{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:09:59Z","timestamp":1790255399931,"version":"4.1.0"},"reference-count":104,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Current approaches for the study of arrhythmogenic Ca\n 2+<\/jats:sup>\n waves in intact cardiac tissue have limited capacity to study the relationship between single\u2010cell properties and the tissue environment. Particularly, wide\u2010field Ca\n 2+<\/jats:sup>\n imaging captures large areas but merges signals from multiple cells, while confocal imaging provides (sub)cellular resolution but is limited to a small number of cells. The aim of this study was to develop an imaging and analysis pipeline capable of extracting single\u2010cell Ca\n 2+<\/jats:sup>\n wave dynamics across large fields within the intact multicellular tissue. Living myocardial slices were prepared from left ventricular tissue from pig and human hearts. Ca\n 2+<\/jats:sup>\n transients and waves reported by Fluo8 were imaged in regions of 20\u2013100 cells at the slice surface. Following a 2\u00a0min conditioning period of 2\u00a0Hz pacing under adrenergic stimulation, Ca\n 2+<\/jats:sup>\n waves were evident during the rest period. Images were recorded at 200\u00a0fps. After image processing, single Ca\n 2+<\/jats:sup>\n waves were identified and propagation paths were tracked using TrackMate. From these tracks, Ca\n 2+<\/jats:sup>\n wave parameters (number of tracks, coordinates and kinetics) were extracted for quantitative analysis and assigned to individual cardiomyocytes using a maximum fluorescence intensity mask to identify cellular borders. In healthy pig cardiac tissue, we captured and quantified single\u2010cell Ca\n 2+<\/jats:sup>\n wave dynamics, detecting variability within the population and an absence of synchronization. The recording of Ca\n 2+<\/jats:sup>\n dynamics across a large cell population and their cell\u2013cell interactions bridges the gap between cell\u2010 and tissue\u2010level observations. Future studies of diseased tissue will offer new insights into mechanisms driving aberrant cellular Ca\n 2+<\/jats:sup>\n activity and the translation into arrhythmias.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n We developed an approach that allows high frame\u2010rate imaging of living cardiac tissue, while retaining capacity to identify Ca\n 2+<\/jats:sup>\n waves in single cells.\n <\/jats:p>\n <\/jats:list-item>\n \n \n In myocardial slice preparations from pig and human hearts, we recorded Ca\n 2+<\/jats:sup>\n waves and, using image analysis tools, tracked their paths and properties simultaneously within individual cells and across a large cell population (20\u2013100 cells) within a region of interest.\n <\/jats:p>\n <\/jats:list-item>\n \n \n This approach bridges a key gap between single\u2010cell observations and whole\u2010tissue behaviour, and can offer deeper insights into how cellular Ca\n 2+<\/jats:sup>\n waves could expand and propagate in the heart.\n <\/jats:p>\n <\/jats:list-item>\n \n Our approach provides a new methodology to study cellular mechanisms that lead to arrhythmias in diseased cardiac tissue.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp288988","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:47:33Z","timestamp":1790254053000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resolution and automated analysis of single\u2010cell Ca\n 2+<\/sup>\n waves within living myocardial tissue slices"],"prefix":"10.1113","author":[{"given":"Darya","family":"Kazakova","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9247-9478","authenticated-orcid":false,"given":"Luka","family":"Nys","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3090-9066","authenticated-orcid":false,"given":"Ankit","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-3523","authenticated-orcid":false,"given":"H. Llewelyn","family":"Roderick","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9609-5507","authenticated-orcid":false,"given":"Karin R.","family":"Sipido","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0488-2410","authenticated-orcid":false,"given":"Eef","family":"Dries","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Experimental Cardiology KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.116036","article-title":"Biomechanical response of ultrathin slices of hypertrophic cardiomyopathy tissue to myosin modulator mavacamten","volume":"170","author":"Amesz J. 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