{"doi":"10.1109/tbme.2021.3120919","title":"Transcranial Theranostic Ultrasound for Pre-Planning and Blood-Brain Barrier Opening: A Feasibility Study Using an Imaging Phased Array In Vitro and In Vivo","abstract":"Focused ultrasound (FUS) for blood-brain barrier (BBB) opening is a safe, reversible and non-invasive strategy for targeted drug delivery to the brain, however extensive pre-planning strategies are necessary for successful FUS-mediated BBB opening through the structurally complex primate skull. Objective: This study aims to demonstrate a pre-planning pipeline consisting of transcranial simulations and in vitro experimentation used to inform synchronous BBB opening and power cavitation imaging (PCI) with a single theranostic ultrasound (TUS) phased array. Methods: Acoustic wave propagation simulation findings of pressure attenuation and focal shift through clinical-CT and micro-CT-based primate skull models were compared, while the latter were used to determine the impact of beam steering angle on focal shift and pressure attenuation. In vitro experimentation with a channel phantom enabled characterization of skull-induced receive focal shift (RFS), while in vivo BBB opening and PCI using in silico and in vitro pre-planning information was conducted using a custom Verasonics/MATLAB script. Results: Simulations confirmed steering angle dependent transcranial focal shift and pressure attenuation, while in vitro experiments revealed minimal (0.30-1.50 mm) skull-induced RFS. In vivo rodent experiments with overlaid primate skull fragments demonstrated successful TUS-mediated BBB opening and spatially correlated power cavitation images (PCI) with regions of BBB opening on T 1 -weighted magnetic resonance images (MRI). Conclusion: We demonstrated the feasibility for TUS-mediated BBB opening in vivo using in silico and in vitro pre-planning information. Significance: TUS as an ultrasound-guided modality for BBB opening could serve as a promising alternative to current FUS-mediated BBB opening configurations in the clinic.","journal":"IEEE Transactions on Biomedical Engineering","year":2021,"id":173856,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473813,"name":"Robin Ji","orcid":"0000-0003-1361-141X","position":1,"is_corresponding":false},{"id":488370,"name":"Alina R. Kline-Schoder","orcid":"0009-0005-4691-4443","position":2,"is_corresponding":false},{"id":712601,"name":"Rebecca L. Noel","orcid":"0000-0003-3478-7254","position":3,"is_corresponding":false},{"id":266230,"name":"Elisa E. Konofagou","orcid":"0000-0002-9636-7936","position":4,"is_corresponding":false},{"id":318540,"name":"Alec J. Batts","orcid":"0000-0002-6979-9389","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:46:54.772014Z","pmid":"34665716","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":[]}