional outcomes displayed moderate R values to functional gait outcomes. Moreover, Pearson correlation analyses showed higher R values between functional gait deficits and increased lesioning of structures associated with motor function, such as the putamen, globus pallidus, and primary somatosensory cortex. This correlation analysis approach helped identify neuroanatomical structures predictive of stroke outcomes and may lead to the translation of this topological analysis approach from preclinical stroke assessment to a clinical biomarker.<\/jats:p>","DOI":"10.1038\/s41598-021-83432-5","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T14:31:41Z","timestamp":1613572301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exploring the predictive value of lesion topology on motor function outcomes in a porcine ischemic stroke model"],"prefix":"10.1038","volume":"11","author":[{"given":"Kelly M.","family":"Scheulin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Jurgielewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha E.","family":"Spellicy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S.","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily W.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A.","family":"Kinder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory A.","family":"Simchick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney E.","family":"Sneed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet A.","family":"Grimes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Stice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin D.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"key":"83432_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1007\/s00234-019-02234-9","volume":"61","author":"C Lin","year":"2019","unstructured":"Lin, C., Chatterjee, N., Lee, J., Harvey, R. & Prabhakaran, S. Predictive value of the combination of lesion location and volume of ischemic infarction with rehabilitation outcomes. Neuroradiology 61, 1131\u20131136. https:\/\/doi.org\/10.1007\/s00234-019-02234-9 (2019).","journal-title":"Neuroradiology"},{"key":"83432_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s12028-013-9838-x","volume":"21","author":"BP Walcott","year":"2014","unstructured":"Walcott, B. P. et al. Outcomes in severe middle cerebral artery ischemic stroke. Neurocrit. Care 21, 20\u201326. https:\/\/doi.org\/10.1007\/s12028-013-9838-x (2014).","journal-title":"Neurocrit. Care"},{"key":"83432_CR3","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1002\/ana.410420206","volume":"42","author":"KO Lovblad","year":"1997","unstructured":"Lovblad, K. O. et al. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome. Ann Neurol 42, 164\u2013170. https:\/\/doi.org\/10.1002\/ana.410420206 (1997).","journal-title":"Ann Neurol"},{"key":"83432_CR4","first-page":"257","volume":"23","author":"SK Schiemanck","year":"2005","unstructured":"Schiemanck, S. K. et al. Ischemic lesion volume correlates with long-term functional outcome and quality of life of middle cerebral artery stroke survivors. Restor. Neurol. Neurosci. 23, 257\u2013263 (2005).","journal-title":"Restor. Neurol. Neurosci."},{"key":"83432_CR5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1177\/154596830501900207","volume":"19","author":"SK Schiemanck","year":"2005","unstructured":"Schiemanck, S. K., Post, M. W., Witkamp, T. D., Kappelle, L. J. & Prevo, A. J. Relationship between ischemic lesion volume and functional status in the 2nd week after middle cerebral artery stroke. Neurorehabil. Neural Repair 19, 133\u2013138. https:\/\/doi.org\/10.1177\/154596830501900207 (2005).","journal-title":"Neurorehabil. Neural Repair"},{"key":"83432_CR6","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1161\/STROKEAHA.114.005152","volume":"45","author":"B Cheng","year":"2014","unstructured":"Cheng, B. et al. Influence of stroke infarct location on functional outcome measured by the modified rankin scale. Stroke 45, 1695\u20131702. https:\/\/doi.org\/10.1161\/STROKEAHA.114.005152 (2014).","journal-title":"Stroke"},{"key":"83432_CR7","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1161\/STROKEAHA.117.017513","volume":"48","author":"M Ernst","year":"2017","unstructured":"Ernst, M. et al. Association of computed tomography ischemic lesion location with functional outcome in acute large vessel occlusion ischemic stroke. Stroke 48, 2426\u20132433. https:\/\/doi.org\/10.1161\/STROKEAHA.117.017513 (2017).","journal-title":"Stroke"},{"key":"83432_CR8","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1161\/STROKEAHA.110.596312","volume":"42","author":"NA Vora","year":"2011","unstructured":"Vora, N. A. et al. A 5-item scale to predict stroke outcome after cortical middle cerebral artery territory infarction: validation from results of the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Stroke 42, 645\u2013649. https:\/\/doi.org\/10.1161\/STROKEAHA.110.596312 (2011).","journal-title":"Stroke"},{"key":"83432_CR9","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.neuropsychologia.2015.07.007","volume":"79","author":"MR Borich","year":"2015","unstructured":"Borich, M. R., Brodie, S. M., Gray, W. A., Ionta, S. & Boyd, L. A. Understanding the role of the primary somatosensory cortex: opportunities for rehabilitation. Neuropsychologia 79, 246\u2013255. https:\/\/doi.org\/10.1016\/j.neuropsychologia.2015.07.007 (2015).","journal-title":"Neuropsychologia"},{"key":"83432_CR10","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/jcbfm.2010.185","volume":"31","author":"B Cheng","year":"2011","unstructured":"Cheng, B. et al. Dynamics of regional distribution of ischemic lesions in middle cerebral artery trunk occlusion relates to collateral circulation. J. Cereb. Blood Flow Metab. 31, 36\u201340. https:\/\/doi.org\/10.1038\/jcbfm.2010.185 (2011).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"83432_CR11","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1159\/000214215","volume":"27","author":"TG Phan","year":"2009","unstructured":"Phan, T. G., Fong, A. C., Donnan, G. A., Srikanth, V. & Reutens, D. C. Digital probabilistic atlas of the border region between the middle and posterior cerebral arteries. Cerebrovasc Dis 27, 529\u2013536. https:\/\/doi.org\/10.1159\/000214215 (2009).","journal-title":"Cerebrovasc Dis"},{"key":"83432_CR12","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1161\/01.STR.0000251792.76080.45","volume":"38","author":"NM Menezes","year":"2007","unstructured":"Menezes, N. M. et al. The real estate factor: quantifying the impact of infarct location on stroke severity. Stroke 38, 194\u2013197. https:\/\/doi.org\/10.1161\/01.STR.0000251792.76080.45 (2007).","journal-title":"Stroke"},{"key":"83432_CR13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1161\/STROKEAHA.115.011242","volume":"47","author":"F Munsch","year":"2016","unstructured":"Munsch, F. et al. Stroke location is an independent predictor of cognitive outcome. Stroke 47, 66\u201373. https:\/\/doi.org\/10.1161\/STROKEAHA.115.011242 (2016).","journal-title":"Stroke"},{"key":"83432_CR14","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1161\/STROKEAHA.115.009643","volume":"46","author":"O Wu","year":"2015","unstructured":"Wu, O. et al. Role of acute lesion topography in initial ischemic stroke severity and long-term functional outcomes. Stroke 46, 2438\u20132444. https:\/\/doi.org\/10.1161\/STROKEAHA.115.009643 (2015).","journal-title":"Stroke"},{"key":"83432_CR15","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1159\/000351147","volume":"35","author":"TG Phan","year":"2013","unstructured":"Phan, T. G. et al. Proof of concept study: relating infarct location to stroke disability in the NINDS rt-PA trial. Cerebrovasc. Dis. 35, 560\u2013565. https:\/\/doi.org\/10.1159\/000351147 (2013).","journal-title":"Cerebrovasc. Dis."},{"key":"83432_CR16","doi-asserted-by":"publisher","first-page":"9498","DOI":"10.1038\/s41598-018-27883-3","volume":"8","author":"C Laredo","year":"2018","unstructured":"Laredo, C. et al. Prognostic significance of infarct size and location: the case of insular stroke. Sci. Rep. 8, 9498. https:\/\/doi.org\/10.1038\/s41598-018-27883-3 (2018).","journal-title":"Sci. Rep."