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Accueil du site > Offres Stages, Thèses, Postdocs > Thèses proposées > Multi-parametric evaluation of tumor microstructure and microvascularization during novel sonosensitization and non-thermal plasma therapies

Multi-parametric evaluation of tumor microstructure and microvascularization during novel sonosensitization and non-thermal plasma therapies

Versions doc du sujet : Sujet de thèse {Word}

PRESENTATION DU SUJET

Research hypothesis : noninvasive multiparametric ultrasonic (US) evaluation of tumors can reveal underlying changes in tumor microstructure and microvascularization produced by two novel therapies : 1) sonosensitization and 2) exposure to non-thermal plasma (NTP). Sonosensitization by acoustic oscillation of intravascular microbubbles has been shown to increase response to chemotherapy. Suggested mechanisms include modification of flow and interstitial fluid pressure (IFP) in the tumor. There is also growing evidence that NTP (a neutral, ionized gas) can be used in cancer therapy. Its specific action on tumors is not well understood, but it has been shown that NTP reactive oxygen species (ROS) can enhance endothelial cell proliferation or apoptosis. US data will be acquired in ectopic murine tumor models for colorectal carcinoma and Lewis lung carcinoma prior to and following sonosensitization, exposure to NTP or sham therapy. Real-time evaluation of microvascular flow based on tracer detection and mathematical models for flow in the system will be made with contrast-enhanced functional US. Effective scattering size and acoustic attenuation related to tissue microstructure will be assessed using spectral and statistical analysis of radiofrequency- US signals. Parametric, 3D maps ( 260 μm resolution) will be calculated from this data to characterize attenuation, scattering microstructure and microvascular function. Invasive reference measurements (microvascular density, cell viability and necrosis, IFP) will also be mapped to 3D cartographic positions and completed by survival curves (Mantel-Cox). A classification method (probability of necrosis/cell death, vascularization) based on combination of sets of imaging parameters will be established. Results will help to better understand and predict effectiveness of these novel therapeutic approaches and contribute to development of ultrasonic techniques for in vivo monitoring.