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Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.ORCID iD: 0000-0002-4757-7232
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.ORCID iD: 0000-0002-5795-9867
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2014 (English)In: Cardiovascular Ultrasound, ISSN 1476-7120, Vol. 12, 24- p.Article in journal (Refereed) Published
Abstract [en]

Background: A novel polymer-shelled contrast agent (CA) with multimodal and target-specific potential was developed recently. To determine its ultrasonic diagnostic features, we evaluated the endocardial border delineation as visualized in a porcine model and the concomitant effect on physiological variables. Methods: Three doses of the novel polymer-shelled CA (1.5 ml, 3 ml, and 5 ml [5 x 10(8) microbubbles (MBs)/ml]) and the commercially available CA SonoVue (1.5 ml [2-5 x 10(8) MBs/ml]) were used. Visual evaluations of ultrasound images of the left ventricle were independently performed by three observers who graded each segment in a 6-segment model as either 0 = not visible, 1 = weakly visible, or 2 = visible. Moreover, the duration of clinically useful contrast enhancement and the left ventricular opacification were determined. During anesthesia, oxygen saturation, heart rate, and arterial pressure were sampled every minute and the effect of injection of CA on these physiological variables was evaluated. Results: The highest dose of the polymer-shelled CA gave results comparable to SonoVue. Thus, no significant difference in the overall segment score distribution (2-47-95 vs. 1-39-104), time for clinically sufficient contrast enhancement (20-40 s for both) and left ventricular overall opacification was found. In contrast, when comparing the endocardial border delineation capacity for different regions SonoVue showed significantly higher segment scores for base and mid, except for the mid region when injecting 1.5 ml of the polymer-shelled CA. Neither high nor low doses of the polymer-shelled CA significantly affected the investigated physiological variables. Conclusions: This study demonstrated that the novel polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological variables.

Place, publisher, year, edition, pages
2014. Vol. 12, 24- p.
Keyword [en]
Contrast agent, Echocardiography, Endocardial border delineation, Microbubbles, Polyvinyl alcohol, Porcine, Ultrasound
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:kth:diva-148611DOI: 10.1186/1476-7120-12-24ISI: 000338893900001ScopusID: 2-s2.0-84910120890OAI: diva2:737187
EU, FP7, Seventh Framework Programme, 3MiCRON (245572)

QC 20150401

Available from: 2014-08-12 Created: 2014-08-11 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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