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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. 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.

SUBMITTER: Roberts VH

PROVIDER: S-EPMC4774055 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.

Roberts Victoria H J VH Lo Jamie O JO Salati Jennifer A JA Lewandowski Katherine S KS Lindner Jonathan R JR Morgan Terry K TK Frias Antonio E AE

American journal of obstetrics and gynecology 20160301 3

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Study design</h4>Pregnant Japanese macaques were studied at mid second trimester and in the early thir ...[more]

PMID: 26928151

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Project description:Key Points Contrast-enhanced ultrasound is a noninvasive imaging modality that may noninvasively assess kidney cortical microvascular perfusion. Contrast-enhanced ultrasound–derived kidney cortical microvascular perfusion is associated with eGFR. Visual Abstract Background Individuals with chronic kidney disease (CKD) have decreased kidney cortical microvascular perfusion, which may lead to worsening kidney function over time, but methods to quantify kidney cortical microvascular perfusion are not feasible to incorporate into clinical practice. Contrast-enhanced ultrasound (CEUS) may quantify kidney cortical microvascular perfusion, which requires further investigation in individuals across the spectrum of kidney function. Methods We performed CEUS on a native kidney of 83 individuals across the spectrum of kidney function and calculated quantitative CEUS-derived kidney cortical microvascular perfusion biomarkers. Participants had a continuous infusion of the microbubble contrast agent (Definity) with a flash-replenishment sequence during their CEUS scan. Lower values of the microbubble velocity (β) and perfusion index (β×A) may represent lower kidney cortical microvascular perfusion. Multivariable linear regression models tested the associations of the microbubble velocity (β) and perfusion index (β×A) with estimated glomerular filtration rate (eGFR). Results Thirty-eight individuals with CKD (mean age±SD 65.2±12.6 years, median [IQR] eGFR 31.5 [18.9–41.5] ml/min per 1.73 m2), 37 individuals with end stage kidney disease (ESKD; age 54.8±12.3 years), and eight healthy volunteers (age 44.1±15.0 years, eGFR 117 [106–120] ml/min per 1.73 m2) underwent CEUS without side effects. Individuals with ESKD had the lowest microbubble velocity (β) and perfusion index (β×A) compared with individuals with CKD and healthy volunteers. The microbubble velocity (β) and perfusion index (β×A) had moderate positive correlations with eGFR (β: rs=0.44, P<0.001; β×A: rs=0.50, P<0.001). After multivariable adjustment, microbubble velocity (β) and perfusion index (β×A) remained significantly associated with eGFR (change in natural log transformed eGFR per 1 unit increase in natural log transformed biomarker: β, 0.38 [95%, CI 0.17 to 0.59]; β×A, 0.79 [95% CI, 0.45 to 1.13]). Conclusions CEUS-derived kidney cortical microvascular perfusion biomarkers are associated with eGFR. Future studies are needed to determine if CEUS-derived kidney cortical microvascular perfusion biomarkers have prognostic value.

Project description:PurposeContrast-enhanced ultrasound imaging has expanded the diagnostic potential of ultrasound by enabling real-time imaging and quantification of tissue perfusion. Several perfusion models and curve fitting methods have been developed to quantify the temporal behavior of tracer signal and standardize perfusion quantification. While the least-squares approach has traditionally been applied for curve fitting, it can be inadequate for noisy and complex data. Moreover, previous research suggests that certain perfusion models may be more relevant depending on the organ or tissue imaged. We propose a multi-model framework to select the most appropriate perfusion model and curve fitting method for each diagnostic application.MethodsOur multi-model approach uses a system identification method, which estimates perfusion parameters from the model with the best fit to a given time-intensity curve. We compared current perfusion quantification methods that use a single perfusion model and curve fitting method and our proposed multi-model framework on bolus 3D dynamic contrast-enhanced ultrasound (DCE-US) in vivo images obtained in mice implanted with a colon cancer, as well as on simulation data. The quality of fit in estimating perfusion parameters was evaluated using the Spearman correlation coefficient, the coefficient of determination (R2 ), and the normalized root-mean-square error (NRMSE) to ensure that the multi-model framework finds the best perfusion model and curve fitting algorithm.ResultsOur multi-model framework outperforms conventional single perfusion model approaches with least-squares optimization, providing more robust perfusion parameter estimation. R2 and NRMSE are 0.98 and 0.18, respectively, for our proposed method. By comparison, the performance of the traditional approach is much more dependent upon the selection of the appropriate model. The R2 and NRMSE are 0.91 and 0.31, respectively.ConclusionsThe proposed multi-model framework for perfusion modeling outperforms the current approach of single perfusion modeling using least-squares optimization and more robustly estimates perfusion parameters when using empiric data labeled by an expert as the gold standard. Our technique is minimally sensitive to issues affecting the accuracy of perfusion parameter estimation, including rise time, noise, region of interest size, and frame rate. This framework could be of key utility in modeling different perfusion systems in different tissues and organs.

Dataset Information

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.

Publications

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.

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