New Imaging Markers for Movement Disorders

  • Christine Ghadery
  • Antonio P. Strafella
Movement Disorders (S Fox, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Movement Disorders


Purpose of Review

For decades, identifying in vivo imaging biomarkers to accurately differentiate between various movement disorders as well as to understand their underlying pathophysiological abnormalities has been the aim of scientific work. Recent advances in multimodal imaging enable the visualization of structural and functional brain changes in these pathological conditions, thus raising the value of imaging techniques as powerful tools to improve sensitivity and specificity of clinical diagnoses. This article reviews well-established and recent developments in imaging markers for movement disorders.

Recent Findings

Whereas several imaging approaches seem to be promising, many modalities are still under development and may not provide decisive answers. Thus, the use of combined imaging modalities as well as the acquisition of methodological consensus in the scientific community may provide more conclusive findings in the future of biomarkers.


Although a single biomarker has yet not been identified, multiple markers derived from different imaging modalities may represent the right approach.


Biomarkers Parkinson’s disease Atypical parkinsonian disorders Transcranial sonography Magnetic resonance imaging Molecular imaging 



This work was supported by the Canadian Institutes of Health Research (MOP 136778). APS is supported by the Canada Research Chair program from the Canadian Institutes of Health Research.

The editors would like to thank Dr. Stanley Fahn for taking the time to review this manuscript.

