Emergence - Emergence

Development of new contrast agents for ultrasound molecular imaging of cardiovascular diseases – MicroSound

Ultrasound visualization of cardiovascular diseases

Development of contrast agents in the form of polymer nano-microparticles for ultrasonic molecular imaging of cardiovascular diseases

Ultrasound molecular imaging of thrombi using polymer particles

With the ageing of the population, the prevalence of atherothrombosis will ineluctably increase in the next years and it is anticipated that 18 million people will die of atherothrombotic events in 2030. The medical markets of contrast agents for medical imaging are estimated to 6.2 billions € in 2009. MicroSound project deals with the challenging development of new diagnostic tools able to detect atherothrombosis events before clinical complications. From patented approaches, this project will carry out the development of a new echogenic contrast agent functionalized by a ligand to allow a large screening of patients. This project proposes to develop functional microparticles loaded with perfluorocarbon as acoustic agent, and functionalized with fucoidan as P-selectin targeting moiety for imaging, at a molecular level, of platelet and endothelial cell activation in vascular thrombosis.

Elaboration of polysaccharide and copolymer particles in aqueous medium will be done according to patented processes. Particle functionalization and loading will be done with fucoidan and perfluorooctylbromide respectively.

Size, surface charge, mass concentration, composition, stability and loading capacity of the particles will be evaluated by numerous sophisticated technologies.

We have developed a specific in vitro set-up for the characterization of suspension echogenicity in circulation.

The specific interaction of fucoidan-functionalized particles with activated platelets will be determined by flow cytometry measurements.

Fucoidan functionalized particles will be labeled with technetium 99 and their distribution will be followed in rats.

In vivo ultrasound evaluations of the particles will be done with a rat model of abdominal aorta aneurysm by the quantification of the signal using of the contrast imaging function of the Vevo 2100 equipment.

The polymer particle have a size of 200 nm, a surface charge of - 30 mV, confirming the presence of fucoidan, a mass concentration of 40 g / L, good stability and a loading level of contrast agent 60%. The acquisition of VisualSonics software was used to determine in vitro echogenic properties of the particles produced.
Functionalized polymer particles interact specifically with activated platelets even under flow.
An abdominal aorta aneurysm model in rats was successfully elaborated and visualized by ultrasound.

Polymer particle coated with fucoidan and loaded with perfluorocarbon have been obtained and characterized physicochemically ; they are echogenic in vitro and are able to interact with activated platelets in vitro statically and under flow.
Finally, abdominal aorta aneurysm experimental model in rats have been elaborated and validated by ultrasound.

A project of invention concerning echogenic functionalized polymer particles is subject to a declaration of intent under evaluation with Inserm-Transfert. MICROSOUND project was valued by three scientific papers (2 published and 1 subject) and in five seminars and a press conference.

Development of imaging technologies as diagnostic surrogate markers is an important challenge for health issue. After moving from morphological approach to functional approach, the new challenge for imaging technology is to shift to molecular imaging. This is true for all fields of pathology, including cardiovascular diseases in human. With the ageing of the population the prevalence of atherothrombosis will ineluctably increase in the next years and it is anticipated that 18 million people will die of atherothrombotic events in 2030. The medical market of contrast agents for medical imaging is estimated to be 6.2 billions € in 2009. However, commercial products are rapidly cleared from the bloodstream moreover do not have any specific affinity for the imaging of atherothrombotic events.
MicroSound project deals with the challenging development of new diagnostic tools able to detect atherothrombosis events before clinical complications. From patented approaches, MicroSound will carry out the development of a new echogenic contrast agent functionalized by a ligand to allow a large screening of patients. MicroSound proposes, according to translational objectives, to develop functional microparticles i) loaded with perfluorocarbon as acoustic agent, and ii) functionalized with fucoidan as P-selectin targeting moiety for imaging, at a molecular level, platelet and endothelial cell activation in vascular thrombosis.
The aim of MicroSound is to provide in vitro and in vivo evidence that perfluorocarbon-loaded microparticles functionalized with fucoidan are efficient acoustic tracers for molecular imaging of cardiovascular pathologic processes. To do this, we will study i) the affinity of microparticles functionalized with fucoidan for activated human platelets and human endothelial cells by flow cytometry measurements, ii) the biodistribution of 99mTc-labeled microparticles in rats and iii) the echogenic properties of microparticles in an aneurysm model in rats.

Project coordinator

Monsieur Cédric CHAUVIERRE (Unité Hémostase, Bio-ingénierie et Remodelage Cardiovasculaires) – cedric.chauvierre@inserm.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Inserm-Transfert Inserm-Transfert
U698 Unité Hémostase, Bio-ingénierie et Remodelage Cardiovasculaires
CEFI -IFR02 Centre d'exploitations fonctionnelles-Imagerie

Help of the ANR 196,784 euros
Beginning and duration of the scientific project: January 2013 - 24 Months

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