{"doi":"10.1186/s12967-024-05096-9","title":"Focused ultrasound-mediated blood–brain barrier opening is safe and feasible with moderately hypofractionated radiotherapy for brainstem diffuse midline glioma","abstract":"Abstract Background Diffuse midline glioma (DMG) is a pediatric tumor with dismal prognosis. Systemic strategies have been unsuccessful and radiotherapy (RT) remains the standard-of-care. A central impediment to treatment is the blood–brain barrier (BBB), which precludes drug delivery to the central nervous system (CNS). Focused ultrasound (FUS) with microbubbles can transiently and non-invasively disrupt the BBB to enhance drug delivery. This study aimed to determine the feasibility of brainstem FUS in combination with clinical doses of RT. We hypothesized that FUS-mediated BBB-opening (BBBO) is safe and feasible with 39 Gy RT. Methods To establish a safety timeline, we administered FUS to the brainstem of non-tumor bearing mice concurrent with or adjuvant to RT; our findings were validated in a syngeneic brainstem murine model of DMG receiving repeated sonication concurrent with RT. The brainstems of male B6 (Cg)-Tyrc-2J/J albino mice were intracranially injected with mouse DMG cells (PDGFB + , H3.3K27M, p53 −/− ). A clinical RT dose of 39 Gy in 13 fractions (39 Gy/13fx) was delivered using the Small Animal Radiation Research Platform (SARRP) or XRAD-320 irradiator. FUS was administered via a 0.5 MHz transducer, with BBBO and tumor volume monitored by magnetic resonance imaging (MRI). Results FUS-mediated BBBO did not affect cardiorespiratory rate, motor function, or tissue integrity in non-tumor bearing mice receiving RT. Tumor-bearing mice tolerated repeated brainstem BBBO concurrent with RT. 39 Gy/13fx offered local control, though disease progression occurred 3–4 weeks post-RT. Conclusion Repeated FUS-mediated BBBO is safe and feasible concurrent with RT. In our syngeneic DMG murine model, progression occurs, serving as an ideal model for future combination testing with RT and FUS-mediated drug delivery.","journal":"Journal of Translational Medicine","year":2024,"id":420228,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640329,"name":"Nicholas McQuillan","orcid":"0000-0002-6589-3204","position":1,"is_corresponding":false},{"id":270520,"name":"Hong-Jian Wei","orcid":"0000-0002-5962-7831","position":2,"is_corresponding":false},{"id":847722,"name":"Matthew Gallitto","orcid":"0000-0002-5210-742X","position":3,"is_corresponding":false},{"id":490745,"name":"Ethan Bendau","orcid":"0000-0003-2621-2768","position":4,"is_corresponding":false},{"id":1211092,"name":"Andrea Webster Carrion","orcid":"0000-0001-5405-5072","position":5,"is_corresponding":false},{"id":1211093,"name":"Xander Berg","orcid":"0009-0003-1365-6877","position":6,"is_corresponding":false},{"id":1206984,"name":"Danae Kokossis","orcid":"0000-0001-6285-3728","position":7,"is_corresponding":false},{"id":270523,"name":"Xu Zhang","orcid":"0000-0002-9817-4492","position":8,"is_corresponding":false},{"id":1205346,"name":"Zhiguo Zhang","orcid":"0000-0003-3982-9900","position":9,"is_corresponding":false},{"id":272737,"name":"Chia‐Ing Jan","orcid":null,"position":10,"is_corresponding":false},{"id":293197,"name":"Akiva Mintz","orcid":"0000-0002-9905-3086","position":11,"is_corresponding":false},{"id":409101,"name":"Robyn D. Gartrell","orcid":"0000-0003-3287-4223","position":12,"is_corresponding":false},{"id":1211641,"name":"Hasan R. Syed","orcid":null,"position":13,"is_corresponding":false},{"id":351787,"name":"Adriana Fonseca","orcid":"0000-0002-6382-6833","position":14,"is_corresponding":false},{"id":998224,"name":"Jovana Pavisic","orcid":"0000-0002-6968-600X","position":15,"is_corresponding":false},{"id":998223,"name":"Luca Szalontay","orcid":"0000-0002-7341-0014","position":16,"is_corresponding":false},{"id":266230,"name":"Elisa E. Konofagou","orcid":"0000-0002-9636-7936","position":17,"is_corresponding":false},{"id":272738,"name":"Stergios Zacharoulis","orcid":null,"position":18,"is_corresponding":false},{"id":259430,"name":"Cheng–Chia Wu","orcid":"0000-0002-5908-0143","position":19,"is_corresponding":false},{"id":503966,"name":"Masih Tazhibi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:25.777459Z","pmid":"38555449","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":[]}