{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T06:42:50Z","timestamp":1794206570177,"version":"4.8.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1125392"],"award-info":[{"award-number":["APP1125392"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Imaging mass cytometry (IMC) affords simultaneous immune\u2010labelling\/imaging of multiple antigens in the same tissue. Methods utilizing multiplex data beyond co\u2010registration are lacking. This study developed and applied an innovative spatial analysis workflow for multiplex imaging data to IMC data determined from cardiac tissues and revealed the mechanism(s) of neutrophil\u2010mediated post\u2010myocardial\u2010infarction damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IMC produced multiplex images with various redox\/inflammatory markers. The cardiac peri\u2010infarct zone (PIZ) was determined to be up to 240\u00a0\u00b5m from the infarct border based on the presence of neutrophils. The tissue region beyond the infarct was defined as the remote area (RA). ImageJ was used to quantify the immunoreactivity. Functional assessments included infarct size, cell necro\/apoptosis, total thiol assay and echocardiogram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of damage markers decreased in order from the infarct area to PIZ and then RA, reflecting the neutrophil density in the regions. Concentrically spaced \u201cshoreline contour analysis\u201d around the cardiac infarct extending into the PIZ showed that immunoreactivity for damage markers decreased linearly with increasing distance from the infarct, concomitant with a decreasing neutrophil\u2010myeloperoxidase (MPO) gradient from the infarct to the PIZ. Stratifying by concentric bands around individual MPO<jats:sup>+<\/jats:sup>\u2010signal identified that the immunoreactivity of haem\u2010oxygenase\u20101 (HO\u20101) and phosphorylated\u2010p38 mitogen\u2010activated protein kinase (pP38) peaked near neutrophils. Furthermore, spatial dependence between neutrophils and markers of cardiac cellular damage was confirmed by nearest\u2010neighbour distance analysis. Post\u2010infarction tissue exhibited declined functional parameters that were associated with neutrophil migration from the infarct to PIZ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This image\u2010based quantitative protocol revealed the spatial association and provided potential molecular pathways responsible for neutrophil\u2010mediated damage post\u2010infarction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13790","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T08:15:03Z","timestamp":1643184903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Multiplex analysis of mass imaging data: Application to the pathology of experimental myocardial infarction"],"prefix":"10.1111","volume":"235","author":[{"given":"Han","family":"Shi","sequence":"first","affiliation":[{"name":"Redox Biology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"El Kazzi","sequence":"additional","affiliation":[{"name":"Redox Biology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Redox Biology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Gao","sequence":"additional","affiliation":[{"name":"Redox Biology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie L.","family":"Schroder","sequence":"additional","affiliation":[{"name":"Redox Biology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-7893","authenticated-orcid":false,"given":"Sally","family":"Vuong","sequence":"additional","affiliation":[{"name":"The Heart Research Institute Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Young","sequence":"additional","affiliation":[{"name":"Australian Centre for Microscopy &amp; Microanalysis Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin S.","family":"Rayner","sequence":"additional","affiliation":[{"name":"The Heart Research Institute Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caryn","family":"van Vreden","sequence":"additional","affiliation":[{"name":"Immunopathology Group Discipline of Pathology Faculty of Medicine and Health Charles Perkins Centre The University of Sydney  Sydney New South Wales Australia"},{"name":"Sydney Cytometry Facility and Ramaciotti Facility for Human Systems Biology The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3877-9772","authenticated-orcid":false,"given":"Nicholas J. 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