Compliance with Ethical Standards

Conflict of Interest

Christine Ghadery and Antonio P. Strafella declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Dexter DT, Jenner P. Parkinson disease: from pathology to molecular disease mechanisms. Free Radic Biol Med. 2013;62:132–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Saeed U, Compagnone J, Aviv RI, Strafella AP, Black SE, Lang AE, Masellis M Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes: current and emerging concepts. Transl Neurodegener 2017 mar 8;6:8-017-0076-6. eCollection 2017.Google Scholar
  3. 3.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181–4.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    de la Fuente-Fernandez R, Schulzer M, Kuramoto L, Cragg J, Ramachandiran N, Au WL, et al. Age-specific progression of nigrostriatal dysfunction in Parkinson’s disease. Ann Neurol. 2011;69(5):803–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Fernandes Rde C, Berg D. Parenchymal imaging in movement disorders. Front Neurol Neurosci. 2015;36:71–82.PubMedCrossRefGoogle Scholar
  6. 6.
    Berg D, Roggendorf W, Schroder U, Klein R, Tatschner T, Benz P, et al. Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol. 2002;59(6):999–1005.PubMedCrossRefGoogle Scholar
  7. 7.
    Walter U, Dressler D, Wolters A, Wittstock M, Greim B, Benecke R. Sonographic discrimination of dementia with Lewy bodies and Parkinson’s disease with dementia. J Neurol. 2006;253(4):448–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Walter U, Dressler D, Wolters A, Probst T, Grossmann A, Benecke R. Sonographic discrimination of corticobasal degeneration vs progressive supranuclear palsy. Neurology. 2004;63(3):504–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Sadowski K, Serafin-Krol M, Szlachta K, Friedman A. Basal ganglia echogenicity in tauopathies. J Neural Transm (Vienna). 2015;122(6):863–5.CrossRefGoogle Scholar
  10. 10.
    Maskova J, Skoloudik D, Burgetova A, Fiala O, Bruha R, Zahorakova D, et al. Comparison of transcranial sonography-magnetic resonance fusion imaging in Wilson’s and early-onset Parkinson’s diseases. Parkinsonism Relat Disord. 2016;28:87–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Bor-Seng-Shu E, Pedroso JL, Felicio AC, de Andrade DC, Teixeira MJ, Braga-Neto P, et al. Substantia nigra echogenicity and imaging of striatal dopamine transporters in Parkinson’s disease: a cross-sectional study. Parkinsonism Relat Disord. 2014;20(5):477–81.PubMedCrossRefGoogle Scholar
  12. 12.
    Tunc S, Graf J, Tadic V, Bruggemann N, Schmidt A, Al-Khaled M, et al. A population-based study on combined markers for early Parkinson’s disease. Mov Disord. 2015;30(4):531–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Fernandes R, Rosso A, Vincent M, et al. Transcranial sonography of substantia nigra: computer-evaluated echogenicity. Mov Disord. 2012;27(suppl 1):S235.Google Scholar
  14. 14.
    Lehericy S, Vaillancourt DE, Seppi K, Monchi O, Rektorova I, Antonini A, et al. The role of high-field magnetic resonance imaging in parkinsonian disorders: pushing the boundaries forward. Mov Disord. 2017;32(4):510–25.PubMedCrossRefGoogle Scholar
  15. 15.
    Summerfield C, Junque C, Tolosa E, Salgado-Pineda P, Gomez-Anson B, Marti MJ, et al. Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study. Arch Neurol. 2005;62(2):281–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Burton EJ, McKeith IG, Burn DJ, Williams ED, O'Brien JT. Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain. 2004;127(Pt 4):791–800.PubMedCrossRefGoogle Scholar
  17. 17.
    Brenneis C, Seppi K, Schocke MF, Muller J, Luginger E, Bosch S, et al. Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord. 2003;18(10):1132–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Price S, Paviour D, Scahill R, Stevens J, Rossor M, Lees A, et al. Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson’s disease. NeuroImage. 2004;23(2):663–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD. Differentiating multiple system atrophy from Parkinson’s disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosurg Psychiatry. 2002;73(5):517–23.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Pitcher TL, Melzer TR, Macaskill MR, Graham CF, Livingston L, Keenan RJ, et al. Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study. Transl Neurodegener. 2012;1(1):17. -9158-1-17 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tinaz S, Courtney MG, Stern CE. Focal cortical and subcortical atrophy in early Parkinson’s disease. Mov Disord. 2011;26(3):436–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Sako W, Murakami N, Izumi Y, Kaji R. The difference in putamen volume between MSA and PD: evidence from a meta-analysis. Parkinsonism Relat Disord. 2014;20(8):873–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Wadia PM, Howard P, Ribeirro MQ, Robblee J, Asante A, Mikulis DJ, et al. The value of GRE, ADC and routine MRI in distinguishing Parkinsonian disorders. Can J Neurol Sci. 2013;40(3):389–402.PubMedCrossRefGoogle Scholar
  24. 24.
    Kollensperger M, Wenning GK. Assessing disease progression with MRI in atypical parkinsonian disorders. Mov Disord. 2009;24(Suppl 2):S699–702.PubMedCrossRefGoogle Scholar
  25. 25.
    Minnerop M, Specht K, Ruhlmann J, Schimke N, Abele M, Weyer A, et al. Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters. NeuroImage. 2007;36(4):1086–95.PubMedCrossRefGoogle Scholar
  26. 26.
    Paviour DC, Price SL, Jahanshahi M, Lees AJ, Fox NC, Longitudinal MRI. In progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy. Brain. 2006;129(Pt 4):1040–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Nicoletti G, Fera F, Condino F, Auteri W, Gallo O, Pugliese P, et al. MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease. Radiology. 2006;239(3):825–30.PubMedCrossRefGoogle Scholar
  28. 28.
    Quattrone A, Nicoletti G, Messina D, Fera F, Condino F, Pugliese P, et al. MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology. 2008;246(1):214–21.PubMedCrossRefGoogle Scholar
  29. 29.
    • Chen S, Tan HY, Wu ZH, Sun CP, He JX, Li XC, et al. Imaging of olfactory bulb and gray matter volumes in brain areas associated with olfactory function in patients with Parkinson’s disease and multiple system atrophy. Eur J Radiol. 2014;83(3):564–70. This study reports reduced volumes of the olfactory bulb in patients with idiopathic Parkinson's disease compared to multiple system atrophy. PubMedCrossRefGoogle Scholar
  30. 30.
    Pietracupa S, Martin-Bastida A, Piccini P. Iron metabolism and its detection through MRI in parkinsonian disorders: a systematic review. Neurol Sci. 2017;38:2095–101.PubMedCrossRefGoogle Scholar
  31. 31.
    Beyer MK, Larsen JP, Aarsland D. Gray matter atrophy in Parkinson disease with dementia and dementia with Lewy bodies. Neurology. 2007;69(8):747–54.PubMedCrossRefGoogle Scholar
  32. 32.
    Goldman JG, Stebbins GT, Bernard B, Stoub TR, Goetz CG, deToledo-Morrell L. Entorhinal cortex atrophy differentiates Parkinson’s disease patients with and without dementia. Mov Disord. 2012;27(6):727–34.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Mak E, Bergsland N, Dwyer MG, Zivadinov R, Kandiah N. Subcortical atrophy is associated with cognitive impairment in mild Parkinson disease: a combined investigation of volumetric changes, cortical thickness, and vertex-based shape analysis. AJNR Am J Neuroradiol. 2014;35(12):2257–64.PubMedCrossRefGoogle Scholar
  34. 34.
    Beyer MK, Aarsland D, Greve OJ, Larsen JP. Visual rating of white matter hyperintensities in Parkinson’s disease. Mov Disord. 2006;21(2):223–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Fanciulli A, Wenning GK. Multiple-system atrophy. N Engl J Med. 2015;372(14):1375–6.PubMedGoogle Scholar
  36. 36.
    Padovani A, Borroni B, Brambati SM, Agosti C, Broli M, Alonso R, et al. Diffusion tensor imaging and voxel based morphometry study in early progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2006;77(4):457–63.PubMedCrossRefGoogle Scholar
  37. 37.
    Boxer AL, Geschwind MD, Belfor N, Gorno-Tempini ML, Schauer GF, Miller BL, et al. Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Arch Neurol. 2006;63(1):81–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Kurata T, Kametaka S, Ohta Y, Morimoto N, Deguchi S, Deguchi K, et al. PSP as distinguished from CBD, MSA-P and PD by clinical and imaging differences at an early stage. Intern Med. 2011;50(22):2775–81.PubMedCrossRefGoogle Scholar
