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With the clinical introduction of linear accelerators combined with magnetic resonance imaging, such as the 1.5T MR-Linac, new opportunities to further improve radiotherapy treatments arrived. The fact that fast 3D imaging of the patient can be acquired during treatment, allows to explore opportunities to track tumor and organ at risk motion during treatment. Nowadays, the use of hypofractionated radiotherapy treatments for prostate cancer has become more common. To proceed with such ultra-hypofractionated schemes, intrafraction motion monitoring is required. The results described in this thesis study showed that it is possible to determine prostate intrafraction motion using 3D cine-MR imaging using implanted fiducial markers and these results were used as input for ground-truth validation in the development of a soft-tissue based tracking algorithm. Analysis and comparison of the soft-tissue results compared to the previously obtained fiducial marker based results showed that the soft-tissue based method outperforms the fiducial marker based method in terms of robustness and rotation accuracy. Using the soft-tissue based tracking method, the intrafraction motion of the first five prostate cancer patients treated on the 1.5T MR-Linac was then determined. Using this study, we showed that high quality 3D cine-MR imaging and prostate tracking during MR-guided radiotherapy is feasible with beam-on. The obtained intrafraction motion was then used to determine the impact of the prostate intrafraction motion on the delivered dose distribution for the first five prostate cancer patients treated on the 1.5T MR-Linac. The pipeline presented in this thesis demonstrated the first MR-Linac dose reconstruction results based on prostate intrafraction tracking using 3D cine-MR imaging and treatment log files. When considering hypofractionated treatment for high-risk prostate cancer patients, intrafraction motion of the seminal vesicles must be taken into account. To our knowledge, this is the first study to investigate six dimensions of freedom seminal vesicle intrafraction motion from 3D cine-MR during actual MR-guided treatments. Results showed that especially seminal vesicle intrafraction rotation motion is significantly larger than found for the prostate. Moreover, this thesis described a study which investigated the efficacy of always applying a subsequent adapt to position (ATP) procedure to counter the prostate intrafraction motion that occurred during the adapt to shape (ATS) procedure for prostate cancer patients treated on the 1.5T MR-Linac. It was found that due to the continuous and stochastical nature of prostate intrafraction motion, margin reduction below 4 mm require fast intrafraction plan adaptation methods. The work described in this thesis contains analyses determining the influence of intrafraction motion on the dose distribution for patients, coverage probability analyses for the prostate and seminal vesicles and investigated the efficacy of using ATP procedures to reduce the effect of intrafraction motion. In essence, this thesis describes methods to determine intrafraction motion and its influence thereof in the setting of MR-guided radiotherapy for prostate cancer patients. The gained knowledge may be used to reduce radiotherapy margins for hypofractionated prostate radiotherapy and the described methods may be used as input for the introduction of fast plan adaptation methods for MR-guided radiotherapy on the 1.5T MR-Linac.

Radiotherapy treatments need adequate quality control (QC) to ensure a correct delivery of the prescribed dose to the target area. One of the most extended safety nets for treatments in conventional radiotherapy machines is in-vivo EPID dosimetry, which uses the dose acquired by an Electronic Portal Imaging Device (EPID) during treatment to accurately reconstruct the dose as it was delivered to the patient.We developed a method to validate radiotherapy treatments delivered on a novel system: the Unity MR-Linac. This machine, which combines a radiation source (linac) and an imaging device (MRI), will help to irradiate tumors more accurately by means of a new range of techniques only available thanks to the image guidance of the MRI during irradiation. The verification of such treatments can be performed by using images of the delivered beam captured by an EPID situated opposite to the radiation source, behind the cryostat of the MRI scanner. This project focuses on the adaptation of an already existing algorithm used with conventional linacs to the new physics and design characteristics of the Unity MR-linac. The main challenge for this adaptation is the presence of the MRI scanner between the patient and the EPID, acting as a secondary source of scatter and as an attenuation medium for the beam.

First, we present two offline position verification methods which can be used in radiotherapy for detecting the position of the bony anatomy of a patient automatically with portal imaging, even if every single portal image of each segment of an (IMRT) treatment beam contains insufficient matching information. Additional position verification fields will no longer be necessary, which speeds up the treatment and reduces the total dose to the patient. Second, a tool is described which enhances the way tumors can be delineated by using multiple imaging modalities. This tool is especially useful when multiple MRI sequences are available as well as the standard planning CT. We also developed a marker which is visible on MRI and on EPID. A separate CT for detecting the markers is no longer needed. The gold marker with steel core can be detected on various MRI sequences, reducing the overall systematic radiotherapy treatment error. The MRI linear accelerator (MRL) facilitates continuous patient anatomy updates regarding translations, rotations and deformations of targets and OAR during a course of radiotherapy. Accounting for this information demands high speed, online IMRT re-optimization. Therefore, we developed a fast IMRT optimization system which combines a GPU based Monte-Carlo dose calculation engine for online beamlet generation (GPUMCD) and a fast inverse dose optimization algorithm (FIDO). We show that for the presented cases the beamlets generation and optimization routines are fast enough for online IMRT planning. Furthermore, there is no influence of the magnetic field on plan quality and complexity, and equal optimization constraints at 0T and 1.5T lead to almost identical dose distributions. One of the most significant effects of the transverse magnetic field on the dose distribution occur around air cavities: the electron return effect (ERE). We investigated the effects of non-stationary spherical air cavities on IMRT dose delivery in 0.35T and 1.5T transverse magnetic fields by using Monte Carlo simulations. Our observations show the intrinsic ERE compensation by equidistant and opposing beam configurations for moving spherical air cavities within the target area. IMRT gives some additional compensation, but only in the case of correct positioning of the air cavity according to the IMRT compensation. For air cavities appearing or disappearing during a fraction this correct positioning is absent and gating or plan re-optimization should be used. Finally, we introduce an online 'virtual couch shift' (VCS): we translate and/or rotate the pre-treatment dose distribution to compensate for the changes in patient anatomy and generate a new plan which delivers the transformed dose distribution automatically. The VCS is the first step towards compensating all anatomical changes (translation, rotations, and deformations) by online re-optimization of the IMRT dose distribution.