Skip to main content
Erschienen in: European Radiology 6/2017

05.10.2016 | Neuro

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

verfasst von: Fabiana C. C. Hirata, João R. Sato, Gilson Vieira, Leandro T. Lucato, Claudia C. Leite, Edson Bor-Seng-Shu, Bruno F. Pastorello, Maria C. G. Otaduy, Khallil T. Chaim, Kenia R. Campanholo, Natalia P. Novaes, Luciano Magalhães Melo, Márcia R. Gonçalves, Felipe Barjud Pereira do Nascimento, Manoel Jacobsen Teixeira, Egberto Reis Barbosa, Edson Amaro Jr, Ellison Fernando Cardoso

Erschienen in: European Radiology | Ausgabe 6/2017

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125:861–870CrossRefPubMed Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125:861–870CrossRefPubMed
2.
Zurück zum Zitat Marquand AF, Filippone M, Ashburner J et al (2013) Automated, high accuracy classification of parkinsonian disorders: a pattern recognition approach. PLoS ONE 8:e69237CrossRefPubMedPubMedCentral Marquand AF, Filippone M, Ashburner J et al (2013) Automated, high accuracy classification of parkinsonian disorders: a pattern recognition approach. PLoS ONE 8:e69237CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Shih MC, Amaro E, Ferraz HB et al (2006) Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil. Arq Neuropsiquiatr 64:628–634CrossRefPubMed Shih MC, Amaro E, Ferraz HB et al (2006) Neuroimaging of the dopamine transporter in Parkinsons disease: first study using [99mTc]-TRODAT-1 and SPECT in Brazil. Arq Neuropsiquiatr 64:628–634CrossRefPubMed
4.
Zurück zum Zitat Vaillancourt DE, Spraker MB, Prodoehl J et al (2009) High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 72:1378–1384CrossRefPubMedPubMedCentral Vaillancourt DE, Spraker MB, Prodoehl J et al (2009) High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 72:1378–1384CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Schwarz ST, Abaei M, Gontu V, Morgan PS, Bajaj N, Auer DP (2013) Diffusion tensor imaging of nigral degeneration in Parkinson’s disease: a region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis. NeuroImage Clin 3:481–488CrossRefPubMedPubMedCentral Schwarz ST, Abaei M, Gontu V, Morgan PS, Bajaj N, Auer DP (2013) Diffusion tensor imaging of nigral degeneration in Parkinson’s disease: a region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis. NeuroImage Clin 3:481–488CrossRefPubMedPubMedCentral
6.
7.
Zurück zum Zitat Obuchowski NA, McClish DK (1997) Sample size determination for diagnostic accuracy studies involving binormal ROC curve indices. Stat Med 16:1529–1542CrossRefPubMed Obuchowski NA, McClish DK (1997) Sample size determination for diagnostic accuracy studies involving binormal ROC curve indices. Stat Med 16:1529–1542CrossRefPubMed
8.
Zurück zum Zitat Raunig DL, McShane LM, Pennello G et al (2015) Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment. Stat Methods Med Res 24:27–67CrossRefPubMed Raunig DL, McShane LM, Pennello G et al (2015) Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment. Stat Methods Med Res 24:27–67CrossRefPubMed
9.
Zurück zum Zitat Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRefPubMed Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536CrossRefPubMed
10.
Zurück zum Zitat Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58:982–990CrossRefPubMed Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58:982–990CrossRefPubMed
11.
Zurück zum Zitat Chan LL, Rumpel H, Yap K et al (2007) Case control study of diffusion tensor imaging in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:1383–1386CrossRefPubMedPubMedCentral Chan LL, Rumpel H, Yap K et al (2007) Case control study of diffusion tensor imaging in Parkinson’s disease. J Neurol Neurosurg Psychiatry 78:1383–1386CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Menke RA, Jbabdi S, Miller KL, Matthews PM, Zarei M (2010) Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson’s disease. NeuroImage 52:1175–1180CrossRefPubMed Menke RA, Jbabdi S, Miller KL, Matthews PM, Zarei M (2010) Connectivity-based segmentation of the substantia nigra in human and its implications in Parkinson’s disease. NeuroImage 52:1175–1180CrossRefPubMed
13.
