The design of a brain and tumor phantom

Abstract

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.