We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name 'Cy-droplet', has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a 'microbubble condensation' method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical 'triggerability' can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release. (C) 2017 The Authors. Published by Elsevier GmbH.

Les opérations chirurgicales pour le traitement des défauts de soutènement d'organes dans les pays industrialisés sont des actes de plus en plus fréquents, et requièrent l'implantation de plus d'un million de prothèses par an. Même si l'usage des prothèses de soutènement a permis de diminuer les complications postopératoires, les taux de réinterventions restent très élevés. Ces travaux présentent différentes stratégies permettant d'apporter de nouvelles propriétés à des treillis en polypropylène, afin d'améliorer leur résistance à l'infection et de permettre leur suivi postopératoire en IRM. Des treillis anti-infectieux sont développés en enrobant les filaments de treillis d'un réservoir de polymère dégradable et biocompatible contenant des agents anti-infectieux, par une technique de pulvérisation à l'aide d'un aérographe. L'association ofloxacine – rifampicine incorporée présente une excellente activité antibactérienne in vitro, et la cinétique de libération prolongée des agents actifs permet d'inhiber la contamination des treillis pendant au moins 72 heures. Les techniques de stérilisation par rayonnement Gamma n'impactent ni la stabilité des agents actifs, ni l'efficacité antibactérienne des treillis anti-infectieux.Afin de permettre une visualisation en IRM des treillis implantés, des polymères ont été synthétisés par greffage d'agent de contraste (DTPA-Gd) sur de la poly(ε-caprolactone) (dégradable) et du poly(acrylate de méthyle) (biostable). Après enrobage des prothèses par ces polymères, le rehaussement du signal induit par la présence du gadolinium permet de visualiser les prothèses à la fois in vitro et in vivo sur différents types d'appareils d'IRM. La stabilité de l'agent de contraste est suffisante pour pouvoir visualiser les treillis pendant plusieurs mois, quelle que soit la technique de stérilisation utilisée. / Soft tissue reinforcement surgical operations in industrial countries are common and require annually at least one million of prostheses for treating this problem. Even if meshes used for organ prolapse surgical procedures allow decreasing postoperatory complications, reinterventions ratio is still relevant. This work present several strategies to bring new properties to polypropylene meshes in order to improve their resistance to infection and enable their postoperative MRI follow-up. Anti-infective meshes are developed by coating the filaments of the meshes with an antibiotics drug reservoir based on degradable and biocompatible polymers, using an airbrush system. Dual ofloxacin-rifampicin antibiotics incorporation on these coated meshes shows an excellent antibacterial activity in vitro and sustained release of the drugs can inhibit meshes contamination for at least 72 hours. Sterilization procedures using Gamma-ray irradiation impact neither the drugs stability nor the anti-infective meshes activity. In order to visualize by Magnetic Resonance Imaging (MRI) meshes after implantation, a contrast agent (DTPA-Gd) is covalently grafted onto the polymeric backbone of poly(ε-caprolactone) (degradable) or poly(methyl acrylate) (biostable). Meshes were coated with these new polymers and MR signal enhancement induced by the presence of gadolinium allows the visualization of the meshes in vitro and in vivo with several MR equipments. Coated meshes are visible during several months, whatever the sterilization procedures, showing the stability of the contrast agent.

Term project describes ultrasound measurements. Describes a devices and measurement principe of ultrasound contrast agents. Part of this work is a measurement program

Ultrasound contrast agents composed of micro-bubble filled with gas are introduced to increase the backscattered power from blood. Their intravenously injection results in the improved contrast in the images. The aim of this master thesis project is to manufacture MB suspension at varied temperature and shear forces and to inspect the size distribution and concentration of the PVA-shelled micro-bubble with standard methods according to the developed protocol. A pulser-receiver (Panametrics PR 5072) setup combined with two transducers (2.25 MHz and 5 MHz) was used to investigate the backscattered enhancement of the micro-bubble suspension. Images were collected with transmission optical microscope (OLYMPUS IX71) with the aid of counting chamber. The diameter and concentration of the micro-bubbles were analyzed by Image J. The pulser-receiver setup was used to test the acoustic response. The mean diameter of micro-bubbles was from 2.03 to 4.38 µm with a standard deviation between 0.40 and 1.12 µm and the micro-bubble concentration varied from 0.07× to 5.22× MBs/ml. The enhancement of the ultrasound backscattered power was greater than 20 dB or even reached 30 dB when the energy was increased. / 3MiCRON

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The use of peruorocarbon lled droplets for use as Phase Changing Contrast Agents (PCCAs) is a promosing eld. These capsules also have potential to be used for mediated drug delivery. The phase change, which has given the capsules their name, is the process when the capsule transforms from a droplet into a bubble. This process is referred to as Acoustic Droplet Vaporization (ADV) and can be induced with the use of ultrasonic waves. In this study a new type of Perfluorpentane (PFC5) capsules which are stabilized with Cellulose Nano Fibers (CNF) have been evaluated for its potential as a PCCA. To investigate this potential a setup was designed in which the capsules could be exposed to ultrasound waves. Following the ultrasound exposure the capsules were visualized under a light transmission microscope. The experiments were conducted for dierent combinations of ultrasound parameters. For each combination eight volume distributions were created, in which two of them as reference cases were not exposed to ultrasound waves. Six cases with the ultrasound ring with different levels of acoustic power, resulting in peak negative pressures ranging from 0.144 to 0.291 MPa. The results showedfthat ADV could be observed when the frequency of the acoustic wave is 3.5 MHz, the pulse repetition frequency is 500 and the burst width is set to 12 cycles. The Peak Negative Pressure (PNP)-threshold for ADV is about 0.200 MPa. When the burst width is set to 8, ADV is also observed however to a lesser extent then when it is set to 12. These results indicate that the CNF-stabilized PFC5 capsules are promising droplets with a potential future as an alternative to currently used PCCAs.

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