Molecular Imaging and Biology

, Volume 9, Issue 4, pp 186–195 | Cite as

Animal Models of Neurodegenerative Disease: Insights from In vivo Imaging Studies

Review Article Special Issue: Molecular Imaging in the Evaluation of Neurodegenerative Diseases
First Online:

Abstract

Animal models have been used extensively to understand the etiology and pathophysiology of human neurodegenerative diseases, and are an essential component in the development of therapeutic interventions for these disorders. In recent years, technical advances in imaging modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have allowed the use of these techniques for the evaluation of functional, neurochemical, and anatomical changes in the brains of animals. Combining animal models of neurodegenerative disorders with neuroimaging provides a powerful tool to follow the disease process, to examine compensatory mechanisms, and to investigate the effects of potential treatments preclinically to derive knowledge that will ultimately inform our clinical decisions. This article reviews the literature on the use of PET and MRI in animal models of Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease, and evaluates the strengths and limitations of brain imaging in animal models of neurodegenerative diseases.

Key words

Animal model PET MRI Parkinson’s disease Huntington’s disease Alzheimer’s disease Monkey Rodent 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Sanchez-Pernaute R, Brownell AL, Jenkins BG, Isacson O (2005) Insights into Parkinson’s disease models and neurotoxicity using non-invasive imaging. Toxicol Appl Pharmacol 207:251–256PubMedCrossRefGoogle Scholar
  2. 2.
    Doudet DJ, Chan GL, Holden JE et al. (1998) 6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys. Synapse 29:225–232PubMedCrossRefGoogle Scholar
  3. 3.
    Melega WP, Raleigh MJ, Stout DB et al. (1996) Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys. Exp Neurol 141:318–329PubMedCrossRefGoogle Scholar
  4. 4.
    Schneider JS, Lidsky TI, Hawks T, Mazziotta JC, Hoffman JM (1995) Differential recovery of volitional motor function, lateralized cognitive function, dopamine agonist-induced rotation and dopaminergic parameters in monkeys made hemi-parkinsonian by intracarotid MPTP infusion. Brain Res 672:112–117PubMedCrossRefGoogle Scholar
  5. 5.
    Doudet DJ, Wyatt RJ, Cannon-Spoor E et al. (1993) 6-[18F]fluoro-L-dopa and cerebral blood flow in unilaterally MPTP-treated monkeys. J Neural Transpl Plast 4:27–38CrossRefGoogle Scholar
  6. 6.
    Yee RE, Irwin I, Milonas C et al. (2001) Novel observations with FDOPA-PET imaging after early nigrostriatal damage. Mov Disord 16:838–848PubMedCrossRefGoogle Scholar
  7. 7.
    Guttman M, Yong VW, Kim SU et al. (1988) Asymptomatic striatal dopamine depletion: PET scans in unilateral MPTP monkeys. Synapse 2:469–473PubMedCrossRefGoogle Scholar
  8. 8.
    Doudet DJ, Miyake H, Finn RT et al. (1989) 6-18F-L-dopa imaging of the dopamine neostriatal system in normal and clinically normal MPTP-treated rhesus monkeys. Exp Brain Res 78:69–80PubMedCrossRefGoogle Scholar
  9. 9.
    Eberling JL, Pivirotto P, Bringas J, Bankiewicz KS (2000) Tremor is associated with PET measures of nigrostriatal dopamine function in MPTP-lesioned monkeys. Exp Neurol 165:342–346PubMedCrossRefGoogle Scholar
  10. 10.
    Eberling JL, Bankiewicz KS, Jordan S, VanBrocklin HF, Jagust WJ (1997) PET studies of functional compensation in a primate model of Parkinson’s disease. Neuroreport 8:2727–2733PubMedCrossRefGoogle Scholar
  11. 11.
    Hantraye P, Brownell AL, Elmaleh D et al. (1992) Dopamine fiber detection by [11C]-CFT and PET in a primate model of parkinsonism. NeuroReport 3:265–268PubMedCrossRefGoogle Scholar
  12. 12.
    Wullner U, Pakzaban P, Brownell AL et al. (1994) Dopamine terminal loss and onset of motor symptoms in MPTP-treated monkeys: a positron emission tomography study with 11C-CFT. Exp Neurol 126:305–309PubMedCrossRefGoogle Scholar
  13. 13.
    Brownell AL, Canales K, Chen YI et al. (2003) Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson’s disease model. NeuroImage 20:1064–1075PubMedCrossRefGoogle Scholar
  14. 14.
    Brownell AL, Jenkins BG, Isacson O (1999) Dopamine imaging markers and predictive mathematical models for progressive degeneration in Parkinson’s disease. Biomed Pharmacother 53:131–140PubMedCrossRefGoogle Scholar
  15. 15.
    Brownell AL, Jenkins BG, Elmaleh DR et al. (1998) Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease. Nat Med 4:1308–1312PubMedCrossRefGoogle Scholar
  16. 16.
    Poyot T, Conde F, Gregoire MC et al. (2001) Anatomic and biochemical correlates of the dopamine transporter ligand 11C-PE2I in normal and parkinsonian primates: comparison with 6-[18F]fluoro-L-dopa. J Cereb Blood Flow Metab 21:782–792PubMedCrossRefGoogle Scholar
  17. 17.
