ArticleScientific reports2018
Safety evaluation of frequent application of microbubble-enhanced focused ultrasound blood-brain-barrier opening.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Towards standardization of the parameters for opening the blood-brain barrier with focused ultrasound to treat glioblastoma multiforme: A systematic review of the devices, animal models, and therapeutic compounds used in rodent tumor models.Frontiers in oncology · 2022Pooled it
- Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors.Science advances · 2021Trial
- Hypoxia-induced circSPECC1 drives temozolomide resistance in glioblastoma via IGF2BP2-mediated PGK1 mRNA stabilization.Cell death & disease · 2026Article
- Induction of subtle blood-brain barrier dysfunction using preclinical diagnostic ultrasound combined with microbubbles.Fluids and barriers of the CNS · 2026Article
- Ultrasound-triggered microbubble delivery of voriconazole for enhanced reduction of Candida albicans biofilms in vitro.Bone & joint research · 2026Article
- Data-Driven Feedback Identifies Focused Ultrasound Exposure Regimens for Improved Nanotheranostic Targeting of the Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- From Ablation to Neuromodulation Platform: The Evolving Role of Magnetic Resonance-Guided Focused Ultrasound in Functional Neurosurgery.Journal of clinical neurology (Seoul, Korea) · 2026Review
- Focused ultrasound enhances targeted curcumin delivery and alleviates behavioral and neuropathological deficits in a Parkinson's disease mouse model.Frontiers in aging neuroscience · 2026Article
- Modeling the synergistic enhancement of drug permeation by a dual-microbubble system under ultrasonic excitation.Drug delivery · 2025Article
- Precise antibody delivery to the brain via nanobubble-actuated focused ultrasound alleviates depression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Data-driven feedback augments ultrasound nanotheranostics in brain tumors.bioRxiv : the preprint server for biology · 2025Article
- Biological profile of breast cancer brain metastasis.Acta neuropathologica communications · 2025Review
- The blood-brain barriers: novel nanocarriers for central nervous system diseases.Journal of nanobiotechnology · 2025Review
- Article
- Cavitation monitoring, treatment strategy, and acoustic simulations of focused ultrasound blood-brain barrier disruption in patients with glioblastoma.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Blood-brain barrier alterations and their impact on Parkinson's disease pathogenesis and therapy.Translational neurodegeneration · 2024Review
- Comprehensive assessment of blood-brain barrier opening and sterile inflammatory response: unraveling the therapeutic window.Scientific reports · 2024Article
- Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease.Pharmaceutics · 2024Article
- Carrier-Free, Amorphous Verteporfin Nanodrug for Enhanced Photodynamic Cancer Therapy and Brain Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Blood-cerebrospinal fluid barrier opening by modified single pulse transcranial focused shockwave.Drug delivery · 2023Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Focused ultrasound (FUS) with the presence of microbubbles induces blood brain barrier (BBB) opening in targeted areas and facilitates drug delivery. However, recent studies have indicated that FUS-BBB opening with excessive exposure levels may be associated with inflammatory response and cellular/tissue damage. Multiple weekly FUS exposures have been shown to be safe for human subjects. However the effect of more frequent FUS exposures is still unknown. This study examines whether frequent focused ultrasound blood brain barrier opening is associated with aggravated behavioral, histopathologic change or brain tissue damage. Two protocols of focused ultrasound blood brain barrier opening were devised using different microbubble doses (0.15 µl/kg and 0.4 µl/kg). Focused ultrasound exposure at a threshold level of BBB-opening, below-threshold level, or above level for intracerebral hemorrhage were delivered every 2 days. Animal behavioral and physiological changes were examined and recorded. Brain tissue was examined for hemorrhage and apoptosis. Results indicate that frequent exposure of excessive focused ultrasound (1.4 mechanical index) produced minor and short-term behavioral changes despite significant tissue damage, while frequent BBB opening with threshold or below-threshold FUS exposure (0.33-0.8 mechanical index) did not cause behavioral or histological change. Immunofluorescent examination of rat brain tissue indicated that excessive doses of microbubble administration induce an apparent cellular apoptotic response, which may be exacerbated by intracerebral hemorrhage. Experimental results suggest that frequent focused ultrasound blood brain barrier opening with sufficient ultrasound exposure level and a microbubble dose can be safe and pose minimal risk to brain tissue.
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