MRI supervised and unsupervised classification of Parkinson's disease and multiple system atrophy
Corresponding Author
Patrice Péran PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Correspondence to: Patrice Péran, UMR 1214 - INSERM/UPS – ToNIC, Toulouse NeuroImaging Center, CHU PURPAN - Pavillon Baudo - Place du Dr Baylac, 31024 Toulouse - Cedex 3, France; E-mail: [email protected]Search for more papers by this authorGaetano Barbagallo MD
Institute of Neurology, University Magna Græcia, Catanzaro, Italy
Search for more papers by this authorFederico Nemmi PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Search for more papers by this authorMaria Sierra MD
Neurology Service, University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain
Search for more papers by this authorMonique Galitzky MD
Centre d'Investigation Clinique (CIC), CHU de Toulouse, Toulouse, France
Search for more papers by this authorAnne Pavy-Le Traon MD, PhD
UMR Institut National de la Santé et de la Recherche Médicale 1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France
Department of Neurology and Institute for Neurosciences, University Hospital of Toulouse, Toulouse, France
Search for more papers by this authorPierre Payoux MD, PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Search for more papers by this authorWassilios G. Meissner MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
Search for more papers by this authorOlivier Rascol MD, PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Université de Toulouse 3, CHU de Toulouse, INSERM, Centre de Reference AMS, Service de Neurologie et de Pharmacologie Clinique, Centre d'Investigation Clinique CIC1436, Réseau NS-Park/FCRIN et Centre of excellence for neurodegenerative disorders (COEN) de Toulouse, Toulouse, France
Search for more papers by this authorCorresponding Author
Patrice Péran PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Correspondence to: Patrice Péran, UMR 1214 - INSERM/UPS – ToNIC, Toulouse NeuroImaging Center, CHU PURPAN - Pavillon Baudo - Place du Dr Baylac, 31024 Toulouse - Cedex 3, France; E-mail: [email protected]Search for more papers by this authorGaetano Barbagallo MD
Institute of Neurology, University Magna Græcia, Catanzaro, Italy
Search for more papers by this authorFederico Nemmi PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Search for more papers by this authorMaria Sierra MD
Neurology Service, University Hospital Marqués de Valdecilla and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Santander, Spain
Search for more papers by this authorMonique Galitzky MD
Centre d'Investigation Clinique (CIC), CHU de Toulouse, Toulouse, France
Search for more papers by this authorAnne Pavy-Le Traon MD, PhD
UMR Institut National de la Santé et de la Recherche Médicale 1048, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France
Department of Neurology and Institute for Neurosciences, University Hospital of Toulouse, Toulouse, France
Search for more papers by this authorPierre Payoux MD, PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Search for more papers by this authorWassilios G. Meissner MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
Search for more papers by this authorOlivier Rascol MD, PhD
ToNIC, Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France
Université de Toulouse 3, CHU de Toulouse, INSERM, Centre de Reference AMS, Service de Neurologie et de Pharmacologie Clinique, Centre d'Investigation Clinique CIC1436, Réseau NS-Park/FCRIN et Centre of excellence for neurodegenerative disorders (COEN) de Toulouse, Toulouse, France
Search for more papers by this authorRelevant conflicts of interest/financial disclosusres: Nothing to report.
Funding agencies: The study was sponsored by Inserm and funded by a “Recherche clinique translationnelle” grant from INSERM-DGOS (2013-2014).
Abstract
Background: Multimodal MRI approach is based on a combination of MRI parameters sensitive to different tissue characteristics (eg, volume atrophy, iron deposition, and microstructural damage). The main objective of the present study was to use a multimodal MRI approach to identify brain differences that could discriminate between matched groups of patients with multiple system atrophy, Parkinson's disease, and healthy controls. We assessed the 2 different MSA variants, namely, MSA-P, with predominant parkinsonism, and MSA-C, with more prominent cerebellar symptoms.
Methods: Twenty-six PD patients, 29 MSA patients (16 MSA-P, 13 MSA-C), and 26 controls underwent 3-T MRI comprising T2*-weighted, T1-weighted, and diffusion tensor imaging scans. Using whole-brain voxel-based MRI, we combined gray-matter density, T2* relaxation rates, and diffusion tensor imaging scalars to compare and discriminate PD, MSA-P, MSA-C, and healthy controls.
