A Clinical System for Non invasive Blood Brain Barrier Opening Using a Neuronavigation Guided Single Element Focused Ultrasound Transducer 1st edition by Antonios Pouliopoulos, Shih Ying Wu, Mark Burgess, Maria Eleni Karakatsani, Hermes Kamimura, Elisa Konofagou

A Clinical System for Non-invasive Blood–Brain Barrier Opening Using a Neuronavigation-Guided Single-Element Focused Ultrasound Transducer 1st edition by Antonios N. Pouliopoulos, Shih-Ying Wu, Mark T. Burgess, Maria Eleni Karakatsani, Hermes A.S. Kamimura, Elisa E. Konofagou – Ebook PDF Instant Download/Delivery

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Author: Antonios Pouliopoulos, Shih Ying Wu, Mark Burgess, Maria Eleni Karakatsani, Hermes Kamimura, Elisa Konofagou

Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is currently being investigated in clinical trials. Here, we describe a portable clinical system with a therapeutic transducer suitable for humans, which eliminates the need for in-line magnetic resonance imaging (MRI) guidance. A neuronavigation-guided 0.25-MHz single-element FUS transducer was developed for non-invasive clinical BBB opening. Numerical simulations and experiments were performed to determine the characteristics of the FUS beam within a human skull. We also validated the feasibility of BBB opening obtained with this system in two non-human primates using U.S. Food and Drug Administration (FDA)-approved treatment parameters. Ultrasound propagation through a human skull fragment caused 44.4 ± 1% pressure attenuation at a normal incidence angle, while the focal size decreased by 3.3 ± 1.4% and 3.9 ± 1.8% along the lateral and axial dimension, respectively. Measured lateral and axial shifts were 0.5 ± 0.4 mm and 2.1 ± 1.1 mm, while simulated shifts were 0.1 ± 0.2 mm and 6.1 ± 2.4 mm, respectively. A 1.5-MHz passive cavitation detector transcranially detected cavitation signals of Definity microbubbles flowing through a vessel-mimicking phantom. T1-weighted MRI confirmed a 153 ± 5.5 mm3 BBB opening in two non-human primates at a mechanical index of 0.4, using Definity microbubbles at the FDA-approved dose for imaging applications, without edema or hemorrhage. In conclusion, we developed a portable system for non-invasive BBB opening in humans, which can be achieved at clinically relevant ultrasound exposures without the need for in-line MRI guidance. The proposed FUS system may accelerate the adoption of non-invasive FUS-mediated therapies due to its fast application, low cost and portability.

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Tags: A Clinical System, Non invasive, Blood Brain Barrier, Neuronavigation, Neuronavigation Guided, Single Element, Ultrasound Transducer, Antonios Pouliopoulos, Shih Ying Wu, Mark Burgess, Maria Eleni Karakatsani, Hermes Kamimura, Elisa Konofagou