title: Imaging biomarkers in Parkinson's disease and Parkinsonian syndromes: current and emerging concepts.
abstract: 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 inin vivoimaging 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.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.|LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Usman
authors.initials: U
authors.lastname: Saeed
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.|LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.
authors.forename: Jordana
authors.initials: J
authors.lastname: Compagnone
authors.affiliation: Department of Medical Imaging, University of Toronto and Division of Neuroradiology, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Aviv
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.|Division of Brain, Imaging & Behaviour - Systems Neuroscience, Toronto Western Hospital, Toronto, Canada.|Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Strafella
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.|LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.|Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.|Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
authors.affiliation: Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.|Movement Disorders Centre, Toronto Western Hospital, Toronto, Canada.|Edmond J. Safra Program in Parkinson's Disease, University Health Network, Toronto, Canada.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.|LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Canada.|Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.|Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room A4-55, Toronto, Ontario M4N 3 M5 Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
keywords: Atypical parkinsonian syndrome; Biomarkers; Diffusion tensor imaging; MRI; Molecular imaging; Myocardial scintigraphy; PET; Parkinson’s disease; SPECT; Transcranial sonography