Results: Our main results showed that this approach reveals multiparametric modifications within the cerebellum and putamen in both MSA-C and MSA-P patients, compared with PD patients. Furthermore, our findings revealed that specific single multimodal MRI markers were sufficient to discriminate MSA-P and MSA-C patients from PD patients. Moreover, the unsupervised analysis based on multimodal MRI data could regroup individuals according to their clinical diagnosis, in most cases.
Conclusions: This study demonstrates that multimodal MRI is able to discriminate patients with PD from those with MSA with high accuracy. The combination of different MR biomarkers could be a great tool in early stage of disease to help diagnosis. © 2018 International Parkinson and Movement Disorder Society
Supporting Information
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Supplementary Information Table 2 |
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References
- 1
Halliday GM,
Holton JL,
Revesz T, et al. Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 2011; 122: 187-204.
- 2
Gilman S,
Wenning GK,
Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71: 670-676.
- 3
Berg D,
Steinberger JD,
Warren Olanow C, et al. Milestones in magnetic resonance imaging and transcranial sonography of movement disorders. Mov Disord 2011; 26: 979-992.
- 4
Martin WRW,
Wieler M,
Gee M. Midbrain iron content in early Parkinson disease: A potential biomarker of disease status. Neurology 2008; 70: 1411-1417.
- 5
Péran P,
Cherubini A,
Assogna F, et al. Magnetic resonance imaging markers of Parkinson's disease nigrostriatal signature. Brain 2010; 133: 3423-3433.
- 6
Vaillancourt DE,
Spraker MB,
Prodoehl J, et al. High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease. Neurology 2009; 72: 1378-1384.
- 7
Meijer FJA,
Aerts MB,
Abdo WF, et al. Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3-year prospective follow-up study. J Neurol 2012; 259: 929-935.
- 8
Scherfler C,
Göbel G,
Müller C, et al. Diagnostic potential of automated subcortical volume segmentation in atypical parkinsonism. Neurology 2016; 86: 1242-1249.
- 9
Huppertz H-J,
Möller L,
Südmeyer M, et al. Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification. Mov Disord 2016; 0: 1-12.
- 10
Planetta PJ,
Ofori E,
Pasternak O, et al. Free-water imaging in Parkinson's disease and atypical parkinsonism. Brain 2016; 139: 495-508.
- 11
Hughes AJ,
Daniel SE,
Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184.
- 12
Hoehn MM,
Yahr MD. Parkinsonism: onset, progression, and mortality. 1967. Neurology 2001; 57: S11-S26.
- 13
Tomlinson CL,
Stowe R,
Patel S, et al. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord 2010; 25: 2649-2653.
- 14 Fahn S ERUDC. The Unified Parkinson's Disease Rating Scale; 1987.
- 15
Péran P,
Cherubini A,
Luccichenti G, et al. Volume and iron content in basal ganglia and thalamus. Hum Brain Mapp 2009; 30: 2667-2675.
- 16
Cherubini A,
Péran P,
Caltagirone C, et al. Aging of subcortical nuclei: microstructural, mineralization and atrophy modifications measured in vivo using MRI. Neuroimage Published Online First: 2009.
- 17
Winkler AM,
Ridgway GR,
Webster MA, et al. Permutation inference for the general linear model. Neuroimage 2014; 92: 381-397.
- 18
Smith SM,
Nichols TE. Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 2009; 44: 83-98.
- 19
Litvan I,
Bhatia KP,
Burn DJ, et al. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for parkinsonian disorders. Mov Disord 2003; 18: 467-486.
- 20
Osaki Y,
Ben-Shlomo Y,
Lees AJ, et al. A validation exercise on the new consensus criteria for multiple system atrophy. Mov Disord 2009; 24: 2272-2276.
- 21
Petrovic IN,
Ling H,
Asi Y, et al. Multiple system atrophy-parkinsonism with slow progression and prolonged survival: A diagnostic catch. Mov Disord 2012; 27: 1186-1190.
