Rapid short-pulsed ultrasound at 300-kHz frequency was investigated as a potential method to increase the blood-brain barrier permeability to various compounds when used in conjunction with microbubble injections. The aim of this work was to determine a safe and effective rapid-short, pulsed ultrasound sequence at 300-kHz to disrupt the blood-brain barrier for drug delivery. To achieve this, a benchtop camera-based ultrasound targeting system was developed, suitable for small animal models. The camera allowed the operator a direct view of the mouse’s head along the axis of the focused ultrasound beam. This greatly reduced the time that each experiment took, as it was no longer required to target using an ultrasound raster pattern to locate a metal target resting on the mouse’s head. This system was then used to test a wide range of ultrasound parameters, including pulse length (1-5 cycles), pulse repetition frequency and the ultrasound phase. It was found that with short ultrasound pulses the ultrasound phase can greatly influence the acoustic response of the microbubble for a given pressure. An Alzheimer’s related drug (C3, Merck) was tested on an Alzheimer’s mouse model (5xFAD) and significant levels of the drug were detected in the
brains of treated mice using high performance liquid chromatography and mass spectrometry. This work was performed with the goal of conducting a multi-week,
longitudinal, treatment study in Alzheimer’s disease mouse models with behavioural monitoring. Preliminary experiments on Alzheimer’s disease mouse models were conducted and the longitudinal study remains for future work.