Molecular imaging using ultrasound makes use of targeted microbubbles. In this study we investigated whether these microbubbles could also be used to induce sonoporation in endothelial cells. ...Lipid-coated microbubbles were targeted to CD31 and insonified at 1
MHz at low peak negative acoustic pressures at six sequences of 10 cycle sine-wave bursts. Vibration of the targeted microbubbles was recorded with the Brandaris-128 high-speed camera (~
13
million frames per second). In total, 31 cells were studied that all had one microbubble (1.2–4.2 micron in diameter) attached per cell. After insonification at 80
kPa, 30% of the cells (n
=
6) had taken up propidium iodide, while this was 20% (n
=
1) at 120
kPa and 83% (n
=
5) at 200
kPa. Irrespective of the peak negative acoustic pressure, uptake of propidium iodide was observed when the relative vibration amplitude of targeted microbubbles was greater than 0.5. No relationship was found between the position of the microbubble on the cell and induction of sonoporation. This study shows that targeted microbubbles can also be used to induce sonoporation, thus making it possible to combine molecular imaging and drug delivery.
Propidium iodide uptake by endothelial cell (in red) induced by microbubbles and diagnostic ultrasound. In fluorescence images: white lines
=
cell contours; green circles
=
position of microbubble. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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Abstract Objective B-mode ultrasound measurement of the carotid intima-media thickness (CIMT) is a widely used marker for atherosclerosis and is associated with future cardiovascular events. This ...article provides a review and meta-analysis of the published evidence on the association of CIMT with future cardiovascular events and its additional value to traditional cardiovascular risk prediction models. Methods A systematic review and meta-analysis of the evidence on the association of CIMT with future cardiovascular events and the additional value of CIMT to traditional cardiovascular risk prediction models was conducted. The association of CIMT with future cardiovascular events and the additional value of CIMT were calculated using random effects analysis. Results The literature search yielded 1196 articles of which 15 articles provided sufficient data for the meta-analysis. A 1 SD increase in CIMT was predictive for myocardial infarction (HR 1.26, 95% CI 1.20–1.31) and for stroke (HR 1.31, 95% CI 1.26–1.36). A 0.1 mm increase in CIMT was predictive for myocardial infarction (HR 1.15, 95% CI 1.12–1.18) and for stroke (HR 1.17, 95% CI 1.15–1.21). The overall performance of risk prediction models did not significantly increase after addition of CIMT data. The areas under the curve increased from 0.726 to 0.729 ( p = 0.8). Conclusions CIMT as measured by B-mode ultrasound is associated with future cardiovascular events. However, the addition of CIMT to traditional cardiovascular risk prediction models does not lead to a statistical significantly increase in performance of those models.
Beamforming of plane-wave ultrasound echo signals in the Fourier domain provides fast and accurate image reconstruction. Conventional implementations perform a k-space interpolation from the uniform ...sampled grid to a nonuniform acoustic dispersion grid. In this paper, we demonstrate that this step can be replaced by a nonuniform Fourier transform. We study the performance of the nonuniform fast Fourier transform (NUFFT) in terms of signal-to-noise ratio and computational cost, and show that the NUFFT offers an advantage in the trade-off between speed and accuracy, compared with other frequency-domain beamforming strategies.
Abstract Patient specific geometrical data on human coronary arteries can be reliably obtained multislice computer tomography (MSCT) imaging. MSCT cannot provide hemodynamic variables, and the ...outflow through the side branches must be estimated. The impact of two different models to determine flow through the side branches on the wall shear stress (WSS) distribution in patient specific geometries is evaluated. Murray's law predicts that the flow ratio through the side branches scales with the ratio of the diameter of the side branches to the third power. The empirical model is based on flow measurements performed by Doriot et al. (2000) in angiographically normal coronary arteries. The fit based on these measurements showed that the flow ratio through the side branches can best be described with a power of 2.27. The experimental data imply that Murray's law underestimates the flow through the side branches. We applied the two models to study the WSS distribution in 6 coronary artery trees. Under steady flow conditions, the average WSS between the side branches differed significantly for the two models: the average WSS was 8% higher for Murray's law and the relative difference ranged from −5% to +27%. These differences scale with the difference in flow rate. Near the bifurcations, the differences in WSS were more pronounced: the size of the low WSS regions was significantly larger when applying the empirical model (13%), ranging from −12% to +68%. Predicting outflow based on Murray's law underestimates the flow through the side branches. Especially near side branches, the regions where atherosclerotic plaques preferentially develop, the differences are significant and application of Murray's law underestimates the size of the low WSS region.
