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Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences: an experimental study in a tissue mimicking flow phantom
KTH, School of Technology and Health (STH), Medical Engineering.ORCID iD: 0000-0002-4757-7232
KTH, School of Technology and Health (STH), Medical Engineering.ORCID iD: 0000-0002-5795-9867
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2013 (English)In: Cardiovascular Ultrasound, ISSN 1476-7120, Vol. 11, 33- p.Article in journal (Refereed) Published
Abstract [en]

Background: A multimodal polymer-shelled contrast agent (CA) with target specific potential was recently developed and tested for its acoustic properties in a single element transducer setup. Since the developed polymeric CA has different chemical composition than the commercially available CAs, there is an interest to study its acoustic response when using clinical ultrasound systems. The aim of this study was therefore to investigate the acoustic response by studying the visualization capability and shadowing effect of three polymer-shelled CAs when using optimized sequences for contrast imaging. Methods: The acoustic response of three types of the multimodal CA was evaluated in a tissue mimicking flow phantom setup by measuring contrast to tissue ratio (CTR) and acoustic shadowing using five image sequences optimized for contrast imaging. The measurements were performed over a mechanical index (MI) range of 0.2-1.2 at three CA concentrations (10(6), 10(5), 10(4) microbubbles/ml). Results: The CTR-values were found to vary with the applied contrast sequence, MI and CA. The highest CTR-values were obtained when a contrast sequence optimized for higher MI imaging was used. At a CA concentration of 106 microbubbles/ml, acoustic shadowing was observed for all contrast sequences and CAs. Conclusions: The CAs showed the potential to enhance ultrasound images generated by available contrast sequences. A CA concentration of 106 MBs/ml implies a non-linear relation between MB concentration and image intensity.

Place, publisher, year, edition, pages
2013. Vol. 11, 33- p.
Keyword [en]
Acoustic shadowing, Contrast agent, Contrast sequences, Contrast to tissue ratio, Flow phantom, Multimodal
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:kth:diva-129627DOI: 10.1186/1476-7120-11-33ISI: 000324140500001ScopusID: 2-s2.0-84883074083OAI: diva2:653220
EU, FP7, Seventh Framework Programme, 245572

QC 20131003

Available from: 2013-10-03 Created: 2013-10-03 Last updated: 2015-04-01Bibliographically approved
In thesis
1. Toward increased applicability of ultrasound contrast agents
Open this publication in new window or tab >>Toward increased applicability of ultrasound contrast agents
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ultrasound is one of the most widely used modalities in medical imaging because of its high cost-effectiveness, wide availability in hospitals, generation of real-time images, and use of nonionizing radiation. However, the image quality can be insufficient in some patients. Introducing a contrast agent (CA), which comprises a suspension of 2–6 mm-sized microbubbles, improves the image quality and thus the image analysis. At present, contrast-enhanced ultrasound is frequently used during standard clinical procedures such as kidney, liver, and cardiac (echocardiography) imaging. Multimodality and targeted imaging are future areas for ultrasound CAs. Multimodality imaging may improve diagnostics by simultaneously providing anatomical and functional information. Targeted imaging may allow for identification of particular diseases.

The work within this thesis focused mainly on a novel multimodal polymer-shelled CA with the potential to be target specific. In Study I, the acoustic response was determined in a flow phantom by evaluating the contrast-to-tissue-ratio when using contrast sequences available in clinical ultrasound systems. This study showed that a high acoustic pressure is needed for optimal visualization of the polymer-shelled CA. In Study II, the in vivo performance of this CA was evaluated in a rat model, and the blood elimination time and subcellular distribution were determined. In Study III, the efficiency in endocardial border delineation was assessed in a pig model. The polymer-shelled CA had a significantly longer blood circulation time than the commercially available CA SonoVue, which is favorable for target-specific CA, in which a long circulation time increases the probability of target-specific binding. Transmission electron microscopic analysis of tissue sections from liver, kidney, spleen and lungs, obtained at different time points after CA injection showed that macrophages were responsible for the elimination of the polymer-shelled CA. A higher dose of the polymer-shelled CA was needed to obtain similar endocardial border delineation efficiency as that obtained using SonoVue. The results of Studies I–III demonstrate that the polymer-shelled CA has potential applicability in medical imaging.

Current guidelines for contrast-enhanced echocardiography are limited to cases of suboptimal image quality or when there is a suspicion of structural abnormalities within the left ventricle. It may be hypothesized that the wider use of contrast-enhanced echocardiography may help to detect some diseases earlier. Study IV assessed the diagnostic outcomes after contrast administration in patients without indications for CA use. The myocardial wall motion score index and ejection fraction were evaluated by experienced and inexperienced readers, and a screening for left ventricular structural abnormalities was performed. More cases of wall motion and structural abnormalities were detected in the contrast-enhanced analysis. Intra- and interobserver variability was lower with the use of CAs. This study suggests that the more widespread use of CAs instead of the current selective approach may contribute to earlier detection of cardiovascular disease.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. xii, 51 p.
TRITA-STH : report, ISSN 1653-3836 ; 2015:3
Contrast agent, Contrast-to-tissue-ratio, Echocardiography, Endocardial border, Microbubbles, Multimodal, Phantom, Polymer, Ultrasound, Wall motion score index.
National Category
Medical Image Processing
Research subject
Technology and Health
urn:nbn:se:kth:diva-163387 (URN)978-91-7595-496-7 (ISBN)
Public defence
2015-04-28, 3-221, Alfred Nobels Allé 10, Huddinge, 10:00 (Swedish)

QC 20150401

Available from: 2015-04-01 Created: 2015-03-31 Last updated: 2015-04-01Bibliographically approved

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