Journal of Neurology

, Volume 259, Issue 9, pp 1769–1780 | Cite as

Positron emission tomography imaging in neurological disorders

Review

Abstract

Positron emission tomography (PET) is a powerful tool for in vivo imaging investigations of human brain function. It provides non-invasive quantification of brain metabolism, receptor binding of various neurotransmitter systems, and alterations in regional blood flow. The use of PET in a clinical setting is still limited due to the high costs of cyclotrons and radiochemical laboratories. However, once these limitations can be bypassed, PET could aid clinical practice by providing a useful imaging technique for the diagnosis, the planning of treatment, and the prediction outcome in various neurological diseases. This review aims to explain the PET imaging technique and its applications in neurological disorders such as Parkinson’s disease, Huntington’s disease, multiple sclerosis, and dementias.

Keywords

PET Parkinson Huntington Multiple sclerosis Dementia 

Notes

Acknowledgments

Our own research is supported by the Michael J Fox Foundation for Parkinson’s Research USA, the Parkinson’s UK and the Cure Huntington’s Disease Initiative Foundation USA.

Conflicts of interest

Nothing to declare.

References

  1. 1.
    Birattari C, Bonardi M, Ferrari A, Milanesi L, Silari M (1987) Biomedical applications of cyclotrons and review of commercially available models. J Med Eng Technol 11:166–176PubMedCrossRefGoogle Scholar
  2. 2.
    Phelps ME (1977) Emission computed tomography. Semin Nucl Med 7:337–365PubMedCrossRefGoogle Scholar
  3. 3.
    Phelps ME (2000) Positron emission tomography provides molecular imaging of biological processes. PNAS 97:9226–9233PubMedCrossRefGoogle Scholar
  4. 4.
    Cherry SR, Woods RP, Hoffman EJ, Mazziotta JC (1993) Improved detection of focal cerebral blood flow changes using three-dimensional positron emission tomography. J Cereb Blood Flow Metab 13:630–638PubMedCrossRefGoogle Scholar
  5. 5.
    Brix G, Zaers J, Adam LE, Bellemann ME, Ostertag H, Trojan H, Haberkorn U, Doll J, Oberdorfer F, Lorenz WJ (1997) Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association. J Nucl Med 38:1614–1623PubMedGoogle Scholar
  6. 6.
    Spinks TJ, Jones T, Bloomfield PM, Bailey DL, Miller M, Hogg D, Jones WF, Vaigneur K, Reed J, Young J, Newport D, Moyers C, Casey ME, Nutt R (2000) Physical characteristics of the ECAT EXACT3D positron tomograph. Phys Med Biol 45:2601–2618PubMedCrossRefGoogle Scholar
  7. 7.
    Kemp BJ, Kim C, Williams JJ, Ganin A, Lowe VJ, National Electrical Manufacturers Association (NEMA) (2006) NEMA NU 2–2001 performance measurements of an LYSO-based PET/CT system in 2D and 3D acquisition modes. J Nucl Med 47:1960–1967PubMedGoogle Scholar
  8. 8.
    Piccini P, Pavese N, Brooks DJ (2003) Endogenous dopamine release after pharmacological challenges in Parkinson’s disease. Ann Neurol 53:647–665PubMedCrossRefGoogle Scholar
  9. 9.
    de la Fuente-Fernández R, Sossi V, Huang Z, Furtado S, Lu JQ, Calne DB, Ruth TJ, Stoessl AJ (2004) Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias. Brain 127:2747–2754PubMedCrossRefGoogle Scholar
  10. 10.
    Piccini P, Lindvall O, Björklund A, Brundin P, Hagell P, Ceravolo R, Oertel W, Quinn N, Samuel M, Rehncrona S, Widner H, Brooks DJ (2000) Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts. Ann Neurol 48:689–695PubMedCrossRefGoogle Scholar
  11. 11.
