title: Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.
abstract: BACKGROUND
  The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited.
  
  
  OBJECTIVE
  We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta.
  
  
  METHODS
  Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion.
  
  
  RESULTS
  In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies.
  
  
  CONCLUSIONS
  Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.
authors.affiliation: Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR. Electronic address: robertsv@ohsu.edu.
authors.forename: Victoria H J
authors.initials: VH
authors.lastname: Roberts
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR.
authors.forename: Jamie O
authors.initials: JO
authors.lastname: Lo
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Salati
authors.affiliation: Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Lewandowski
authors.affiliation: Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.affiliation: Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR; Department of Pathology, Oregon Health & Science University, Portland, OR.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Morgan
authors.affiliation: Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR; Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR; Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR.
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Frias
mesh_terms: D000465:Algorithms; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002824:Chorionic Villi / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D003287:Contrast Media / Q000009:adverse effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008251:Macaca; D045423:Microbubbles / Q000009:adverse effects; D021041:Placental Circulation; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000502:physiology; D011262:Pregnancy Trimester, Second / Q000502:physiology; D011263:Pregnancy Trimester, Third / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D014327:Trophoblasts / Q000648:ultrastructure; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D018840:HSP70 Heat-Shock Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D053148:Caspase 3
keywords: Japanese macaque; contrast-enhanced ultrasound imaging; placenta; placental perfusion