Victoria H J Roberts1, Jamie O Lo2, Jennifer A Salati2, Katherine S Lewandowski3, Jonathan R Lindner4, Terry K Morgan5, Antonio E Frias6. 1. Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR. Electronic address: robertsv@ohsu.edu. 2. Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR. 3. Division of Diabetes, Obesity & Metabolism, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR. 4. Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR. 5. Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR; Department of Pathology, Oregon Health & Science University, Portland, OR. 6. 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.
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. STUDY DESIGN: 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.
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. STUDY DESIGN: 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: Jamie O Lo; Matthias C Schabel; Victoria H J Roberts; Terry K Morgan; Juha P Rasanen; Christopher D Kroenke; Sophie R Shoemaker; Eliot R Spindel; Antonio E Frias Journal: Am J Obstet Gynecol Date: 2015-03 Impact factor: 8.661
Authors: Victoria H J Roberts; Lynley D Pound; Stephanie R Thorn; Melanie B Gillingham; Kent L Thornburg; Jacob E Friedman; Antonio E Frias; Kevin L Grove Journal: FASEB J Date: 2014-02-21 Impact factor: 5.191
Authors: Ya Ni Liu; Jaspreet Khangura; Aris Xie; J Todd Belcik; Yue Qi; Brian P Davidson; Yan Zhao; Sajeevani Kim; Yoichi Inaba; Jonathan R Lindner Journal: J Am Soc Echocardiogr Date: 2013-09-12 Impact factor: 5.251
Authors: André Dallmann; Ibrahim Ince; Michaela Meyer; Stefan Willmann; Thomas Eissing; Georg Hempel Journal: Clin Pharmacokinet Date: 2017-11 Impact factor: 6.447
Authors: Victoria H J Roberts; Jamie O Lo; Katherine S Lewandowski; Peter Blundell; Kevin L Grove; Christopher D Kroenke; Elinor L Sullivan; Charles T Roberts; Antonio E Frias Journal: Reprod Sci Date: 2017-04-26 Impact factor: 3.060
Authors: Kelly Kuo; Victoria H J Roberts; Jessica Gaffney; Diana L Takahashi; Terry Morgan; Jamie O Lo; Richard L Stouffer; Antonio E Frias Journal: Endocrinology Date: 2019-08-01 Impact factor: 4.736
Authors: Brooks D Lindsey; Sarah E Shelton; K Heath Martin; Kathryn A Ozgun; Juan D Rojas; F Stuart Foster; Paul A Dayton Journal: Ann Biomed Eng Date: 2016-11-10 Impact factor: 3.934
Authors: Jeffery S Babischkin; Graham W Aberdeen; Jonathan R Lindner; Thomas W Bonagura; Gerald J Pepe; Eugene D Albrecht Journal: Endocrinology Date: 2019-06-01 Impact factor: 4.736
Authors: Sonnet S Jonker; Lowell Davis; Divya Soman; J Todd Belcik; Brian P Davidson; Tamara M Atkinson; Adrienne Wilburn; Samantha Louey; George D Giraud; Jonathan R Lindner Journal: J Physiol Date: 2016-07-18 Impact factor: 5.182
Authors: Tomasz J Czernuszewicz; Virginie Papadopoulou; Juan D Rojas; Rajalekha M Rajamahendiran; Jonathan Perdomo; James Butler; Max Harlacher; Graeme O'Connell; Dženan Zukić; Stephen R Aylward; Paul A Dayton; Ryan C Gessner Journal: Rev Sci Instrum Date: 2018-07 Impact factor: 1.523
Authors: Juan D Rojas; Virginie Papadopoulou; Tomasz J Czernuszewicz; Rajalekha M Rajamahendiran; Anna Chytil; Yun-Chen Chiang; Diana C Chong; Victoria L Bautch; W Kimryn Rathmell; Stephen Aylward; Ryan C Gessner; Paul A Dayton Journal: IEEE Trans Biomed Eng Date: 2018-07-27 Impact factor: 4.538