    Sawamoto N, Piccini P, Hotton G, Pavese N, Thielemans K, Brooks DJ (2008) Cognitive deficits and striato-frontal dopamine release in Parkinson’s disease. Brain 131:1294–1302PubMedCrossRefGoogle Scholar
  12. 12.
    Goerendt IK, Messa C, Lawrence AD, Grasby PM, Piccini P, Brooks DJ, PET study (2003) Dopamine release during sequential finger movements in health and Parkinson’s disease: a PET study. Brain 126:312–325PubMedCrossRefGoogle Scholar
  13. 13.
    Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27:1533–1539PubMedCrossRefGoogle Scholar
  14. 14.
    Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. Neuroimage 4:153–158PubMedCrossRefGoogle Scholar
  15. 15.
    Gunn RN, Lammertsma AA, Hume SP, Cunningham VJ (1997) Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage 6:279–287PubMedCrossRefGoogle Scholar
  16. 16.
    Montgomery AJ, Thielemans K, Mehta MA, Turkheimer F, Mustafovic S, Grasby PM (2006) Correction of head movement on PET studies: comparison of methods. J Nucl Med 47:1936–1944PubMedGoogle Scholar
  17. 17.
    Garnett ES, Firnau G, Nahmias C (1983) Dopamine visualized in the basal ganglia of living man. Nature 305:137–138PubMedCrossRefGoogle Scholar
  18. 18.
    Vingerhoets FJ, Schulzer M, Calne DB, Snow BJ (1997) Which clinical sign of Parkinson’s disease best reflects the nigrostriatal lesion? Ann Neurol 41:58–64PubMedCrossRefGoogle Scholar
  19. 19.
    Broussolle E, Dentresangle C, Landais P, Garcia-Larrea L, Pollak P, Croisile B, Hibert O, Bonnefoi F, Galy G, Froment JC, Comar D (1999) The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson’s disease. J Neurol Sci 166:141–151PubMedCrossRefGoogle Scholar
  20. 20.
    Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114:2283–2301PubMedCrossRefGoogle Scholar
  21. 21.
    Brück A, Aalto S, Rauhala E, Bergman J, Marttila R, Rinne JO (2009) A follow-up study on 6-[18F] fluoro-l-dopa uptake in early Parkinson’s disease shows nonlinear progression in the putamen. Mov Disord 24:1009–1015PubMedCrossRefGoogle Scholar
  22. 22.
    Hilker R, Schweitzer K, Coburger S, Ghaemi M, Weisenbach S, Jacobs AH, Rudolf J, Herholz K, Heiss WD (2005) Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity. Arch Neurol 62:378–382PubMedCrossRefGoogle Scholar
  23. 23.
    Nandhagopal R, Kuramoto L, Schulzer M, Mak E, Cragg J, Lee CS, McKenzie J, McCormick S, Samii A, Troiano A, Ruth TJ, Sossi V, de la Fuente-Fernandez R, Calne DB, Stoessl AJ (2009) Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study. Brain 132:2970–2979PubMedCrossRefGoogle Scholar
  24. 24.
    Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, Wudel J, Pal PK, de la Fuente Fernandez R, Calne DB, Stoessl AJ (2000) In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol 47:493–503PubMedCrossRefGoogle Scholar
  25. 25.
    de la Fernández Fuente R, Sossi V, McCormick S, Schulzer M, Ruth TJ, Stoessl AJ (2009) Visualizing vesicular dopamine dynamics in Parkinson’s disease. Synapse 63:713–716CrossRefGoogle Scholar
  26. 26.
    Leenders KL, Salmon EP, Tyrrell P, Perani D, Brooks DJ, Sager H, Jones T, Marsden CD, Frackowiak RS (1990) The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson’s disease. Arch Neurol 47:1290–1298PubMedCrossRefGoogle Scholar
  27. 27.
    Salmon E, Brooks DJ, Leenders KL, Turton DR, Hume SP, Cremer JE, Jones T, Frackowiak RS (1990) A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography. J Cereb Blood Flow Metab 10:307–316PubMedCrossRefGoogle Scholar
  28. 28.
