New MRI diagnostic methods in Parkinson's disease: evaluating nigral degeneration

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Abstract

Research Center of Neurology, Moscow, Russia

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a characteristic pathological hallmark of loss of the dopaminergic neurons in the compact part of the substantia nigra in the midbrain. Despite the significant progress made in learning about this disease, early diagnosis continues to be a complex clinical issue. Currently, many studies are focused on finding and implementing meaningful markers which are valid for the early PD diagnosis. One of the most promising areas in that field is investigation of specific changes in the substantia nigra, found when examining the nigrosomes (specific clusters of the dopaminergic neurons) and neuromelanin, using high-field magnetic resonance imaging (MRI).

This article presents the current understanding of the structural and functional organization of the substantia nigra, and examines in detail the new informative MRI-markers of neurodegeneration in PD: the loss of dorsolateral nigral hyperintensity (disappearance of the nigrosome-1) and a reduction in the intensity/area of the magnetic resonance signal from the substantia nigra when imaging the neuromelanin. We present our own experience of using the abovementioned technologies to diagnose PD, by analysing susceptibility-weighted images and images taken in neuromelanin-sensitive MRI mode.

About the authors

Sergey N. Illarioshkin

Research Center of Neurology

Email: ekfedotova@gmail.com
Россия, Moscow

Rodion N. Konovalov

Research Center of Neurology

Email: ekfedotova@gmail.com
Россия, Moscow

Ekaterina Yu. Fedotova

Research Center of Neurology

Author for correspondence.
Email: ekfedotova@gmail.com
Россия, Moscow

Anna N. Moskalenko

Research Center of Neurology

Email: ekfedotova@gmail.com
Россия, Moscow

References

  1. Pringsheim T., Jette N., Frolkis A., Steeves T.D. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 2014; 29: 1583–1590. doi: 10.1002/mds.25945. PMID: 24976103.
  2. Illarioshkin S.N., Levin O.S. (eds.) [Guidelines for the diagnosis and treatment of Parkinson's disease]. Moscow, 2017. 336 p. (In Russ.)
  3. Tolosa E., Wenning G., Poewe W. The diagnosis of Parkinson’s disease. Lancet Neurol 2006; 5: 75–86. doi: 10.1016/S1474-4422(05)70285-4. PMID: 16361025.
  4. Illarioshkin S.N., Vlasenko A.G., Fedotova E.Yu. [Modern possibilities of identifying the latent stage of the neurodegenerative process]. Annals of clinical and experimental neurology 2013; 2: 39–50. (In Russ.)
  5. Poewe W., Seppi K., Tanner C.M. et al. Parkinson disease. Nat Rev Dis Primers 2017; 3: 17013. doi: 10.1038/nrdp.2017.13. PMID: 28332488.
  6. Postuma R.B., Berg D., Stern M. et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30: 1591–1601. doi: 10.1002/mds.26424. PMID: 26474316.
  7. Noyce A., Bandopadhyay R. Parkinson’s disease: basic pathomechanisms and a clinical overview. Adv Neurobiol 2017; 15: 55–92. doi: 10.1007/978-3-319-57193-5_3. PMID: 28674978.
  8. Selikhova M.V., Katunina E.A., Whone A. [PET and SPECT in the assessment of monoaminergic brain systems in extrapyramidal disorders]. Annals of clinical and experimental neurology 2019; 13(2): 69 – 78. doi: 10.25692/ACEN.2019.2.8. (In Russ.)
