Evidence map›Paper›PMID 31345243›Full record

ArticleJournal of neuroinflammation2019

In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound: [18F]DPA-714 PET study.

Sanhita Sinharay, Tsang-Wei Tu, Zsofia I Kovacs, William Schreiber-Stainthorp, Maggie Sundby, Xiang Zhang, Georgios Z Papadakis, William C Reid, Joseph A Frank, Dima A Hammoud

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

39 citing papers in PubMed, 59 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

10 authors at 6 institutions in 3 countries.

Sanhita SinharayHammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA.
Tsang-Wei TuFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Zsofia I KovacsFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
William Schreiber-StainthorpHammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA.
Maggie SundbyFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Xiang ZhangImaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, USA.
Georgios Z PapadakisHammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA.
William C ReidHammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA.
Joseph A FrankFrank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Dima A HammoudHammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA. hammoudd@cc.nih.gov.ORCID http://orcid.org/0000-0001-7406-7871
National Institutes of Health · USNational Institutes of Health Clinical Center · USHoward University · USInstitute for Biomedical Engineering · CHThe University of Texas MD Anderson Cancer Center · USUniversity of Crete · GR

Funding

Research_ProjectU54HD090257 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI GUAY-WOODFORD, LISA MARIE · 2016 to 2020
$5.9M
Preclinical high intensity focused ultrasound: mechanisms and applicationsZIACL040014 · CLC · CLINICAL CENTER · PI FRANK, JOSEPH · 2009 to 2025
$0k
Center for Neuroscience and Regenerative Medicine CNRM-89-3899NIBIB NIH HHS Intramural programNICHD NIH HHS U54 HD090257NIH Clinical Center intramural program
6 · The paper itself

Abstract

backgroundMagnetic resonance imaging (MRI)-guided pulsed focused ultrasound combined with the infusion of microbubbles (pFUS+MB) induces transient blood-brain barrier opening (BBBO) in targeted regions. pFUS+MB, through the facilitation of neurotherapeutics' delivery, has been advocated as an adjuvant treatment for neurodegenerative diseases and malignancies. Sterile neuroinflammation has been recently described following pFUS+MB BBBO. In this study, we used PET imaging with [18F]-DPA714, a biomarker of translocator protein (TSPO), to assess for neuroinflammatory changes following single and multiple pFUS+MB sessions.

methodsThree groups of Sprague-Dawley female rats received MRI-guided pFUS+MB (Optison™; 5-8 × 10

resultsIn all groups, [18F]DPA-714 binding was increased at the sonicated compared to non-sonicated brain (%ID/cc ratios > 1). Immunohistopathology showed increased staining for microglial and astrocytic markers in the sonicated frontal cortex compared to contralateral brain and to a lesser extent in the sonicated hippocampus. Using MRI, we documented BBB disruption immediately after sonication with resolution of BBBO 24 h later. We found more T2* hypointense voxels with increasing number of sonications. In a longitudinal group of animals imaged after two and after six sonications, there was no cumulative increase of neuroinflammation on PET.

conclusionUsing [18F]DPA-714 PET, we documented in vivo neuroinflammatory changes in association with pFUS+MB. Our protocol (utilizing PCD feedback to minimize damage) resulted in neuroinflammation visualized 24 h post one sonication. Our findings were supported by immunohistochemistry showing microglial activation and astrocytosis. Experimental sonication parameters intended for BBB disruption should be evaluated for neuroinflammatory sequelae prior to implementation in clinical trials.

Indexed as

AnimalsAstrocytesBlood-Brain BarrierBrainFemaleMagnetic Resonance ImagingMicrogliaPositron Emission Tomography Computed TomographyRatsRats, Sprague-DawleySonication[18F]DPA-714 PETMagnetic resonance imagingNeuroinflammationPulsed focused ultrasoundTranslocator protein

Identifiers

PMID31345243
PMCPMC6657093
OpenAlexW2962775812

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.