Document Type : Original Article


1 Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Neurology, Atieh Hospital, Tehran, Iran

3 Department of Radiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Community and Family Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Background: The accuracy of current laboratory and imaging studies for diagnosis and monitoring of Parkinson’s disease (PD) severity is low and diagnosis is mainly dependent on clinical examination. Proton magnetic resonance spectroscopy (MRS) is a non-invasive technique that can assess the chemical profile of the brain. In this study, we evaluated the utility of proton MRS in diagnosis of PD and determination of its severity.
Methods: Patients with PD and healthy age-matched controls were studied using proton MRS. The level of N-acetylaspartate (NAA), total creatine (Cr), and total choline (Cho), and their ratios were calculated in substantia nigra (SN), putamen (Pu), and motor cortex. PD severity was assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale.
Results: Compared to 25 healthy controls (18 men, age: 59.00 ± 8.39 years), our 30 patients with PD (24 men, age: 63.80 ± 12.00 years, 29 under treatment) showed no significant difference in the metabolite ratios in SN, Pu, and motor cortex. Nigral level of NAA/Cr was significantly correlated with total UPDRS score in patients with PD (r = -0.35, P = 0.08). Moreover, patients with PD with Hoehn and Yahr scale score ≥ 2 had a lower NAA/Cr level in SN compared to patients with a lower stage.
Conclusion: This study shows that 1.5 tesla proton MRS is unable to detect metabolite abnormalities in patients with PD who are under treatment. However, the NAA/Cr ratio in the SN might be a useful imaging biomarker for evaluation of disease severity in these patients.


