FOCUSED ULTRASOUND FOR THE TREATMENT OF GLIOBLASTOMA MULTIFORME: FROM COMPUTER MODELLING TO BLOOD BRAIN BARRIER OPENINGS

Glioblastoma Multiforme (GBM) is a aggressive cancer of the brain characterized by low long term survival rates. Even with current standards of care being continually refined, it is still one of the deadliest cancers. Although still a relatively niche field, the use of ultrasound as a therapeutic medium in the form of focused ultrasound (FUS) has been on the rise in the last decade as a potential clinical standard treatment of GBM. This type of treatment involves the focusing of high intensity ultrasound waves into tiny millimeter sized regions. If the resulting intensity in the created focal region is high enough, then it has the potential to create therapeutic change. This change can come in the form of hyperthermia induced ablations of tumors, or at lower intensities can combine with microbubbles to induce temporary openings in the blood brain barrier (BBB). These are just a few examples of how FUS can lead to treatment of GBM. At Johns Hopkins University (JHU), there has been a lack of FUS research in the past. For a highly touted medical research institution such as JHU, not undergoing this type of research is doing a disservice to many people suffering from GBM. In order to accelerate at a speed at which this technology can be available to people suffering from GBM, a three-pronged plan of attack has been started at the HEPIUS Innovation Lab to undergo pre-clinical FUS research. First, a computer model was developed that emulates how a FUS therapy would affect tissues of different type over time. The model was developed to characterize both the acoustic profiles and resulting thermal effects of the FUS beam. This simulation was applied to a water environment, and then was compared to a potential tumor-brain environment with and without a skull present to see how well high intensity FUS stimuli can lead to a thermal ablation. Next, a bench-top FUS research platform was used to characterize the FUS output from multi-element transducers. This platform is the NeuroFUS system, which contains 4 different transducers at varying center frequencies. The characterization of the NeuroFUS system in a water tank is important for determining how it can affect tissue, and prevent undesired effects. Once characterized, this system can be i used for both in vivo and in vitro neurosurgical experimentation. Finally, pre-clinical in vivo research is important for determining how a FUS treatment will affect a complex biological environment. The RK-50 is a highly versatile and relatively new top of the line in vivo FUS research platform acquired by the HEPIUS Innovation Lab. Using this system, BBB openings were attempted in mice as a proof of concept for how this system can be used for future research