In vivo dosimetry in experimental tumor models

 Recent advances in radiotherapy have enabled highly conformal dose distributions, allowing efficient healthy tissue sparing. Unfortunately, the situation is complicated for thoracoabdominal tumours, which are subject to respiratory motion. 4D CT and, more recently, respiratory-resolved MRI have been used to quantify and account for this motion by implementing large safety margins, when calculating the treatment plan. As such, underdosage of the tumour is prevented but at the cost of high healthy tissue exposures, risking secondary malignancies. In addition, concern is raised to what extent a short-term medical examination can really capture the tumour motion, given the irregularity of spontaneous breathing. The latter has also confounded many of the motion management strategies proposed to date. In this project, we want to preclinically evaluate the use of mechanically-assisted non-invasive ventilation (MANIV) to increase the reproducibility of tumour motion as assessed by respiratory-resolved MRI. In addition, rapid shallow breathing will be evaluated as a promising motion reduction approach. To enable noninvasive in vivo evaluation of healthy tissue sparing using MANIV, a novel injectable dosimeter based on perfluorocarbon nanodroplets serving as a phase-change ultrasound contrast agents, will be used. First the proposed dosimeter will be fully characterised and finally implemented in a preclinical trial assessing the benefits of MANIV in radiotherapy.