Development of a holmium microsphere administration device for treatment of brain malignancies

Brain cancer is a major health problem and currently used treatment methods are considered suboptimal. Micro-brachytherapy with radioactive Holmium-166 showed to be an effective palliative care method for primary and metastatic brain tumors and intratumoral administration with holmium microspheres (HoMS) showed very promising results with respect to the amount of treatment sessions, hospitalization stay and side effects. This study evaluates the state-of-the-art of available treatment methods for brain malignancies in order to develop a standardized intratumoral administration device for holmium microspheres, where dosimetry, local distribution and visualization of the microparticles are considered most important. The prototype, designed, manufactured and validated within this study creates a tumor-extracorporeal duct for a non-active steerable inner needle to control spatial intratumoral deposition of the HoMS. Validation of the administration device is done by accuracy tests during incision in gelatin phantoms, fluid flow tests with a HoMS suspension and imaging tests with 1.5T MRI for the quantification of artefacts. The inner needle has a pre-bend tip that can achieve a horizontal and vertical displacement of respectively 13.0 and 15.6 mm with an error kept below 2.0 mm in 3-dimensional space (94%) , depending on target depth, during incision in a homogeneous porcine gelatin phantom mimicking the stiffest tumor tissue found in literature. Adjustments of stylet depth and orientation will allow for deposition of HoMS over a surface of 5.8 cm2 and with the aid of this delivery device tumors normally treated by SRS, considering the size (diameter l 30 mm), can be treated. To localize the needle and the holmium microspheres in the phantom real-time 1.5T MRI is used. The tests within this study show a high accuracy with a visualization error of 0.1 - 1.1 mm for the titanium outer needle and an error of 0.2 - 0.5 mm for the nitinol inner needle, depending on needle angle towards the magnetic field. Future research can be performed with the administration device prototype to define right dosimetry, distribution and volume of the HoMS for effective treatment of specific braintumors.