{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:51:22Z","timestamp":1773161482916,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mindray Medical Italy Srl (Milan, Italy).","award":["xx"],"award-info":[{"award-number":["xx"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>In cystic endometrial hyperplasia (CEH)\u2013pyometra syndrome, toxic factors and endometrial remodeling culminate in changes characterized by exudative and degenerative inflammatory reaction. Recent studies on hemodynamic found an increased blood flow and lower vascular resistance in uterine arteries, suggesting color Doppler ultrasound as an adjunctive tool for quantitative assessment of endometrial vascularization during pyometra. The aim of this study was to assess, through contrast-enhanced ultrasound (CEUS) exam, the vascularization in endometrial microvessels in CEH-pyometra in order to evaluate the possibility of application in this syndrome. In twelve female dogs with clinical symptoms related to pyometra, B-mode, color Doppler and CEUS exams were performed. In CEH-pyometra uteri, histopathological examination revealed severe CEH and pyometra, immunohistochemical stain with CD 34 confirmed the presence of angiogenesis. CEUS exams revealed a widespread, intense and rapidly developing homogeneous enhancement of the hyperplastic endometrium, with absence of signal only in cystic areas. All parameters of the quantitative analysis were not significantly influenced by region of interest dimension and position. CEUS has the potential to improve clinical not invasive evaluations in the CEH-pyometra syndrome and virtually in CEH-mucometra.<\/jats:p>","DOI":"10.3390\/ani10081368","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T07:25:03Z","timestamp":1597044303000},"page":"1368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Contrast-Enhanced Ultrasound in Cystic Endometrial Hyperplasia\u2013Pyometra Complex in the Bitch: A Preliminary Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4812-0402","authenticated-orcid":false,"given":"Marco","family":"Quartuccio","sequence":"first","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3242-1817","authenticated-orcid":false,"given":"Luigi","family":"Liotta","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santo","family":"Cristarella","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3436-2814","authenticated-orcid":false,"given":"Giovanni","family":"Lanteri","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Ieni","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"D\u2019Arrigo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4527-7030","authenticated-orcid":false,"given":"Massimo","family":"De Majo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, University of Messina, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1439-0531.2004.00489.x","article-title":"Ultrasonography and cystic hyperplasia-pyometra complex in the bitch","volume":"39","author":"Bigliardi","year":"2004","journal-title":"Reprod. Domest. Anim."},{"key":"ref_2","first-page":"58","article-title":"Cystic endometrial hyperplasia-pyometra syndrome in bitches: Identification of hemodynamic, inflammatory, and cell proliferation changes","volume":"96","author":"Veiga","year":"2017","journal-title":"Biol. Reprod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.theriogenology.2008.04.041","article-title":"Cystic endometrial hyperplasia, pseudo-placentational endometrial hyperplasia, and other cystic conditions of the canine and feline uterus","volume":"70","author":"Schlafer","year":"2008","journal-title":"Theriogenology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1439-0531.2009.01393.x","article-title":"Prostaglandin synthesis genes are differentially transcripted in normal and pyometra endometria of bitches","volume":"44","author":"Silva","year":"2009","journal-title":"Reprod. Domest. Anim."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hagman, R., R\u00f6nnberg, E., and Pejler, G. (2009). Canine uterine bacterial infection induces upregulation of proteolysis-related genes and downregulation of homeiobox and zinc finger factors. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008039"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Voorwald, F.A., Marchi, F.A., Villacis, R.A., Alves, C.E., Toniollo, G.H., Amorim, R.L., Drigo, S.A., and Rogatto, S.R. (2015). Molecular expression profile reveals potential biomarkers and therapeutic targets in canine endometrial lesions. PLoS ONE, 29.","DOI":"10.1371\/journal.pone.0133894"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.theriogenology.2009.08.002","article-title":"Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor expression and localization in the canine endometrium during the estrous cycle and in bitches with pyometra","volume":"73","author":"Kida","year":"2010","journal-title":"Theriogenology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0014-5793(95)00956-A","article-title":"Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: A potential mechanism for inflammatory angiogenesis","volume":"372","author":"Crofford","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1074\/jbc.271.2.736","article-title":"Interleukin 