    Tedroff J, Aquilonius SM, Laihinen A, Rinne U, Hartvig P, Anderson J, Lundqvist H, Haa paranta M, Solin O, Antoni G, Gee AD, Ullin J, Långström B (1990) Striatal kinetics of [11C]-(+)- nomifensine and 6-[18F]fluoro-L-dopa in Parkinson’s disease measured with positron emission tomography. Acta Neurol Scand 81:24–30PubMedCrossRefGoogle Scholar
  29. 29.
    Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Snyder SH, Ravert HT, Dannals RF (1993) Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson’s disease. Ann Neurol 34:423–431PubMedCrossRefGoogle Scholar
  30. 30.
    Marié RM, Barré L, Rioux P, Allain P (1995) Lecheva- lier B, Baron JC (1995) PET imaging of neocortical monoaminergic terminals in Parkinson’s disease. J Neural Transm Park Dis Dement Sect 9:55–71PubMedCrossRefGoogle Scholar
  31. 31.
    Guttman M, Burkholder J, Kish SJ, Hussey D, Wilson A, DaSilva J, Houle S (1997) [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson’s disease: implications for the symptomatic threshold. Neurology 48:1578–1583PubMedCrossRefGoogle Scholar
  32. 32.
    Rinne JO, Laihinen A, Ruottinen H, Ruot- salainen U, Någren K, Lehikoinen P, Oikonen V, Rinne UK (1995) Increased density of dopamine D2 receptors in the putamen, but not in the caudate nucleus in early Parkinson’s disease: a PET study with [11C]raclopride. J Neurol Sci 132:156–161Google Scholar
  33. 33.
    Politis M, Piccini P, Pavese N, Koh SB, Brooks DJ (2008) Evidence of dopamine dysfunction in the hypothalamus of patients with Parkinson’s disease: an in vivo 11C-raclopride PET study. Exp Neurol 214:112–116PubMedCrossRefGoogle Scholar
  34. 34.
    Brooks DJ (1993) PET studies on the early and differential diagnosis of Parkinson’s disease. Neurology 43:S6–S16PubMedGoogle Scholar
  35. 35.
    Burn DJ, Sawle GV, Brooks DJ (1994) Differential diagnosis of Parkinson’s disease, multiple system atrophy, and Steele–Richardson–Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data. J Neurol Neurosurg Psychiatry 57:278–284PubMedCrossRefGoogle Scholar
  36. 36.
    Politis M, Wu K, Molloy S, Bain GP, Chaudhuri P, Piccini P (2010) Parkinson’s disease symptoms: the patient’s perspective. Mov Disord 25:1646–1651PubMedCrossRefGoogle Scholar
  37. 37.
    Fox SH, Chuang R, Brotchie JM (2009) Serotonin and Parkinson’s disease: on movement, mood, and madness. Mov Disord 24:1255–1266PubMedCrossRefGoogle Scholar
  38. 38.
    Politis M, Wu K, Loane C, Kiferle L, Molloy S, Brooks DJ, Piccini P (2010) Staging of serotonergic dysfunction in Parkinson’s disease: an in vivo 11C-DASB PET study. Neurobiol Dis 40:216–221PubMedCrossRefGoogle Scholar
  39. 39.
    Politis M, Wu K, Loane C, Turkheimer FE, Molloy S, Brooks DJ, Piccini P (2010) Depressive symptoms in PD correlate with higher 5-HTT binding in raphe and limbic structures. Neurology 75:1920–1927PubMedCrossRefGoogle Scholar
  40. 40.
    Politis M, Loane C, Wu K, Brooks DJ, Piccini P (2011) Serotonergic mediated body mass index changes in Parkinson’s disease. Neurobiol Dis 43:609–615PubMedCrossRefGoogle Scholar
  41. 41.
    O’Sullivan SS, Wu K, Politis M, Lawrence AD, Evans AH, Bose SK, Djamshidian A, Lees AJ, Piccini P (2011) Cue-induced striatal dopamine release in Parkinson’s disease-associated impulsive-compulsive behaviours. Brain 134:969–978PubMedCrossRefGoogle Scholar
  42. 42.
    Lindvall O, Björklund A (2004) Cell therapy in Parkinson’s disease. NeuroRx 1:382–393PubMedCrossRefGoogle Scholar
  43. 43.