  9. Brooks D.J. Molecular imaging of dopamine transporters. Ageing Res Rev 2016; 30: 114–121. doi: 10.1016/j.arr.2015.12.009. PMID: 26802555.
  10. Piccini P., Whone A. Functional brain imaging in the differential diagnosis of Parkinson's disease. Lancet Neurol 2004; 3: 284–290. doi: 10.1016/S1474-4422(04)00736-7. PMID: 15099543.
  11. Loane C., Polities M. Positron emission tomography neuroimaging in Parkinson’s disease. Am J Transl Res 2011; 3: 323–341. PMID: 21904653.
  12. Berg D., Behnke S., Walter U. Application of transcranial sonography in extrapyramidal disorder: updated recommendation. Ultraschall Med 2006; 27: 12−19. doi: 10.1055/s-2005-858962. PMID: 16470475.
  13. Berardelli A., Wenning G.K., Antonini A. et al. EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. Eur J Neurol 2013; 20: 16–34. doi: 10.1111/ene.12022 PMID: 23279440.
  14. Shafieesabet A., Fereshtehnejad S.M., Shafieesabet A. et al. Hyperechogenicity of substantia nigra for differential diagnosis of Parkinson's disease: A meta-analysis. Parkinsonism Relat Disord 2017; 42: 1–11. doi: 10.1016/j.parkreldis.2017.06.006. PMID: 28647434.
  15. Illarioshkin S.N., Chechetkin A.O., Fedotova E.Yu. [Transcranial sonography for extrapyramidal diseases]. Мoscow: АТМО, 2014. 176 p. (In Russ.)
  16. Heim B., Krismer F., De Marzi R., Seppi K. Magnetic resonance imaging for the diagnosis of Parkinson’s disease. J Neural Transm 2017; 124: 915–964. doi: 10.1007/s00702-017-1717-8 PMID: 28378231.
  17. Alonso B.C., Hidalgo-Tobón C.C., Menéndez-González M. et al. Magnetic resonance techniques applied to the diagnosis and treatment of Parkinson’s disease. Front Neurol 2015; 6: 146. doi: 10.3389/fneur.2015.00146. PMID: 26191037.
  18. Müller H.-P., Kassubek J. Computerized magnetic resonance imaging-based neuroimaging of neurodegenerative diseases. Front Neurol 2019; 10: 237. doi: 10.3389/fneur.2019.00237. PMID: 30930844.
  19. Damier P., Hirsch E.С., Agid Y., Graybiel A.M. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson's disease. Brain 1999; 122; 1437–1448. doi: 10.1093/brain/122.8.1437. PMID: 10430830.
  20. Reiter E., Mueller C., Pinter B. et al. Dorsolateral nigral hyperintensity on 3.0T susceptibility-weighted imaging in neurodegenerative Parkinsonism. Mov Disord 2015; 30: 1068–1076. doi: 10.1002/mds.26171. PMID: 25773707.
  21. Schwarz S.T., Mouginb O., Xinga Y. et al. Parkinson's disease related signal change in the nigrosomes 1–5 and the substantia nigra using T2* weighted 7T MRI. Neuroimage Clin 2018; 19: 683–689. doi: 10.1016/j.nicl.2018.05.027. PMID: 29872633.
  22. Blazejewska A.I., Schwarz S.T. Visualization of nigrosome 1 and its loss in PD. Pathoanatomical correlation and in vivo 7 T MRI. Neurology 2013; 81: 534–540. doi: 10.1212/WNL.0b013e31829e6fd2. PMID: 23843466.
  23. Jin L., Wang J., Wang C. et al. Combined visualization of nigrosome-1 and neuromelanin in the substantia nigra using 3T MRI for the differential diagnosis of essential tremor and de novo Parkinson’s disease. Front Neurol 2019; 10: 100. doi: 10.3389/fneur.2019.00100. PMID: 30809189.
  24. Noh Y., Sung Y.H., Lee J. Nigrosome 1 detection at 3T MRI for the diagnosis of early-stage idiopathic Parkinson disease: Assessment of diagnostic accuracy and agreement on imaging asymmetry and clinical laterality. AJNR Am J Neuroradiol 2015; 36: 2010–2016. doi: 10.3174/ajnr.A4412. PMID: 26294646.
