title: Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.
abstract: OBJECTIVE
  Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy.
  
  
  METHODS
  Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures.
  
  
  RESULTS
  In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2= 91.9 %).
  
  
  CONCLUSIONS
  SN-FA cannot be used as an isolated measure to diagnose PD.
  
  
  CONCLUSIONS
  • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Fabiana C C
authors.initials: FCC
authors.lastname: Hirata
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.|Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil.
authors.forename: João R
authors.initials: JR
authors.lastname: Sato
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Gilson
authors.initials: G
authors.lastname: Vieira
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Leandro T
authors.initials: LT
authors.lastname: Lucato
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Leite
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, Brazil.|Department of Neurology, University of São Paulo, São Paulo, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Bor-Seng-Shu
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Bruno F
authors.initials: BF
authors.lastname: Pastorello
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Maria C G
authors.initials: MCG
authors.lastname: Otaduy
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Khallil T
authors.initials: KT
authors.lastname: Chaim
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.
authors.forename: Kenia R
authors.initials: KR
authors.lastname: Campanholo
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, Brazil.|Department of Neurology, University of São Paulo, São Paulo, Brazil.
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Novaes
authors.affiliation: Department of Neurology, University of São Paulo, São Paulo, Brazil.
authors.forename: Luciano Magalhães
authors.initials: LM
authors.lastname: Melo
authors.affiliation: Department of Neurology, University of São Paulo, São Paulo, Brazil.
authors.forename: Márcia R
authors.initials: MR
authors.lastname: Gonçalves
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.|Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Felipe Barjud Pereira
authors.initials: FBP
authors.lastname: do Nascimento
authors.affiliation: Department of Neurosurgery, University of São Paulo, São Paulo, Brazil.
authors.forename: Manoel Jacobsen
authors.initials: MJ
authors.lastname: Teixeira
authors.affiliation: Department of Neurology, University of São Paulo, São Paulo, Brazil.
authors.forename: Egberto Reis
authors.initials: ER
authors.lastname: Barbosa
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil.|Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Amaro
authors.affiliation: LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil. lim@usp.br.|Hospital Israelita Albert Einstein, São Paulo, Brazil. lim@usp.br.|Institute of Mathematics and Statistics University of São Paulo (IME-USP), São Paulo, Brazil. lim@usp.br.
authors.forename: Ellison Fernando
authors.initials: EF
authors.lastname: Cardoso
mesh_terms: D000368:Aged; D016880:Anisotropy; D015415:Biomarkers; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards; D008297:Male; D010300:Parkinson Disease / Q000473:pathology*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D015415:Biomarkers
keywords: Diffusion-weighted imaging (DWI); Essential tremor; Magnetic resonance imaging (MRI); Parkinson’s disease/Parkinsonism; Sensitivity and specificity