Zurück zum Zitat Péran P, Cherubini A, Assogna F et al (2010) Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain 133:3423–3433CrossRefPubMed Péran P, Cherubini A, Assogna F et al (2010) Magnetic resonance imaging markers of Parkinson’s disease nigrostriatal signature. Brain 133:3423–3433CrossRefPubMed
14.
Zurück zum Zitat Rolheiser TM, Fulton HG, Good KP et al (2011) Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson’s disease. J Neurol 258:1254–1260CrossRefPubMed Rolheiser TM, Fulton HG, Good KP et al (2011) Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson’s disease. J Neurol 258:1254–1260CrossRefPubMed
15.
Zurück zum Zitat Wang JJ, Lin WY, Lu CS et al (2011) Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology 261:210–217CrossRefPubMed Wang JJ, Lin WY, Lu CS et al (2011) Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology 261:210–217CrossRefPubMed
16.
Zurück zum Zitat Zhan W, Kang GA, Glass GA et al (2012) Regional alterations of brain microstructure in Parkinson’s disease using diffusion tensor imaging. Mov Disord 27:90–97CrossRefPubMed Zhan W, Kang GA, Glass GA et al (2012) Regional alterations of brain microstructure in Parkinson’s disease using diffusion tensor imaging. Mov Disord 27:90–97CrossRefPubMed
17.
Zurück zum Zitat Prakash BD, Sitoh Y-Y, Tan LC, Au WL (2012) Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson’s disease. Parkinsonism Relat Disord 18:1029–1033CrossRefPubMed Prakash BD, Sitoh Y-Y, Tan LC, Au WL (2012) Asymmetrical diffusion tensor imaging indices of the rostral substantia nigra in Parkinson’s disease. Parkinsonism Relat Disord 18:1029–1033CrossRefPubMed
18.
Zurück zum Zitat Du G, Lewis MM, Styner M et al (2011) Combined R2* and diffusion tensor imaging changes in the substantia nigra in Parkinson’s disease. Mov Disord 26:1627–1632CrossRefPubMedPubMedCentral Du G, Lewis MM, Styner M et al (2011) Combined R2* and diffusion tensor imaging changes in the substantia nigra in Parkinson’s disease. Mov Disord 26:1627–1632CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Skorpil M, Söderlund V, Sundin A, Svenningsson P (2012) MRI diffusion in Parkinson“s disease: using the technique”s inherent directional information to study the olfactory bulb and substantia nigra. J Parkinsons Dis 2:171–180PubMed Skorpil M, Söderlund V, Sundin A, Svenningsson P (2012) MRI diffusion in Parkinson“s disease: using the technique”s inherent directional information to study the olfactory bulb and substantia nigra. J Parkinsons Dis 2:171–180PubMed
20.
Zurück zum Zitat Scherfler C, Esterhammer R, Nocker M et al (2013) Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease. Brain 136:3028–3037CrossRefPubMed Scherfler C, Esterhammer R, Nocker M et al (2013) Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson’s disease. Brain 136:3028–3037CrossRefPubMed
21.
Zurück zum Zitat Perea RD, Rada RC, Wilson J et al (2013) A comparative white matter study with Parkinson’s disease, Parkinson’s disease with dementia and Alzheimer’s disease. J Alzheimers Dis Parkinsonism 3:123PubMedPubMedCentral Perea RD, Rada RC, Wilson J et al (2013) A comparative white matter study with Parkinson’s disease, Parkinson’s disease with dementia and Alzheimer’s disease. J Alzheimers Dis Parkinsonism 3:123PubMedPubMedCentral
22.
Zurück zum Zitat Chan L-L, Ng K-M, Rumpel H, Fook-Chong S, Li HH, Tan EK (2014) Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism. Parkinsonism Relat Disord 20:53–59CrossRefPubMed Chan L-L, Ng K-M, Rumpel H, Fook-Chong S, Li HH, Tan EK (2014) Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism. Parkinsonism Relat Disord 20:53–59CrossRefPubMed
23.
Zurück zum Zitat Lenfeldt N, Larsson A, Nyberg L, Birgander R, Forsgren L (2015) Fractional anisotropy in the substantia nigra in Parkinson’s disease: a complex picture. Eur J Neurol 22:1408–1414CrossRefPubMed Lenfeldt N, Larsson A, Nyberg L, Birgander R, Forsgren L (2015) Fractional anisotropy in the substantia nigra in Parkinson’s disease: a complex picture. Eur J Neurol 22:1408–1414CrossRefPubMed
24.
Zurück zum Zitat Jiang M-F, Shi F, Niu G-M, Xie SH, Yu SY (2015) A novel method for evaluating brain function and microstructural changes in Parkinson’s disease. Neural Regen Res 10:2025–2028CrossRefPubMedPubMedCentral Jiang M-F, Shi F, Niu G-M, Xie SH, Yu SY (2015) A novel method for evaluating brain function and microstructural changes in Parkinson’s disease. Neural Regen Res 10:2025–2028CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Schuff N, Wu I-W, Buckley S et al (2015) Diffusion imaging of nigral alterations in early Parkinson’s disease with dopaminergic deficits. Mov Disord 30:1885–1892CrossRefPubMed Schuff N, Wu I-W, Buckley S et al (2015) Diffusion imaging of nigral alterations in early Parkinson’s disease with dopaminergic deficits. Mov Disord 30:1885–1892CrossRefPubMed