    Politis M (2011) Optimizing functional imaging protocols for assessing the outcome of fetal cell transplantation in Parkinson’s disease. BMC Med 9:50PubMedCrossRefGoogle Scholar
  44. 44.
    Politis M, Wu K, Loane C, Quinn NP, Brooks DJ, Rehncrona S, Bjorklund A, Lindvall O, Piccini P (2010) Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci Transl Med 2:38–46Google Scholar
  45. 45.
    Politis M, Oertel WH, Wu K, Quinn NP, Pogarell O, Brooks DJ, Bjorklund A, Lindvall O, Piccini P (2011) Graft-induced dyskinesias in Parkinson’s disease: high striatal serotonin/dopamine transporter ratio. Mov Disord 26:1997–2003PubMedCrossRefGoogle Scholar
  46. 46.
    Politis M (2010) Dyskinesias after neural transplantation in Parkinson’s disease: what do we know and what is next? BMC Med 8:80PubMedCrossRefGoogle Scholar
  47. 47.
    Ginovart N, Lundin A, Farde L, Halldin C, Bäckman L, Swahn CG, Pauli S, Sedvall G (1997) PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington’s disease. Brain 120:503–514PubMedCrossRefGoogle Scholar
  48. 48.
    Antonini A, Leenders KL, Eidelberg D (1998) [11C]raclopride-PET studies of the Huntington’s disease rate of progression: relevance of the trinucleotide repeat length. Ann Neurol 43:253–255PubMedCrossRefGoogle Scholar
  49. 49.
    Andrews TC, Weeks RA, Turjanski N, Gunn RN, Watkins LH, Sahakian B, Hodges JR, Rosser AE, Wood NW, Brooks DJ (1999) Huntington’s disease progression PET and clinical observations. Brain 122:2353–2363PubMedCrossRefGoogle Scholar
  50. 50.
    Lawrence AD, Weeks RA, Brooks DJ, Andrews TC, Watkins LH, Harding AE, Robbins TW, Sahakian BJ (1998) The relationship between striatal dopamine receptor binding and cognitive performance in Huntington’s disease. Brain 121:1343–1355PubMedCrossRefGoogle Scholar
  51. 51.
    Pavese N, Andrews TC, Brooks DJ, Ho AK, Rosser AE, Barker RA, Robbins TW, Sahakian BJ, Dunnett SB, Piccini P (2003) Progressive striatal and cortical dopamine receptor dysfunction in Huntington’s disease: a PET study. Brain 126:1127–1135PubMedCrossRefGoogle Scholar
  52. 52.
    Pavese N, Politis M, Tai YF, Barker RA, Tabrizi SJ, Mason SL, Brooks DJ, Piccini P (2010) Cortical dopamine dysfunction in symptomatic and premanifest Huntington’s disease gene carriers. Neurobiol Dis 37:356–361PubMedCrossRefGoogle Scholar
  53. 53.
    Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, Brooks DJ, Piccini P (2006) Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66:1638–1643PubMedCrossRefGoogle Scholar
  54. 54.
    Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P (2007) Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain 130:1759–1766PubMedCrossRefGoogle Scholar
  55. 55.
    Politis M, Pavese N, Tai YF, Tabrizi SJ, Barker RA, Piccini P (2008) Hypothalamic involvement in Huntington’s disease: an in vivo PET study. Brain 131:2860–2869PubMedCrossRefGoogle Scholar
  56. 56.
    Politis M, Pavese N, Tai YF, Kiferle L, Mason SL, Brooks DJ, Tabrizi SJ, Barker RA, Piccini P (2011) Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum Brain Mapp 32:258–270PubMedCrossRefGoogle Scholar
  57. 57.
    Weeks RA, Ceballos-Baumann A, Piccini P, Boecker H, Harding AE, Brooks DJ (1997) Cortical control of movement in Huntington’s disease, A PET activation study. Brain 120:1569–1578PubMedCrossRefGoogle Scholar
  58. 58.
    Feigin A, Leenders KL, Moeller JR, Missimer J, Kuenig G, Spetsieris P, Antonini A, Eidelberg D (2001) Metabolic network abnormalities in early Huntington’s disease: an [(18)F]FDG PET study. J Nucl Med 42:1591–1595PubMedGoogle Scholar
