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Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

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M Callens

M Callens1*, E Verboven1 , E D'Agostino2 , H Pfeiffer3 , J D'hooge4 , K Van Den Abeele1 , (1) Department of Physics, Wave Propagation and Signal Processing, KU Leuven KULAK, Kortrijk, Belgium, (2) DoseVue NV, Hasselt, Belgium, (3) Department of Materials Engineering, KU Leuven, Leuven, Belgium, (4) Department of Cardiovascular Sciences, Bio-Medical Science Group, KU Leuven, Leuven, Belgium

Presentations

WE-D-210-4 (Wednesday, July 15, 2015) 11:00 AM - 12:15 PM Room: 210


Purpose: Ultrasound contrast agents (UCA's) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose.

Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0-150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy.

Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment.

Conclusion: Diacetylene-containing microbubbles are polymerizable under influence of ionizing radiation and are a promising design concept within the development of a novel non-invasive in-vivo radiation dosimeter for external beam radiation therapy.

Funding Support, Disclosures, and Conflict of Interest: This work was funded by the Research Foundation - Flanders (FWO).


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