{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T01:27:27Z","timestamp":1786584447489,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,10]]},"group-title":"Pathology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Child Health and Human Development","award":["R01 HD103443"],"award-info":[{"award-number":["R01 HD103443"]}]},{"name":"National Institute of Child Health and Human Development","award":["T32 HD101384"],"award-info":[{"award-number":["T32 HD101384"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["K01 AI182448"],"award-info":[{"award-number":["K01 AI182448"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI132519"],"award-info":[{"award-number":["R01 AI132519"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["P51 OD011106"],"award-info":[{"award-number":["P51 OD011106"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"crossref","award":["C06 RR020141"],"award-info":[{"award-number":["C06 RR020141"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>While placental perfusion and pathology jointly affect pregnancy outcomes, cotyledon-specific perfusion across gestation and its correlation with local injury is not yet well understood. Ferumoxytol dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a promising way to noninvasively identify cotyledons across gestation and quantify longitudinal cotyledon-specific perfusion changes. Additionally, intraplacental injection of bioactive fibrin sealant allows us to model thrombotic placental injury and further assess cotyledon-level relationships between perfusion and significant injury.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Pregnant rhesus macaques (N=13) received intrauterine saline or fibrin sealant injections at gestational day (GD) \u223c101 and underwent ferumoxytol DCE-MRI at GDs \u223c100, 115, and 145. Placental perfusion domains derived from contrast arrival time were segmented at each imaging time point and matched to cotyledons identified following tissue collection by cesarean section, with cotyledon perfusion quantified longitudinally and correlated with cotyledon-specific quantitative histopathology.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All pregnancies were successfully carried to term. Fibrin sealant injections induced significantly higher levels of placental pathology compared to saline controls. MRI-derived perfusion domains were largely consistent across gestation and showed predominantly one-to-one correspondence with term cotyledons, with successful perfusion-pathology pairing achieved in 153 cotyledons. Longitudinal cotyledon perfusion changes showed significant positive correlations with villous agglutination injuries.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    Feasibility of noninvasively tracking placental cotyledon perfusion using ferumoxytol DCE-MRI was demonstrated, and the efficacy of the rhesus macaque thrombotic injury model was confirmed. The positive perfusion-pathology correlations suggested intrinsic placental regulatory mechanisms and functional plasticity. This new framework is promising for future translational studies and validation of\n                    <jats:italic>ex vivo<\/jats:italic>\n                    cotyledon perfusion models.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Longitudinal tracking of placental perfusion domains with ferumoxytol MRI<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Successful matching of cotyledons and MRI-derived perfusion domains<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Confirmed thrombotic injury-model induced cotyledon pathology<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Maternal perfusion compensation in presence of villous pathology<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.04.742075","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T01:50:19Z","timestamp":1786413019000},"source":"Crossref","is-referenced-by-count":0,"title":["Ferumoxytol dynamic contrast-enhanced MRI for\n                  <i>in vivo<\/i>\n                  longitudinal cotyledon perfusion assessment with pathology correlation in a rhesus macaque thrombotic injury model"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-4412","authenticated-orcid":false,"given":"Ruo-Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan T.","family":"Keding","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"},{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1223 Capitol Ct, Madison, WI, 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiming","family":"Edmondson","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Vazquez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"},{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1223 Capitol Ct, Madison, WI, 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Antony","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705, USA"},{"name":"Department of Radiology, University of Wisconsin-Madison, 600 Highland Ave, Madison, WI, 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaddeus G.","family":"Golos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"},{"name":"Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1223 Capitol Ct, Madison, WI, 53715, USA"},{"name":"Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Dr, Madison, WI, 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar K.","family":"Stanic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 202 South Park St, Madison, WI, 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-1930","authenticated-orcid":false,"given":"Oliver","family":"Wieben","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland 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