26.
Zurück zum Zitat Zhang G, Zhang Y, Zhang C et al. Research article diffusion kurtosis imaging of substantia nigra is a sensitive method for early diagnosis and disease evaluation in Parkinson’s disease. Parkinson’s disease. Hindawi Publishing Corporation. 2015; Article ID 207624: 1–5 doi: 10.1155/2015/207624 Zhang G, Zhang Y, Zhang C et al. Research article diffusion kurtosis imaging of substantia nigra is a sensitive method for early diagnosis and disease evaluation in Parkinson’s disease. Parkinson’s disease. Hindawi Publishing Corporation. 2015; Article ID 207624: 1–5 doi: 10.​1155/​2015/​207624
27.
Zurück zum Zitat Langley J, Huddleston DE, Merritt M et al (2016) Diffusion tensor imaging of the substantia nigra in Parkinson’s disease revisited. Hum Brain Mapp 37:2547–2556CrossRefPubMed Langley J, Huddleston DE, Merritt M et al (2016) Diffusion tensor imaging of the substantia nigra in Parkinson’s disease revisited. Hum Brain Mapp 37:2547–2556CrossRefPubMed
28.
Zurück zum Zitat Nagae LM, Honce JM, Tanabe J, Shelton E, Sillau SH, Berman BD (2016) Microstructural changes within the basal ganglia differ between Parkinson disease subtypes. Front Neuroanat 10:17CrossRefPubMedPubMedCentral Nagae LM, Honce JM, Tanabe J, Shelton E, Sillau SH, Berman BD (2016) Microstructural changes within the basal ganglia differ between Parkinson disease subtypes. Front Neuroanat 10:17CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Loane C, Politis M, Kefalopoulou Z et al (2016) Aberrant nigral diffusion in Parkinson’s disease: a longitudinal diffusion tensor imaging study. Mov Disord 31:1020–1026CrossRefPubMed Loane C, Politis M, Kefalopoulou Z et al (2016) Aberrant nigral diffusion in Parkinson’s disease: a longitudinal diffusion tensor imaging study. Mov Disord 31:1020–1026CrossRefPubMed
30.
Zurück zum Zitat Kamagata K, Hatano T, Okuzumi A et al (2016) Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease. Eur Radiol 26:2567–2577CrossRefPubMed Kamagata K, Hatano T, Okuzumi A et al (2016) Neurite orientation dispersion and density imaging in the substantia nigra in idiopathic Parkinson disease. Eur Radiol 26:2567–2577CrossRefPubMed
31.
Zurück zum Zitat Jones DK (2004) The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 51:807–815CrossRefPubMed Jones DK (2004) The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 51:807–815CrossRefPubMed
32.
Zurück zum Zitat Jones DK, Knösche TR, Turner R (2013) White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. NeuroImage 73:239–254CrossRefPubMed Jones DK, Knösche TR, Turner R (2013) White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. NeuroImage 73:239–254CrossRefPubMed
33.
Zurück zum Zitat Yendiki A, Koldewyn K, Kakunoori S, Kanwisher N, Fischl B (2014) Spurious group differences due to head motion in a diffusion MRI study. NeuroImage 88:79–90CrossRefPubMed Yendiki A, Koldewyn K, Kakunoori S, Kanwisher N, Fischl B (2014) Spurious group differences due to head motion in a diffusion MRI study. NeuroImage 88:79–90CrossRefPubMed
34.
Zurück zum Zitat Jellinger K, Kienzl E, Rumpelmair G, Riederer P, Stachelberger H, Ben-Shachar D, Youdim MB (1992) Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. J Neurochem 59:1168–1171CrossRefPubMed Jellinger K, Kienzl E, Rumpelmair G, Riederer P, Stachelberger H, Ben-Shachar D, Youdim MB (1992) Iron-melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. J Neurochem 59:1168–1171CrossRefPubMed
35.
Zurück zum Zitat Zhang J, Tao R, Liu C et al (2013) Possible effects of iron deposition on the measurement of DTI metrics in deep gray matter nuclei: an in vitro and in vivo study. Neurosci Lett 551:47–52CrossRefPubMed Zhang J, Tao R, Liu C et al (2013) Possible effects of iron deposition on the measurement of DTI metrics in deep gray matter nuclei: an in vitro and in vivo study. Neurosci Lett 551:47–52CrossRefPubMed
36.
