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Support vector machine-based classification of Alzheimer’s disease from whole-brain anatomical MRI

  • Diagnostic Neuroradiology
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Abstract

Purpose

We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with Alzheimer’s disease (AD) and elderly control subjects.

Materials and methods

We studied 16 patients with AD [mean age ± standard deviation (SD) = 74.1 ± 5.2 years, mini-mental score examination (MMSE) = 23.1 ± 2.9] and 22 elderly controls (72.3 ± 5.0 years, MMSE = 28.5 ± 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results.

Results

We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%).

Conclusions

Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD.

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References

  1. Brookmeyer R, Gray S, Kawas C (1998) Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88:1337–1342

    Article  PubMed  CAS  Google Scholar 

  2. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117 doi:10.1016/S0140-6736(05)67889-0

    Article  PubMed  Google Scholar 

  3. Ramaroson H, Helmer C, Barberger-Gateau P, Letenneur L, Dartigues J (2003) Prevalence of dementia and Alzheimer’s disease among subjects aged 75 years or over: updated results of the PAQUID cohort. Rev Neurol (Paris) 159:405–411 (in French)

    CAS  Google Scholar 

  4. Winblad B, Wimo A (1999) Assessing the societal impact of acetylcholinesterase inhibitor therapies. Alzheimer Dis Assoc Disord 13(Suppl 2):S9–S19 doi:10.1097/00002093-199911002-00003

    Article  PubMed  Google Scholar 

  5. DeKosky ST, Marek K (2003) Looking backward to move forward: early detection of neurodegenerative disorders. Science 302:830–834 doi:10.1126/science.1090349

    Article  PubMed  CAS  Google Scholar 

  6. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194 doi:10.1111/j.1365-2796.2004.01388.x

    Article  PubMed  CAS  Google Scholar 

  7. Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund L, Nordberg A, Bäckman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment—beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246 doi:10.1111/j.1365-2796.2004.01380.x

    Article  PubMed  CAS  Google Scholar 

  8. Braak H, Braak E (1995) Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 16:271–278 (discussion 278–284) doi:10.1016/0197-4580(95)00021-6

    Article  PubMed  CAS  Google Scholar 

  9. Bastos Leite AJ, Scheltens P, Barkhof F (2004) Pathological aging of the brain: an overview. Top Magn Reson Imaging 15:369–389 doi:10.1097/01.rmr.0000168070.90113.dc

    Article  PubMed  Google Scholar 

  10. Glodzik-Sobanska L, Rusinek H, Mosconi L, Li Y, Zhan J, de Santi S, Convit A, Rich K, Brys M, de Leon MJ (2005) The role of quantitative structural imaging in the early diagnosis of Alzheimer’s disease. Neuroimaging Clin N Am 15:803–826 doi:10.1016/j.nic.2005.09.004

    Article  PubMed  Google Scholar 

  11. Xu Y, Jack CR Jr, O’Brien PC, Kokmen E, Smith GE, Ivnik RJ, Boeve BF, Tangalos RG, Petersen RC (2000) Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology 54:1760–1767

    PubMed  CAS  Google Scholar 

  12. Frisoni GB, Laakso MP, Beltramello A, Geroldi C, Bianchetti A, Soininen H, Trabucchi M (1999) Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer’s disease. Neurology 52:91–100

    PubMed  CAS  Google Scholar 

  13. Laakso MP, Soininen H, Partanen K, Lehtovirta M, Hallikainen M, Hänninen T, Helkala EL, Vainio P, Riekkinen PJS (1998) MRI of the hippocampus in Alzheimer’s disease: sensitivity, specificity, and analysis of the incorrectly classified subjects. Neurobiol Aging 19:23–31 doi:10.1016/S0197-4580(98)00006-2

    Article  PubMed  CAS  Google Scholar 

  14. Lehéricy S, Baulac M, Chiras J, Piérot L, Martin N, Pillon B, Deweer B, Dubois B, Marsault C (1994) Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. Am J Neuroradiol 15:929–937

    PubMed  Google Scholar 

  15. Jack CR Jr, Petersen RC, O’Brien PC, Tangalos EG (1992) MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease. Neurology 42:183–188

    PubMed  Google Scholar 

  16. Pennanen C, Kivipelto M, Tuomainen S, Hartikainen P, Hänninen T, Laakso MP, Hallikainen M, Vanhanen M, Nissinen A, Helkala E, Vainio P, Vanninen R, Partanen K, Soininen H (2004) Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging 25:303–310 doi:10.1016/S0197-4580(03)00084-8

    Article  PubMed  Google Scholar 

  17. Du AT, Schuff N, Amend D, Laakso MP, Hsu YY, Jagust WJ, Yaffe K, Kramer JH, Reed B, Norman D, Chui HC, Weiner MW (2001) Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 71:441–447 doi:10.1136/jnnp.71.4.441

