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Ultrasound contrast materials in cardiovascular medicine: from perfusion assessment to molecular imaging.

ABSTRACT: Ultrasound imaging is widely used in cardiovascular diagnostics. Contrast agents expand the range of tasks that ultrasound can perform. In the clinic in the USA, endocardial border delineation and left ventricle opacification have been an approved indication for more than a decade. However, myocardial perfusion contrast ultrasound studies are still at the clinical trials stage. Blood pool contrast and perfusion in other tissues might be an easier indication to achieve: general blood pool ultrasound contrast is in wider use in Europe, Canada, Japan, and China. Targeted (molecular) contrast microbubbles will be the next generation of ultrasound imaging probes, capable of specific delineation of the areas of disease by adherence to molecular targets. The shell of targeted microbubbles (currently in the preclinical research and early stage clinical trials) is decorated with the ligands (antibodies, peptides or mimetics, hormones, and carbohydrates) that ensure firm binding to the molecular markers of disease.

SUBMITTER: Klibanov AL

PROVIDER: S-EPMC3816116 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Ultrasound contrast materials in cardiovascular medicine: from perfusion assessment to molecular imaging.

Klibanov Alexander L AL

Journal of cardiovascular translational research 20130803 5

Ultrasound imaging is widely used in cardiovascular diagnostics. Contrast agents expand the range of tasks that ultrasound can perform. In the clinic in the USA, endocardial border delineation and left ventricle opacification have been an approved indication for more than a decade. However, myocardial perfusion contrast ultrasound studies are still at the clinical trials stage. Blood pool contrast and perfusion in other tissues might be an easier indication to achieve: general blood pool ultraso ...[more]

PMID: 23913363

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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.

Project description:BackgroundThere is growing interest in limb contrast-enhanced ultrasound (CEU) perfusion imaging for the evaluation of peripheral artery disease. Because of low resting microvascular blood flow in skeletal muscle, signal enhancement during limb CEU is prohibitively low for real-time imaging. The aim of this study was to test the hypothesis that this obstacle can be overcome by intermediate- rather than low-power CEU when performed with an acoustically resilient microbubble agent.MethodsViscoelastic properties of Definity and Sonazoid were assessed by measuring bulk modulus during incremental increases in ambient pressure to 200 mm Hg. Comparison of in vivo microbubble destruction and signal enhancement at a mechanical index (MI) of 0.1 to 0.4 was performed by sequential reduction in pulsing interval from 10 to 0.05 sec during limb CEU at 7 MHz in mice and 1.8 MHz in dogs. Destruction was also assessed by broadband signal generation during passive cavitation detection. Real-time CEU perfusion imaging with destruction-replenishment was then performed at 1.8 MHz in dogs using an MI of 0.1, 0.2, or 0.3.ResultsSonazoid had a higher bulk modulus than Definity (66 ± 12 vs 29 ± 2 kPa, P = .02) and exhibited less inertial cavitation (destruction) at MIs ≥ 0.2. On in vivo CEU, maximal signal intensity increased incrementally with MI for both agents and was equivalent between agents except at an MI of 0.1 (60% and 85% lower for Sonazoid at 7 and 1.8 MHz, respectively, P < .05). However, on progressive shortening of the pulsing interval, Definity was nearly completely destroyed at MIs ≥ 0.2 at 1.8 and 7 MHz, whereas Sonazoid was destroyed only at 1.8 MHz at MIs ≥ 0.3. As a result, real-time CEU perfusion imaging demonstrated approximately fourfold greater enhancement for Sonazoid at an MI of 0.3 to 0.4.ConclusionsRobust signal enhancement during real-time CEU perfusion imaging of the limb is possible when using intermediate-power imaging coupled with a durable microbubble contrast agent.

Project description: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.

Dataset Information

Ultrasound contrast materials in cardiovascular medicine: from perfusion assessment to molecular imaging.

Publications

Ultrasound contrast materials in cardiovascular medicine: from perfusion assessment to molecular imaging.

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