ArticlePloS one2015
Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 106 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
106 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- Focused ultrasound-mediated enhancement of blood-brain barrier permeability for brain tumor treatment: a systematic review of clinical trials.Journal of neuro-oncology · 2024Pooled it
- MRI Guided Focused Ultrasound-Mediated Delivery of Therapeutic Cells to the Brain: A Review of the State-of-the-Art Methodology and Future Applications.Frontiers in neurology · 2021Pooled it
- Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.Nature communications · 2024Trial
- Focused Ultrasound Modulation of PGC-1α Pathways in Neurological Disease: Mechanistic Rationale and Translational Opportunities.Molecular neurobiology · 2026Review
- Advanced Drug Delivery Strategies for Overcoming Biological Barriers: Tumor Microenvironment and Blood-Brain Barrier.Drugs in R&D · 2026Review
- Precision Drug Delivery Strategies for Treatment-Resistant Depression: Opportunities and Challenges of FUS-BBBO and Spatial Molecular Profiling.Drug design, development and therapy · 2026Review
- Nitrous oxide enhances MR-guided focused ultrasound delivery of gene therapy to the murine hippocampus.Gene therapy · 2025Article
- Breaking Barriers in Huntington's Disease Therapy: Focused Ultrasound for Targeted Drug Delivery.Neurochemical research · 2025Review
- Acoustic immune reprogramming: a novel paradigm for spatiotemporally controlled immune regulation using ultrasound-responsive nanoplatforms.Frontiers in immunology · 2025Review
- Pulsed focused ultrasound alters the proteomic profile of the tumor microenvironment in a syngeneic mouse model of glioblastoma.Journal of neuro-oncology · 2024Article
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Acoustically targeted measurement of transgene expression in the brain.Science advances · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Review
- Characterization of the responses of brain macrophages to focused ultrasound-mediated blood-brain barrier opening.Nature biomedical engineering · 2024Article
- Remotely controlled drug release in deep brain regions of non-human primates.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Selective Uptake of Macromolecules to the Brain in Microfluidics and Animal Models Using the HAVN1 Peptide as a Blood-Brain Barrier Modulator.Molecular pharmaceutics · 2024Article
- Acoustically targeted noninvasive gene therapy in large brain volumes.Gene therapy · 2024Article
- A Systematic Review of Nanomedicine in Glioblastoma Treatment: Clinical Efficacy, Safety, and Future Directions.Brain sciences · 2023Review
- Real-Time Passive Acoustic Mapping With Enhanced Spatial Resolution in Neuronavigation-Guided Focused Ultrasound for Blood-Brain Barrier Opening.IEEE transactions on bio-medical engineering · 2023Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500 kHz, 200-400 kPa, 4-5 μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4-20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of' visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4-5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.