Rapid Skull Decalcification for Improved Ultrasound Transmission in Brain Imaging and Histotripsy: A Proof-of-Concept Study in Rat

Abstract

Ultrasound imaging and therapy of the brain is impeded by the reflection and attenuation characteristics of the skull, especially for high frequency imaging. In this study, the potential utility of surgically thinning and chemically decalcifying a region of skull bone was explored acutely in rats in vivo. It was found that thinning the skull to approximately 35 μm thickness and decalcifying with 20% ethylenediaminetetraacetic acid (EDTA) for at least 30 min effectively rendered the treated bone acoustically transparent for 5.4 MHz ultrasound therapy (histotripsy) signals and for 30 MHz ultrasound imaging signals. Simultaneous low intensity 1 MHz sonication of the site accelerated the process to achieve skull transparency levels at 15 min that were similar to 30 min without sonication. There was histological evidence of tissue damage caused by EDTA solution on the surface of the brain, depending on treatment duration. The long-term significance of this tissue effect and the longevity of the ultrasound transmission improvement are not yet clear.

Note:
Funding Information: This work was funded by the Canadian Institutes of Health Research (Funding Reference No PJT-183717).

Conflict of Interests: The authors TL and JB hold inventorship of a provisional patent (Applicant: Daxsonics Ultrasound Inc., Halifax, NS, Canada) which covers the commercial/medical application of the accelerated decalcification and sonication procedure described in this study.

Ethical Approval: All procedures were approved by the Dalhousie University Committee for Laboratory Animals (protocol 23-077).

Keywords: acoustic transmission, transcranial ultrasound, bone decalcification, Ultrasound imaging, Histotripsy