First in-vivo Demonstration of Bilateral Blood-Brain Barrier Opening Using Acoustic Holograms in Mice
| Autor: | Francisco Camarena, Antonios N. Pouliopoulos, Sergio Jiménez-Gambín, Elisa E. Konofagou, Noé Jiménez, Jose M. Benlloch |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Blood-brain barrier opening Materials science Focused ultrasound business.industry Central nervous system Ultrasound Acoustic hologram Blood–brain barrier 01 natural sciences Extravasation 03 medical and health sciences medicine.anatomical_structure Targeted drug delivery In vivo FISICA APLICADA Lens (anatomy) 0103 physical sciences medicine Microbubbles business 010301 acoustics 030304 developmental biology Biomedical engineering |
| Zdroj: | RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia instname |
| DOI: | 10.1109/ius46767.2020.9251487 |
| Popis: | [EN] Focused ultrasound (FUS) with microbubbles allows for non-invasive targeted drug delivery into the central nervous system (CNS) by temporally and locally disrupting the bloodbrain barrier (BBB). However, current FUS technologies are not able to simultaneously target several brain structures. In this work, we open the BBB in two regions in a murine brain using a single-element transducer with a coupled 3D-printed holographic lens, which is designed to simultaneously create two symmetric foci in anesthetized mice in vivo. The proposed approach shows many advantages: (1) simple and low-cost; (2) correction of aberrations due to skull and water cone; and (3) multiple BBB opening (BBBO) locations with only one sonication, becoming a time- and cost-effective therapeutic system for neurological diseases. For the in-vivo experiment, contrast-enhanced, T1- weighted MRI scan was conducted following BBBO, showing gadolinium extravasation at two symmetric focal spots. The two BBBO regions were separated by 3.0 +- 0.7 mm (n=5 mice) compared to 5.3 mm in full-wave simulations. This work shows the capability of bifocal ultrasound generation in separate animals using a unique uCT scan. A bilateral BBBO was achieved with a single sonication using a holographic lens in mice, thus improving the efficiency and defining a new approach for several neurodegenerative diseases targeting symmetric brain structures, e.g. hippocampus, putamen or caudate. This study demonstrates the feasibility of hologram-assisted BBBO for targeted drug delivery in the CNS in symmetric regions in separate hemispheres. This research has been supported by the Spanish Ministry of Science, Innovation and Universities through grants Juan de la Cierva - Incorporacion (IJC2018-037897-I) and PID2019-111436RB-C22, by the Agencia Valenciana de la Innovación through grant INNVAL10/19/016, by Generalitat Valenciana through grants No. ACIF/2017/045 and BEFPI/2019/075, and by the National Institutes of Health through grants 5R01EB009041 and 5R01AG038961. Action co-financed by the European Union through the Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER) of the Comunitat Valenciana 2014-2020 (IDIFEDER/2018/022). |
| Databáze: | OpenAIRE |
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