  39. 39.
    Josephs KA, Whitwell JL, Dickson DW, Boeve BF, Knopman DS, Petersen RC, et al. Voxel-based morphometry in autopsy proven PSP and CBD. Neurobiol Aging. 2008 Feb;29(2):280–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Groschel K, Hauser TK, Luft A, Patronas N, Dichgans J, Litvan I, et al. Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration. NeuroImage. 2004;21(2):714–24.PubMedCrossRefGoogle Scholar
  41. 41.
    Schofield EC, Caine D, Kril JJ, Cordato NJ, Halliday GM. Staging disease severity in movement disorder tauopathies: brain atrophy separates progressive supranuclear palsy from corticobasal degeneration. Mov Disord. 2005;20(1):34–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, DeArmond SJ, et al. Clinicopathological correlations in corticobasal degeneration. Ann Neurol. 2011;70(2):327–40.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    • Kaasinen V, Kangassalo N, Gardberg M, Isotalo J, Karhu J, Parkkola R, et al. Midbrain-to-pons ratio in autopsy-confirmed progressive supranuclear palsy: replication in an independent cohort. Neurol Sci. 2015;36(7):1251–3. This study replicated findings on the midbrain-to-pons ratio which demonstrated high specificity and sensitivity for the diagnosis of progressive supranuclear palsy. PubMedCrossRefGoogle Scholar
  44. 44.
    Josephs KA, Tang-Wai DF, Edland SD, Knopman DS, Dickson DW, Parisi JE, et al. Correlation between antemortem magnetic resonance imaging findings and pathologically confirmed corticobasal degeneration. Arch Neurol. 2004;61(12):1881–4.PubMedCrossRefGoogle Scholar
  45. 45.
    McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005;65(12):1863–72.PubMedCrossRefGoogle Scholar
  46. 46.
    Weintraub D, Dietz N, Duda JE, Wolk DA, Doshi J, Xie SX, et al. Alzheimer’s disease pattern of brain atrophy predicts cognitive decline in Parkinson’s disease. Brain. 2012;135(Pt 1):170–80.PubMedCrossRefGoogle Scholar
  47. 47.
    • Du G, Liu T, Lewis MM, Kong L, Wang Y, Connor J, et al. Quantitative susceptibility mapping of the midbrain in Parkinson’s disease. Mov Disord. 2016;31(3):317–24. The authors of this study revealed that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD. PubMedCrossRefGoogle Scholar
  48. 48.
    Reimao S, Ferreira S, Nunes RG, Pita Lobo P, Neutel D, Abreu D, 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(2):368–74.PubMedCrossRefGoogle Scholar
  49. 49.
    Dexter DT, Jenner P, Schapira AH, Marsden CD. Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia. The Royal Kings and Queens Parkinson's Disease Research Group. Ann Neurol. 1992;32(Suppl):S94–100.PubMedCrossRefGoogle Scholar
  50. 50.
    Boelmans K, Holst B, Hackius M, Finsterbusch J, Gerloff C, Fiehler J, et al. Brain iron deposition fingerprints in Parkinson’s disease and progressive supranuclear palsy. Mov Disord. 2012;27(3):421–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Sakurai K, Imabayashi E, Tokumaru AM, Ito K, Shimoji K, Nakagawa M, et al. Volume of interest analysis of spatially normalized PRESTO imaging to differentiate between Parkinson disease and atypical Parkinsonian syndrome. Magn Reson Med Sci. 2017;16(1):16–22.PubMedCrossRefGoogle Scholar
  52. 52.
    Blazejewska AI, Schwarz ST, Pitiot A, Stephenson MC, Lowe J, Bajaj N, et al. Visualization of nigrosome 1 and its loss in PD: pathoanatomical correlation and in vivo 7 T MRI. Neurology. 2013;81(6):534–40.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    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(4):619–23.PubMedCrossRefGoogle Scholar
  54. 54.
    •• De Marzi R, Seppi K, Hogl B, Muller C, Scherfler C, Stefani A, et al. Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility-weighted imaging in idiopathic rapid eye movement sleep behavior disorder. Ann Neurol. 2016;79(6):1026–30. This study identified the absence of dorsolateral nigral hyperintensity on high-field susceptibility-weighted imaging as a potential biomarker for prodromal degenerative parkinsonism in idiopathic rapid eye movement sleep behavior disorder. PubMedCrossRefGoogle Scholar
  55. 55.
    Double KL, Gerlach M, Schunemann V, Trautwein AX, Zecca L, Gallorini M, et al. Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochem Pharmacol. 2003;66(3):489–94.PubMedCrossRefGoogle Scholar