  1. GBD 2016 Parkinson's Disease Collaborators. Global, regional, and national burden of Parkinson's disease, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018; 17(11): 939-53.
  2. Dorsey ER, Sherer T, Okun MS, Bloem BR. The emerging evidence of the parkinson pandemic. J Parkinsons Dis 2018; 8(s1): S3-S8.
  3. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017; 3: 17013.
  4. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30(12): 1591-601.
  5. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB. Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord 2019; 34(10): 1464-70.
  6. Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology 2016; 86(6): 566-76.
  7. Danielsen ER, Ross B. Magnetic resonance spectroscopy diagnosis of neurological diseases. New York, NY: M. Dekker; 1999.
  8. Ciurleo R, Di LG, Bramanti P, Marino S. Magnetic resonance spectroscopy: an in vivo molecular imaging biomarker for Parkinson's disease? Biomed Res Int 2014; 2014: 519816.
  9. Politis M. Neuroimaging in Parkinson disease: From research setting to clinical practice. Nat Rev Neurol 2014; 10(12): 708-22.
  10. Saeed U, Compagnone J, Aviv RI, Strafella AP, Black SE, Lang AE, et al. Imaging biomarkers in Parkinson's disease and Parkinsonian syndromes: Current and emerging concepts. Transl Neurodegener 2017; 6: 8.
  11. Tedeschi G, Litvan I, Bonavita S, Bertolino A, Lundbom N, Patronas NJ, et al. Proton magnetic resonance spectroscopic imaging in progressive supranuclear palsy, Parkinson's disease and corticobasal degeneration. Brain 1997; 120 (Pt 9): 1541-52.
  12. Clarke CE, Lowry M. Basal ganglia metabolite concentrations in idiopathic Parkinson's disease and multiple system atrophy measured by proton magnetic resonance spectroscopy. Eur J Neurol 2000; 7(6): 661-5.
  13. O'Neill J, Schuff N, Marks WJ, Feiwell R, Aminoff MJ, Weiner MW. Quantitative 1H magnetic resonance spectroscopy and MRI of Parkinson's disease. Mov Disord 2002; 17(5): 917-27.
  14. Greenwald MK, Woodcock EA, Khatib D, Stanley JA. Methadone maintenance dose modulates anterior cingulate glutamate levels in heroin-dependent individuals: A preliminary in vivo (1)H MRS study. Psychiatry Res 2015; 233(2): 218-24.
  15. Ernst T, Chang L, Leonido-Yee M, Speck O. Evidence for long-term neurotoxicity associated with methamphetamine abuse: A 1H MRS study. Neurology 2000; 54(6): 1344-9.
  16. Fahn, S., Elton, R. and Members of the UPDRS Development Committee (1987) The Unified Parkinson's Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, Goldstein M, editors. Recent developments in Parkinson's disease. Florham Park, NJ: McMellam Health Care Information; 1987. p. 153-63.
  17. Hoehn MM, Yahr MD. Parkinsonism: Onset, progression and mortality. Neurology 1967; 17(5): 427-42.
  18. Cao H, Shi J, Cao B, Kang B, Zhang M, Qu Q. Evaluation of the Braak staging of brain pathology with (1)H-MRS in patients with Parkinson's disease. Neurosci Lett 2017; 660: 57-62.
  19. Groger A, Kolb R, Schafer R, Klose U. Dopamine reduction in the substantia nigra of Parkinson's disease patients confirmed by in vivo magnetic resonance spectroscopic imaging. PLoS One 2014; 9(1): e84081.
  20. Ciurleo R, Bonanno L, Di Lorenzo G, Bramanti P, Marino S. Metabolic changes in de novo Parkinson's disease after dopaminergic therapy: A proton magnetic resonance spectroscopy study. Neurosci Lett 2015; 599: 55-60.
  21. Lucetti C, Del DP, Gambaccini G, Ceravolo R, Logi C, Berti C, et al. Influences of dopaminergic treatment on motor cortex in Parkinson disease: A MRI/MRS study. Mov Disord 2007; 22(15): 2170-5.
  22. Ellis CM, Lemmens G, Williams SC, Simmons A, Dawson J, Leigh PN, et al. Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: A proton magnetic resonance spectroscopy study. Neurology 1997; 49(2): 438-44.
  23. Mazuel L, Chassain C, Jean B, Pereira B, Cladiere A, Speziale C, et al. Proton MR spectroscopy for diagnosis and evaluation of treatment efficacy in Parkinson disease. Radiology 2016; 278(2): 505-13.
  24. Lucetti C, Del DP, Gambaccini G, Bernardini S, Bianchi MC, Tosetti M, et al. Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson's disease patients. Neurol Sci 2001; 22(1): 69-70.
  25. Wu G, Shen YJ, Huang MH, Xing Z, Liu Y, Chen J. Proton MR spectroscopy for monitoring pathologic changes in the substantia nigra and globus pallidus in Parkinson disease. AJR Am J Roentgenol 2016; 206(2): 385-9.
  26. Zhou B, Yuan F, He Z, Tan C. Application of proton magnetic resonance spectroscopy on substantia nigra metabolites in Parkinson's disease. Brain Imaging Behav 2014; 8(1): 97-101.
  27. Weiduschat N, Mao X, Beal MF, Nirenberg MJ, Shungu DC, Henchcliffe C. Usefulness of proton and phosphorus MR spectroscopic imaging for early diagnosis of Parkinson's disease. J Neuroimaging 2015; 25(1): 105-10.
  28. Modrego PJ, Fayed N, Artal J, Olmos S. Correlation of findings in advanced MRI techniques with global severity scales in patients with Parkinson disease. Acad Radiol 2011; 18(2): 235-41.
  29. Henchcliffe C, Shungu DC, Mao X, Huang C, Nirenberg MJ, Jenkins BG, et al. Multinuclear magnetic resonance spectroscopy for in vivo assessment of mitochondrial dysfunction in Parkinson's disease. Ann N Y Acad Sci 2008; 1147: 206-20.
  30. Bourdy R, Sanchez-Catalan MJ, Kaufling J, Balcita-Pedicino JJ, Freund-Mercier MJ, Veinante P, et al. Control of the nigrostriatal dopamine neuron activity and motor function by the tail of the ventral tegmental area. Neuropsychopharmacology 2014; 39(12): 2788-98.