},{"key":"83432_CR17","doi-asserted-by":"publisher","first-page":"40","DOI":"10.3174\/ajnr.A4091","volume":"36","author":"VM Timpone","year":"2015","unstructured":"Timpone, V. M. et al. Percentage insula ribbon infarction of >50% identifies patients likely to have poor clinical outcome despite small DWI infarct volume. AJNR Am. J. Neuroradiol. 36, 40\u201345. https:\/\/doi.org\/10.3174\/ajnr.A4091 (2015).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"83432_CR18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3174\/ajnr.A4970","volume":"38","author":"S Payabvash","year":"2017","unstructured":"Payabvash, S., Taleb, S., Benson, J. C. & McKinney, A. M. Acute ischemic stroke infarct topology: association with lesion volume and severity of symptoms at admission and discharge. AJNR Am. J. Neuroradiol. 38, 58\u201363. https:\/\/doi.org\/10.3174\/ajnr.A4970 (2017).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"83432_CR19","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1161\/STROKEAHA.108.541128","volume":"40","author":"M Fisher","year":"2009","unstructured":"Fisher, M. et al. Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40, 2244\u20132250. https:\/\/doi.org\/10.1161\/STROKEAHA.108.541128 (2009).","journal-title":"Stroke"},{"key":"83432_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-017-0554-2","author":"DW McBride","year":"2017","unstructured":"McBride, D. W. & Zhang, J. H. Precision stroke animal models: the permanent mcao model should be the primary model not transient MCAO. Transl. Stroke Res. https:\/\/doi.org\/10.1007\/s12975-017-0554-2 (2017).","journal-title":"Transl. Stroke Res."},{"key":"83432_CR21","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.neubiorev.2007.02.003","volume":"31","author":"NM Lind","year":"2007","unstructured":"Lind, N. M. et al. The use of pigs in neuroscience: modeling brain disorders. Neurosci. Biobehav. Rev. 31, 728\u2013751. https:\/\/doi.org\/10.1016\/j.neubiorev.2007.02.003 (2007).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"83432_CR22","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/7854_2010_112","volume":"7","author":"ET Gieling","year":"2011","unstructured":"Gieling, E. T., Schuurman, T., Nordquist, R. E. & van der Staay, F. J. The pig as a model animal for studying cognition and neurobehavioral disorders. Curr. Top. Behav. Neurosci. 7, 359\u2013383. https:\/\/doi.org\/10.1007\/7854_2010_112 (2011).","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"83432_CR23","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jneumeth.2010.07.041","volume":"192","author":"S Saikali","year":"2010","unstructured":"Saikali, S. et al. A three-dimensional digital segmented and deformable brain atlas of the domestic pig. J. Neurosci. Methods 192, 102\u2013109. https:\/\/doi.org\/10.1016\/j.jneumeth.2010.07.041 (2010).","journal-title":"J. Neurosci. Methods"},{"key":"83432_CR24","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0102-18.2018","author":"AV Ulyanova","year":"2018","unstructured":"Ulyanova, A. V. et al. Electrophysiological signature reveals laminar structure of the porcine hippocampus. eNeuro https:\/\/doi.org\/10.1523\/ENEURO.0102-18.2018 (2018).","journal-title":"eNeuro"},{"key":"83432_CR25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/hipo.450040112","volume":"4","author":"IE Holm","year":"1994","unstructured":"Holm, I. E. & West, M. J. Hippocampus of the domestic pig: a stereological study of subdivisional volumes and neuron numbers. Hippocampus 4, 115\u2013125. https:\/\/doi.org\/10.1002\/hipo.450040112 (1994).","journal-title":"Hippocampus"},{"key":"83432_CR26","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/0306-4522(86)90113-2","volume":"18","author":"R Matsas","year":"1986","unstructured":"Matsas, R., Kenny, A. J. & Turner, A. J. An immunohistochemical study of endopeptidase-24.11 (\u201cenkephalinase\u201d) in the pig nervous system. Neuroscience 18, 991\u20131012. https:\/\/doi.org\/10.1016\/0306-4522(86)90113-2 (1986).","journal-title":"Neuroscience"},{"key":"83432_CR27","unstructured":"Hof, P. R., Young, W. G., Bloom, F. & Belichenko, P. Comparative Cytoarchitectonic Atlas of the C57BL\/6 and\n129\/Sv Mouse Brains (Elsevier, Amsterdam, 2000)."