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.

Percutaneous coronary intervention (PCI) is one of the main medical procedures employed for the treatment of coronary artery disease. During this procedure, the coronary arteries are visualized using X-ray imaging. However, it only generates 2D images which can complicate several tasks, including assessing the lesion and correctly placing a stent. To overcome this limitation, researchers of Philips Research are developing technologies that allow the implementation of 3D imaging data derived from coronary CT angiography in the catheterization laboratory. Throughout the development, a coronary artery network phantom could serve as a beneficial tool. Such a phantom should be anthropomorphic and have realistic imaging and mechanical properties. Additionally, it should serve as a platform on which a basic PCI procedure can be performed. No commercially or academically developed phantom satisfies these criteria, thus the objective for this project was to design and develop an anthropomorphic coronary artery network phantom with realistic imaging and mechanical properties, which can be used to mimic both healthy and atherosclerotic human coronary arteries. A material study was initially conducted to find the most suitable materials for the development of the phantom. During the first stage, the radiodensity of several materials was measured. Based on those results, and other factors such as safety, usability and durability, it was concluded that PlatSil Gel 25 would be used for the development of the arterial wall. Additionally, the heart and non-calcified lesions were to be made from VytaFlex 20 in combination with BaSO4. The calcified lesions were to be made from PlatSil Gel 25 and also required the addition of BaSO4 to increase their radiodensity. After the imaging tests, uniaxial tensile tests were conducted to measure the stiffness of PlatSil Gel 25 samples with different concentrations of PlatSil hardener. These results demonstrated that PlatSil Gel 25 has a comparable stiffness to that of healthy human coronary arteries in the longitudinal direction. When combined with the hardener, it can also mimic the stiffness of atherosclerotic coronary arteries. After the material study, the coronary artery network phantom was designed and developed. The design comprises a simplified representation of the heart, and an arterial network that consists of the coronary artery network and a simplified representation of the arterial pathway distal to the aortic root. To manufacture the arterial network, a water-soluble 3D-printed mould was manually coated with PlatSil Gel 25 and subsequently dissolved in water. Due to the solubility of the mould, it was possible to manufacture a geometrically complex and hollow arterial network as a single part. Additionally, it was demonstrated that this manufacturing method can be used to include lesions within the arterial wall, and that its stiffness can be locally changed. During the evaluation of the final phantom, its geometrical, imaging and mechanical properties were assessed and compared with the formulated requirements. Based on the results it can be concluded that the phantom meets many of the requirements. Furthermore, it was demonstrated that a guidewire can be inserted into the arterial network and manipulated up to the end of the left circumflex artery. Nevertheless, the evaluation also revealed some areas of improvement. Most notable are the improvements related to the imaging properties of the phantom. For example, the radiodensity of the arterial wall was slightly too high. In addition, the attenuation was not uniform throughout the parts of the phantom that contained BaSO4, as was evident from X-ray and CT images. In conclusion, this project demonstrated that the utilized manufacturing method and materials can be used to develop a healthy and atherosclerotic coronary artery network phantom, that possesses realistic geometrical, imaging and mechanical properties. Additionally, it has the potential to serve as a platform on which a basic PCI procedure can be performed. Nevertheless, several areas of improvement related to both the manufacturing method and phantom remain, which might form the foundation for a future project.

Background Current neurosurgical visualisation systems, operating microscopes as well as exoscopic systems, display problems that make their performance suboptimal. Operating microscopes severely restrict ergonomics, occasionally leading to pain or injuries. Existing exoscope systems have diverse limitations, therefore not yet being able to completely replace the neurosurgical operating microscope. A plan was made to develop a new and improved visualisation system, tackling the problems encountered with standard operating microscopes, as well as existing exoscope systems. This will be done by developing technology that integrates three important techniques which hold the potential to improve neurosurgical outcome, i.e. surgical visualisation, navigation technology, and 3D X-ray imaging. The rising temperature in this system might cause unwanted deformations which lead to inaccuracies in the visualisation. Therefore the objective of this thesis is to firstly develop a virtual model of this system and secondly, to evaluate the thermal stability through simulations, in order to ensure that the system's accuracy is adequate despite potential deformations due to increased temperature. Hence the research question: "Is the thermal stability of the new exoscope concept sufficient for adequate accuracy?'' Method To ensure the new visualisation system possesses all essential features required for improving and possibly replacing the current visualisation systems, its requirements are summarised. This set the foundation of the new system's design. The best concept is elaborated upon after evaluating different design concepts, meaning that different combinations of materials, frames, and mounts were designed. To evaluate which set-up best performs in regard to stability, simulations were carried out with 3D models of the concepts. These simulations were performed in COMSOL Multiphysics, a programme that can calculate heat transfer and displacement throughout the system, mapping out how susceptible the concept is to increasing temperature. Results A total of 23 simulations were carried out in COMSOL Multiphysics. The first five aimed to provide insight into important material properties, which was used in the next stage to select four different materials: anodised aluminium alloy 6061, stainless steel 304, invar, and silicon nitride. The next simulations evaluated the different combinations of frames, mounts and materials, concluding that the design made out of invar, displayed the least deformations. This selection was made based on displacements found in the zoom and the navigation lenses. These would eventually translate into a certain image shift, reducing the system's accuracy. After finding the most stable design, the absolute image shift was calculated from the displacements. The shift reached a maximum of approximately 0.10 mm for the navigation lens and 0.18 mm for the zoom lens. Conclusion Despite the increasing temperature and other possible effects as gravity, the image shift remained within acceptable limits. This means the virtual concept has thermal stability high enough to provide adequate accuracy during surgery. The new exoscope system is therefore feasible in terms of stability, meaning that the integration of the navigation and the 3D X-ray systems could be a valuable improvement to the current neurosurgical visualisation systems.