4D offline PET-based treatment verification in ion beam therapy

Abstract

Due to the accessible sharp dose gradients, external beam radiotherapy with protons and heavier ions enables a highly conformal adaptation of the delivered dose to arbitrarily shaped tumour volumes. However, this high conformity is accompanied by an increased sensitivity to potential uncertainties, e.g., due to changes in the patient anatomy. Additional challenges are imposed by respiratory motion which does not only lead to rapid changes of the patient anatomy, but, in the cased of actively scanned ions beams, also to the formation of dose inhomogeneities. Therefore, it is highly desirable to verify the actual application of the treatment and to detect possible deviations with respect to the planned irradiation. At present, the only clinically implemented approach for a close-in-time verification of single treatment fractions is based on detecting the distribution of β+-emitter formed in nuclear fragmentation reactions during the irradiation by means of positron emission tomography (PET). For this purpose, a commercial PET/CT (computed tomography) scanner has been installed directly next to the treatment rooms at the Heidelberg Ion-Beam Therapy Center (HIT). Up to present, the application of this treatment verification technique is, however, still limited to static target volumes. This thesis aimed at investigating the feasibility and performance of PET-based treatment verification under consideration of organ motion. In experimental irradiation studies with moving phantoms, not only the practicability of PET-based treatment monitoring for moving targets, using a commercial PET/CT device, could be shown for the first time, but also the potential of this technique to detect motion-related deviations from the planned treatment with sub-millimetre accuracy. The first application to four exemplary hepato-cellular carcinoma patient cases under substantially more challenging clinical conditions indicated potential for improvement by taking organ motion into consideration, particularly for patients exhibiting motion amplitudes of above 1cm and a sufficiently large number of detected true coincidences during their post-irradiation PET scan. Despite the application of an optimised PET image reconstruction scheme, as retrieved from a dedicated phantom imaging study in the scope of this work, the small number of counts and the resulting high level of image noise were identified as a major limiting factor for the detection of motion-induced dose inhomogeneities within the patient. Moreover, the biological washout modelling of the irradiation-induced isotopes proved to be not sufficiently accurate and thereby impede a quantitative analysis of measured and simulated data under consideration of target motion. In future, improvements are particularly foreseen through dedicated noise-robust time-resolved (4D) image reconstruction algorithms, an improved tracking of the organ motion, e.g., by ultrasound (US) imaging, as implemented for the first time in 4D PET imaging in the scope of this work, as well as by patient-specific washout models