},{"key":"83432_CR28","unstructured":"Parent, A. & Carpenter, M. B. Carpenter's Human Neuroanatomy, Ninth Edition (Williams and Wilkins, Baltimore, 1996)."},{"key":"83432_CR29","doi-asserted-by":"publisher","first-page":"10075","DOI":"10.1038\/s41598-017-10406-x","volume":"7","author":"EW Baker","year":"2017","unstructured":"Baker, E. W. et al. Induced pluripotent stem cell-derived neural stem cell therapy enhances recovery in an ischemic stroke pig model. Sci. Rep. 7, 10075. https:\/\/doi.org\/10.1038\/s41598-017-10406-x (2017).","journal-title":"Sci. Rep."},{"key":"83432_CR30","doi-asserted-by":"publisher","first-page":"146778","DOI":"10.1016\/j.brainres.2020.146778","volume":"1736","author":"EE Kaiser","year":"2020","unstructured":"Kaiser, E. E. et al. Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke. Brain Res. 1736, 146778. https:\/\/doi.org\/10.1016\/j.brainres.2020.146778 (2020).","journal-title":"Brain Res."},{"key":"83432_CR31","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/2040-7378-6-5","volume":"6","author":"SR Platt","year":"2014","unstructured":"Platt, S. R. et al. Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. Exp. Transl. Stroke Med. 6, 5. https:\/\/doi.org\/10.1186\/2040-7378-6-5 (2014).","journal-title":"Exp. Transl. Stroke Med."},{"key":"83432_CR32","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1161\/STROKEAHA.117.020353","volume":"49","author":"RL Webb","year":"2018","unstructured":"Webb, R. L. et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke 49, 1248\u20131256. https:\/\/doi.org\/10.1161\/STROKEAHA.117.020353 (2018).","journal-title":"Stroke"},{"key":"83432_CR33","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.4103\/1673-5374.274324","volume":"15","author":"EE Kaiser","year":"2020","unstructured":"Kaiser, E. E. & West, F. D. Large animal ischemic stroke models: replicating human stroke pathophysiology. Neural. Regen. Res. 15, 1377\u20131387. https:\/\/doi.org\/10.4103\/1673-5374.274324 (2020).","journal-title":"Neural. Regen. Res."},{"key":"83432_CR34","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-019-00753-4","author":"SE Spellicy","year":"2019","unstructured":"Spellicy, S. E. et al. Neural stem cell extracellular vesicles disrupt midline shift predictive outcomes in porcine ischemic stroke model. Transl. Stroke Res. https:\/\/doi.org\/10.1007\/s12975-019-00753-4 (2019).","journal-title":"Transl. Stroke Res."},{"key":"83432_CR35","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.neucli.2015.09.005","volume":"45","author":"C Beyaert","year":"2015","unstructured":"Beyaert, C., Vasa, R. & Frykberg, G. E. Gait post-stroke: Pathophysiology and rehabilitation strategies. Neurophysiol. Clin. 45, 335\u2013355. https:\/\/doi.org\/10.1016\/j.neucli.2015.09.005 (2015).","journal-title":"Neurophysiol. Clin."},{"key":"83432_CR36","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.pmrj.2013.12.017","volume":"6","author":"B Balaban","year":"2014","unstructured":"Balaban, B. & Tok, F. Gait disturbances in patients with stroke. PMR 6, 635\u2013642. https:\/\/doi.org\/10.1016\/j.pmrj.2013.12.017 (2014).","journal-title":"PMR"},{"key":"83432_CR37","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.physbeh.2013.11.004","volume":"125","author":"KJ Duberstein","year":"2014","unstructured":"Duberstein, K. J. et al. Gait analysis in a pre- and post-ischemic stroke biomedical pig model. Physiol. Behav. 125, 8\u201316. https:\/\/doi.org\/10.1016\/j.physbeh.2013.11.004 (2014).","journal-title":"Physiol. Behav."},{"key":"83432_CR38","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.nicl.2017.02.023","volume":"14","author":"JC Stewart","year":"2017","unstructured":"Stewart, J. C. et al. Role of corpus callosum integrity in arm function differs based on motor severity after stroke. Neuroimage Clin. 14, 641\u2013647. https:\/\/doi.org\/10.1016\/j.nicl.2017.02.023 (2017).","journal-title":"Neuroimage Clin."