Glioblastoma multiforme tumors (GBM) are the most frequent and aggressive brain tumor type and have a very low survival rate. In order to improve the patient’s outcome for a patient suffering from GBM the production of brain phantoms can be of great help. A brain phantom can be used for multiple purposes, such as neurological planning, training and for testing new medical devices. Nevertheless, no brain phantom has been created with realistic stiffness yet. Investigating the stiffness of the brain is challenging, due to the complexity of the brain and for not being able to touch it in person. However, through a relatively new technology called magnetic resonance elastography (MRE), it is possible to examine the stiffness of the brain. Hence, the
objective for this thesis was to develop a brain phantom with a GBM tumor with similar stiffness compared to the biological human brain and tumor tissue.

In the literatureMRE data can be found on the complex shear modulus of the brain and tumors, which can be converted to an indicative Young’s modulus (E*). The indicative Young’s modulus will be used as a guideline for the desired stiffness needed for the production of a brain phantom. First various polyvinyl alcohol (PVA) samples were made and a compression test was carried out to derive the Young’s modulus (E). By comparing E with E* , it can be seen which PVA sample most resembles the brain and tumor tissue. Thereafter, the head phantom is created, which consists of 3 different production processes; production of the mould, production of the skull and production of the brain phantom. Firstly, the moulds for the brain phantom and tumor are 3D printed using polylactic acid (PLA). The skull phantom is derived from a patient specific CT scan, and is 3D printed with PLA. The brain phantom itself is made of 4,8 wt% PVA and 2 freeze-thaw (FT) cycles, and the tumor phantom is made of 5,2 wt% PVA and 1 FT cycle. The mass fractions and FT cycles have the closest stiffness compared to real brain and tumor tissue and were therefore selected. Within the brain phantom a hollow space is created where the tumor can be placed in. For a parallel project of the TU Delft and Utrecht University a brain phantom was required. For this specific case a brain phantom was produced with barium sulfate (BaSO4), which functions as a contrast additive for CT and MRI. Therefore, the second brain phantom
was made of 4,8 wt% PVA, 1 wt% BaSO4 and 2 FT cycles. The tumor phantom with BaSO4 failed and therefore the first tumor without BaSO4 was used for this use case. An experiment was carried out where a HoMS substance was injected into the tumor phantom. During the experiment 9 CT scans and 2 MRI scans were carried out. Due to the MRI and CT scans it could be investigated whether the tumor was in place and
whether the brain phantom was visible in the CT and MRI. After the use case one more mechanical test was carried out consisting of PVA samples with BaSO4 to examine whether BaSO4 has an effect on the stiffness of the phantom.

The results of the mechanical test led to a desired mass fraction and FT cycle that can represent the brain and tumor phantom. These were immediately used for the production of the brain and tumor phantom. The Young’s modulus of the brain phantom (E = 8,9 kPa) is a little stiffer compared to the actual brain tissue (E* =
9,57 kPa). The Young’s modulus of the tumor phantom (E = 5,8 kPa) is softer compared to the GBM tissue (E* = 4,93 kPa). However, adding BaSO4 to the PVA solution changed the stiffness of the PVA samples, has had an effect on the compactness of the samples, and the BaSO4 did not dissolve properly. In the results of the CT and MRI scans it was found that the BaSO4 was only visible in the inferior part of the brain. In addition, the brain and tumor phantom were clearly visible in theMRI and CT scans. It is therefore not recommended to use BaSO4 for future research. Furthermore, the CT scan showed that the tumor phantom was well surrounded
by the brain phantom and stayed in place even when the tumor was inserted by a cannula. The results show that a brain phantom with a tumor phantom can be produced. However, some improvements to the design of the mould are needed, because the mould was leaking, which subsequently led to an anatomically incorrect brain phantom.

This thesis project leads to the following conclusion; it is possible to produce a brain phantom with a GBM tumor phantom with comparable stiffness to the actual brain and GBM tissue. However, it can not be concluded that the various stiffness’s are exactly the same as the actual brain and GBM tissue, but it is close to the values found in the literature.

