Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and idiopathic Parkinson’s disease (IPD) can be clinically indistinguishable, especially in the early stages, despite distinct patterns of molecular pathology. Structural neuroimaging holds promise for providing objective biomarkers for discriminating these diseases at the single subject level but all studies to date have reported incomplete separation of disease groups. In this study, we employed multi-class pattern recognition to assess the value of anatomical patterns derived from a widely available structural neuroimaging sequence for automated classification of these disorders. To achieve this, 17 patients with PSP, 14 with IPD and 19 with MSA were scanned using structural MRI along with 19 healthy controls (HCs). An advanced probabilistic pattern recognition approach was employed to evaluate the diagnostic value of several pre-defined anatomical patterns for discriminating the disorders, including: (i) a subcortical motor network; (ii) each of its component regions and (iii) the whole brain. All disease groups could be discriminated simultaneously with high accuracy using the subcortical motor network. The region providing the most accurate predictions overall was the midbrain/brainstem, which discriminated all disease groups from one another and from HCs. The subcortical network also produced more accurate predictions than the whole brain and all of its constituent regions. PSP was accurately predicted from the midbrain/brainstem, cerebellum and all basal ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from the midbrain/brainstem only. This study demonstrates that automated analysis of structural MRI can accurately predict diagnosis in individual patients with Parkinsonian disorders, and identifies distinct patterns of regional atrophy particularly useful for this process.
References
[1]
Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE et al. (2003) SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord 18: 467-486. doi:10.1002/mds.10459. PubMed: 12722160.
[2]
Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K et al. (1994) Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology 44: 2015-2019. doi:10.1212/WNL.44.11.2015. PubMed: 7969952.
[3]
Papp MI, Lantos PL (1994) The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology. Brain 117: 235-243. doi:10.1093/brain/117.2.235. PubMed: 8186951.
[4]
Braak H, Braak E (2000) Pathoanatomy of Parkinson’s disease. J Neurol 247: 3-10. doi:10.1007/s004150050002. PubMed: 10701890.
[5]
Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Sch?fer H et al. (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355: 896-908. doi:10.1056/NEJMoa060281. PubMed: 16943402.
[6]
Shih LC, Tarsy D (2007) Deep brain stimulation for the treatment of atypical parkinsonism. Mov Disord 22: 2149-2155. doi:10.1002/mds.21648. PubMed: 17659638.
[7]
Paviour DC, Price SL, Stevens JM, Lees AJ, Fox NC (2005) Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology 64: 675-679. doi:10.1212/01.WNL.0000151854.85743.C7. PubMed: 15728291.
[8]
Nicoletti G, Fera F, Condino F, Auteri W, Gallo O et al. (2006) MR imaging of middle cerebellar peduncle width: Differentiation of multiple system atrophy from Parkinson disease. Radiology 239: 825-830. doi:10.1148/radiol.2393050459. PubMed: 16714464.
[9]
Quattrone A, Nicoletti G, Messina D, Fera F, Condino F et al. (2008) MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology 246: 214-221. PubMed: 17991785.
[10]
Rolland Y, Verin M, Payan CA, Duchesne S, Kraft E et al. (2011) A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability. J Neurol Neurosurg, Psychiatry 82: 1025-1032. doi:10.1136/jnnp.2010.214890.
[11]
Brenneis C, Seppi K, Schocke MF, Müller J, Luginger E et al. (2003) Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Mov Disord 18: 1132-1138. doi:10.1002/mds.10502. PubMed: 14534916.
[12]
Price S, Paviour D, Scahill R, Stevens J, Rossor M et al. (2004) Voxel-based morphometry detects patterns of atrophy that help differentiate progressive supranuclear palsy and Parkinson’s disease. NeuroImage 23: 663-669. doi:10.1016/j.neuroimage.2004.06.013. PubMed: 15488416.
[13]
Cordato NJ, Duggins AJ, Halliday GM, Morris JGL, Pantelis C (2005) Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy. Brain 128: 1259-1266. doi:10.1093/brain/awh508. PubMed: 15843423.
[14]
Minnerop M, Specht K, Ruhlmann J, Schimke N, Abele M et al. (2007) Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy - A comparison between clinical subtypes and correlations with clinical parameters. NeuroImage 36: 1086-1095. doi:10.1016/j.neuroimage.2007.04.028. PubMed: 17512219.
