Two centuries ago in 1817, James Parkinson provided the first medical description of Parkinson’s disease, later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants (also termed, Parkinson-plus syndromes). Today, Parkinson’s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million. Conversely, atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson’s disease, but are uncommon distinct clinicopathological diseases. Decades of scientific advancements have vastly improved our understanding of these disorders, including improvements in in vivo imaging for biomarker identification. Multimodal imaging for the visualization of structural and functional brain changes is especially important, as it allows a ‘window’ into the underlying pathophysiological abnormalities. In this article, we first present an overview of the cardinal clinical and neuropathological features of, 1) synucleinopathies: Parkinson’s disease and other Lewy body spectrum disorders, as well as multiple system atrophy, and 2) tauopathies: progressive supranuclear palsy, and corticobasal degeneration. A comprehensive presentation of well-established and emerging imaging biomarkers for each disorder are then discussed. Biomarkers for the following imaging modalities are reviewed: 1) structural magnetic resonance imaging (MRI) using T1, T2, and susceptibility-weighted sequences for volumetric and voxel-based morphometric analyses, as well as MRI derived visual signatures, 2) diffusion tensor MRI for the assessment of white matter tract injury and microstructural integrity, 3) proton magnetic resonance spectroscopy for quantifying proton-containing brain metabolites, 4) single photon emission computed tomography for the evaluation of nigrostriatal integrity (as assessed by presynaptic dopamine transporters and postsynaptic dopamine D2 receptors), and cerebral perfusion, 5) positron emission tomography for gauging nigrostriatal functions, glucose metabolism, amyloid and tau molecular imaging, as well as neuroinflammation, 6) myocardial scintigraphy for dysautonomia, and 7) transcranial sonography for measuring substantia nigra and lentiform nucleus echogenicity. Imaging biomarkers, using the ‘multimodal approach’, may aid in making early, accurate and objective diagnostic decisions, highlight neuroanatomical and pathophysiological mechanisms, as well as assist in evaluating disease progression and therapeutic responses to drugs in clinical trials.
Parkinson’s Disease Foundation - Statistics on Parkinson's. Available from. http://www.pdf.org/en/parkinson_statistics. Accessed 14 Dec 2016
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;1:1–8. CrossRef
Oikawa H, Sasaki M, Tamakawa Y, Ehara S, Tohyama K. The substantia nigra in Parkinson disease: proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings. Am J Neuroradiol. 2002;23:1747–56. PubMed
Minati L, Grisoli M, Carella F, De Simone T, Bruzzone MG, Savoiardo M. Imaging degeneration of the substantia nigra in Parkinson disease with inversion-recovery MR imaging. Am J Neuroradiol. 2007;28:309–13. PubMed
Monchi O, Hanganu A, Bellec P. Markers of cognitive decline in PD: the case for heterogeneity. Park Relat Disord. 2016;24:8–14. CrossRef
Whitwell JL, Xu J, Mandrekar JN, Gunter JL, Jack CR, Josephs KA. Rates of brain atrophy and clinical decline over 6 and 12-month intervals in PSP: Determining sample size for treatment trials. Park Relat Disord. 2012;18:252–6. CrossRef
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;61:1881–4. PubMed
Boelmans K, Bodammer NC, Suchorska B, Kaufmann J, Ebersbach G, Heinze HJ, et al. Diffusion tensor imaging of the corpus callosum differentiates corticobasal syndrome from Parkinson’s disease. Park Relat Disord. 2010;16:498–502. CrossRef
Negoro K, Tada Y, Ogasawara J, Kawai M, Morimatsu M, Hashida M, et al. Proton magnetic resonance spectroscopy in corticobasal degeneration and progressive supranuclear palsy. Geriatr Gerontol Int. 2004;4:84–92. CrossRef
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. 2015;278:142764.
Brücke T, Asenbaum S, Pirker W, Djamshidian S, Wenger S, Wöber C, et al. Measurement of the dopaminergic degeneration in Parkinson’s disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive Supranuclear palsy. J Neural Transm Suppl. 1997;50:9–24. PubMedCrossRef
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;303–12.
