Evidence map›Paper›PMID 27799546›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

In vivo nanoparticle imaging of innate immune cells can serve as a marker of disease severity in a model of multiple sclerosis.

Klara Kirschbaum, Jana K Sonner, Matthias W Zeller, Katrin Deumelandt, Julia Bode, Rakesh Sharma, Thomas Krüwel, Manuel Fischer, Angelika Hoffmann, Milene Costa da Silva and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
9.6field-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.

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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  7. Article
  8. Article
  9. Metal-based nanoparticle in cancer treatment: lessons learned and challenges.Frontiers in bioengineering and biotechnology · 2024
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  14. A pH-responsive TNature communications · 2022
    Article
  15. Article
  16. Nanotherapeutics and the Brain.Annual review of chemical and biomolecular engineering · 2022
    Review
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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

18 authors at 7 institutions in 3 countries.

Klara KirschbaumGerman Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Jana K SonnerGerman Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Matthias W ZellerCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115.
Katrin DeumelandtGerman Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Julia BodeSchaller Research Group, University of Heidelberg and DKFZ, 69120 Heidelberg, Germany.
Rakesh SharmaSchaller Research Group, University of Heidelberg and DKFZ, 69120 Heidelberg, Germany.
Thomas KrüwelSchaller Research Group, University of Heidelberg and DKFZ, 69120 Heidelberg, Germany.
Manuel FischerDepartment of Neuroradiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Angelika HoffmannDepartment of Neuroradiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Milene Costa da SilvaDepartment of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Martina U MuckenthalerDepartment of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Wolfgang WickDepartment of Neurology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany.
Björn TewsSchaller Research Group, University of Heidelberg and DKFZ, 69120 Heidelberg, Germany.
John W ChenCenter for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115.
Sabine HeilandDepartment of Neuroradiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Martin BendszusDepartment of Neuroradiology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Michael PlattenGerman Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Michael O BreckwoldtGerman Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; michael.breckwoldt@med.uni-heidelberg.de.
Heidelberg University · DEUniversity Hospital Heidelberg · DEGerman Cancer Research Center · DEHarvard University · USMassachusetts General Hospital · USNational Center for Tumor Diseases · DEUniversidade do Porto · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Innate immune cells play a key role in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Current clinical imaging is restricted to visualizing secondary effects of inflammation, such as gliosis and blood-brain barrier disruption. Advanced molecular imaging, such as iron oxide nanoparticle imaging, can allow direct imaging of cellular and molecular activity, but the exact cell types that phagocytose nanoparticles in vivo and how phagocytic activity relates to disease severity is not well understood. In this study we used MRI to map inflammatory infiltrates using high-field MRI and fluorescently labeled cross-linked iron oxide nanoparticles for cell tracking. We confirmed nanoparticle uptake and MR detectability ex vivo. Using in vivo MRI, we identified extensive nanoparticle signal in the cerebellar white matter and circumscribed cortical gray matter lesions that developed during the disease course (4.6-fold increase of nanoparticle accumulation in EAE compared with healthy controls, P < 0.001). Nanoparticles showed good cellular specificity for innate immune cells in vivo, labeling activated microglia, infiltrating macrophages, and neutrophils, whereas there was only sparse uptake by adaptive immune cells. Importantly, nanoparticle signal correlated better with clinical disease than conventional gadolinium (Gd) imaging (r, 0.83 for nanoparticles vs. 0.71 for Gd-imaging, P < 0.001). We validated our approach using the Food and Drug Administration-approved iron oxide nanoparticle ferumoxytol. Our results show that noninvasive molecular imaging of innate immune responses can serve as an imaging biomarker of disease activity in autoimmune-mediated neuroinflammation with potential clinical applications in a wide range of inflammatory diseases.

Indexed as

AnimalsBrainEncephalomyelitis, Autoimmune, ExperimentalFemaleImmunity, InnateMacrophagesMagnetic Resonance ImagingMagnetite NanoparticlesMiceMicrogliaMultiple SclerosisPhagocytosisSeverity of Illness IndexMagnetite NanoparticlesEAEMRImultiple sclerosisnanoparticle imagingUSPIO

Identifiers

PMID27799546
PMCPMC5135308
OpenAlexW2540248011

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.