6 induces the expression of vascular endothelial growth factor","volume":"271","author":"Cohen","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1053\/plac.1998.0350","article-title":"Immunohistochemical localization of vascular endothelial growth factor (VEGF) and its two specific receptors, FLT-1 and KDR, in the porcine placenta and non-pregnant uterus","volume":"20","author":"Winther","year":"1999","journal-title":"Placenta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3109\/08977199609034566","article-title":"Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor","volume":"13","author":"Yoshida","year":"1996","journal-title":"Growth Factors"},{"key":"ref_12","unstructured":"Concannon, P.W., Verstegen, J., and England, G. (2003). Ultrasound imaging of the reproductive tract of the bitch. Recent Advances in Small Animal Reproduction, IVIS. Document A1226.0303."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1053\/j.tcam.2008.11.002","article-title":"Reproductive ultrasound of the bitch and queen","volume":"24","author":"Davidson","year":"2009","journal-title":"Top. Companion Anim. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.tvjl.2013.02.015","article-title":"Uterine artery blood flow characteristics assessed during oestrus and the early luteal phase of pregnant and non-pregnant bitches","volume":"197","author":"Freeman","year":"2013","journal-title":"Vet. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.tvjl.2010.08.013","article-title":"Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs","volume":"190","author":"Blanco","year":"2011","journal-title":"Vet. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.anireprosci.2013.07.013","article-title":"Doppler ultrasonographic assessment of uterine arteries during normal canine puerperium","volume":"141","author":"Batista","year":"2013","journal-title":"Anim. Reprod. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.theriogenology.2015.12.008","article-title":"Uterine blood flow evaluation in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex","volume":"85","author":"Batista","year":"2016","journal-title":"Theriogenology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/j.1740-8261.2004.04094.x","article-title":"Contrast harmonic ultrasound of spontaneous liver nodules in 32 dogs","volume":"45","author":"Iani","year":"2004","journal-title":"Vet. Radiol. Ultrasound"},{"key":"ref_19","first-page":"6076","article-title":"Contrast-Enhanced ultrasound features of malignant focal liver masses in dogs","volume":"10","author":"Burti","year":"2020","journal-title":"Nat. Res. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1740-8261.2007.00277.x","article-title":"Contrast harmonic imaging of the normal canine spleen","volume":"48","author":"Ohlerth","year":"2007","journal-title":"Vet. Radiol. Ultrasound"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1740-8261.2008.00343.x","article-title":"Use of contrast-enhanced ultrasound for characterization of focal splenic lesions","volume":"49","author":"Rossi","year":"2008","journal-title":"Vet. Radiol. Ultrasound"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"460","DOI":"10.2460\/javma.234.4.460","article-title":"Review of clinical characteristics and applications of contrast-enhanced ultrasonography in dogs","volume":"234","author":"Haers","year":"2009","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/j.1740-8261.2010.01690.x","article-title":"Contrast harmonic ultrasonographic appearance of focal space-occupying renal lesions","volume":"51","author":"Haers","year":"2010","journal-title":"Vet. Radiol. Ultrasound"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Macr\u00ec, F., Di Pietro, S., Mangano, C., Pugliese, M., Mazzullo, G., Iannelli, N.M., Angileri, V., Morabito, S., and De Majo, M. (2018). Quantitative evaluation of canine urinary bladder transitional cell carcinoma using contrast-enhanced ultrasonography. BMC Vet. Res., 14.","DOI":"10.1186\/s12917-018-1384-5"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.17221\/101\/2017-VETMED","article-title":"Contrast-Enhanced ultrasound evaluation of testicular interstitial cell tumours in conscious non-sedated dogs","volume":"63","author":"Quartuccio","year":"2018","journal-title":"Vet. Med. Czech"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/rda.12250","article-title":"Use of contrast-enhanced ultrasonography in chronic pathologic canine testes","volume":"49","author":"Volta","year":"2014","journal-title":"Reprod. Domest. Anim."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1439-0531.2010.01629.x","article-title":"Assessment of vascular perfusion kinetics using contrast-enhanced ultrasound for the diagnosis of prostatic disease in dogs","volume":"46","author":"Vignoli","year":"2011","journal-title":"Reprod. Domest. Anim."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1159\/000020993","article-title":"Contrast-Enhanced ultrasonography of uteroplacental circulation does not evoke harmful CTG changes or perinatal events","volume":"15","author":"Orden","year":"2000","journal-title":"Fetal Diagn. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5005\/jp-journals-10009-1094","article-title":"Contrast-Enhanced ultrasound in obstetrics and gynecology","volume":"1","author":"Murotsuki","year":"2007","journal-title":"Donald Sch. J. Ultrasound Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zhou, Y.J., Yuan, M.L., Li, R., Zhu, L.P., and Chen, Z.H. (2013). Real-Time placental perfusion on contrast-enhanced ultrasound and parametric imaging analysis in rats at different gestation time and different portions of placenta. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058986"},{"key":"ref_31","first-page":"1","article-title":"Quantitative assessment of placental perfusion by contrast-enhanced ultra-sound in macaques and human subjects","volume":"369","author":"Oberts","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jevs.2017.02.011","article-title":"Contrast-Enhanced ultrasonography (CEUS) of the uterus during normal equine pregnancy: Preliminary report in two mares","volume":"54","author":"Freccero","year":"2017","journal-title":"J. Equine Vet. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.theriogenology.2018.10.027","article-title":"Contrast-Enhanced ultrasonography of maternal and fetal blood flows in pregnant bitches","volume":"125","author":"Orlandi","year":"2019","journal-title":"Theriogenology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.anireprosci.2018.08.036","article-title":"B-Mode and contrast-enhanced ultrasonography of the mammary gland during the estrous cycle of dogs","volume":"199","author":"Vanderperrena","year":"2018","journal-title":"Anim. Reprod. Sci."},{"key":"ref_35","first-page":"433","article-title":"Role of contrast-enhanced ultrasound (CEUS) in the diagnosis of endometrial pathology","volume":"88","author":"Pop","year":"2015","journal-title":"Clujul Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3763","DOI":"10.3892\/ol.2016.5206","article-title":"Quantitative contrast-enhanced ultrasonography for the differential diagnosis of endometrial hyperplasia and endometrial neoplasms","volume":"12","author":"Liu","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_37","first-page":"171","article-title":"Infertility in a bitch associated with short interestrous intervals and cyst follicles: A case report","volume":"20","author":"Shille","year":"1984","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_38","unstructured":"SAS Institute (2017). SAS\/STAT\u00ae Users Guide, SAS Inst. Inc.. Version 9.3."},{"key":"ref_39","first-page":"1102","article-title":"The cystic hyperplasia-pyometra complex in the bitch","volume":"70","author":"Dow","year":"1958","journal-title":"Vet. Rec."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/S0093-691X(01)00498-8","article-title":"Cystic endometrial hyperplasia-piome-tra complex in the bitch: Should the two entities disconnected?","volume":"55","author":"Ducatelle","year":"2001","journal-title":"Theriogenology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.theriogenology.2012.07.009","article-title":"Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic","volume":"78","author":"England","year":"2012","journal-title":"Theriogenology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1098\/rsfs.2011.0026","article-title":"Quantitative contrast-enhanced ultrasound imaging: A review of sources of variability","volume":"1","author":"Tang","year":"2011","journal-title":"Interface Focus"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.theriogenology.2012.09.005","article-title":"Findings in uterine biopsies obtained by laparotomy from bitches with unexplained infertility or pregnancy loss: An observational study","volume":"79","author":"Mir","year":"2013","journal-title":"Theriogenology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2460\/javma.244.2.180","article-title":"Histopathologic findings in uterine biopsy samples from subfertile bitches: 399 cases (1990\u20132005)","volume":"244","author":"Gifford","year":"2014","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s12663-011-0234-9","article-title":"Essentials before sending biopsy specimens: A surgeon\u2019s prospective and pathologists concern","volume":"10","author":"Jain","year":"2011","journal-title":"J. Maxillofac. Oral Surg."},{"key":"ref_46","first-page":"61","article-title":"Development of a technique for transcervical collection of uterine tissue in bitches","volume":"57","author":"Wilke","year":"2001","journal-title":"J. Reprod. Fertil. Suppl."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/rda.12109","article-title":"Diagnostic value of transcervical endometrial biopsies in domestic dogs compared with full-thickness uterine sections","volume":"47","author":"Christensen","year":"2012","journal-title":"Reprod. Domest. Anim."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/8\/1368\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:57:34Z","timestamp":1760176654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/10\/8\/1368"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ani10081368"],"URL":"https:\/\/doi.org\/10.3390\/ani10081368","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]}}}