  25. Schwarz S.T., Xing Y., Naidu S. et al. Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson’s disease). BMJ Open 2017; 7: e016904. doi: 10.1136/bmjopen-2017-016904. PMID: 29247084.
  26. Meijer F.J.A., Goraj B., Bloemc B.R., Esselink R.A.J. Clinical application of brain MRI in the diagnostic work-up of parkinsonism. J Parkinsons Dis 2017; 7: 211–217. doi: 10.3233/JPD-150733. PMID: 28282809.
  27. Schmidt M.A., Engelhorn T., Marxreiter F. et al. Ultra high-field SWI of the substantia nigra at 7T: reliability and consistency of the swallow-tail sign. BMC Neurol 2017; 17: 194. doi: 10.1186/s12883-017-0975-2. PMID: 29073886.
  28. Schwarz S.T., Afzal M., Morgan P.S. et al. 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. PlosOne 2014; 9: e93814. doi: 10.1371/journal.pone.0093814. PMID: 24710392.
  29. Gramsch C., Reuter I., Kraff O., Nigrosome 1 visibility at susceptibility weighted 7T MRI — a dependable diagnostic marker for Parkinson's disease or merely an inconsistent age-dependent imaging finding? Plos One 2017; 12: e0185489. doi: 10.1371/journal.pone.0185489. PMID: 29016618.
  30. Lehericy S., Bardinet E., Poupon C. et al. 7 Tesla magnetic resonance imaging: a closer look at substantia nigra anatomy in Parkinson’s disease. Mov Disord 2014; 29: 1574–1581. doi: 10.1002/mds.26043. PMID: 25308960.
  31. Cosottini M., Frosini D., Pesaresi I. et al. MR imaging of the substantia nigra at 7 T enables diagnosis of Parkinson disease. Radiology. 2014; 271: 831–838. doi: 10.1148/radiol.14131448. PMID: 24601752.
  32. Gao P., Zhou P.Y., Wang P.Q. et al. Universality analysis of the existence of substantia nigra ‘swallow tail’ appearance of non-Parkinson patients in 3T SWI. Eur Rev Med Pharmacol Sci 2016; 20: 1307–1314. PMID: 27097951.
  33. Sung Y.H., Noh Y., Lee J., Kim E.Y. Drug-induced Parkinsonism versus idiopathic Parkinson disease: utility of nigrosome 1 with 3-T imaging. Radiology 2016; 279: 849–858. doi: 10.1148/radiol.2015151466. PMID: 26690908.
  34. Frosini D., Cosottini M., Volterrani D., Ceravolo R. Neuroimaging in Parkinson’s disease: focus on substantia nigra and nigro-striatal projection. Curr Opin Neurol 2017, 30: 416–426. doi: 10.1097/WCO.0000000000000463. PMID: 28537985.
  35. Pavese N., Tai Y.E. Nigrosome imaging and neuromelanin sensitive MRI in diagnostic evaluation of parkinsonism. Mov Disord Clin Pract 2018; 5: 131–140. doi: 10.1002/mdc3.12590. PMID: 30363419.
  36. Mahlknecht P., Krismer F., Poewe W., Seppi K. Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson’s disease. Mov Disord 2017; 32: 619–623. doi: 10.1002/mds.26932. PMID: 28151553.
  37. Bae Y.J., Kim J.M., Kim E. et al. Loss of nigral hyperintensity on 3 Tesla MRI of parkinsonism: comparison with (123) I-FP-CIT SPECT. Mov Disord 2016; 31: 684–692. doi: 10.1002/mds.26584. PMID: 26990970.
  38. Kim J.M., Jeong H.J., Bae Y.J. et al. Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Parkinsonism Relat Disord 2016; 26: 47–54. doi: 10.1016/j.parkreldis.2016.01.023. PMID: 26951846.
  39. Haacke E.M., Liu S., Buch S. et al. Quantitative susceptibility mapping: current status and future directions. Magn Reson Imaging 2015; 33: 1–25. doi: 10.1016/j.mri.2014.09.004. PMID: 25267705.
