{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:55:00Z","timestamp":1787032500127,"version":"build-2736575974"},"posted":{"date-parts":[[2026,5,21]]},"group-title":"Pathology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01-HD103443"],"award-info":[{"award-number":["R01-HD103443"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P51-OD011106"],"award-info":[{"award-number":["P51-OD011106"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K01AI82448"],"award-info":[{"award-number":["K01AI82448"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["L70HD119811"],"award-info":[{"award-number":["L70HD119811"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AI175753-01"],"award-info":[{"award-number":["AI175753-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL163623-01A1"],"award-info":[{"award-number":["HL163623-01A1"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Healthy and diseased placentae alike often display some degree of pathology. However, quantitative techniques to characterize common pathologies and their relationship to local maternal hemodynamics in healthy primate placentae are currently limited.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Placentae from seven rhesus macaques were imaged by MRI at three time points across mid-to late-gestation, to quantify placental blood volume, flow, and perfusion from maternal spiral arteries across pregnancy. Near term, we collected placental cotyledons, digitized hematoxylin\/eosin-stained slides, then segmented and annotated sub-tissues and major pathologies (intervillous gaps, fibrin deposition, villous agglutination, inflammatory agglutination, and stromal mineralization) within each cotyledon. Individual pathologies were assessed in relation to each other and MRI perfusion metrics, in a cotyledon-specific manner. Parallel analyses were performed to investigate both basic (Spearman correlation) and animal variance-negated (dimensionality-reduction) relationships.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Cotyledons with increased stromal mineralization demonstrated low blood perfusion across pregnancy, alongside significant compensatory changes. Mineralization was further associated with decreased fetal weight, across all sub-tissues. Dimensionality reduction revealed maternal vascular malperfusion-associated pathologies as the largest contributor to dataset variance. Additionally, pathologies commonly associated with healthy placental function demonstrated low cotyledon blood flow and volume at all timepoints, with no evidence of compensatory changes across gestation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Comprehensive digital annotation revealed several relationships connecting pathology and maternal blood perfusion in the healthy primate pregnancy, at the smallest functional unit of the placenta. This methodological framework embeds pathologist-refined morphological expertise into a quantitative, spatially resolved format that can ground, rather than be replaced by, unsupervised computational approaches to placental analysis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.18.726079","type":"posted-content","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T19:30:36Z","timestamp":1779391836000},"source":"Crossref","is-referenced-by-count":1,"title":["Bridging Cotyledon Pathology and Perfusion in Healthy Primate Pregnancy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9341-6502","authenticated-orcid":false,"given":"Logan T.","family":"Keding","sequence":"first","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-4412","authenticated-orcid":false,"given":"Ruo-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-6712","authenticated-orcid":false,"given":"Taylor J.","family":"Keding","sequence":"additional","affiliation":[{"name":"Department of Psychology, Yale University, 100 College St, New Haven, CT, 06510 USA"},{"name":"Child Study Center, Yale University, 230 South Frontage Road, New Haven, CT 06520 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8052-3850","authenticated-orcid":false,"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":"Crystal G.","family":"Bockoven","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 1685 Highland Ave, Madison, WI, 53705 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-4337","authenticated-orcid":false,"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"}]},{"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 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-6436","authenticated-orcid":false,"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"}]}],"member":"54368","reference":[{"key":"2026052506150815000_2026.05.18.726079v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2025.06.004"},{"key":"2026052506150815000_2026.05.18.726079v1.2","doi-asserted-by":"crossref","unstructured":"T.Y. Khong , E.E. Mooney , P.G.J. Nikkels , T.K. Morgan , S.J. Gordijn , Pathology of the Placenta: A Practical Guide, Springer, Cham, 2019.","DOI":"10.1007\/978-3-319-97214-5"},{"key":"2026052506150815000_2026.05.18.726079v1.3","unstructured":"J.E. Wardinger , S. Ambati , Placental Insufficiency, in: StatPearls, StatPearls Publishing, Treasure Island (FL), 2024. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK563171\/ (accessed August 28, 2024)."