Erro R, Schneider SA, Quinn NP, Bhatia KP. What do patients with scans without evidence of dopaminergic deficit (SWEDD) have? New evidence and continuing controversies. J Neurol Neurosurg Psychiatry. 2016:87(3):319-23.
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. Park Relat Disord. 2013;19:222–6. CrossRef
Song IU, Yoo I, Chung YA, Jeong J. The value of brain perfusion SPECT for differentiation between mildly symptomatic idiopathic Parkinson’s disease and the Parkinson variant of multiple system atrophy. Nucl Med Commun England. 2015;36:1049–54. CrossRef
Matsui H, Udaka F, Miyoshi T, Hara N, Tamura A, Oda M, et al. Brain perfusion differences between Parkinson’s disease and multiple system atrophy with predominant parkinsonian features. Park Relat Disord. 2005;11:227–32. CrossRef
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 (2010). 2013;47:44–51. CrossRef
Brooks DJ, Ibanez V, Sawle GV, Playford ED, Quinn N, Mathias CJ, et al. Striatal D2 receptor status in patients with Parkinson’s disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography. Ann Neurol. 1992;31:184–92. PubMedCrossRef
Akdemir UO, Tokcaer AB, Karakus A, Kapucu LO. Brain 18 F-FDG PET imaging in the differential diagnosis of parkinsonism. Clin Nucl Med. 2014;93:e220–6. CrossRef
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;29:380–7. PubMedCrossRef
Botha H, Whitwell JL, Madhaven A, Senjem ML, Lowe V, Josephs KA. The pimple sign of progressive supranuclear palsy syndrome. Park Relat Disord. 2014;20:180–5. CrossRef
Harding AJ, Halliday GM. Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol. 2001;102:355–63. PubMed
Claassen DO, Lowe VJ, Peller PJ, Petersen RC, Josephs KA. Amyloid and glucose imaging in dementia with Lewy bodies and multiple systems atrophy. Park Relat Disord. 2011;17:160–5. CrossRef
Kepe V, Bordelon Y, Boxer A, Huang SC, Liu J, Thiede FC, et al. PET imaging of neuropathology in tauopathies: progressive Supranuclear palsy. J Alzheimer’s Dis. 2013;36:145–53.
Xia C-F, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, et al. [18 F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimer’s Dement. 2013;9:666–76. CrossRef
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. 2016. doi: 10.1002/mds.26844 [Epub ahead of print].
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. Alzheimer’s Dement J Alzheimer’s Assoc. 2015;11:608–21. e7. CrossRef
Yokokura M, Terada T, Bunai T, Nakaizumi K, Takebayashi K, Iwata Y, et al. Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195. J Cereb Blood Flow Metab. 2016. [Epub ahead of print].
Gasnier B, Roisin MP, Scherman D, Coornaert S, Desplanches G, Henry JP. Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes. Mol Pharmacol. 1986;29:275–80. PubMed
Raffel DM, Koeppe RA, Little R, Wang C-N, Liu S, Junck L, et al. PET measurement of cardiac and nigrostriatal denervation in Parkinsonian syndromes. J Nucl Med. 2006;47:1769–77. PubMed
Taki J, Nakajima K, Hwang EH, Matsunari I, Komai K, Yoshita M, et al. Peripheral sympathetic dysfunction in patients with Parkinson’s disease without autonomic failure is heart selective and disease specific. EurJ Nucl Med. 2000;27:566–73. CrossRef
Takatsu H, Nishida H, Matsuo H, Watanabe S, Nagashima K, Wada H, et al. Cardiac sympathetic denervation from the early stage of Parkinson’s disease: clinical and experimental studies with radiolabeled MIBG. J Nucl Med. 2000;41:71–7. PubMed
Sadowski K, Serafin-Król M, Szlachta K, Friedman A. Basal ganglia echogenicity in tauopathies. J Neural Transm (Vienna). 2015;122:863–5. CrossRef
- Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes: current and emerging concepts
Richard I. Aviv
Antonio P. Strafella
Sandra E. Black
Anthony E. Lang
- BioMed Central