Trial reportProceedings of the National Academy of Sciences of the United States of America2020
Noninvasive hippocampal blood-brain barrier opening in Alzheimer's disease with focused ultrasound.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
186 citing papers in PubMed, 5 syntheses or guidelines pooled it, 339 citations in OpenAlex.
- Ultrasound-induced blood-brain barrier opening in Alzheimer's disease: a systematic review of clinical studies.Aging clinical and experimental research · 2026Pooled it
- Safety, Efficacy and Clinical Applications of Focused Ultrasound-Mediated Blood Brain Barrier Opening in Alzheimer's Disease: A Systematic Review.The journal of prevention of Alzheimer's disease · 2024Pooled it
- Focused ultrasound therapy for Alzheimer's disease: exploring the potential for targeted amyloid disaggregation.Frontiers in neurology · 2024Pooled it
- Connectomic neuromodulation for Alzheimer's disease: A systematic review and meta-analysis of invasive and non-invasive techniques.Translational psychiatry · 2022Pooled it
- Multi-mechanical waves against Alzheimer's disease pathology: a systematic review.Translational neurodegeneration · 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
- Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease.Fluids and barriers of the CNS · 2023Trial
- Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer's disease with an implantable ultrasound device.Alzheimer's research & therapy · 2022Trial
- Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound.Proceedings of the National Academy of Sciences of the United States of America · 2021Trial
- Low-intensity pulsed ultrasound combined with microbubbles enhances amphotericin B delivery across the blood-brain barrier for improved therapy of cryptococcal meningitis.Drug delivery · 2026Article
- Neuromodulation techniques targeting neurotransmitter dysfunction: Innovation in treatments for Alzheimer's disease.Neural regeneration research · 2026Article
- Article
- High pressure transcranial focused ultrasound stimulation induces parameter-dependent cell-type specific effects.Microsystems & nanoengineering · 2026Review
- Applications of transcranial focused ultrasound for primary brain tumors.Neuro-oncology advances · 2026Review
- Noninvasive enrichment of circulating tumor biomarkers in a mouse model of diffuse midline glioma using focused ultrasound.Neuro-oncology advances · 2026Review
- Focused ultrasound expands intra-CSF AAV delivery to deep brain regions in rats and non-human primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Non-invasive Neuromodulation Targeting Approach by Mapping Stimulations and Lesions That Modify Visual Memory.bioRxiv : the preprint server for biology · 2026Article
- Intranasal vs. Device-Assisted Drug Delivery: Advantages and Limitations for the Delivery of Biopharmaceuticals to the CNS.Pharmaceutics · 2026Review
- Epilepsy: Molecular Pathogenesis and Emerging Therapies.MedComm · 2026Review
- Review
126 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The blood-brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer's disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.
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What OpenQuestion holds
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.