Therapeutic ultrasound arrays for transcranial non-invasive and localized drug delivery
File(s)
Author(s)
Jiang, Zheng
Type
Thesis
Abstract
The blood-brain barrier (BBB) is a natural, semi-permeable, physical transport and metabolic barrier that not only protects the brain from toxic substances, but also prevents the molecule drugs from entering. This disables the treatment of some brain diseases, such as Alzheimer’s disease and brain tumours. Focussed ultrasound in combination with microbubbles has been shown capable of delivering drugs across the BBB locally and non-invasively. When using a Rapid Short-Pulse (RaSP) sequence, the drugs can be delivered more safely and uniformly. However, there are currently no therapeutic systems designed for short-pulse ultrasound. In this thesis, we have presented a system specifically designed for delivering drugs across the BBB with short-pulse ultrasound.
We first designed and built a lead zirconate titanate-polyvinylidene fluoride (PZT-PVDF) stacked transducer using a fast-prototyping process. The transducer could simultaneously emit short-pulse ultrasound with the PZT and receive broadband signals with the PVDF at the same location. We then incorporated 32 of these transducers into a focussed array. The 32 elements were built individually then assembled onto a 3D-printed dome-shaped frame. The array could use PZTs to focus ultrasound and steer the focus within a 30 mm range. It was also capable of focussing ultrasound and receiving broadband acoustic emissions from microbubbles through an ex vivo human skull. Finally, we designed and built an array with 8 small PVDF sensors to develop a better understanding of what a good feedback control system should be. We investigated the PVDF array’s ability to detect microbubble emissions and localize microbubbles. Through this work, we built a series of new technologies for short-pulse ultrasound therapies. These technologies have the potential to improve the safety and performance of drug delivery across the BBB. The next step is to use this new hardware and improve feedback control system for a safer treatment.
We first designed and built a lead zirconate titanate-polyvinylidene fluoride (PZT-PVDF) stacked transducer using a fast-prototyping process. The transducer could simultaneously emit short-pulse ultrasound with the PZT and receive broadband signals with the PVDF at the same location. We then incorporated 32 of these transducers into a focussed array. The 32 elements were built individually then assembled onto a 3D-printed dome-shaped frame. The array could use PZTs to focus ultrasound and steer the focus within a 30 mm range. It was also capable of focussing ultrasound and receiving broadband acoustic emissions from microbubbles through an ex vivo human skull. Finally, we designed and built an array with 8 small PVDF sensors to develop a better understanding of what a good feedback control system should be. We investigated the PVDF array’s ability to detect microbubble emissions and localize microbubbles. Through this work, we built a series of new technologies for short-pulse ultrasound therapies. These technologies have the potential to improve the safety and performance of drug delivery across the BBB. The next step is to use this new hardware and improve feedback control system for a safer treatment.
Version
Open Access
Date Issued
2022-08
Date Awarded
2022-10
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Choi, James
Dickinson, Robert
Sponsor
Alzheimer’s Research UK
Wellcome Trust (London, England)
Grant Number
ARUK-IRG2017A-7
213038/Z/18/Z
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)