    Article  PubMed  CAS  Google Scholar 

  18. De Santi S, de Leon MJ, Rusinek H, Convit A, Tarshish CY, Roche A, Tsui WH, Kandil E, Boppana M, Daisley K, Wang GJ, Schlyer D, Fowler J (2001) Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging 22:529–539 doi:10.1016/S0197-4580(01)00230-5

    Article  PubMed  Google Scholar 

  19. Convit A, De Leon MJ, Tarshish C, De Santi S, Tsui W, Rusinek H, George A (1997) Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease. Neurobiol Aging 18:131–138 doi:10.1016/S0197-4580(97)00001-8

    Article  PubMed  CAS  Google Scholar 

  20. Chetelat G, Baron J (2003) Early diagnosis of Alzheimer’s disease: contribution of structural neuroimaging. Neuroimage 18:525–541 doi:10.1016/S1053-8119(02)00026-5

    Article  PubMed  Google Scholar 

  21. Lao Z, Shen D, Xue Z, Karacali B, Resnick SM, Davatzikos C (2004) Morphological classification of brains via high-dimensional shape transformations and machine learning methods. Neuroimage 21:46–57 doi:10.1016/j.neuroimage.2003.09.027

    Article  PubMed  Google Scholar 

  22. Fan Y, Shen D, Davatzikos C (2005) Classification of structural images via high-dimensional image warping, robust feature extraction, and SVM. Med Image Comput Comput Assist Interv Int Conf 8:1–8

    Article  CAS  Google Scholar 

  23. Cortes C, Vapnik V (1995) Support-Vector Networks. Mach Learn 20:273–297

    Google Scholar 

  24. Fan Y, Batmanghelich N, Clark CM, Davatzikos C (2008) Spatial patterns of brain atrophy in MCI patients, identified via high-dimensional pattern classification, predict subsequent cognitive decline. Neuroimage 39:1731–1743 doi:10.1016/j.neuroimage.2007.10.031

    Article  PubMed  Google Scholar 

  25. Klöppel S, Stonnington CM, Chu C, Draganski B, Scahill RI, Rohrer JD, Fox NC, Jack CR Jr, Ashburner J, Frackowiak RSJ (2008) Automatic classification of MR scans in Alzheimer’s disease. Brain 131:681–689 doi:10.1093/brain/awm319

    Article  PubMed  Google Scholar 

  26. Vemuri P, Gunter JL, Senjem ML, Whitwell JL, Kantarci K, Knopman DS, Boeve BF, Petersen RC, Jack CR Jr (2008) Alzheimer’s disease diagnosis in individual subjects using structural MR images: Validation studies. Neuroimage 39:1186–1197 doi:10.1016/j.neuroimage.2007.09.073

    Article  PubMed  Google Scholar 

  27. Teipel SJ, Born C, Ewers M, Bokde ALW, Reiser MF, Möller H, Hampel H (2007) Multivariate deformation-based analysis of brain atrophy to predict Alzheimer’s disease in mild cognitive impairment. Neuroimage 38:13–24 doi:10.1016/j.neuroimage.2007.07.008

    Article  PubMed  Google Scholar 

  28. Davatzikos C, Fan Y, Wu X, Shen D, Resnick SM (2008) Detection of prodromal Alzheimer’s disease via pattern classification of magnetic resonance imaging. Neurobiol Aging 29:514–523 doi:10.1016/j.neurobiolaging.2006.11.010

    Article  PubMed  Google Scholar 

  29. Davatzikos C, Resnick SM, Wu X, Parmpi P, Clark CM (2008) Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI. Neuroimage 41:1220–1227 doi:10.1016/j.neuroimage.2008.03.050

    Article  PubMed  CAS  Google Scholar 

  30. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    PubMed  CAS  Google Scholar 

  31. Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414

    PubMed  CAS  Google Scholar 

  32. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198 doi:10.1016/0022-3956(75)90026-6

    Article  PubMed  CAS  Google Scholar 

  33. Benton AL (1968) Genuine memory deficits in dementia. Neuropsychologia 6:53–60 doi:10.1016/0028-3932(68)90038-9

    Article  Google Scholar 

  34. Sano M, Stern Y, Mayeux R, Hartman S, Devanand DP (1987) A standardized technique for establishing the onset symptoms of probable Alzheimer’s disease. J Clin Exp Neuropsychol 9:65

    Google Scholar 

  35. Stern Y, Albert M, Brandt J, Jacobs DM, Tang MX, Marder K, Bell K, Sano M, Devanand DP, Bylsma F et al (1994) Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: prospective analyses from the Predictors Study. Neurology 44:2300–2307

    PubMed  CAS  Google Scholar 

  36. Stern Y, Mayeux R, Sano M, Hauser WA, Bush T (1987) Predictors of disease course in patients with probable Alzheimer’s disease. Neurology 37:1649–1653

    PubMed  CAS  Google Scholar 

  37. Grober E, Buschke H (1987) Genuine memory deficits in dementia. Dev Neuropsychol 3:13–36

    Article  Google Scholar 

  38. Goldblum MC, Gomez CM, Dalla Barba G, Boller F, Deweer B, Hahn V, Dubois B (1998) The influence of semantic and perceptual encoding on recognition memory in Alzheimer’s disease. Neuropsychologia 36:717–729 doi:10.1016/S0028-3932(98)00007-4

