Change search
ReferencesLink to record
Permanent link

Direct link
Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: An acoustic characterization and optical visualization
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. (Contrast Enhanced Medical Imaging)
Department of Biomedical Engineering, Thoraxcenter, Erasmus MC,.
Department of Biomedical Engineering, Thoraxcenter, Erasmus MC.
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
Show others and affiliations
2014 (English)In: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, ISSN 0885-3010, E-ISSN 1525-8955, Vol. 62, no 3, 451-462 p., 7055440Article in journal (Refereed) Published
Abstract [en]

This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.

Place, publisher, year, edition, pages
2014. Vol. 62, no 3, 451-462 p., 7055440
National Category
Medical Equipment Engineering Medical Image Processing Medical Materials
URN: urn:nbn:se:kth:diva-159768DOI: 10.1109/TUFFC.2014.006732ISI: 000351446800006ScopusID: 2-s2.0-84924942910OAI: diva2:787417

The study was financed by EU-grants (3MiCRON ) and strategic money from the Karolinska Institutet.

QC 20150409

Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2015-08-26Bibliographically approved
In thesis
1. Nano-Engineered Contrast Agents: Toward Multimodal Imaging and Acoustophoresis
Open this publication in new window or tab >>Nano-Engineered Contrast Agents: Toward Multimodal Imaging and Acoustophoresis
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Diagnostic ultrasound (US) is safer, quicker and cheaper than other diagnostic imaging modalities. Over the past two decades, the applications of US imaging has been widened due to the development of injectable, compressible and encapsulated microbubbles (MBs) that provide an opportunity to improve conventional echocardiographic imaging, blood flow assessment and molecular imaging. The encapsulating material is manufactured by different biocompatible materials such as proteins, lipids or polymers. In current research, researchers modify the encapsulated shell with the help of advanced molecular chemistry techniques to load them with dyes (for fluorescent imaging), nanoparticles and radioisotopes (for multimodal imaging) or functional ligands or therapeutic gases (for local drug delivery). The echogenicity and the radial oscillation of MBs is the result of their compressibility, which undoubtedly varies with the encapsulated shell characteristics such as rigidity or elasticity.

In this thesis, we present acoustic properties of novel type of polyvinyl alcohol (PVA)-shelled microbubble (PVA-MB) that was further modified with superparamagnetic iron oxide nanoparticles (SPIONs) to work as a dual-modal contrast agent for magnetic resonance (MR) imaging along with US imaging. Apparently, the shell modification changes their mechanical characteristics, which affects their acoustic properties. The overall objective of the thesis is to investigate the acoustic properties of modified and unmodified PVA-MBs at different ultrasound parameters.

The acoustic and mechanical characterization of SPIONs modified PVA-MBs revealed that the acoustical response depends on the SPION inclusion strategy. However they retain the same structural characteristics after the modification. The modified MBs with SPIONs included on the surface of the PVA shell exhibit a soft-shelled behavior and produce a higher echogenicity than the MBs with the SPIONs inside the PVA shell. The fracturing mechanism of the unmodified PVA-MBs was identified to be different from the other fracturing mechanisms of conventional MBs. With the interaction of high-pressure bursts, the air gas core is squeezed out through small punctures in the PVA shell. During the fracturing, the PVA-MBs exhibit asymmetric (other modes) oscillations, resulting in sub- and ultra-harmonic generation. Exploiting the US imaging at the other modes of the oscillation of the PVA-MBs would provide an opportunity to visualize very low concentrations of (down to single) PVA-MBs. We further introduced the PVA-MBs along with particles mimicking red blood cells in an acoustic standing-wave field to observe the acoustic radiation force effect. We observed that the compressible PVA-MBs drawn toward pressure antinode while the solid blood phantoms moved toward the pressure node. This acoustic separation method (acoustophoresis) could be an efficient tool for studying the bioclearance of the PVA-MBs in the body, either by collecting blood samples (in-vitro) or by using the extracorporeal medical procedure (ex-vivo) at different organs.

Overall, this work contributes significant feedback for chemists (to optimize the nanoparticle inclusion) and imaging groups (to develop new imaging sequences), and the positive findings pave new paths and provide triggers to engage in further research. 

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2015. x, 53 p.
TRITA-STH : report, ISSN 1653-3836 ; 2015:5
Nano-engineered microbubbles, SPION nanoparticles, Acoustic characterization of MBs, Fracturing mechanism of MBs, Opto-acoustics, Acoustophoresis
National Category
Medical Laboratory and Measurements Technologies Medical Image Processing Nano Technology Signal Processing Polymer Technologies
Research subject
Physics; Järnvägsgruppen - Ljud och vibrationer; Technology and Health
urn:nbn:se:kth:diva-172397 (URN)978-91-7595-648-0 (ISBN)
Public defence
2015-09-22, 3221, Alfred Nobels Álle 8, Hudding, 09:00 (English)
EU, FP7, Seventh Framework Programme, 245572

QC 20150827

Available from: 2015-08-26 Created: 2015-08-20 Last updated: 2015-08-27Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textScopus

Search in DiVA

By author/editor
Kothapalli, Veera Venkata Satya NarayBrodin, Lars-ÅkeJanerot Sjöberg, BirgittaGrishenkov, Dmitry
By organisation
Medical ImagingMedical Engineering
In the same journal
IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Medical Equipment EngineeringMedical Image ProcessingMedical Materials

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 61 hits
ReferencesLink to record
Permanent link

Direct link