},{"key":"2026052506150815000_2026.05.18.726079v1.4","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0225-CC"},{"key":"2026052506150815000_2026.05.18.726079v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00747-4"},{"key":"2026052506150815000_2026.05.18.726079v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.05.025"},{"key":"2026052506150815000_2026.05.18.726079v1.7","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002264"},{"key":"2026052506150815000_2026.05.18.726079v1.8","doi-asserted-by":"publisher","DOI":"10.1515\/jpm-2018-0055"},{"key":"2026052506150815000_2026.05.18.726079v1.9","doi-asserted-by":"publisher","DOI":"10.3389\/fcdhc.2021.807192"},{"key":"2026052506150815000_2026.05.18.726079v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1958.tb08870.x"},{"key":"2026052506150815000_2026.05.18.726079v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2022.12.001"},{"key":"2026052506150815000_2026.05.18.726079v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25264"},{"key":"2026052506150815000_2026.05.18.726079v1.13","doi-asserted-by":"publisher","DOI":"10.1177\/0192623308326095"},{"key":"2026052506150815000_2026.05.18.726079v1.14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00160"},{"key":"2026052506150815000_2026.05.18.726079v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2025.10.002"},{"key":"2026052506150815000_2026.05.18.726079v1.16","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174419000539"},{"key":"2026052506150815000_2026.05.18.726079v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioac168"},{"key":"2026052506150815000_2026.05.18.726079v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2025.07.083"},{"key":"2026052506150815000_2026.05.18.726079v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2019.10.006"},{"key":"2026052506150815000_2026.05.18.726079v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27548"},{"key":"2026052506150815000_2026.05.18.726079v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29291"},{"key":"2026052506150815000_2026.05.18.726079v1.22","doi-asserted-by":"publisher","DOI":"10.31300\/TDB.14.2021.63-72"},{"key":"2026052506150815000_2026.05.18.726079v1.23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000676"},{"key":"2026052506150815000_2026.05.18.726079v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-23941-0"},{"key":"2026052506150815000_2026.05.18.726079v1.25","first-page":"855","article-title":"Trophoblast interaction with fibrin matrix. Epithelialization of perivillous fibrin deposits as a mechanism for villous repair in the human placenta","volume":"136","year":"1990","journal-title":"Am. J. Pathol"},{"key":"2026052506150815000_2026.05.18.726079v1.26","doi-asserted-by":"publisher","DOI":"10.1111\/jog.70052"},{"key":"2026052506150815000_2026.05.18.726079v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2016.10.009"},{"key":"2026052506150815000_2026.05.18.726079v1.28","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1038358"},{"key":"2026052506150815000_2026.05.18.726079v1.29","doi-asserted-by":"publisher","DOI":"10.1890\/0012-9658(2003)084"},{"key":"2026052506150815000_2026.05.18.726079v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3795(85)90187-9"},{"key":"2026052506150815000_2026.05.18.726079v1.31","doi-asserted-by":"publisher","DOI":"10.1890\/0012-9615(1999)069[0001:DBRATM]2.0.CO;2"},{"key":"2026052506150815000_2026.05.18.726079v1.32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-0998.2010.02866.x"},{"key":"2026052506150815000_2026.05.18.726079v1.33","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"2026052506150815000_2026.05.18.726079v1.34","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2001.0626"},{"key":"2026052506150815000_2026.05.18.726079v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2012.10.002"},{"key":"2026052506150815000_2026.05.18.726079v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2019.07.011"},{"key":"2026052506150815000_2026.05.18.726079v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2018.03.004"},{"key":"2026052506150815000_2026.05.18.726079v1.38","doi-asserted-by":"publisher","DOI":"10.1017\/9781316848616.008"},{"key":"2026052506150815000_2026.05.18.726079v1.39","unstructured":"Y. Wang , S. Zhao , Structure of the Placenta, in: Vasc. Biol. Placenta, Morgan & Claypool Life Sciences, 2010."},{"key":"2026052506150815000_2026.05.18.726079v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2014.01.008"},{"key":"2026052506150815000_2026.05.18.726079v1.41","doi-asserted-by":"publisher","DOI":"10.1177\/030098588602300413"},{"key":"2026052506150815000_2026.05.18.726079v1.42","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1157-z"},{"key":"2026052506150815000_2026.05.18.726079v1.43","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.55.643.362"},{"key":"2026052506150815000_2026.05.18.726079v1.44","doi-asserted-by":"publisher","DOI":"10.5566\/ias.v20.p1-7"},{"key":"2026052506150815000_2026.05.18.726079v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2024.102089"},{"key":"2026052506150815000_2026.05.18.726079v1.46","doi-asserted-by":"publisher","DOI":"10.1111\/apm.12833"},{"key":"2026052506150815000_2026.05.18.726079v1.47","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.17837"},{"key":"2026052506150815000_2026.05.18.726079v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(64)90948-2"},{"key":"2026052506150815000_2026.05.18.726079v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.02.009"},{"key":"2026052506150815000_2026.05.18.726079v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.10.003"},{"key":"2026052506150815000_2026.05.18.726079v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2006.12.024"},{"key":"2026052506150815000_2026.05.18.726079v1.52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317189"},{"key":"2026052506150815000_2026.05.18.726079v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2024.12.020"},{"key":"2026052506150815000_2026.05.18.726079v1.54","doi-asserted-by":"publisher","DOI":"10.1101\/2022.11.21.517353"},{"key":"2026052506150815000_2026.05.18.726079v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpi.2024.100413"},{"key":"2026052506150815000_2026.05.18.726079v1.56","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2022.3202759"},{"key":"2026052506150815000_2026.05.18.726079v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46986-2"},{"key":"2026052506150815000_2026.05.18.726079v1.58","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2024.39.e271"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.05.18.726079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T13:15:14Z","timestamp":1779714914000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.05.18.726079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":58,"URL":"https:\/\/doi.org\/10.64898\/2026.05.18.726079","relation":{},"subject":[],"published":{"date-parts":[[2026,5,21]]},"subtype":"preprint"}}