title: Metabolic spatial connectivity in amyotrophic lateral sclerosis as revealed by independent component analysis.
abstract: OBJECTIVE
  Positron emission tomography (PET) and volume of interest (VOI) analysis have recently shown in amyotrophic lateral sclerosis (ALS) an accuracy of 93% in differentiating patients from controls. The aim of this study was to disclose by spatial independent component analysis (ICA) the brain networks involved in ALS pathological processes and evaluate their discriminative value in separating patients from controls.
  
  
  METHODS
  Two hundred fifty-nine ALS patients and 40 age- and sex-matched control subjects underwent brain 18F-2-fluoro-2-deoxy-D-glucose PET (FDG-PET). Spatial ICA of the preprocessed FDG-PET images was performed. Intensity values were converted to z-scores and binary masks were used as data-driven VOIs. The accuracy of this classifier was tested versus a validated system processing intensity signals in 27 brain meta-VOIs. A support vector machine was independently applied to both datasets and the 'leave-one-out' technique verified the general validity of results.
  
  
  RESULTS
  The 8 components selected as pathophysiologically meaningful discriminated patients from controls with 99.0% accuracy, the discriminating value of bilateral cerebellum/midbrain alone representing 96.3%. Among the meta-VOIs, right temporal lobe alone reached an accuracy of 93.7%.
  
  
  CONCLUSIONS
  Spatial ICA identified in a very large cohort of ALS patients distinct spatial networks showing a high discriminatory value, improving substantially on the previously obtained accuracy. The cerebellar/midbrain component accounted for the highest accuracy in separating ALS patients from controls. Spatial ICA and multivariate analysis perform better than univariate semi-quantification methods in identifying the neurodegenerative features of ALS and pave the way for inclusion of PET in clinical trials and early diagnosis.
authors.affiliation: Institute of Cognitive Sciences and Technologies, C.N.R, Rome, Italy.|Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Pagani
authors.affiliation: Department of Hospital Physics, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Öberg
authors.affiliation: Institute of Molecular Bioimaging and Physiology - C.N.R. - Genoa Unit, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Carli
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience University of Turin, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience University of Turin, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.affiliation: Clinical Neurology Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Mother-Child Health (DINOGMI) University of Genoa, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: Department of Health Sciences, Nuclear Medicine Unit, University of Genoa, Genoa, Italy.|Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: Positron Emission Tomography Centre IRMET S.P.A, Euromedic Inc, Turin, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Fania
authors.affiliation: Positron Emission Tomography Centre IRMET S.P.A, Euromedic Inc, Turin, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Cistaro
authors.affiliation: ALS Center, 'Rita Levi Montalcini' Department of Neuroscience University of Turin, Turin, Italy.|CNR, Associate Researcher at Institute of Cognitive Sciences and Technologies, C.N.R, Rome, Italy.|Neuroscience Institute of Turin, Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D015331:Cohort Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D049268:Positron-Emission Tomography / Q000379:methods; D012372:ROC Curve; D019275:Radiopharmaceuticals; D012146:Rest; D055815:Young Adult
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: amyotrophic lateral sclerosis; discriminant analysis; independent component analysis; meta-volumes of interest; positron emission tomography