[15]
Mahlknecht P, Hotter A, Hussl A, Esterhammer R, Schocke M et al. (2010) Significance of MRI in Diagnosis and Differential Diagnosis of Parkinson’s Disease. Neurodegener Dis 7: 300-318. doi:10.1159/000314495. PubMed: 20616565.
[16]
Orrù G, Pettersson-Yeo W, Marquand AF, Sartori G, Mechelli A (2012) Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: A critical review. Neurosci Biobehav Rev 36: 1140-1152. doi:10.1016/j.neubiorev.2012.01.004. PubMed: 22305994.
[17]
Kl?ppel S, Abdulkadir A, Jack CR Jr., Koutsouleris N, Mour?o-Miranda J et al. (2012) Diagnostic neuroimaging across diseases. NeuroImage 61: 457-463. doi:10.1016/j.neuroimage.2011.11.002. PubMed: 22094642.
[18]
Kl?ppel S, Stonnington CM, Chu C, Draganski B, Scahill RI et al. (2008) Automatic classification of MR scans in Alzheimers disease. Brain 131: 681-689. doi:10.1093/brain/awm319. PubMed: 18202106.
[19]
Kl?ppel S, Chu C, Tan GC, Draganski B, Johnson H et al. (2009) Automatic detection of preclinical neurodegeneration Presymptomatic Huntington disease. Neurology 72: 426-431. doi:10.1212/01.wnl.0000341768.28646.b6. PubMed: 19188573.
[20]
Duchesne S, Rolland Y, Vérin M (2009) Automated Computer Differential Classification in Parkinsonian Syndromes via Pattern Analysis on MRI. Acad Radiol 16: 61-70. doi:10.1016/j.acra.2008.05.024. PubMed: 19064213.
[21]
Focke NK, Helms G, Scheewe S, Pantel PM, Bachmann CG et al. (2011) Individual Voxel-Based Subtype Prediction can Differentiate Progressive Supranuclear Palsy from Idiopathic Parkinson Syndrome and Healthy Controls. Hum Brain Mapp 32: 1905-1915. doi:10.1002/hbm.21161. PubMed: 21246668.
[22]
Ozawa T, Paviour D, Quinn NP, Josephs KA, Sangha H et al. (2004) The spectrum of pathological involvement of the striatonigral and olivopontocerebellar systems in multiple system atrophy: clinicopathological correlations. Brain 127: 2657-2671. doi:10.1093/brain/awh303. PubMed: 15509623.
[23]
Jubault T, Brambati SM, Degroot C, Kullmann B, Strafella AP et al. (2009) Regional Brain Stem Atrophy in Idiopathic Parkinson’s Disease Detected by Anatomical MRI. PLOS ONE 4: e8247. PubMed: 20011063.
[24]
Josephs KA, Whitwell JL, Dickson DW, Boeve BF, Knopman DS et al. (2008) Voxel-based morphometry in autopsy proven PSP and CBD. Neurobiology of Aging 29: 280-289. doi:10.1016/j.neurobiolaging.2006.09.019. PubMed: 17097770.
[25]
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical-diagnosis of idiopathic Parkinson’s disease - a clinicopathological study of 100 cases. J Neurol Neurosurg, Psychiatry 55: 181-184. doi:10.1136/jnnp.55.3.181.
[26]
Litvan I, Agid Y, Calne D, Campbell G, Dubois B et al. (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy. Steele: Richardson-Olszewski syndrome): Report. of the NINDS-SPSP International Workshop. Neurology 47: 1-9.
[27]
Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y et al. (1999) Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 163: 94-98. doi:10.1016/S0022-510X(98)00304-9. PubMed: 10223419.
[28]
Blain CRV, Barker GJ, Jarosz JM, Coyle NA, Landau S et al. (2006) Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI. Neurology 67: 2199-2205. doi:10.1212/01.wnl.0000249307.59950.f8. PubMed: 17190944.
[29]
Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C et al. (2009) Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study. Brain 132: 156-171. PubMed: 19029129.
[30]
Williams DR, de Silva R, Paviour DC, Pittman A, Watt HC et al. (2005) Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism. Brain 128: 1247–58. PubMed: 15788542.
[31]
Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ et al. (2008) Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71: 670–6. PubMed: 18725592.