Zurück zum Zitat Landman BA, Farrell JA, Jones CK, Smith SA, Prince JL, Mori S (2007) Effects of diffusion weighting schemes on the reproducibility of DTI-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5T. NeuroImage 36:1123–1138CrossRefPubMed Landman BA, Farrell JA, Jones CK, Smith SA, Prince JL, Mori S (2007) Effects of diffusion weighting schemes on the reproducibility of DTI-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5T. NeuroImage 36:1123–1138CrossRefPubMed
37.
Zurück zum Zitat Bisdas S, Bohning DE, Besenski N, Nicholas JS, Rumboldt Z (2008) Reproducibility, interrater agreement, and age-related changes of fractional anisotropy measures at 3T in healthy subjects: effect of the applied b-value. AJNR Am J Neuroradiol 29:1128–1133CrossRefPubMed Bisdas S, Bohning DE, Besenski N, Nicholas JS, Rumboldt Z (2008) Reproducibility, interrater agreement, and age-related changes of fractional anisotropy measures at 3T in healthy subjects: effect of the applied b-value. AJNR Am J Neuroradiol 29:1128–1133CrossRefPubMed
38.
Zurück zum Zitat Jones DK, Basser PJ (2004) “Squashing peanuts and smashing pumpkins”: how noise distorts diffusion-weighted MR data. Magn Reson Med 52:979–993CrossRefPubMed Jones DK, Basser PJ (2004) “Squashing peanuts and smashing pumpkins”: how noise distorts diffusion-weighted MR data. Magn Reson Med 52:979–993CrossRefPubMed
39.
Zurück zum Zitat Teipel SJ, Reuter S, Stieltjes B et al (2011) Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study. Psychiatry Res 194:363–371CrossRefPubMed Teipel SJ, Reuter S, Stieltjes B et al (2011) Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study. Psychiatry Res 194:363–371CrossRefPubMed
40.
Zurück zum Zitat Pepe MS (2003) The statistical evaluation of medical tests for classification and prediction. Oxford University Press, Oxford Pepe MS (2003) The statistical evaluation of medical tests for classification and prediction. Oxford University Press, Oxford
41.
Zurück zum Zitat Cosottini M, Frosini D, Pesaresi I et al (2014) MR imaging of the Substantia Nigra at 7 T enables diagnosis of Parkinson disease. Radiology 271:831–838CrossRefPubMed Cosottini M, Frosini D, Pesaresi I et al (2014) MR imaging of the Substantia Nigra at 7 T enables diagnosis of Parkinson disease. Radiology 271:831–838CrossRefPubMed
42.
Zurück zum Zitat Blazejewska AI, Schwarz ST, Pitiot A et al (2013) Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI. Neurology 81:534–540CrossRefPubMedPubMedCentral Blazejewska AI, Schwarz ST, Pitiot A et al (2013) Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI. Neurology 81:534–540CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Schwarz ST, Afzal M, Morgan PS, Bajaj N, Gowland PA, Auer DP (2014) The “swallow tail” appearance of the healthy Nigrosome – A new accurate test of Parkinson’s disease: a case-control and retrospective cross-sectional MRI Study at 3T. PLoS One 9:e93814CrossRefPubMedPubMedCentral Schwarz ST, Afzal M, Morgan PS, Bajaj N, Gowland PA, Auer DP (2014) The “swallow tail” appearance of the healthy Nigrosome – A new accurate test of Parkinson’s disease: a case-control and retrospective cross-sectional MRI Study at 3T. PLoS One 9:e93814CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Kim J-M, Jeong H-J, Bae YJ et al (2016) Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Parkinsonism Relat Disord 26:47–54CrossRefPubMed Kim J-M, Jeong H-J, Bae YJ et al (2016) Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Parkinsonism Relat Disord 26:47–54CrossRefPubMed
Metadaten
Titel
Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson’s disease: A diagnostic performance study and meta-analysis
verfasst von
Fabiana C. C. Hirata
João R. Sato
Gilson Vieira
Leandro T. Lucato
Claudia C. Leite
Edson Bor-Seng-Shu
Bruno F. Pastorello
Maria C. G. Otaduy
Khallil T. Chaim
Kenia R. Campanholo
Natalia P. Novaes
Luciano Magalhães Melo
Márcia R. Gonçalves
Felipe Barjud Pereira do Nascimento
Manoel Jacobsen Teixeira
Egberto Reis Barbosa
Edson Amaro Jr
Ellison Fernando Cardoso
Publikationsdatum
05.10.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Radiology / Ausgabe 6/2017
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-016-4611-0

Weitere Artikel der Ausgabe 6/2017

European Radiology 6/2017 Zur Ausgabe

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.