Sentinel lymph node biopsy (SLNB) is a procedure that is used to determine the stage of disease of melanoma patients and determine further treatment. However, the morbidities accompanied with this procedure are not negligible (e.g., wound infection, lymphoedema and seroma). With the goal reduce the incidence of morbidities, this thesis investigated the possibility of minimally invasive sentinel lymph node biopsy (MISLNB). Preceding this thesis, a literature study was written by the writer of this thesis to examine whether there was already a possible solution for this problem. This literature study showed that there are no off the shelf available solutions for MISLNB. Therefore, three solution with the reduction of comorbidities and the importance of \textit{en bloc} excision at their core were proposed. These solutions were found through literature, patents, and some ingenuity. The solution with the highest probability was selected to develop further. This concept was then subjected to different experiments to determine whether it was viable option for MISLNB. This study also aimed to fill some of the missing data on the material behaviour of lymph nodes (LN), specifically stress-strain behaviour under compression. By using a set of requirements one solution was selected to be the most viable given the available information. This solution was called the Pull-and-Harvest method. This concept uses a vacuum to grip the sentinel lymph node (SLN) and stash it in a tube, hereafter a snare would cut the lymph ducts and blood vessels. This concept scored well mainly due to the low risk of damaging SLN and its simplicity. The next step was to determine whether this concept was a feasible solution to MISLNB. The problem was divided into three subproblems to estimate this feasibility. The first being the force required to separate the SLN from its surrounding tissue. Since no data on this subject was available a simplified model was created to estimate this value based on the stretch of lymph ducts. The second part of this problem was, determining the force required to stash the SLN inside the tubular volume. Finally, the maximal force of two silicon suction cups was determined. From these experiments several conclusions could be drawn: the conical silicon suction cups used in this study are very inefficient (10%) efficiency) for gripping LNs, these suction cups will stash the LNs but probably not with the additional estimated adherence force and the risk of damaging the LN using a vacuum seems to be low. Based on these observations during these experiments possible ways of were suggested and could make the Pull-and-Harvest a viable procedure. Lastly stress-strain behaviour of LNs could be described using an exponential relationship. This thesis outlines the problem of MISLNB and highlights the areas of interest for further research. However, there is more research and development needed to find a definitive solution for MISLNB.

Prostate cancer is the most common cancer in men and third in terms of mortality. High dose rate brachytherapy is a common and effective treatment to treat this cancer. High dose rate brachytherapy requires the implantation of several needles into the prostate trough which a radiation source is introduced. This implantation can present a number of difficulties. Steerable needles have been proposed to address some of these difficulties. The literature review in Appendix A has identified a number of possible advantages using a steerable needle could have in high dose-rate brachytherapy of the prostate. This thesis aims to develop a steerable needle system enabling the surgeon to place a needle more accurately, combat pubic arch interference, and circumvent ureteral occlusion while not interfering in the general course of the procedure.

This steerable needle was developed according to several design guidelines and optimisation parameters. A mathematical model and simulation were used to predict the behaviour of the needle and identify which parameters influence its functioning. By developing a number of concepts and evaluating their performance according to the set design guidelines a final design was formulated. A phantom was developed to be able to evaluate the performance of the design. By comparing the performance of the developed steerable needle to commercially available non-steered needles we hope to show the possible performance benefit of the developed needle.

The steerable needle has shown to perform, at minimum, non-inferiorly to a commercially available non-steerable needle. A small cost-effectiveness analysis has shown the possibility of the developed system to be cost-effective. While the developed steerable needle allows a surgeon to steer a needle during needle implantation and possibly increase the needle endpoint accuracy, the question remains whether this will result in a more favourable outcome of the high dose-rate brachytherapy procedure.

Brain, outside the body, will decay quickly, causing ex vivo studies to be difficult. Having a phantom model has a great beneficial value for numerous reasons. Phantoms are, among others, used in research centres, to validate new equipment, to develop biomechanical models or to test new treatment methods. They are representations of organs or tissues made from tissues that mimicking the desired properties of the organ. This thesis research is performed in collaboration with Philips Healthcare research department. They benefit from having a brain phantom for the development of a new endoscopic tool that incorporates virtual reality images in the view. Existing phantoms are usually expensive and are not meant for destruction by needle interventions or endoscopic interventions, or are a very rough representation of reality. For this study, it was the aim to develop an anthropomorphic brain phantom containing the hollow space of the ventricles of the brain, with the correct mechanical and optical characteristics. From a digital 3D mesh brain, moulds were made to assess different ways to produce a brain phantom with ventricles. From literature, the tissue mimicking material (TMM) PVA was selected to use for the production of the phantom. After evaluation of the different approaches to fabricate a phantom, it was decided to produce the hollow spaces of the ventricles by using 3D printed soluble PVA, to be removed out of the model after casting. This was done by 3D printing a brain mould in which a 3D printed PVA ventricle could be inserted. A solution of 6% PVA as tissue mimicking material was used. After the mould and production principle of the model was finalized, the imaging part was assessed. In order for the phantom to be used in CT imaging, barium sulphate was added to the PVA solution as a contrast enhancing material. Two phantoms were made with 1% and 2% barium sulphate. Finally, to assess the shape and the quality of the ventricles in the phantom, the phantom was scanned with a CT scan at Philips Healthcare in Best, the Netherlands. The CT files were evaluated using RadiAnt and 3D slicer to assess the ventricular shape and position. 3D slicer was also used to segment the ventricle shape out of the designed models to compare with the originally developed ventricle structure. This study functions as a proof of concept for the development of a PVA brain phantom containing ventricles produced with 3D printed soluble PVA. All in all, the overall evaluation of the prototypes have shown to be promising models for the development of a brain phantom using PVA and ‘homemade’ fabrication techniques. The use of 3D printed soluble PVA is a novelty in this field of application. It makes the design easy to develop and easily adjusted to patient-specific cases as personalized models can be made.