},{"key":"83432_CR39","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1002\/hbm.21417","volume":"33","author":"LE Wang","year":"2012","unstructured":"Wang, L. E. et al. Degeneration of corpus callosum and recovery of motor function after stroke: a multimodal magnetic resonance imaging study. Human Brain Mapp. 33, 2941\u20132956. https:\/\/doi.org\/10.1002\/hbm.21417 (2012).","journal-title":"Human Brain Mapp."},{"key":"83432_CR40","doi-asserted-by":"publisher","first-page":"131","DOI":"10.5853\/jos.2014.16.3.131","volume":"16","author":"BJ Kim","year":"2014","unstructured":"Kim, B. J. et al. Magnetic resonance imaging in acute ischemic stroke treatment. J. Stroke 16, 131\u2013145. https:\/\/doi.org\/10.5853\/jos.2014.16.3.131 (2014).","journal-title":"J. Stroke"},{"key":"83432_CR41","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1161\/01.str.31.11.2597","volume":"31","author":"VN Thijs","year":"2000","unstructured":"Thijs, V. N. et al. Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis. Stroke 31, 2597\u20132602. https:\/\/doi.org\/10.1161\/01.str.31.11.2597 (2000).","journal-title":"Stroke"},{"key":"83432_CR42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1161\/01.str.30.2.293","volume":"30","author":"JL Saver","year":"1999","unstructured":"Saver, J. L. et al. Infarct volume as a surrogate or auxiliary outcome measure in ischemic stroke clinical trials. The RANTTAS investigators. Stroke 30, 293\u2013298. https:\/\/doi.org\/10.1161\/01.str.30.2.293 (1999).","journal-title":"Stroke"},{"key":"83432_CR43","doi-asserted-by":"publisher","first-page":"e00972","DOI":"10.1002\/brb3.972","volume":"8","author":"VW Lau","year":"2018","unstructured":"Lau, V. W., Platt, S. R., Grace, H. E., Baker, E. W. & West, F. D. Human iNPC therapy leads to improvement in functional neurologic outcomes in a pig ischemic stroke model. Brain Behav. 8, e00972. https:\/\/doi.org\/10.1002\/brb3.972 (2018).","journal-title":"Brain Behav."},{"key":"83432_CR44","unstructured":"Navarro-Orozco, D. & Sanchez-Manso, J. C. Neuroanatomy, Middle Cerebral Artery (StatPearls, Treasure Island, FL, 2020)."},{"key":"83432_CR45","unstructured":"Nogles, T. E. & Galuska, M. A. Middle Cerebral Artery Stroke (StatPearls, Treasure Island, FL, 2020)."},{"key":"83432_CR46","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1212\/WNL.0b013e318258f799","volume":"78","author":"S Payabvash","year":"2012","unstructured":"Payabvash, S. et al. Location-weighted CTP analysis predicts early motor improvement in stroke: a preliminary study. Neurology 78, 1853\u20131859. https:\/\/doi.org\/10.1212\/WNL.0b013e318258f799 (2012).","journal-title":"Neurology"},{"key":"83432_CR47","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1161\/STROKEAHA.110.600940","volume":"42","author":"S Payabvash","year":"2011","unstructured":"Payabvash, S. et al. Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific computed tomography perfusion thresholds in acute stroke patients. Stroke 42, 1255\u20131260. https:\/\/doi.org\/10.1161\/STROKEAHA.110.600940 (2011).","journal-title":"Stroke"},{"key":"83432_CR48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/s0165-0270(00)00351-4","volume":"105","author":"G Kito","year":"2001","unstructured":"Kito, G. et al. Experimental thromboembolic stroke in cynomolgus monkey. J. Neurosci. Methods 105, 45\u201353. https:\/\/doi.org\/10.1016\/s0165-0270(00)00351-4 (2001).","journal-title":"J. Neurosci. Methods"},{"key":"83432_CR49","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1097\/01.PHM.0000087490.74582.E0","volume":"82","author":"EB Titianova","year":"2003","unstructured":"Titianova, E. B., Pitkanen, K., Paakkonen, A., Sivenius, J. & Tarkka, I. M. Gait characteristics and functional ambulation profile in patients with chronic unilateral stroke. Am. J. Phys. Med. Rehabil. 