title: Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) PET as a biomarker to discriminate patients from controls.
  
  
  METHODS
  A total of 195 patients with ALS and 40 controls underwent brain (18)F-FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS were also investigated. Twenty-five bilateral cortical and subcortical volumes of interest and cerebellum were taken into account, and (18)F-FDG uptakes were individually normalized by whole-brain values. Group analyses investigated the ALS-related metabolic changes. Discriminant analysis investigating sensitivity and specificity was performed using the 51 volumes of interest as well as age and sex. Metabolic connectivity was explored by voxel-wise interregional correlation analysis.
  
  
  RESULTS
  Hypometabolism was found in frontal, motor, and occipital cortex and hypermetabolism in midbrain, temporal pole, and hippocampus in patients with ALS compared to controls. A similar metabolic pattern was also found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a specificity of 83% in separating patients from controls. Connectivity analysis found a highly significant positive correlation between midbrain and white matter in corticospinal tracts in patients with ALS.
  
  
  CONCLUSIONS
  (18)F-FDG distribution changes in ALS showed a clear pattern of hypometabolism in frontal and occipital cortex and hypermetabolism in midbrain. The latter might be interpreted as the neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis resulted in high sensitivity and specificity in differentiating patients with ALS from controls. Once validated by diseased-control studies, the present methodology might represent a potentially useful biomarker for ALS diagnosis.
  
  
  METHODS
  This study provides Class III evidence that (18)F-FDG-PET accurately distinguishes patients with ALS from normal controls (sensitivity 95.4%, specificity 82.5%).
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy. marco.pagani@istc.cnr.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Pagani
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Maria Consuelo
authors.initials: MC
authors.lastname: Valentini
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Johanna
authors.initials: J
authors.lastname: Öberg
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bertuzzo
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Carli
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Fania
authors.affiliation: From the Institute of Cognitive Sciences and Technologies (M.P., A. Cistaro), CNR, Rome, Italy; Departments of Nuclear Medicine (M.P.) and Hospital Physics (J.O.), Karolinska Hospital, Stockholm, Sweden; ALS Center (A. Chiò, A. Calvo, C.M., D.B.), "Rita Levi Montalcini" Department of Neuroscience, University of Turin, Italy; Neuroscience Institute of Turin (A. Chiò), Italy; Department of Neuroradiology (M.C.V.), CTO Hospital, Turin, Italy; Clinical Neurology Unit (F.N.), Department of Neurosciences, Ophthalmology and Genetics (DINOGMI) and Department of Health Sciences (S.M.), Nuclear Medicine Unit, Department of Internal Medicine, University of Genoa, Italy; Institute of Molecular Bioimaging and Physiology (F.D.), CNR Genoa Unit, Italy; and Positron Emission Tomography Center IRMET S.p.A. (P.F., A. Cistaro), Euromedic Inc., Turin, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Cistaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging*; D016022:Case-Control Studies; D016002:Discriminant Analysis; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18