  59. 59.
    Künig G, Leenders KL, Sanchez-Pernaute R, Antonini A, Vontobel P, Verhagen A, Günther I (2000) Benzodiazepine receptor binding in Huntington’s disease: [11C]flumazenil uptake measured using positron emission tomography. Ann Neurol 47:644–648PubMedCrossRefGoogle Scholar
  60. 60.
    Furtado S, Sossi V, Hauser RA, Samii A, Schulzer M, Murphy CB, Freeman TB, Stoessl AJ (2005) Positron emission tomography after fetal transplantation in Huntington’s disease. Ann Neurol 58:331–337PubMedCrossRefGoogle Scholar
  61. 61.
    Gaura V, Bachoud-Lévi AC, Ribeiro MJ, Nguyen JP, Frouin V, Baudic S, Brugières P, Mangin JF, Boissé MF, Palfi S, Cesaro P, Samson Y, Hantraye P, Peschanski M, Remy P (2004) Striatal neural grafting improves cortical metabolism in Huntington’s disease patients. Brain 127:65–72PubMedCrossRefGoogle Scholar
  62. 62.
    Kiferle L, Politis M, Muraro PA, Piccini P (2011) Positron emission tomography imaging in multiple sclerosis-current status and future applications. Eur J Neurol 18:226–231PubMedCrossRefGoogle Scholar
  63. 63.
    Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123:2321–2337PubMedCrossRefGoogle Scholar
  64. 64.
    Debruyne JC, Versijpt J, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2003) PET visualization of microglia in multiple sclerosis patients using [11C]PK11195. Eur J Neurol 10:257–264PubMedCrossRefGoogle Scholar
  65. 65.
    Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2005) Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 11:127–134PubMedCrossRefGoogle Scholar
  66. 66.
    Politis M, Giannetti P, Su P, Turkheimer F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini P (2012) Increased PK11195 PET binding in the cortex of MS patients correlates with disability. Neurology (in press)Google Scholar
  67. 67.
    Pozzilli C, Fieschi C, Perani D, Paulesu E, Comi G, Bastianello S, Bernardi S, Bettinardi V, Bozzao L, Canal N et al (1992) Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis. J Neurol Sci 112:51–57PubMedCrossRefGoogle Scholar
  68. 68.
    Paulesu E, Perani D, Fazio F, Comi G, Pozzilli C, Martinelli V, Filippi M, Bettinardi V, Sirabian G, Passafiume D, Anzini A, Lenzi GL, Canal N, Fieschi C (1996) Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study. Neuroimage 4:87–96PubMedCrossRefGoogle Scholar
  69. 69.
    Roelcke U, Kappos L, Lechner-Scott J, Brunnschweiler H, Huber S, Ammann W, Plohmann A, Dellas S, Maguire RP, Missimer J, Radü EW, Steck A, Leenders KL (1997) Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study. Neurology 48:1566–1571PubMedCrossRefGoogle Scholar
  70. 70.
    Blinkenberg M, Jensen CV, Holm S, Paulson OB, Sørensen PS (1999) A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS. Neurology 53:149–153PubMedCrossRefGoogle Scholar
  71. 71.
    Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S (1998) Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Ann Nucl Med 12:89–94PubMedCrossRefGoogle Scholar
  72. 72.
    Stankoff B, Freeman L, Aigrot MS, Chardain A, Dollé F, Williams A, Galanaud D, Armand L, Lehericy S, Lubetzki C, Zalc B, Bottlaender M (2011) Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-¹¹C]-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole. Ann Neurol 69:673–680PubMedCrossRefGoogle Scholar
  73. 73.
    Wimo A, Winblad B, Aguero-Torres H, von Strauss E (2003) The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord 17:63–67PubMedCrossRefGoogle Scholar
