{"doi":"10.1109/ius46767.2020.9251487","title":"First in-vivo Demonstration of Bilateral Blood-Brain Barrier Opening Using Acoustic Holograms in Mice","abstract":"Focused ultrasound (FUS) with microbubbles allows for non-invasive targeted drug delivery into the central nervous system (CNS) by temporally and locally disrupting the blood-brain 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 μCT 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.","journal":"RiuNet (Universitat Politècnica de València)","year":2020,"id":125597,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":572251,"name":"Nóe Jiménez","orcid":"0000-0002-6539-670X","position":1,"is_corresponding":false},{"id":237783,"name":"J. Benlloch","orcid":"0000-0001-6073-1436","position":2,"is_corresponding":false},{"id":572252,"name":"Francisco Camarena","orcid":"0000-0002-6713-1414","position":3,"is_corresponding":false},{"id":270521,"name":"Antonios N. Pouliopoulos","orcid":"0000-0002-8891-1495","position":4,"is_corresponding":false},{"id":266230,"name":"Elisa E. Konofagou","orcid":"0000-0002-9636-7936","position":5,"is_corresponding":false},{"id":572250,"name":"Sergio Jiménez-Gambín","orcid":"0000-0003-4172-8340","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-18T23:15:19.482428Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}