- 22
Meissner WG,
Laurencin C,
Tranchant C, et al. Outcome of deep brain stimulation in slowly progressive multiple system atrophy: a clinico-pathological series and review of the literature. Parkinsonism Relat Disord 2016; 24: 69-75.
- 23
Barbagallo G,
Sierra-Peña M,
Nemmi F, et al. Multimodal MRI assessment of nigro-striatal pathway in multiple system atrophy and Parkinson disease. Mov Disord 2016; 31: 325-334.
- 24
Dexter DT,
Carayon A,
Javoy-Agid F, et al. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain 1991; 114(Part 4): 1953-1975.
- 25
Sofic E,
Paulus W,
Jellinger K, et al. Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J Neurochem 1991; 56: 978-982.
- 26
Baudrexel S,
Nürnberger L,
Rüb U, et al. Quantitative mapping of T1 and T2* discloses nigral and brainstem pathology in early Parkinson's disease. Neuroimage 2010; 51: 512-520.
- 27
Langkammer C,
Pirpamer L,
Seiler S, et al. Quantitative Susceptibility Mapping in Parkinson's Disease. PLoS One 2016; 11: e0162460.
- 28
Reiter E,
Mueller C,
Pinter B, et al. Dorsolateral nigral hyperintensity on 3.0T susceptibility-weighted imaging in neurodegenerative Parkinsonism. Mov Disord 2015; 30: 1068-1076.
- 29
Langley J,
Huddleston DE,
Merritt M, et al. Diffusion tensor imaging of the substantia nigra in Parkinson's disease revisited. Hum Brain Mapp 2016; 37: 2547-2556.
- 30
Schwarz ST,
Abaei M,
Gontu V, et al. Diffusion tensor imaging of nigral degeneration in Parkinson's disease: A region-of-interest and voxel-based study at 3 T and systematic review with meta-analysis. Neuroimage Clin 2013; 3: 481-488.
- 31
Brenneis C,
Seppi K,
Schocke MF, et al. Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord 2003; 18: 1132-1138.
- 32
Tir M,
Delmaire C,
le Thuc V, et al. Motor-related circuit dysfunction in MSA-P: usefulness of combined whole-brain imaging analysis. Mov Disord 2009; 24: 863-870.
- 33
Focke NK,
Helms G,
Pantel PM, et al. Differentiation of typical and atypical Parkinson syndromes by quantitative MR imaging. AJNR Am J Neuroradiol 2011; 32: 2087-2092.
- 34
Lee J-H,
Baek S-Y,
Song Y, et al. The neuromelanin-related T2* contrast in postmortem human substantia nigra with 7T MRI. Sci Rep 2016; 6: 32647.
- 35
Nicoletti G,
Rizzo G,
Barbagallo G, et al. Diffusivity of cerebellar hemispheres enables discrimination of cerebellar or parkinsonian multiple system atrophy from progressive supranuclear palsy–Richardson syndrome and Parkinson disease. Radiology 2013; 267: 843-850.
- 36
Worker A,
Blain C,
Jarosz J, et al. Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study. PLoS One 2014; 9: e112638.
- 37
Pellecchia MT,
Barone P,
Mollica C, et al. Diffusion-weighted imaging in multiple system atrophy: A comparison between clinical subtypes. Mov Disord 2009; 24: 689-696.
- 38
Nicoletti G,
Fera F,
Condino F, et al. MR Imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease. Radiology 2006; 239: 825-830.
- 39
Paviour DC,
Thornton JS,
Lees AJ, et al. Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy. Mov Disord 2007; 22: 68-74.
- 40
Wu Y-T,
Shyu K-K,
Jao C-W, et al. Quantifying cerebellar atrophy in multiple system atrophy of the cerebellar type (MSA-C) using three-dimensional gyrification index analysis. Neuroimage 2012; 61: 1-9.
- 41
Lee J-H,
Han Y-H,
Kang B-M, et al. Quantitative assessment of subcortical atrophy and iron content in progressive supranuclear palsy and parkinsonian variant of multiple system atrophy. J Neurol 2013; 260: 2094-2101.
- 42
Lee EA,
Cho HI,
Kim SS, et al. Comparison of magnetic resonance imaging in subtypes of multiple system atrophy. Parkinsonism Relat Disord 2004; 10: 363-368.
