{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:50:46Z","timestamp":1765371046943,"version":"3.46.0"},"posted":{"date-parts":[[2025,12,8]]},"group-title":"Bioengineering","reference-count":34,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"crossref","award":["R01HL137984","R01HL169378","F31HL158217","U54HL165442","U01HL166058"],"award-info":[{"award-number":["R01HL137984","R01HL169378","F31HL158217","U54HL165442","U01HL166058"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs","award":["W81XWH22-1-0058","W81XWH22-1-0561"],"award-info":[{"award-number":["W81XWH22-1-0058","W81XWH22-1-0561"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["227477"],"award-info":[{"award-number":["227477"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Reactive oxygen species (ROS) contribute to myocardial ischemia-reperfusion injury (IRI), but in-vivo data on the spatial myocardial distribution and systemic effects of ROS after IRI remain limited. This multimodal CMR and PET\/CT study aimed to non-invasively image ROS activity in a clinically-relevant swine model of IRI using [18F]ROStrace, a fluorine-18-labeled analogue of dihydroethidium (DHE), and to investigate regional changes in ROS activity in the infarcted myocardium during the subacute post-IRI phase.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>IRI was induced by percutaneous occlusion of the left anterior descending artery for 90 minutes in swine (N=9). CMR and whole-body PET\/CT imaging with [18F]ROStrace were performed before myocardial infarction (MI) and 3-5 days post-MI to assess ROS in non-infarct myocardium, lungs, bone marrow, spleen and skeletal muscle. Late gadolinium enhanced CMR was performed to structurally characterize infarct regions. Post-MI, in vivo [18F]ROStrace signal in infarcted myocardium was compared with remote, non-infarcted myocardium and validated via ex vivo DHE fluorescent imaging. Bulk RNA-sequencing (RNA-seq) and Gene Ontology pathway analysis were conducted on biopsies from infarct and remote myocardial tissue to identify differentially expressed genes and pathways connected to oxidative stress.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During the subacute phase following MI, [18F]ROStrace fractional uptake rate (FUR; min-1) was significantly increased in skeletal muscle, compared to baseline (0.011\u00b10.003 vs 0.016\u00b10.005, p=0.04), with a trend toward increased FUR in bone marrow (0.046\u00b10.009 vs 0.056\u00b10.011, p=0.12) and the left ventricular free wall (0.067\u00b10.007 vs 0.073\u00b10.010, p=0.15). Within the myocardium, [18F]ROStrace FUR ((min-1)\/(mL\/min\/g)) was significantly higher in infarcted compared to non-infarcted myocardium regions (0.110\u00b10.034, vs 0.148\u00b10.035, p=0.0005). DHE staining confirmed elevated ROS levels in the infarcted myocardium. RNA-seq identified 8,707 differentially expressed genes between infarct and remote myocardium, with downregulated pathways in the infarct associated with mitochondrial function, cellular respiration, and metabolic adaptation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study demonstrated MI ROS imaging using [18F]ROStrace using a whole-body PET\/CT scanner and structural assessment with CMR. Systemic and myocardial increases in ROS activity were observed post-MI, accompanied by substantial molecular alterations in infarcted tissue. These findings show potential imaging strategies to evaluate therapeutic targets that can mitigate oxidative stress after MI.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.04.691257","type":"posted-content","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T04:40:18Z","timestamp":1765255218000},"source":"Crossref","is-referenced-by-count":0,"title":["In vivo imaging of reactive oxygen species after myocardial ischemia-reperfusion injury: a large animal multimodal imaging and transcriptomic 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