Evidence map›Paper›PMID 36076213›Full record

ArticleFluids and barriers of the CNS2022

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model.

Tasneem A Arsiwala, Samuel A Sprowls, Kathryn E Blethen, Ross A Fladeland, Cullen P Wolford, Brooke N Kielkowski, Morgan J Glass, Peng Wang, Olivia Wilson, Jeffrey S Carpenter and 4 more

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 14% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 25 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Tasneem A ArsiwalaDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Samuel A SprowlsDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Kathryn E BlethenDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Ross A FladelandDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Cullen P WolfordDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Brooke N KielkowskiDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Morgan J GlassDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA.
Peng WangRockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Olivia WilsonRockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Jeffrey S CarpenterRockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Manish RanjanRockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Victor FinomoreDepartments of Neuroscience, Neuroradiology, and Neurosurgery, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Ali RezaiRockefeller Neuroscience Institute, West Virginia University, 1 Medical Center Dr, Morgantown, WV, 26505, USA.
Paul R LockmanDepartment of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, HSC, Morgantown, 1 Medical Center Dr, Morgantown, WV, 26506, USA. prlockman@hsc.wvu.edu.
West Virginia University · USBlanchette Rockefeller Neurosciences Institute · USCleveland Clinic Lerner College of Medicine · US

Funding

WV INBRE: The Inhibitor of Growth Family Member 4 (ING4) inhibits L-Type Amino Acid Transporter 1 (LAT1) expression to suppress Breast CancerP20GM103434 · NIGMS · MARSHALL UNIVERSITY · PI Stanley M. Hileman · 2012 to 2026
$61.1M
WVU Flow Cytometry and Single Cell Core Facility (FCSCCF)P20GM121322 · NIGMS · WEST VIRGINIA UNIVERSITY · PI Dominique Bollino · 2018 to 2026
$22.4M
Sex Differences in Blood-Brain and Blood-Tumor Barrier Dynamics in GlioblastomaK00CA253768 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SPROWLS, SAMUEL ADAM TYLER · 2022 to 2024
$281k
Translational use of focused ultrasound to increase blood-tumor barrier permeability as a mechanism to increase drug accumulation into brain metastases of breast cancerF99CA264445 · NCI · WEST VIRGINIA UNIVERSITY · PI ARSIWALA, TASNEEM · 2021 to 2022
$85k
NCI NIH HHS 1F99CA264445-01NCI NIH HHS 4K00CA253768-03NCI NIH HHS F99 CA264445NCI NIH HHS K00 CA253768NIGMS NIH HHS P20 GM103434NIGMS NIH HHS P20 GM121322NIGMS NIH HHS P20GM121322NIGMS NIH HHS P20GM121322-03S1
6 · The paper itself

Abstract

backgroundSystemic drug delivery to the central nervous system is limited by presence of the blood-brain barrier (BBB). Low intensity focused ultrasound (LiFUS) is a non-invasive technique to disrupt the BBB, though there is a lack of understanding of the relationship between LiFUS parameters, such as cavitation dose, time of sonication, microbubble dose, and the time course and magnitude of BBB disruption. Discrepancies in these data arise from experimentation with modified, clinically untranslatable transducers and inconsistent parameters for sonication. In this report, we characterize microbubble and cavitation doses as LiFUS variables as they pertain to the time course and size of BBB opening with a clinical Insightec FUS system.

methodsFemale Nu/Nu athymic mice were exposed to LiFUS using the ExAblate Neuro system (v7.4, Insightec, Haifa, Israel) following target verification with magnetic resonance imaging (MRI). Microbubble and cavitation doses ranged from 4-400 μL/kg, and 0.1-1.5 cavitation dose, respectively. The time course and magnitude of BBB opening was evaluated using fluorescent tracers, ranging in size from 105-10,000 Da, administered intravenously at different times pre- or post-LiFUS. Quantitative autoradiography and fluorescence microscopy were used to quantify tracer accumulation in brain.

resultsWe observed a microbubble and cavitation dose dependent increase in tracer uptake within brain after LiFUS. Tracer accumulation was size dependent, with

conclusionThe magnitude of LiFUS mediated BBB opening correlates with concentration of microbubbles, cavitation dose as well as time of tracer administration post-sonication. These data help define the window of maximal BBB opening and applicable sonication parameters on a clinically translatable and commercially available FUS system that can be used to improve passive permeability and accumulation of therapeutics targeting the brain.

Indexed as

Blood-Brain BarrierMicrobubblesAnimalsBrainDrug Delivery SystemsFemaleMagnetic Resonance ImagingMicePermeabilitySonicationBlood–Brain barrierDisruptionExAblate NeuroFocused ultrasound

Identifiers

PMID36076213
PMCPMC9461249
OpenAlexW4295084700

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.