  74. 74.
    Mosconi L, Mistur R, Switalski R, Tsui WH, Glodzik L, Li Y, Pirraglia E, De Santi S, Reisberg B, Wisniewski T, de Leon MJ (2009) FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease. Eur J Nucl Med Mol Imaging 36:811–822PubMedCrossRefGoogle Scholar
  75. 75.
    Mosconi L (2005) Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 32:486–510PubMedCrossRefGoogle Scholar
  76. 76.
    Jagust W, Reed B, Mungas D, Ellis W, Decarli C (2007) What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology 69:871–877PubMedCrossRefGoogle Scholar
  77. 77.
    Tartaglia MC, Rosen HJ, Miller BL (2011) Neuroimaging in dementia. Neurotherapeutics 8:82–92PubMedCrossRefGoogle Scholar
  78. 78.
    Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, Schwaiger M, Kurz A (2003) Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 30:1104–1113PubMedCrossRefGoogle Scholar
  79. 79.
    Drzezga A, Grimmer T, Riemenschneider M, Lautenschlager N, Siebner H, Alexopoulus P, Minoshima S, Schwaiger M, Kurz A (2005) Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med 46:1625–1632PubMedGoogle Scholar
  80. 80.
    Mosconi L, Brys M, Glodzik-Sobanska L, De Santi S, Rusinek H, de Leon MJ (2007) Early detection of Alzheimer’s disease using neuroimaging. Exp Gerontol 42:129–138PubMedCrossRefGoogle Scholar
  81. 81.
    Rabinovici GD, Jagust WJ (2009) Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav Neurol 21:117–128PubMedGoogle Scholar
  82. 82.
    Price JC, Klunk WE, Lopresti BJ, Lu X, Hoge JA, Ziolko SK, Holt DP, Meltzer CC, DeKosky ST, Mathis CA (2005) Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab 25:1528–1547PubMedCrossRefGoogle Scholar
  83. 83.
    Archer HA, Edison P, Brooks DJ, Barnes J, Frost C, Yeatman T, Fox NC, Rossor MN (2006) Amyloid load and cerebral atrophy in Alzheimer’s disease: an 11C-PIB positron emission tomography study. Ann Neurol 60:145–147PubMedCrossRefGoogle Scholar
  84. 84.
    Kemppainen NM, Aalto S, Wilson IA, Någren K, Helin S, Brück A, Oikonen V, Kailajärvi M, Scheinin M, Viitanen M, Parkkola R, Rinne JO (2006) Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 67:1575–1580PubMedCrossRefGoogle Scholar
  85. 85.
    Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC (2006) [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology 67:446–452PubMedCrossRefGoogle Scholar
  86. 86.
    Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, Fripp J, Tochon-Danguy H, Morandeau L, O’Keefe G, Price R, Raniga P, Robins P, Acosta O, Lenzo N, Szoeke C, Salvado O, Head R, Martins R, Masters CL, Ames D, Villemagne VL (2010) Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31:1275–1283PubMedCrossRefGoogle Scholar
  87. 87.
    Forsberg A, Engler H, Almkvist O, Blomquist G, Hagman G, Wall A, Ringheim A, Långström B, Nordberg A (2008) PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging 29:1456–1465PubMedCrossRefGoogle Scholar
  88. 88.
    Okello A, Koivunen J, Edison P, Archer HA, Turkheimer FE, Någren K, Bullock R, Walker Z, Kennedy A, Fox NC, Rossor MN, Rinne JO, Brooks DJ (2009) Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology 73:754–760PubMedCrossRefGoogle Scholar
  89. 89.
    Jack CR Jr, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, Zeng G, Bernstein MA, Gunter JL, Pankratz VS, Aisen PS, Weiner MW, Petersen RC, Shaw LM, Trojanowski JQ, Knopman DS, Initiative Alzheimer’s Disease Neuroimaging (2010) Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease. Brain 133:3336–3348PubMedCrossRefGoogle Scholar
