Imaging of glia activation in people with primary lateral sclerosis

Sabrina Paganoni; Mohamad J. Alshikho; Nicole R. Zürcher; Paul Cernasov; Suma Babu; Marco L. Loggia; James Chan; Daniel B. Chonde; David Izquierdo Garcia; Ciprian Catana; Caterina Mainero; Bruce R. Rosen; Merit E. Cudkowicz; Jacob M. Hooker; Nazem Atassi

NeuroImage: Clinical (Jan 2018)

Imaging of glia activation in people with primary lateral sclerosis

Sabrina Paganoni,
Mohamad J. Alshikho,
Nicole R. Zürcher,
Paul Cernasov,
Suma Babu,
Marco L. Loggia,
James Chan,
Daniel B. Chonde,
David Izquierdo Garcia,
Ciprian Catana,
Caterina Mainero,
Bruce R. Rosen,
Merit E. Cudkowicz,
Jacob M. Hooker,
Nazem Atassi

Affiliations

Sabrina Paganoni: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA, USA
Mohamad J. Alshikho: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA; A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Nicole R. Zürcher: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Paul Cernasov: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA
Suma Babu: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA
Marco L. Loggia: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
James Chan: Biostatistics Center, Massachusetts General Hospital, Boston, MA, USA
Daniel B. Chonde: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
David Izquierdo Garcia: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Ciprian Catana: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Caterina Mainero: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Bruce R. Rosen: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Merit E. Cudkowicz: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA
Jacob M. Hooker: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Nazem Atassi: Harvard Medical School, Department of Neurology, Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA; Corresponding author at: Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, 165 Cambridge Street, Suite 656, Boston, 02114, MA, USA.

Journal volume & issue: Vol. 17
pp. 347 – 353

Abstract

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Background: Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives: To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods: Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [11C]-PBR28 was used to obtain PET-based measures of 18kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity. Results: PET data showed increased [11C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy. Conclusions: This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [11C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS. Keywords: Diffusion, PET, TSPO, Primary lateral sclerosis, Amyotrophic lateral sclerosis, [11C]-PBR28

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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