  56. 56.
    •• Reimao S, Pita Lobo P, Neutel D, Guedes LC, Coelho M, Rosa MM, et al. Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson’s disease. Mov Disord. 2015;30(7):953–9. This study revealed that neuromelanin-sensitive MRI techniques can discriminate essential tremor from early-stage tremor-dominant Parkinson's disease. PubMedCrossRefGoogle Scholar
  57. 57.
    Cochrane CJ, Ebmeier KP. Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis. Neurology. 2013;80(9):857–64.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Schocke MF, Seppi K, Esterhammer R, Kremser C, Mair KJ, Czermak BV, et al. Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson’s disease. NeuroImage. 2004;21(4):1443–51.PubMedCrossRefGoogle Scholar
  59. 59.
    Baudrexel S, Seifried C, Penndorf B, Klein JC, Middendorp M, Steinmetz H, et al. The value of putaminal diffusion imaging versus 18-fluorodeoxyglucose positron emission tomography for the differential diagnosis of the Parkinson variant of multiple system atrophy. Mov Disord. 2014;29(3):380–7.PubMedCrossRefGoogle Scholar
  60. 60.
    •• Ofori E, Krismer F, Burciu RG, Pasternak O, McCracken JL, Lewis MM, et al. Free water improves detection of changes in the substantia nigra in parkinsonism: a multisite study. Mov Disord 2017 Jul 17. This multisite study used single- and bi-tensor models of diffusion magnetic resonance imaging to evaluate changes in the substantia nigra in PD, MSA, and PSP. Google Scholar
  61. 61.
    Ciurleo R, Di Lorenzo G, Bramanti P, Marino S. Magnetic resonance spectroscopy: an in vivo molecular imaging biomarker for Parkinson’s disease? Biomed Res Int 2014;2014:519816, 1, 10.Google Scholar
  62. 62.
    Kim J, Criaud M, Cho S, Cirarda M, Mihaescu A, Coakeley S, et al. Abnormal intrinsic brain functional network dynamics in Parkinson’s disease. Brain : a journal of neurology 2017;accepted, 140, 2955, 2967.Google Scholar
  63. 63.
    Brooks DJ. Technology insight: imaging neurodegeneration in Parkinson’s disease. Nat Clin Pract Neurol. 2008;4(5):267–77.PubMedCrossRefGoogle Scholar
  64. 64.
    Broussolle E, Dentresangle C, Landais P, Garcia-Larrea L, Pollak P, Croisile B, et al. The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson’s disease. J Neurol Sci. 1999;166(2):141–51.PubMedCrossRefGoogle Scholar
  65. 65.
    Otsuka M, Ichiya Y, Hosokawa S, Kuwabara Y, Tahara T, Fukumura T, et al. Striatal blood flow, glucose metabolism and 18F-dopa uptake: difference in Parkinson’s disease and atypical parkinsonism. J Neurol Neurosurg Psychiatry. 1991;54(10):898–904.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Politis M. Neuroimaging in Parkinson disease: from research setting to clinical practice. Nat Rev Neurol. 2014;10(12):708–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Klaffke S, Kuhn AA, Plotkin M, Amthauer H, Harnack D, Felix R, et al. Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration. Mov Disord. 2006;21(10):1724–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Im JH, Chung SJ, Kim JS, Lee MC. Differential patterns of dopamine transporter loss in the basal ganglia of progressive supranuclear palsy and Parkinson’s disease: analysis with [(123)I]IPT single photon emission computed tomography. J Neurol Sci. 2006;244(1–2):103–9.PubMedCrossRefGoogle Scholar
  69. 69.
    O'Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004;61(6):919–25.PubMedCrossRefGoogle Scholar
  70. 70.
    Pirker S, Perju-Dumbrava L, Kovacs GG, Traub-Weidinger T, Pirker W. Progressive dopamine transporter binding loss in autopsy-confirmed corticobasal degeneration. J Parkinsons Dis. 2015;5(4):907–12.PubMedCrossRefGoogle Scholar
  71. 71.
    Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol. 2000;47(4):493–503.PubMedCrossRefGoogle Scholar
  72. 72.
    Antonini A, Schwarz J, Oertel WH, Beer HF, Madeja UD, Leenders KL. [11C]raclopride and positron emission tomography in previously untreated patients with Parkinson’s disease: influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors. Neurology. 1994;44(7):1325–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Ichise M, Kim YJ, Ballinger JR, Vines D, Erami SS, Tanaka F, et al. SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD. Neurology. 1999;52(6):1206–14.PubMedCrossRefGoogle Scholar
