Trial reportFluids and barriers of the CNS2023
Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease.
Trial report in Fluids and barriers of the CNS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03671889 (Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable Alzheimer's Disease), which is not on this map. Cited by 40 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.
Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable Alzheimer's Disease
Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 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
- Focused ultrasound therapy for Alzheimer's disease: exploring the potential for targeted amyloid disaggregation.Frontiers in neurology · 2024Pooled it
- Pharmacokinetic Analysis of Carboplatin and Fluorescein Brain Retention following Ultrasound-Based Blood-Brain Barrier Opening.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Focused Ultrasound is Poised to Take Non-Viral Gene Therapies to the Blood-Brain Barrier - and Beyond.Cell biomaterials · 2026Article
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Quantitative Susceptibility Mapping Shows Size-dependent Focused Ultrasound-mediated Therapeutic Delivery to Naive Brain and Gliomas in Mice.Radiology · 2026Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Low-intensity transcranial ultrasound neuromodulation promotes neuronal regeneration: A new hope for noninvasive treatment of neurodegenerative diseases.Neural regeneration research · 2026Article
- E-selectin-targeted microbubbles combined with ultrasound improves renoprotective effects of methylprednisolone on cisplatin-induced acute kidney injury in rats.Scientific reports · 2026Article
- Small Particles, Big Impact: Inorganic Nanotechnology for Glioblastoma.Molecules (Basel, Switzerland) · 2026Review
- Visualization of gadolinium transport across the blood-brain barrier along perivascular clearance pathways.European radiology experimental · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Glymphatic-meningeal lymphatic system imbalance: a peripheral-to-central inflammatory bridge in perioperative neurocognitive disorders.Frontiers in immunology · 2026Review
- Beyond the Leak: Advanced MRI Assessment of the Blood-Brain Barrier in Neurodegeneration.Neuro-degenerative diseases · 2026Review
- The glymphatic system in neurodegenerative diseases and brain tumors: mechanistic insights, biomarker advances, and therapeutic opportunities.Acta neuropathologica communications · 2025Review
- 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
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Brain Endothelial Cells in Blood-Brain Barrier Regulation and Neurological Therapy.International journal of molecular sciences · 2025Review
- Advances in brain-targeted delivery strategies and natural product-mediated enhancement of blood-brain barrier permeability.Journal of nanobiotechnology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFocused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer's disease (AD).
methodsAt a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles. In all, 77 treatment sites were evaluated and encompassed hippocampal, frontal, and parietal brain regions. Post-FUS imaging changes, including susceptibility effects and spatiotemporal gadolinium-based contrast agent enhancement patterns, were analyzed using serial 3.0-Tesla MRI.
resultsPost-FUS MRI revealed expected intraparenchymal contrast extravasation due to BBB opening at all targeted brain sites. Immediately upon BBB opening, hyperconcentration of intravenously-administered contrast tracer was consistently observed around intracerebral veins. Following BBB closure, within 24-48 h of FUS intervention, permeabilization of intraparenchymal veins was observed and persisted for up to one week. Notably, extraparenchymal meningeal venous permeabilization and associated CSF effusions were also elicited and persisted up to 11 days post FUS treatment, prior to complete spontaneous resolution in all participants. Mild susceptibility effects were detected, however no overt intracranial hemorrhage or other serious adverse effects occurred in any participant.
conclusionsFUS-mediated BBB opening is safely and reproducibly achieved in multifocal brain regions of persons with AD. Post-FUS tracer enhancement phenomena suggest the existence of a brain-wide perivenous fluid efflux pathway in humans and demonstrate reactive physiological changes involving these conduit spaces in the delayed, subacute phase following BBB disruption. The delayed reactive venous and perivenous changes are consistent with a dynamic, zonal exudative response to upstream capillary manipulation. Further preclinical and clinical investigations of these FUS-related imaging phenomena and of intracerebral perivenous compartment changes are needed to elucidate physiology of this pathway as well as biological effects of FUS administered with and without adjuvant neurotherapeutics.
trial registrationClinicalTrials.gov identifier: NCT03671889, registered 9/14/2018.
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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.