Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy 1H-MRS in amyotrophic lateral sclerosis

Eva-Maria Ratai; Mohamad J. Alshikho; Nicole R. Zürcher; Marco L. Loggia; Catherine L. Cebulla; Paul Cernasov; Beverly Reynolds; Jennifer Fish; Raghav Seth; Suma Babu; Sabrina Paganoni; Jacob M. Hooker; Nazem Atassi

NeuroImage: Clinical (Jan 2018)

Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance spectroscopy 1H-MRS in amyotrophic lateral sclerosis

Eva-Maria Ratai,
Mohamad J. Alshikho,
Nicole R. Zürcher,
Marco L. Loggia,
Catherine L. Cebulla,
Paul Cernasov,
Beverly Reynolds,
Jennifer Fish,
Raghav Seth,
Suma Babu,
Sabrina Paganoni,
Jacob M. Hooker,
Nazem Atassi

Affiliations

Eva-Maria Ratai: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Radiology, Neuroradiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Mohamad J. Alshikho: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Nicole R. Zürcher: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Marco L. Loggia: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Catherine L. Cebulla: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Paul Cernasov: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Beverly Reynolds: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Jennifer Fish: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Raghav Seth: A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
Suma Babu: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Sabrina Paganoni: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 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: Neurological Clinical Research Institute (NCRI), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 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. 20
pp. 357 – 364

Abstract

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Objective: To determine the relationship between brain tissue metabolites measured by in vivo magnetic resonance spectroscopy (1H-MRS), and glial activation assessed with [11C]-PBR28 uptake in people with amyotrophic lateral sclerosis (ALS). Methods: Forty ALS participants were evaluated clinically using the revised ALS functional rating scale (ALSFRS-R) and upper motor neuron burden (UMNB). All participants underwent simultaneous brain [11C]-PBR28 PET and MR imaging including diffusion tensor imaging to acquire fractional anisotropy (FA). [11C]-PBR28 uptake was measured as standardized uptake values normalized by whole brain mean (SUVR). 1H-MRS metabolite ratios (myo-inositol/creatine, mI/Cr; N-acetylaspartate/creatine, NAA/Cr) were measured within the precentral gyri and brain stem (regions known to be involved in ALS pathophysiology), and precuneus (which served as a control region). Whole brain voxel-wise correlation analyses were employed to identify brain regions exhibiting an association between metabolites within the VOIs and [11C]-PBR28 uptake. Results: In the precentral gyri, [11C]-PBR28 uptake correlated positively with mI/Cr and negatively with NAA/Cr. The same correlations were not statistically significant in the brain stem, or in the control precuneus region. Whole brain voxel-wise correlation analyses between the estimated brain metabolites within the VOIs and SUVR were highly correlated in the precentral gyri. Decreased FA values in the precentral gyri were correlated with reduced NAA/Cr and elevated mI/Cr. Higher UMNB was correlated with increased [11C]-PBR28 uptake and mI/Cr, and decreased NAA/Cr. ALSFRS-R total score correlated positively with NAA/Cr and negatively with mI/Cr. Conclusion: Integrated PET-MR and 1H-MRS imaging demonstrates associations between markers for neuronal integrity and neuroinflammation and may provide valuable insights into disease mechanisms in ALS. Keywords: 1H-MRS, PET, Glial activation, Amyotrophic lateral sclerosis, [11C]-PBR28, DTI

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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