Cavitation control and imaging for focused ultrasound brain therapy
Cavitation-mediated focused ultrasound (FUS) is currently the only method of reversible
blood-brain barrier disruption (BBBD) for targeted drug delivery without incision or
radiation. A significant challenge for its clinical translation is a lack of reliable
and precise real-time treatment control and imaging methods, especially in brain
applications where B-mode ultrasound and ... read moremagnetic resonance imaging are unable to
visualize microbubble sources transcranially and tissue temperature change in deep brain
targets. This thesis develops several acoustic methods to improve the low-frequency FUS
focusing, the feedback control of cavitation behavior and drug delivery thereof, and the
localization ability of passive cavitation imaging (PCI). Firstly, to maximize the
clinical relevance of small animal investigations, a dual-aperture FUS system was
designed for low-frequency (274.3kHz) cavitation-mediated FUS therapy via temporal
modulation of the wave interference pattern. In addition, a closed-loop, real-time
control paradigm is shown capable of sustaining stable microbubble oscillations at a
preset level while minimizing transient and violent microbubble collapsing that may
result in vascular damage. After optimizing key ultrasound parameters and microbubble
administration protocols, this cavitation controller was investigated to realize
on-demand drug delivery with modulated BBBD. Tested at clinically relevant frequency in
healthy and tumor-bearing rats, our approach enables targeted delivery of predefined
drug concentrations within a therapeutically effective range in both normal tissue and
glioma, while maintaining a safe exposure level. Finally, to refine the localization
ability of traditional PCI, adaptive beamforming methods with diagonal loading were
applied to the imaging algorithm. A white noise gain constraint was used to adaptively
control the loading level so that the sensitivity of minimum variance distortionless
response beamformer can be adjusted in a spatially selective manner, which result in
significant improvement in image resolution and
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Electrical Engineering.
Advisors: Eric Miller, and Nathan McDannold.
Committee: Brian Tracey, and Paul Barbone.
Keywords: Electrical engineering, Acoustics, and Biomedical engineering.read less