[32]
Hoehn MM, Yahr MD (1967) Parkinsonism - onset, progression and mortality. Neurology 17: 427–442 &. doi:10.1212/WNL.17.5.427. . PubMed : 6067254.
[33]
Schwab RS, England AC (1968) Projection techniques for evaluating surgery in Parkinson’s Disease. Third Symposium on Parkinson’s Disease, Royal College of Surgeons in Edinburgh, May. E S Livingstone Ltd 20-22: 152-157.
[34]
Payan CAM, Vidailhet M, Lacomblez L, Viallet F, Borg M et al. (2002) Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS): Construction and validation of a functional scale for disease progression assessment in Parkinson Plus Syndromes, Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA). Mov Disord 17: S256-S256.
[35]
Bronte-Stewart HM, Minn AY, Rodrigues K, Buckley EL, Nashner LM (2002) Postural instability in idiopathic Parkinson’s disease: the role of medication and unilateral pallidotomy. Brain 125: 2100-2114. doi:10.1093/brain/awf207. PubMed: 12183355.
[36]
Filippone M, Marquand AF, Blain CRV, Williams SCR, Mour?o-Miranda J et al. (2012) Probabilistic prediction of neurological disorders with a statistical assessment of neuroimaging data modalities. Annals Appl Statistics, 6(4): 1883-1905. doi:10.1214/12-AOAS562.
[37]
Singh N, Fletcher PT, Preston JS, Ha L, King R et al. (2010) Multivariate Statistical Analysis of Deformation Momenta Relating Anatomical Shape to Neuropsychological Measures. Medical Images Computing Computer-Assist Interv-MICCAI 6363: 529-537. PubMed: 20879441.
[38]
Marquand AF, Mour?o-Miranda J, Brammer MJ, Cleare AJ, Fu CHY (2008) Neuroanatomy of verbal working memory as a diagnostic biomarker for depression. Neuroreport 19: 1507-1511. doi:10.1097/WNR.0b013e328310425e. PubMed: 18797307.
[39]
Mour?o-Miranda J, Oliveira L, Ladouceur CD, Marquand A, Brammer M et al. (2012) Pattern Recognition and Functional Neuroimaging Help to Discriminate Healthy Adolescents at Risk for Mood Disorders from Low Risk Adolescents. PLOS ONE 7: e29482. PubMed: 22355302.
[40]
Marquand AF, O’Daly OG, De Simoni S, Alsop DC, Maguire RP et al. (2012) Dissociable effects of methylphenidate, atomoxetine and placebo on regional cerebral blood flow in healthy volunteers at rest: A multi-class pattern recognition approach. Neuroimage 60: 1015–24. PubMed: 22266414.
[41]
Mour?o-Miranda J, Almeida JR, Hassel S, de Oliveira L, Versace A et al. (2012) Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression. Bipolar Disord 14: 451-460. doi:10.1111/j.1399-5618.2012.01019.x. PubMed: 22631624.
[42]
Marquand AF, De Simoni S, O’Daly OG, Williams SC, Mour?o-Miranda J et al. (2011) Pattern classification of working memory networks reveals differential effects of methylphenidate, atomoxetine, and placebo in healthy volunteers. Neuropsychopharmacology 36: 1237-1247. doi:10.1038/npp.2011.9. PubMed: 21346736.
[43]
Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ (2001) What features improve the accuracy of clinical diagnosis in Parkinson’s disease: A clinicopathologic study. Neurology 57: 1142–6. PubMed: 1603339.
[44]
Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125.
[45]
Burton EJ, McKeith IG, Burn DJ, Williams ED, O’Brien JT (2004) Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain 127: 791-800. doi:10.1093/brain/awh088. PubMed: 14749292.
[46]
Chu C, Hsu A-L, Chou K-H, Bandettini P, Lin C et al. (2012) Does feature selection improve classification accuracy? Impact of sample size and feature selection on classification using anatomical magnetic resonance images. Neuroimage 60: 59-70. doi:10.1016/j.neuroimage.2011.11.066. PubMed: 22166797.
[47]
Brodersen KH, Cheng Soon O, Stephan KE, Buhmann JM (2010) The balanced accuracy and its posterior distribution. Proceedings of the 20th International Conference on Pattern Recognition(ICPR 2010).