20 years of ultrasound contrast agent modeling Faez, T.; Emmer, M.; Kooiman, K. ...
IEEE transactions on ultrasonics, ferroelectrics, and frequency control,
2013-January, 2013-Jan, 2013-01-00, 20130101, Letnik:
60, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The merits of ultrasound contrast agents (UCAs) were already known in the 1960s. It was, however, not until the 1990s that UCAs were clinically approved and marketed. In these years, it was realized ...that the UCAs are not just efficient ultrasound scatterers, but that their main constituent, the coated gas microbubble, acts as a nonlinear resonator and, as such, is capable of generating harmonic energy. Subharmonic, ultraharmonic, and higher harmonic frequencies of the transmitted ultrasound frequency have been reported. This opened up new prospects for their use and several detection strategies have been developed to exploit this harmonic energy to discriminate the contrast bubbles from surrounding tissue. This insight created a need for tools to study coated bubble behavior in an ultrasound field and the first models were developed. Since then, 20 years have elapsed, in which a broad range of UCAs and UCA models have been developed. Although the models have helped in understanding the responses of coated bubbles, the influence of the coating has not been fully elucidated to date and UCA models are still being improved. The aim of this review paper is to offer an overview in these developments and indicate future directions for research.
The vulnerable atherosclerotic plaque is believed to be at the root of the majority of acute coronary events. Even though the exact origins of plaque vulnerability remain elusive, the thin-cap ...fibroatheroma, characterized by a lipid-rich necrotic core covered by a thin fibrous cap, is considered to be the most prominent type of vulnerable plaque. No clinically available imaging technique can characterize atherosclerotic lesions to the extent needed to determine plaque vulnerability prognostically. Intravascular photoacoustic imaging (IVPA) has the potential to take a significant step in that direction by imaging both plaque structure and composition. IVPA is a natural extension of intravascular ultrasound that adds tissue type specificity to the images. IVPA utilizes the optical contrast provided by the differences in the absorption spectra of plaque components to image composition. Its capability to image lipids in human coronary atherosclerosis has been shown extensively ex vivo and has recently been translated to an in vivo animal model. Other disease markers that have been successfully targeted are calcium and inflammatory markers, such as macrophages and matrix metalloproteinase; the latter two through application of exogenous contrast agents. By simultaneously displaying plaque morphology and composition, IVPA can provide a powerful prognostic marker for disease progression, and as such has the potential to transform the current practice in percutaneous coronary intervention.
We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. ...A 1.25 mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30 MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm. Simultaneous imaging with intravascular ultrasound was performed.
Atherosclerosis is a lipid and inflammation-driven disease of the arteries that is characterized by gradual buildup of plaques in the vascular wall. A so-called vulnerable plaque, consisting of a ...lipid-rich necrotic core contained by a thin fibrous cap, may rupture and trigger thrombus formation, which can lead to ischemia in the heart (heart attack) or in the brain (stroke). In this study, we present a protocol to investigate the lipid composition of advanced human carotid plaques using matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI), providing a framework that should enable the discrimination of vulnerable from stable plaques based on lipid composition. We optimized the tissue preparation and imaging methods by systematically analyzing data from three specimens: two human carotid endarterectomy samples (advanced plaque) and one autopsy sample (early stage plaque). We show a robust data reduction method and evaluate the variability of the endarterectomy samples. We found diacylglycerols to be more abundant in a thrombotic area compared to other plaque areas and could distinguish advanced plaque from early stage plaque based on cholesteryl ester composition. We plan to use this systematic approach to analyze a larger dataset of carotid atherosclerotic plaques.
Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed ...evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.
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