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Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson’s disease: A diagnostic performance study and meta-analysis

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Abstract

Objectives

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.

Key Points

• 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.

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Acknowledgments

The authors thank the Brazil Parkinson-Association for helping to contact volunteers during the recruitment phase; Adelinda da Silva Arruda Gonçalves, Karina Fernandes Dias Correa e Alda Fernandes Castro for administrative support; and Dr. Marcelo Buarque Gusmão Funari, Head of the Radiology Department of the Hospital Israelita Albert Einstein for supporting this study. We also thank the R-Community for providing and maintaining a free software environment for statistical computing and graphics and full financial support from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo).

The scientific guarantor of this publication is Ellison Fernando Cardoso. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. This study has received support from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) - Grant number: 2011/18747. Three of the authors have significant statistical expertise (João Ricardo Sato, Gilson Vieira and Ellison Fernando Cardoso). Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects in this study. Methodology: prospective, diagnostic study, multicentre study.

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Authors and Affiliations

  1. LIM-44, Department of Radiology, University of São Paulo, Rua Oscar Freire, 1967, Apto. 43A, Cerqueira César, São Paulo, SP, Brazil

    Fabiana C. C. Hirata, João R. Sato, Gilson Vieira, Leandro T. Lucato, Claudia C. Leite, Bruno F. Pastorello, Maria C. G. Otaduy, Khallil T. Chaim, Kenia R. Campanholo, Felipe Barjud Pereira do Nascimento, Edson Amaro Jr & Ellison Fernando Cardoso

  2. Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil

    João R. Sato

  3. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Edson Bor-Seng-Shu, Natalia P. Novaes, Felipe Barjud Pereira do Nascimento, Edson Amaro Jr & Ellison Fernando Cardoso

  4. Department of Neurology, University of São Paulo, São Paulo, Brazil

    Edson Bor-Seng-Shu, Natalia P. Novaes, Luciano Magalhães Melo, Márcia R. Gonçalves & Egberto Reis Barbosa

  5. Department of Neurosurgery, University of São Paulo, São Paulo, Brazil

    Manoel Jacobsen Teixeira

  6. Institute of Mathematics and Statistics University of São Paulo (IME-USP), São Paulo, Brazil

    Ellison Fernando Cardoso

Authors
  1. Fabiana C. C. Hirata
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  8. Maria C. G. Otaduy
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  9. Khallil T. Chaim
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  10. Kenia R. Campanholo
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  12. Luciano Magalhães Melo
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  13. Márcia R. Gonçalves
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  15. Manoel Jacobsen Teixeira
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  17. Edson Amaro Jr
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  18. Ellison Fernando Cardoso
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Correspondence to Ellison Fernando Cardoso.

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Hirata, F.C.C., Sato, J.R., Vieira, G. et al. Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson’s disease: A diagnostic performance study and meta-analysis. Eur Radiol 27, 2640–2648 (2017). https://doi.org/10.1007/s00330-016-4611-0

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