Acoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model

[EN] Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS tec...

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Detalhes bibliográficos
Autores: Jiménez-Gambín, Sergio, Pouliopoulos, Antonios N., Konofagou, Elisa E., Jimenez, Noe|||0000-0002-6539-670X, Benlloch Baviera, Jose María|||0000-0001-6073-1436, Camarena Femenia, Francisco|||0000-0002-6713-1414
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/187196
Acesso em linha:https://riunet.upv.es/handle/10251/187196
Access Level:acceso abierto
Palavra-chave:Acoustic holograms
Blood-brain barrier
Transcranial focused ultrasound
FISICA APLICADA
Descrição
Resumo:[EN] Transcranial focused ultrasound (FUS) in conjunction with circulating microbubbles injection is the sole non-invasive technique that temporally and locally opens the blood-brain barrier (BBB), allowing targeted drug delivery into the central nervous system (CNS). However, single-element FUS technologies do not allow the simultaneous targeting of several brain structures with high-resolution, and multi-element devices are required to compensate the aberrations introduced by the skull. In this work, we present the first preclinical application of acoustic holograms to perform a bilateral BBB opening in two mirrored regions in mice. The system consisted of a single-element focused transducer working at 1.68 MHz, coupled to a 3D-printed acoustic hologram designed to produce two symmetric foci in anesthetized mice in vivo and, simultaneously, compensate the aberrations of the wavefront caused by the skull bones. T1-weighed MR images showed gadolinium extravasation at two symmetric quasi-spherical focal spots. By encoding time-reversed fields, holograms are capable of focusing acoustic energy with a resolution near the diffraction limit at multiple spots inside the skull of small preclinical animals. This work demonstrates the feasibility of hologram-assisted BBB opening for low-cost and highly-localized targeted drug delivery in the CNS in symmetric regions of separate hemispheres.