82, 778\u2013786. https:\/\/doi.org\/10.1097\/01.PHM.0000087490.74582.E0 (2003).","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"83432_CR50","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.jht.2012.06.005","volume":"26","author":"CE Lang","year":"2013","unstructured":"Lang, C. E., Bland, M. D., Bailey, R. R., Schaefer, S. Y. & Birkenmeier, R. L. Assessment of upper extremity impairment, function, and activity after stroke: foundations for clinical decision making. J. Hand Ther. 26, 104\u2013114. https:\/\/doi.org\/10.1016\/j.jht.2012.06.005 (2013).","journal-title":"J. Hand Ther."},{"key":"83432_CR51","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/S1474-4422(09)70150-4","volume":"8","author":"P Langhorne","year":"2009","unstructured":"Langhorne, P., Coupar, F. & Pollock, A. Motor recovery after stroke: a systematic review. Lancet Neurol. 8, 741\u2013754. https:\/\/doi.org\/10.1016\/S1474-4422(09)70150-4 (2009).","journal-title":"Lancet Neurol."},{"key":"83432_CR52","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1161\/STROKEAHA.110.599340","volume":"42","author":"JD Riley","year":"2011","unstructured":"Riley, J. D. et al. Anatomy of stroke injury predicts gains from therapy. Stroke 42, 421\u2013426. https:\/\/doi.org\/10.1161\/STROKEAHA.110.599340 (2011).","journal-title":"Stroke"},{"key":"83432_CR53","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fnana.2017.00030","volume":"11","author":"Y Saga","year":"2017","unstructured":"Saga, Y., Hoshi, E. & Tremblay, L. Roles of multiple globus pallidus territories of monkeys and humans in motivation, cognition and action: an anatomical physiological and pathophysiological review. Front. Neuroanat. 11, 30. https:\/\/doi.org\/10.3389\/fnana.2017.00030 (2017).","journal-title":"Front. Neuroanat."},{"key":"83432_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/wcs.1403","author":"C Blair","year":"2017","unstructured":"Blair, C. Educating executive function. Wiley Interdiscip. Rev. Cogn. Sci. https:\/\/doi.org\/10.1002\/wcs.1403 (2017).","journal-title":"Wiley Interdiscip. Rev. Cogn. Sci."},{"key":"83432_CR55","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/cphy.c160032","volume":"7","author":"SM Sherman","year":"2017","unstructured":"Sherman, S. M. Functioning of circuits connecting thalamus and cortex. Compr. Physiol. 7, 713\u2013739. https:\/\/doi.org\/10.1002\/cphy.c160032 (2017).","journal-title":"Compr. Physiol."},{"key":"83432_CR56","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1007\/s00221-017-4905-8","volume":"235","author":"MJ Gillies","year":"2017","unstructured":"Gillies, M. J. et al. The cognitive role of the globus pallidus interna; insights from disease states. Exp. Brain Res. 235, 1455\u20131465. https:\/\/doi.org\/10.1007\/s00221-017-4905-8 (2017).","journal-title":"Exp. Brain Res."},{"key":"83432_CR57","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1161\/STROKEAHA.106.475483","volume":"38","author":"YS Ng","year":"2007","unstructured":"Ng, Y. S., Stein, J., Ning, M. & Black-Schaffer, R. M. Comparison of clinical characteristics and functional outcomes of ischemic stroke in different vascular territories. Stroke 38, 2309\u20132314. https:\/\/doi.org\/10.1161\/STROKEAHA.106.475483 (2007).","journal-title":"Stroke"},{"key":"83432_CR58","doi-asserted-by":"publisher","first-page":"2200","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.04.003","volume":"27","author":"G Furlanis","year":"2018","unstructured":"Furlanis, G. et al. Ischemic volume and neurological deficit: correlation of computed tomography perfusion with the national institutes of health stroke scale score in acute ischemic stroke. J. Stroke Cerebrovasc. Dis. 27, 2200\u20132207. https:\/\/doi.org\/10.1016\/j.jstrokecerebrovasdis.2018.04.003 (2018).","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"83432_CR59","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.3174\/ajnr.A5821","volume":"39","author":"M Ernst","year":"2018","unstructured":"Ernst, M. et al. Impact of ischemic lesion location on the mrs score in patients with ischemic stroke: a voxel-based approach. AJNR Am. J. Neuroradiol. 