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

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

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dc.contributor.author Jiménez-Gambín, Sergio es_ES
dc.contributor.author Jimenez, Noe es_ES
dc.contributor.author Pouliopoulos, Antonios N. es_ES
dc.contributor.author Benlloch Baviera, Jose María es_ES
dc.contributor.author Konofagou, Elisa E. es_ES
dc.contributor.author Camarena Femenia, Francisco es_ES
dc.date.accessioned 2022-10-06T18:05:46Z
dc.date.available 2022-10-06T18:05:46Z
dc.date.issued 2022-04 es_ES
dc.identifier.issn 0018-9294 es_ES
dc.identifier.uri http://hdl.handle.net/10251/187196
dc.description.abstract [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. es_ES
dc.description.sponsorship This work was supported in part by the Spanish Ministry of Science, Innovation, and Universities (MICINN) through Grants "Juan de la Cierva -Incorporacion" IJC2018-037897-I, and PID2019-111436RB-C22, in part by the Agencia Valenciana de la Innovacio through Grants INNVAL10/19/016, INNCON/2021/8, and INNVA1/2020/92, in part by Generalitat Valenciana through Grants ACIF/2017/045, AICO/2020/268, and BEFPI/2019/075, and in part 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 (IDIFEDER/2018/022 and IDIFEDER/2021/004) es_ES
dc.language Inglés es_ES
dc.publisher Institute of Electrical and Electronics Engineers es_ES
dc.relation.ispartof IEEE Transactions on Biomedical Engineering es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Acoustic holograms es_ES
dc.subject Blood-brain barrier es_ES
dc.subject Transcranial focused ultrasound es_ES
dc.subject.classification FISICA APLICADA es_ES
dc.title Acoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1109/TBME.2021.3115553 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-111436RB-C22/ES/NEW TECHNIQUES FOR MULTIMODAL MOLECULAR ELASTOGRAPHIC IMAGING/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//BEFPI%2F2019%2F075/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/NIH//5R01EB009041/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/NIH//5R01AG038961/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/Agència Valenciana de la Innovació//INNVAL10%2F19%2F016//Dispositivo médico no invasivo para tratamiento de enfermedades neurológicas/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GENERALITAT VALENCIANA//ACIF%2F2017%2F045//AYUDA PREDOCTORAL CONSELLERIA-JIMENEZ GAMBIN/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/EDUC.INVEST.CULT.DEP//IDIFEDER%2F2018%2F022//EQUIPOS PARA TECNICAS MIXTAS ELECTROMAGNETICAS-ULTRASONICAS PARA IMAGEN MEDICA/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AGENCIA ESTATAL DE INVESTIGACION//IJC2018-037897-I//AYUDA JUAN DE LA CIERVA INCORPORACION-JIMENEZ GONZALEZ/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AGENCIA VALENCIANA DE LA INNOVACION//INNVA1%2F2020%2F92//DISPOSITIVO DE IMAGEN ELASTOGRAFICA CUANTITATIVA EMPLEANDO VORTICES ACUSTICOS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GENERALITAT VALENCIANA//AICO%2F2020%2F268//DESARROLLO DE UN SISTEMA MAGNÉTICO-ULTRASÓNICO DE IMAGEN MÉDICA (MUSMI) / es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AGENCIA VALENCIANA DE LA INNOVACION//INNCON%2F2021%2F8//TECNOLOGIAS FISICAS DE MONITORIZACION Y TRATAMIENTO/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Instituto de Instrumentación para Imagen Molecular - Institut d'Instrumentació per a Imatge Molecular es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada es_ES
dc.description.bibliographicCitation Jiménez-Gambín, S.; Jimenez, N.; Pouliopoulos, AN.; Benlloch Baviera, JM.; Konofagou, EE.; Camarena Femenia, F. (2022). Acoustic Holograms for Bilateral Blood-Brain Barrier Opening in a Mouse Model. IEEE Transactions on Biomedical Engineering. 69(4):1359-1368. https://doi.org/10.1109/TBME.2021.3115553 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1109/TBME.2021.3115553 es_ES
dc.description.upvformatpinicio 1359 es_ES
dc.description.upvformatpfin 1368 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 69 es_ES
dc.description.issue 4 es_ES
dc.identifier.pmid 34570701 es_ES
dc.identifier.pmcid PMC9058858 es_ES
dc.relation.pasarela S\465559 es_ES
dc.contributor.funder GENERALITAT VALENCIANA es_ES
dc.contributor.funder AGENCIA ESTATAL DE INVESTIGACION es_ES
dc.contributor.funder AGENCIA VALENCIANA DE LA INNOVACION es_ES
dc.contributor.funder National Institutes of Health, EEUU es_ES
dc.contributor.funder Agència Valenciana de la Innovació es_ES
upv.costeAPC 600 es_ES


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