    Article  PubMed  CAS  Google Scholar 

  39. Benton AL (1974) The revised visual retention test: clinical and experimental applications. Psychological Corporation, New York

    Google Scholar 

  40. Sirigu A, Cohen L, Duhamel JR, Pillon B, Dubois B, Agid Y (1995) A selective impairment of hand posture for object utilization in apraxia. Cortex 31:41–55

    PubMed  CAS  Google Scholar 

  41. Mayeux R, Rosen W (1983) The dementias. Raven, New York

    Google Scholar 

  42. Deloche G, Hannequin D (1997) Test de dénomination orale d’images D080. Les Editions du Centre de Psychologie Appliquée, Paris

    Google Scholar 

  43. Kaplan E, Goodglass H, Weintraub S (1983) The Boston Naming Test. Lea and Febiger, Philadelphia

    Google Scholar 

  44. Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a Frontal Assessment Battery at bedside. Neurology 55:1621–1626

    PubMed  CAS  Google Scholar 

  45. Dorion AA, Sarazin M, Hasboun D, Hahn-Barma V, Dubois B, Zouaoui A, Marsault C, Duyme M (2002) Relationship between attentional performance and corpus callosum morphometry in patients with Alzheimer’s disease. Neuropsychologia 40:946–956 doi:10.1016/S0028-3932(01)00150-6

    Article  PubMed  Google Scholar 

  46. Robbins TW, James M, Owen AM, Sahakian BJ, Lawrence AD, McInnes L, Rabbitt PM (1998) A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery. J Int Neuropsychol Soc 4:474–490 doi:10.1017/S1355617798455073

    Article  PubMed  CAS  Google Scholar 

  47. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15:273–289 doi:10.1006/nimg.2001.0978

    Article  PubMed  CAS  Google Scholar 

  48. Ashburner J, Friston K (2003) Image segmentation. In: Frackowiak R, Friston K, Frith C, Dolan R, Price C, Zeki S, Ashburner J, Penny W (eds) Human brain function, 2nd edn. Academic, San Diego, pp 695–706

    Google Scholar 

  49. Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme Medical Publisher, New York

    Google Scholar 

  50. Ashburner J, Friston KJ (1999) Nonlinear spatial normalization using basis functions. Hum Brain Mapp 7:254–266 doi:10.1002/(SICI)1097-0193(1999)7:4<254::AID-HBM4>3.0.CO;2-G

    Article  PubMed  CAS  Google Scholar 

  51. Ashburner J, Andersson JL, Friston KJ (2000) Image registration using a symmetric prior—in three dimensions. Hum Brain Mapp 9:212–225 doi:10.1002/(SICI)1097-0193(200004)9:4<212::AID-HBM3>3.0.CO;2-#

    Article  PubMed  CAS  Google Scholar 

  52. Redner R, Walker H (1984) Mixture densities, maximum likelihood and the EM algorithm. SIAM Rev 26:195–239 doi:10.1137/1026034

    Article  Google Scholar 

  53. Efron B, Tibshirani RJ (1993) An introduction to the bootstrap. Chapman and Hall, New York

    Google Scholar 

  54. Burton EJ, Karas G, Paling SM, Barber R, Williams ED, Ballard CG, McKeith IG, Scheltens P, Barkhof F, O’Brien JT (2002) Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry. Neuroimage 17:618–630 doi:10.1016/S1053-8119(02)91197-3

    Article  PubMed  CAS  Google Scholar 

  55. Barber R, McKeith IG, Ballard C, Gholkar A, O’Brien JT (2001) A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer’s disease: magnetic resonance imaging volumetric study. Dement Geriatr Cogn Disord 12:198–205 doi:10.1159/000051258

    Article  PubMed  CAS  Google Scholar 

  56. 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

    Article  PubMed  Google Scholar 

  57. Ballmaier M, O’Brien JT, Burton EJ, Thompson PM, Rex DE, Narr KL, McKeith IG, DeLuca H, Toga AW (2004) Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer’s disease using cortical pattern matching: diagnosis and gender effects. Neuroimage 23:325–335 doi:10.1016/j.neuroimage.2004.04.026

    Article  PubMed  Google Scholar 

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Conflict of interest statement

S. Kinkingnéhun has a financial relationship with e(ye)BRAIN. B. Dubois and H. Benali consult for e(ye)BRAIN.

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Correspondence to Mélanie Pélégrini-Issac.

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Magnin, B., Mesrob, L., Kinkingnéhun, S. et al. Support vector machine-based classification of Alzheimer’s disease from whole-brain anatomical MRI. Neuroradiology 51, 73–83 (2009). https://doi.org/10.1007/s00234-008-0463-x

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  • DOI: https://doi.org/10.1007/s00234-008-0463-x

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