39, 1989\u20131994. https:\/\/doi.org\/10.3174\/ajnr.A5821 (2018).","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"83432_CR60","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.neuroimage.2009.08.044","volume":"49","author":"R Lo","year":"2010","unstructured":"Lo, R., Gitelman, D., Levy, R., Hulvershorn, J. & Parrish, T. Identification of critical areas for motor function recovery in chronic stroke subjects using voxel-based lesion symptom mapping. Neuroimage 49, 9\u201318. https:\/\/doi.org\/10.1016\/j.neuroimage.2009.08.044 (2010).","journal-title":"Neuroimage"},{"key":"83432_CR61","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1177\/0271678X17726635","volume":"39","author":"S Koch","year":"2019","unstructured":"Koch, S. et al. Atlas registration for edema-corrected MRI lesion volume in mouse stroke models. J. Cereb. Blood Flow Metab. 39, 313\u2013323. https:\/\/doi.org\/10.1177\/0271678X17726635 (2019).","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"83432_CR62","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1161\/STROKEAHA.119.025738","volume":"50","author":"SI Ktena","year":"2019","unstructured":"Ktena, S. I. et al. Brain connectivity measures improve modeling of functional outcome after acute ischemic stroke. Stroke 50, 2761\u20132767. https:\/\/doi.org\/10.1161\/STROKEAHA.119.025738 (2019).","journal-title":"Stroke"},{"key":"83432_CR63","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1007\/s12975-019-0689-4","volume":"10","author":"MR Etherton","year":"2019","unstructured":"Etherton, M. R. et al. White matter integrity and early outcomes after acute ischemic stroke. Transl. Stroke Res. 10, 630\u2013638. https:\/\/doi.org\/10.1007\/s12975-019-0689-4 (2019).","journal-title":"Transl. Stroke Res."},{"key":"83432_CR64","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.neuroscience.2017.09.009","volume":"364","author":"J Zhang","year":"2017","unstructured":"Zhang, J. et al. Disrupted structural and functional connectivity networks in ischemic stroke patients. Neuroscience 364, 212\u2013225. https:\/\/doi.org\/10.1016\/j.neuroscience.2017.09.009 (2017).","journal-title":"Neuroscience"},{"key":"83432_CR65","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1002\/ana.21925","volume":"66","author":"SJ Vannucci","year":"2009","unstructured":"Vannucci, S. J. & Hurn, P. D. Gender differences in pediatric stroke: is elevated testosterone a risk factor for boys?. Ann. Neurol. 66, 713\u2013714. https:\/\/doi.org\/10.1002\/ana.21925 (2009).","journal-title":"Ann. Neurol."},{"key":"83432_CR66","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/s0006-8993(98)00327-8","volume":"796","author":"T Hawk","year":"1998","unstructured":"Hawk, T., Zhang, Y. Q., Rajakumar, G., Day, A. L. & Simpkins, J. W. Testosterone increases and estradiol decreases middle cerebral artery occlusion lesion size in male rats. Brain Res. 796, 296\u2013298. https:\/\/doi.org\/10.1016\/s0006-8993(98)00327-8 (1998).","journal-title":"Brain Res."},{"key":"83432_CR67","doi-asserted-by":"publisher","first-page":"319","DOI":"10.2217\/whe.11.22","volume":"7","author":"B Manwani","year":"2011","unstructured":"Manwani, B. & McCullough, L. D. Sexual dimorphism in ischemic stroke: lessons from the laboratory. Womens Health (Lond). 7, 319\u2013339. https:\/\/doi.org\/10.2217\/whe.11.22 (2011).","journal-title":"Womens Health (Lond)."},{"key":"83432_CR68","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/S1474-4422(11)70269-1","volume":"11","author":"L Lisabeth","year":"2012","unstructured":"Lisabeth, L. & Bushnell, C. Stroke risk in women: the role of menopause and hormone therapy. Lancet Neurol. 11, 82\u201391. https:\/\/doi.org\/10.1016\/S1474-4422(11)70269-1 (2012).","journal-title":"Lancet Neurol."},{"key":"83432_CR69","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/2040-7378-6-5","volume":"6","author":"SR Platt","year":"2014","unstructured":"Platt, S. R. et al. Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model. Exp. Trans. Stroke Med. 6, 5\u20135. https:\/\/doi.org\/10.1186\/2040-7378-6-5 (2014).","journal-title":"Exp. Trans. Stroke Med."