  90. 90.
    Grimmer T, Henriksen G, Wester HJ, Förstl H, Klunk WE, Mathis CA, Kurz A, Drzezga A (2009) Clinical severity of Alzheimer’s disease is associated with PIB uptake in PET. Neurobiol Aging 30:1902–1909PubMedCrossRefGoogle Scholar
  91. 91.
    Villemagne VL, Pike KE, Darby D, Maruff P, Savage G, Ng S, Ackermann U, Cowie TF, Currie J, Chan SG, Jones G, Tochon-Danguy H, O’Keefe G, Masters CL, Rowe CC (2008) Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia 46:1688–1697PubMedCrossRefGoogle Scholar
  92. 92.
    Edison P, Rowe CC, Rinne JO, Ng S, Ahmed I, Kemppainen N, Villemagne VL, O’Keefe G, Någren K, Chaudhury KR, Masters CL, Brooks DJ (2008) Amyloid load in Parkinson’s disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry 79:1331–1338PubMedCrossRefGoogle Scholar
  93. 93.
    Maetzler W, Reimold M, Liepelt I, Solbach C, Leyhe T, Schweitzer K, Eschweiler GW, Mittelbronn M, Gaenslen A, Uebele M, Reischl G, Gasser T, Machulla HJ, Bares R, Berg D (2008) [11C]PIB binding in Parkinson’s disease dementia. Neuroimage 39:1027–1033PubMedCrossRefGoogle Scholar
  94. 94.
    Drzezga A, Grimmer T, Henriksen G, Stangier I, Perneczky R, Diehl-Schmid J, Mathis CA, Klunk WE, Price J, DeKosky S, Wester HJ, Schwaiger M, Kurz A (2008) Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease. Neuroimage 39:619–633PubMedCrossRefGoogle Scholar
  95. 95.
    Engler H, Santillo AF, Wang SX, Lindau M, Savitcheva I, Nordberg A, Lannfelt L, Långström B, Kilander L (2008) In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging 35:100–106PubMedCrossRefGoogle Scholar
  96. 96.
    Koole M, Lewis DM, Buckley C, Nelissen N, Vandenbulcke M, Brooks DJ, Vandenberghe R, Van Laere K (2009) Whole-body biodistribution and radiation dosimetry of 18F-GE067: a radioligand for in vivo brain amyloid imaging. J Nucl Med 50:818–822PubMedCrossRefGoogle Scholar
  97. 97.
    Choi SR, Golding G, Zhuang Z, Zhang W, Lim N, Hefti F, Benedum TE, Kilbourn MR, Skovronsky D, Kung HF (2009) Preclinical properties of 18F-AV-45: a PET agent for Abeta plaques in the brain. J Nucl Med 50:1887–1894PubMedCrossRefGoogle Scholar
  98. 98.
    Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O’Keefe G, Tochon-Danguy H, Chan G, Berlangieri SU, Jones G, Dickinson-Rowe KL, Kung HP, Zhang W, Kung MP, Skovronsky D, Dyrks T, Holl G, Krause S, Friebe M, Lehman L, Lindemann S, Dinkelborg LM, Masters CL, Villemagne VL (2008) Imaging of amyloid beta in Alzheimer’s disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol 7:129–135PubMedCrossRefGoogle Scholar
  99. 99.
    Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB (2001) In vivo measurement of activated microglia in dementia. Lancet 358:461–467PubMedCrossRefGoogle Scholar
  100. 100.
    Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, Walker Z, Kennedy A, Fox N, Rossor M, Brooks DJ (2009) Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72:56–62PubMedCrossRefGoogle Scholar
  101. 101.
    Wiley CA, Lopresti BJ, Venneti S, Price J, Klunk WE, DeKosky ST, Mathis CA (2009) Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol 66:60–67PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Division of Experimental Medicine, Faculty of Medicine, Centre for Neuroscience, Hammersmith HospitalImperial College LondonLondonUK

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