title: Automated neuromelanin imaging as a diagnostic biomarker for Parkinson's disease.
abstract: BACKGROUND
  We aimed to analyze the diagnostic accuracy of an automated segmentation and quantification method of the SNc and locus coeruleus (LC) volumes based on neuromelanin (NM)-sensitive MRI (NM-MRI) in patients with idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD).
  
  
  METHODS
  Thirty-six patients (23 idiopathic and 13 monogenic PARKIN or LRRK2 mutations) and 37 age-matched healthy controls underwent 3T-NM-MRI. SNc and LC volumetry were performed using fully automated multi-image atlas segmentation. The diagnostic performance to differentiate PD from controls was measured using the area under the curve (AUC) and likelihood ratios based on receiver operating characteristic (ROC) analyses.
  
  
  RESULTS
  We found a significant reduction of SNc and LC volumes in patients, when compared to controls. ROC analysis showed better diagnostic accuracy when using SNc volume than LC volume. Significant differences between ipsilateral and contralateral SNc volumes, in relation to the more clinically affected side, were found in patients with iPD (P = 0.007). Contralateral atrophy in the SNc showed the highest power to discriminate PD subjects from controls (AUC, 0.93-0.94; sensitivity, 91%-92%; specificity, 89%; positive likelihood ratio: 8.4-8.5; negative likelihood ratio: 0.09-0.1 at a single cut-off point). Interval likelihood ratios for contralateral SNc volume improved the diagnostic accuracy of volumetric measurements.
  
  
  CONCLUSIONS
  SNc and LC volumetry based on NM-MRI resulting from the automated segmentation and quantification technique can yield high diagnostic accuracy for differentiating PD from health and might be an unbiased disease biomarker. © 2015 International Parkinson and Movement Disorder Society.
authors.affiliation: Neuroimaging Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Castellanos
authors.affiliation: Neuroimaging Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Fernández-Seara
authors.affiliation: Neurogenetics Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Lorenzo-Betancor
authors.affiliation: Neurogenetics Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Ortega-Cubero
authors.affiliation: Pulmonary Department, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Puigvert
authors.affiliation: Cancer Imaging Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Uranga
authors.affiliation: Neuroimaging Laboratory, University of Navarra, Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vidorreta
authors.affiliation: Neuroimaging Laboratory, University of Navarra, Pamplona, Spain.|Neurogenetics Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: Jaione
authors.initials: J
authors.lastname: Irigoyen
authors.affiliation: Neurogenetics Laboratory, University of Navarra, Pamplona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Lorenzo
authors.affiliation: Cancer Imaging Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|Bioengineering and Aerospace Engineering Department, University Carlos III of Madrid and Gregorio Marañon Health Research Institute, Madrid, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Muñoz-Barrutia
authors.affiliation: Cancer Imaging Laboratory, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortiz-de-Solorzano
authors.affiliation: Neurogenetics Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain.|Department of Neurology, Hospital Universitari Mutua de Terrassa, University of Barcelona, Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.affiliation: Neuroimaging Laboratory, University of Navarra, Pamplona, Spain.|CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.|Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Pastor
mesh_terms: D000368:Aged; D015415:Biomarkers; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D008297:Male; D008543:Melanins; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D015415:Biomarkers; D008543:Melanins; C014121:neuromelanin
keywords: Parkinson's; diagnosis; magnetic resonance imaging; neuromelanin; substantia nigra