},{"key":"83432_CR70","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jneumeth.2016.03.001","volume":"264","author":"X Li","year":"2016","unstructured":"Li, X., Morgan, P. S., Ashburner, J., Smith, J. & Rorden, C. The first step for neuroimaging data analysis: DICOM to NIfTI conversion. J. Neurosci. Methods 264, 47\u201356. https:\/\/doi.org\/10.1016\/j.jneumeth.2016.03.001 (2016).","journal-title":"J. Neurosci. Methods"},{"key":"83432_CR71","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.mri.2012.05.001","volume":"30","author":"A Fedorov","year":"2012","unstructured":"Fedorov, A. et al. 3D slicer as an image computing platform for the quantitative imaging network. Magn. Reson. Imag. 30, 1323\u20131341. https:\/\/doi.org\/10.1016\/j.mri.2012.05.001 (2012).","journal-title":"Magn. Reson. Imag."},{"key":"83432_CR72","unstructured":"72Ashburner, J. et al. SPM12 manual. http:\/\/www.fil.ion.ucl.ac.uk\/spm\/doc\/spm12manual.pdf (2016)."},{"key":"83432_CR73","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1006\/nimg.1997.0290","volume":"6","author":"J Ashburner","year":"1997","unstructured":"Ashburner, J. & Friston, K. Multimodal image coregistration and partitioning: a unified framework. Neuroimage 6, 209\u2013217. https:\/\/doi.org\/10.1006\/nimg.1997.0290 (1997).","journal-title":"Neuroimage"},{"key":"83432_CR74","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/(SICI)1097-0193(1999)7:4<254::AID-HBM4>3.0.CO;2-G","volume":"7","author":"J Ashburner","year":"1999","unstructured":"Ashburner, J. & Friston, K. J. Nonlinear spatial normalization using basis functions. Human Brain Mapp. 7, 254\u2013266 (1999).","journal-title":"Human Brain Mapp."},{"key":"83432_CR75","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.neuroimage.2011.09.015","volume":"62","author":"M Jenkinson","year":"2012","unstructured":"Jenkinson, M., Beckmann, C. F., Behrens, T. E., Woolrich, M. W. & Smith, S. M. Fsl. Neuroimage 62, 782\u2013790. https:\/\/doi.org\/10.1016\/j.neuroimage.2011.09.015 (2012).","journal-title":"Neuroimage"},{"issue":"Suppl 1","key":"83432_CR76","doi-asserted-by":"publisher","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","volume":"23","author":"SM Smith","year":"2004","unstructured":"Smith, S. M. et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1), S208-219. https:\/\/doi.org\/10.1016\/j.neuroimage.2004.07.051 (2004).","journal-title":"Neuroimage"},{"key":"83432_CR77","doi-asserted-by":"publisher","first-page":"S173","DOI":"10.1016\/j.neuroimage.2008.10.055","volume":"45","author":"MW Woolrich","year":"2009","unstructured":"Woolrich, M. W. et al. Bayesian analysis of neuroimaging data in FSL. Neuroimage 45, S173-186. https:\/\/doi.org\/10.1016\/j.neuroimage.2008.10.055 (2009).","journal-title":"Neuroimage"},{"key":"83432_CR78","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1186\/s12859-017-1934-z","volume":"18","author":"CT Rueden","year":"2017","unstructured":"Rueden, C. T. et al. Image J2: imageJ for the next generation of scientific image data. BMC Bioinform. 18, 529. https:\/\/doi.org\/10.1186\/s12859-017-1934-z (2017).","journal-title":"BMC Bioinform."},{"key":"83432_CR79","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682. https:\/\/doi.org\/10.1038\/nmeth.2019 (2012).","journal-title":"Nat. Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83432-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83432-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83432-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T03:55:15Z","timestamp":1670039715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83432-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,15]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["83432"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-83432-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,15]]},"assertion":[{"value":"14 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"SLS is a stockholder in Aruna Bio Inc and was a part-time employee of Aruna Bio Inc during the study. EWB was a full-time employee of Aruna Bio Inc during the study. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3814"}}