Evidence map›Paper›PMID 33399511›Full record

Trial reportRadiology2021

Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease.

Rashi I Mehta, Jeffrey S Carpenter, Rupal I Mehta, Marc W Haut, Manish Ranjan, Umer Najib, Paul Lockman, Peng Wang, Pierre-François D'haese, Ali R Rezai

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Radiology, 2021. 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 54 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 3 pooled it
9.9field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT03671889 narecruitingnot on this map

Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable Alzheimer's Disease

TypeinterventionalSponsorInSightecRan2018 to 2030Enrolled50ConditionsAlzheimer DiseaseArmsBlood Brain Barrier (BBB) Disruption
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 118 citations in OpenAlex.

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  17. sMagma (New York, N.Y.) · 2024
    Article
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  20. Remotely controlled drug release in deep brain regions of non-human primates.Journal of controlled release : official journal of the Controlled Release Society · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Rashi I MehtaFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0002-2532-7435
Jeffrey S CarpenterFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0001-6966-7987
Rupal I MehtaFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0003-4917-6907
Marc W HautFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0003-0235-362X
Manish RanjanFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0002-7780-0378
Umer NajibFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0002-1116-9229
Paul LockmanFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0002-6995-9944
Peng WangFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).
Pierre-François D'haeseFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).ORCID 0000-0003-2027-3009
Ali R RezaiFrom the Departments of Neuroradiology (Rashi I. Mehta, J.S.C., P.W., P.F.D.), Radiology (Rashi I. Mehta, J.S.C.), and Neuroscience (Rashi I. Mehta, J.S.C., M.W.H., P.L., A.R.R.); Rockefeller Neuroscience Institute (Rashi I. Mehta, J.S.C., M.W.H., M.R., U.N., P.L., P.W., P.F.D., A.R.R.); and Departments of Behavioral Medicine and Psychiatry (M.W.H.), Neurosurgery (M.W.H., M.R., A.R.R.), Neurology (M.W.H., U.N.), and Pharmaceutical Sciences (P.L.), West Virginia University, 1 Medical Center Dr, Morgantown, WV 26505; Center for Translational Neuromedicine, University of Rochester, Rochester, NY (Rupal I. Mehta); and Alzheimer's Disease Center and Department of Pathology, Rush University Medical Center, Chicago, Ill (Rupal I. Mehta).
West Virginia University · USNeuroscience Institute · IT

Funding

West Virginia IDEA-CTRU54GM104942 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Laura F. Gibson · 2012 to 2026
$81.0M
WVU Flow Cytometry and Single Cell Core Facility (FCSCCF)P20GM121322 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Sharan Kumar Reddy Bobbala · 2018 to 2026
$22.4M
Alpha-Endosulfine in Post-Ischemic Neuronal ApoptosisK08NS089830 · NINDS · UNIVERSITY OF ROCHESTER · PI MEHTA, RUPAL I. · 2014 to 2018
$771k
NIGMS NIH HHS P20 GM121322NIGMS NIH HHS U54 GM104942NINDS NIH HHS K08 NS089830
6 · The paper itself

Abstract

Background Opening of the blood-brain barrier (BBB) induced with MRI-guided focused ultrasound has been shown in experimental animal models to reduce amyloid-β plaque burden, improve memory performance, and facilitate delivery of therapeutic agents to the brain. However, physiologic effects of this procedure in humans with Alzheimer disease (AD) require further investigation. Purpose To assess imaging effects of focused ultrasound-induced BBB opening in the hippocampus of human participants with early AD and to evaluate fluid flow patterns after BBB opening by using serial contrast-enhanced MRI. Materials and Methods Study participants with early AD recruited to a Health Insurance Portability and Accountability Act-compliant, prospective, ongoing phase II clinical trial (ClinicalTrials.gov identifier, NCT03671889) underwent three separate focused ultrasound-induced BBB opening procedures that used a 220-kHz transducer with a concomitant intravenous microbubble contrast agent administered at 2-week intervals targeting the hippocampus and entorhinal cortex between October 2018 and May 2019. Posttreatment effects and gadolinium-based contrast agent enhancement patterns were evaluated by using 3.0-T MRI. Results Three women (aged 61, 72, and 73 years) consecutively enrolled in the trial successfully completed repeated focused ultrasound-induced BBB opening of the hippocampus and entorhinal cortex. Postprocedure contrast enhancement was clearly identified within the targeted brain volumes, indicating immediate spatially precise BBB opening. Parenchymal enhancement resolved within 24 hours after all treatments, confirming BBB closure. Transient perivenous enhancement was consistently observed during the acute phase after BBB opening. Notably, contrast enhancement reappeared in the perivenular regions after BBB closure. This imaging marker is consistent with blood-meningeal barrier permeability and persisted for 24-48 hours before spontaneous resolution. No evidence of intracranial hemorrhage or other adverse effect was identified. Conclusion MRI-guided focused ultrasound-induced blood-brain barrier opening was safely performed in the hippocampi of three participants with Alzheimer disease without any adverse effects. Posttreatment MRI reveals a unique spatiotemporal contrast enhancement pattern that suggests a perivenular immunologic healing response downstream from targeted sites. © RSNA, 2021

Indexed as

AgedAlzheimer DiseaseBlood-Brain BarrierContrast MediaDrug Delivery SystemsEntorhinal CortexFemaleHippocampusHumansMagnetic Resonance Imaging, InterventionalMiddle AgedProspective StudiesUltrasonic TherapyContrast Media

Identifiers

PMID33399511
PMCPMC7924515
OpenAlexW3120769833

What OpenQuestion holds

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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.