New Imaging Markers for 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.
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.
KeywordsBiomarkers 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
- 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
- 9.Sadowski K, Serafin-Krol M, Szlachta K, Friedman A. Basal ganglia echogenicity in tauopathies. J Neural Transm (Vienna). 2015;122(6):863–5.Google Scholar
- 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
- 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. PubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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. PubMedGoogle Scholar
- 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. PubMedGoogle Scholar
- 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. PubMedGoogle Scholar
- 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. PubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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.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.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
- 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.PubMedGoogle Scholar
- 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
- 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.PubMedGoogle Scholar
- 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.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
- 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. PubMedGoogle Scholar
- 106.Coakeley S, Strafella AP. Imaging tau pathology in Parkinsonisms. NPJ Parkinsons Dis 2017 29;3:22-017-0023-3. eCollection 2017.Google Scholar