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April 23, 2019; 92 (17) Article

Imaging of neuroinflammation in migraine with aura

A [11C]PBR28 PET/MRI study

Daniel S. Albrecht, Caterina Mainero, Eri Ichijo, Noreen Ward, Cristina Granziera, Nicole R. Zürcher, Oluwaseun Akeju, Guillaume Bonnier, Julie Price, Jacob M. Hooker, Vitaly Napadow, Marco L. Loggia, View ORCID ProfileNouchine Hadjikhani
First published March 27, 2019, DOI: https://doi.org/10.1212/WNL.0000000000007371
Daniel S. Albrecht
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Caterina Mainero
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Eri Ichijo
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Noreen Ward
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Cristina Granziera
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Nicole R. Zürcher
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Oluwaseun Akeju
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Guillaume Bonnier
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Julie Price
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Jacob M. Hooker
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Vitaly Napadow
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Marco L. Loggia
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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Nouchine Hadjikhani
From the A.A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown.
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  • ORCID record for Nouchine Hadjikhani
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Imaging of neuroinflammation in migraine with aura
A [11C]PBR28 PET/MRI study
Daniel S. Albrecht, Caterina Mainero, Eri Ichijo, Noreen Ward, Cristina Granziera, Nicole R. Zürcher, Oluwaseun Akeju, Guillaume Bonnier, Julie Price, Jacob M. Hooker, Vitaly Napadow, Marco L. Loggia, Nouchine Hadjikhani
Neurology Apr 2019, 92 (17) e2038-e2050; DOI: 10.1212/WNL.0000000000007371

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Abstract

Objective To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions.

Methods Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [11C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups, and regressed against clinical variables, using region of interest and whole-brain voxelwise analyses.

Results Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas (e.g., thalamus and primary/secondary somatosensory and insular cortices) as well as in areas previously shown to be involved in CSD generation (visual cortex). SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks.

Conclusions These findings demonstrate that migraine with aura is associated with neuroimmune activation/neuroinflammation, and support a possible link between CSD and glial activation, previously observed in animals.

Glossary

ACC=
anterior cingulate cortex;
CSD=
cortical spreading depression;
IHS=
International Headache Society;
MNI=
Montreal Neurological Institute;
MPRAGE=
magnetization-prepared rapid gradient echo;
NSAID=
nonsteroidal anti-inflammatory drug;
ROI=
region of interest;
SUV=
standardized uptake value;
SUVR=
standardized uptake value ratio;
TSPO=
translocator protein

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally to this work as co–senior authors.

  • Received July 2, 2018.
  • Accepted in final form January 7, 2019.
  • © 2019 American Academy of Neurology
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Letters: Rapid online correspondence

  • Reader response: Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study
    • Vinod K. Gupta, Physician, Migraine-Headache Institute, Gupta Medical Centre (New Delhi, India)
    Submitted April 28, 2019
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