  40. Postuma R.B., Berg D., Stern M. et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30: 1591–1601. doi: 10.1002/mds.26424. PMID: 26474316.
  41. Illarioshkin S.N., Ivanova-Smolenskaya I.A. [Shivering hyperkinesis. A guide for doctors]. Moscow: Atmosphere, 2011. 360 p. (In Russ.)
  42. Speelman P.B., de Haan R.J., CARPA-study group. Clinical heterogeneity in newly diagnosed Parkinson’s disease. J Neurol 2008; 255: 716–722. doi: 10.1007/s00415-008-0782-1. PMID: 18344057.
  43. Zecca L., Tampellini D., Gerlach M. et al. Substantia nigra neuromelanin: structure, synthesis, and behavior. Mol Pathol 2001; 54: 414–418. PMID: 11724917.
  44. Sasaki M., Shibata E., Tohyama K. et al. Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson’s disease. Neuroreport 2006; 17: 1215–1218. doi: 10.1097/01.wnr.0000227984.84927.a7. PMID: 16837857.
  45. Kashihara K., Shinya T., Higaki F. Reduction of neuromelanin-positive nigral volume in patients with MSA, PSP and CBD. Intern Med 2011; 50: 1683–1687. doi: 10.2169/internalmedicine.50.5101. PMID: 21841326.
  46. Ohtsuka C., Sasaki M., Konno K. et al. Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson’s disease using neuromelanin-sensitive MR imaging. Neurosci Lett 2013; 541: 93–98 doi: 10.1016/j.neulet.2013.02.012. PMID: 23428505.
  47. Matsuura K., Maeda M., Tabei K.I. et al. A longitudinal study of neuromelanin-sensitive magnetic resonance imaging in Parkinson’s disease. Neurosci Lett 2016; 633: 112–117. doi: 10.1016/j.neulet.2016.09.011. PMID: 27619539.
  48. Schwarz S.T., Xing Y., Tomar P. et al. In vivo assessment of brainstem depigmentation in Parkinson disease: potential as a severity marker for multicenter studies. Radiology 2017; 283: 789–798 doi: 10.1148/radiol.2016160662. PMID: 27820685.
  49. Reimão S., Ferreira S., Nunes R.G. et al. Magnetic resonance correlation of iron content with neuromelanin in the substantia nigra of early-stage Parkinson’s disease. Eur J Neurol 2016; 23: 368–374. doi: 10.1111/ene.12838. PMID: 26518135.
  50. Kashihara K., Shinya T., Higaki F. Neuromelanin magnetic resonance imaging of nigral volume loss in patients with Parkinson's disease. J Clin Neurosci 2011; 18: 1093–1096. doi: 10.1016/j.jocn.2010.08.043. PMID: 21719292.
  51. Reimão S., Pita P., Neutel D. et al. Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson’s disease. Mov Disord 2015; 30: 953–959. doi: 10.1002/mds.26182. PMID: 25758364.
  52. Wang J., Li Y., Huang Z. et al. Neuromelanin-sensitive magnetic resonance imaging features of the substantia nigra and locus coeruleus in de novo Parkinson’s disease and its phenotypes. Eur J Neurol 2018; 25: 949–973. doi: 10.1111/ene.13628. PMID: 29520900.
  53. Castellanos G., Fernández-Seara V.A., Lorenzo-Betancor O. et al. Automated neuromelanin imaging as a diagnostic biomarker for Parkinson’s disease. Mov Disord 2015; 30: 945–952. doi: 10.1002/mds.26201. PMID: 25772492.
  54. Isaias I.U., Trujillo P., Summers P. et al. Neuromelanin imaging and dopaminergic loss in Parkinson’s disease. Front Aging Neurosci 2016; 8: 196. doi: 10.3389/fnagi.2016.00196. PMID: 27597825.

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Copyright (c) 2019 Illarioshkin S.N., Konovalov R.N., Fedotova E.Y., Moskalenko A.N.

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