  74. 74.
    Kim YJ, Ichise M, Ballinger JR, Vines D, Erami SS, Tatschida T, et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov Disord. 2002;17(2):303–12.PubMedCrossRefGoogle Scholar
  75. 75.
    Antonini A, Leenders KL, Vontobel P, Maguire RP, Missimer J, Psylla M, et al. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease. Brain 1997 120 ( Pt 12)(Pt 12):2187–2195.Google Scholar
  76. 76.
    Pirker S, Perju-Dumbrava L, Kovacs GG, Traub-Weidinger T, Asenbaum S, Pirker W. Dopamine D2 receptor SPECT in corticobasal syndrome and autopsy-confirmed corticobasal degeneration. Parkinsonism Relat Disord. 2013;19(2):222–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Koch W, Hamann C, Radau PE, Tatsch K. Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism? Eur J Nucl Med Mol Imaging. 2007;34(8):1265–73.PubMedCrossRefGoogle Scholar
  78. 78.
    Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Oertel WH, et al. Serotonin neuron loss and nonmotor symptoms continue in Parkinson’s patients treated with dopamine grafts. Sci Transl Med. 2012;4(128):128ra41.PubMedCrossRefGoogle Scholar
  79. 79.
    Roussakis AA, Politis M, Towey D, Piccini P. Serotonin-to-dopamine transporter ratios in Parkinson disease: relevance for dyskinesias. Neurology. 2016;86(12):1152–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Politis M, Oertel WH, Wu K, Quinn NP, Pogarell O, Brooks DJ, et al. Graft-induced dyskinesias in Parkinson’s disease: high striatal serotonin/dopamine transporter ratio. Mov Disord. 2011;26(11):1997–2003.PubMedCrossRefGoogle Scholar
  81. 81.
    Niccolini F, Foltynie T, Reis Marques T, Muhlert N, Tziortzi AC, Searle GE, et al. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson’s disease. Brain. 2015;138(Pt 10):3003–15.PubMedCrossRefGoogle Scholar
  82. 82.
    Jin S, Oh M, Oh SJ, Oh JS, Lee SJ, Chung SJ, et al. Differential diagnosis of parkinsonism using dual-phase F-18 FP-CIT PET imaging. Nucl Med Mol Imaging. 2013;47(1):44–51.PubMedCrossRefGoogle Scholar
  83. 83.
    Fazio P, Svenningsson P, Forsberg A, Jonsson EG, Amini N, Nakao R, et al. Quantitative analysis of (1)(8)F-(E)-N-(3-Iodoprop-2-Enyl)-2beta-Carbofluoroethoxy-3beta-(4′-methyl-phenyl) nortropane binding to the dopamine transporter in Parkinson disease. J Nucl Med. 2015;56(5):714–20.PubMedCrossRefGoogle Scholar
  84. 84.
    Gomperts SN, Locascio JJ, Marquie M, Santarlasci AL, Rentz DM, Maye J, et al. Brain amyloid and cognition in Lewy body diseases. Mov Disord. 2012;27(8):965–73.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Foster ER, Campbell MC, Burack MA, Hartlein J, Flores HP, Cairns NJ, et al. Amyloid imaging of Lewy body-associated disorders. Mov Disord. 2010;25(15):2516–23.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Donaghy P, Thomas AJ, O'Brien JT. Amyloid PET imaging in Lewy body disorders. Am J Geriatr Psychiatry. 2015;23(1):23–37.PubMedCrossRefGoogle Scholar
  87. 87.
    Kepe V, Bordelon Y, Boxer A, Huang SC, Liu J, Thiede FC, et al. PET imaging of neuropathology in tauopathies: progressive supranuclear palsy. J Alzheimers Dis. 2013;36(1):145–53.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Cho H, Choi JY, Hwang MS, Lee SH, Ryu YH, Lee MS, et al. Subcortical 18 F-AV-1451 binding patterns in progressive supranuclear palsy. Mov Disord. 2017;32(1):134–40.PubMedCrossRefGoogle Scholar
  89. 89.
    Hammes J, Bischof GN, Giehl K, Faber J, Drzezga A, Klockgether T, et al. Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy. Mov Disord. 2017;32(1):170–1.PubMedCrossRefGoogle Scholar
  90. 90.
    •• Coakeley S, Cho SS, Koshimori Y, Rusjan P, Ghadery C, Kim J, et al. [18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. Brain Struct Funct 2017 Sep 7. This study detected that [18F]AV-1451 may be the first PET radiotracer capable of imaging neurodegeneration of the substantia nigra in parkinsonisms. Google Scholar
  91. 91.
    Coakeley S, Cho SS, Koshimori Y, Rusjan P, Harris M, Ghadery C, et al. Positron emission tomography imaging of tau pathology in progressive supranuclear palsy. J Cereb Blood Flow Metab 2016 Jan 01:271678X16683695.Google Scholar
  92. 92.
    Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003 Sep 9;61(5):686–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Kobylecki C, Counsell SJ, Cabanel N, Wachter T, Turkheimer FE, Eggert K, et al. Diffusion-weighted imaging and its relationship to microglial activation in parkinsonian syndromes. Parkinsonism Relat Disord. 2013;19(5):527–32.PubMedCrossRefGoogle Scholar
  94. 94.
    Gerhard A, Watts J, Trender-Gerhard I, Turkheimer F, Banati RB, Bhatia K, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19(10):1221–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Gerhard A, Trender-Gerhard I, Turkheimer F, Quinn NP, Bhatia KP, Brooks DJ. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord. 2006;21(1):89–93.PubMedCrossRefGoogle Scholar
  96. 96.
    Terada T, Yokokura M, Yoshikawa E, Futatsubashi M, Kono S, Konishi T, et al. Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study. Ann Nucl Med. 2016;30:579–87.PubMedCrossRefGoogle Scholar
  97. 97.
    Edison P, Ahmed I, Fan Z, Hinz R, Gelosa G, Ray Chaudhuri K, et al. Microglia, amyloid, and glucose metabolism in Parkinson’s disease with and without dementia. Neuropsychopharmacology. 2013;38(6):938–49.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Fan Z, Aman Y, Ahmed I, Chetelat G, Landeau B, Ray Chaudhuri K, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement. 2015;11(6):608–21.e7.PubMedCrossRefGoogle Scholar
  99. 99.
    Iannaccone S, Cerami C, Alessio M, Garibotto V, Panzacchi A, Olivieri S, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19(1):47–52.PubMedCrossRefGoogle Scholar
  100. 100.
    Ghadery C, Koshimori Y, Coakeley S, Harris M, Rusjan P, Kim J, et al. Microglial activation in Parkinson’s disease using [18F]-FEPPA. J Neuroinflammation. 2017;14(1):8. -016-0778-1 PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Koshimori Y, Ko JH, Mizrahi R, Rusjan P, Mabrouk R, Jacobs MF, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10(9):e0138721.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Botha H, Whitwell JL, Madhaven A, Senjem ML, Lowe V, Josephs KA. The pimple sign of progressive supranuclear palsy syndrome. Parkinsonism Relat Disord. 2014;20(2):180–5.PubMedCrossRefGoogle Scholar
  103. 103.
    Niethammer M, Tang CC, Feigin A, Allen PJ, Heinen L, Hellwig S, et al. A disease-specific metabolic brain network associated with corticobasal degeneration. Brain. 2014;137(Pt 11):3036–46.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Tripathi M, Dhawan V, Peng S, Kushwaha S, Batla A, Jaimini A, et al. Differential diagnosis of parkinsonian syndromes using F-18 fluorodeoxyglucose positron emission tomography. Neuroradiology. 2013 Mar;55(4):483–92.PubMedCrossRefGoogle Scholar
  105. 105.
    •• Holtbernd F, Ma Y, Peng S, Schwartz F, Timmermann L, Kracht L, et al. Dopaminergic correlates of metabolic network activity in Parkinson’s disease. Hum Brain Mapp. 2015;36(9):3575–85. This study found that Parkinson’s disease motor- and cognition-related metabolic patterns correlated significantly with PET indices of presynaptic dopaminergic functioning in patients with Parkinson's disease. PubMedCrossRefGoogle Scholar
  106. 106.
    Coakeley S, Strafella AP. Imaging tau pathology in Parkinsonisms. NPJ Parkinsons Dis 2017 29;3:22-017-0023-3. eCollection 2017.Google Scholar
  107. 107.
    Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nat Rev Drug Discov. 2010;9(12):971–88.PubMedCrossRefGoogle Scholar
  108. 108.
    Koshimori Y, Ko JH, Mizrahi R, Rusjan P, Mabrouk R, Jacobs MF, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10(9):e0138721.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Gjerloff T, Fedorova T, Knudsen K, Munk OL, Nahimi A, Jacobsen S, et al. Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain. 2015;138(Pt 3):653–63.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Neurology Division, Department of Medicine, Toronto Western HospitalUHN, University of TorontoTorontoCanada
  2. 2.Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research InstituteUHN, University of TorontoTorontoCanada
  3. 3.Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthUniversity of TorontoTorontoCanada

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