    Doudet DJ, Jivan S, Ruth TJ, Holden JE (2002) Density and affinity of the dopamine D2 receptors in aged symptomatic and asymptomatic MPTP-treated monkeys: PET studies with [11C]raclopride. Synapse 44:198–202PubMedCrossRefGoogle Scholar
  18. 18.
    Hantraye P, Loc’h C, Tacke U et al. (1986) “In vivo” visualization by positron emission tomography of the progressive striatal dopamine receptor damage occurring in MPTP-intoxicated non-human primates. Life Sci 39:1375–1382PubMedCrossRefGoogle Scholar
  19. 19.
    Doudet DJ, Jivan S, Ruth TJ, Wyatt RJ (2002) In vivo PET studies of the dopamine D1 receptors in rhesus monkeys with long-term MPTP-induced Parkinsonism. Synapse 44:111–115PubMedCrossRefGoogle Scholar
  20. 20.
    Cohen RM, Carson RE, Wyatt RJ, Doudet DJ (1999) Opiate receptor avidity is reduced bilaterally in rhesus monkeys unilaterally lesioned with MPTP. Synapse 33:282–288PubMedCrossRefGoogle Scholar
  21. 21.
    Yee RE, Huang SC, Togasaki DM et al. (2002) Imaging and therapeutics: the role of neuronal transport in the regional specificity of L-DOPA accumulation in brain. Mol Imaging Biol 4:208–218PubMedCrossRefGoogle Scholar
  22. 22.
    Doudet DJ, Rosa-Neto P, Munk OL et al. (2006) Effect of age on markers for monoaminergic neurons of normal and MPTP-lesioned rhesus monkeys: a multi-tracer PET study. NeuroImage 30:26–35PubMedCrossRefGoogle Scholar
  23. 23.
    Lee CS, Samii A, Sossi V et al. (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
  24. 24.
    Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455PubMedCrossRefGoogle Scholar
  25. 25.
    Cohen RM, Carson RE, Aigner TG, Doudet DJ (1998) Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys. Brain Res 806:292–296PubMedCrossRefGoogle Scholar
  26. 26.
    Miletich RS, Bankiewicz KS, Quarantelli M et al (1994) MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys. Ann Neurol 35:689–697PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang Z, Zhang M, Ai Y, Avison C, Gash DM (1999) MPTP-Induced pallidal lesions in rhesus monkeys. Exp Neurol 155:140–149PubMedCrossRefGoogle Scholar
  28. 28.
    Sharma SK, Ebadi M (2005) Distribution kinetics of 18F-DOPA in weaver mutant mice. Brain Res Mol Brain Res 139:23–30PubMedCrossRefGoogle Scholar
  29. 29.
    Sharma SK, El Refaey H, Ebadi M (2006) Complex-1 activity and (18)F-DOPA uptake in genetically engineered mouse model of Parkinson’s disease and the neuroprotective role of coenzyme Q(10). Brain Res Bull 70:22–32PubMedCrossRefGoogle Scholar
  30. 30.
    Honer M, Hengerer B, Blagoev M et al. (2006) Comparison of [18F]FDOPA, [18F]FMT and [18F]FECNT for imaging dopaminergic neurotransmission in mice. Nucl Med Biol 33:607–614PubMedGoogle Scholar
  31. 31.
    Hume SP, Lammertsma AA, Myers R et al. (1996) The potential of high-resolution positron emission tomography to monitor striatal dopaminergic function in rat models of disease. J Neurosci Methods 67:103–112PubMedGoogle Scholar
  32. 32.
    Forsback S, Niemi R, Marjamaki P et al. (2004) Uptake of 6-[18F]fluoro-L-dopa and [18F]CFT reflect nigral neuronal loss in a rat model of Parkinson’s disease. Synapse 51:119-127PubMedCrossRefGoogle Scholar
  33. 33.
    Strome EM, Cepeda IL, Sossi V, Doudet DJ (2006) Evaluation of the integrity of the dopamine system in a rodent model of Parkinson’s disease: small animal PET compared to behavioral assessment and autoradiography. Mol Imaging Biol 8:292–299PubMedCrossRefGoogle Scholar
  34. 34.
    Sossi V, Holden JE, Topping GJ et al. (2007) In vivo measurement of density and affinity of the monoamine vesicular transporter in a unilateral 6-hydroxydopamine rat model of PD. J Cereb Blood Flow Metab (in press). DOI 10.1038/sj.jcbfm.9600446
  35. 35.
    Nguyen TV, Brownell AL, Iris Chen YC et al. (2000) Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET. Synapse 36:57–65PubMedCrossRefGoogle Scholar
  36. 36.
    Hume SP, Opacka-Juffry J, Myers R et al. (1995) Effect of L-dopa and 6-hydroxydopamine lesioning on [11C]raclopride binding in rat striatum, quantified using PET. Synapse 21:45–53PubMedCrossRefGoogle Scholar
  37. 37.
    Nikolaus S, Larisch R, Beu M et al. (2003) Bilateral increase in striatal dopamine D2 receptor density in the 6-hydroxydopamine-lesioned rat: a serial in vivo investigation with small animal PET. Eur J Nucl Med Mol Imaging 30:390–395PubMedCrossRefGoogle Scholar
  38. 38.
    Inaji M, Okauchi T, Ando K et al. (2005) Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats. Brain Res 1064:136–145PubMedCrossRefGoogle Scholar
  39. 39.
    Cicchetti F, Brownell AL, Williams K et al. (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991–998PubMedCrossRefGoogle Scholar
  40. 40.
    Sanchez-Pernaute R, Ferree A, Cooper O et al. (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation 1:6PubMedCrossRefGoogle Scholar
  41. 41.
    Chen YC, Galpern WR, Brownell AL et al. (1997) Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: correlation with PET, microdialysis, and behavioral data. Magn Reson Med 38:389–398PubMedCrossRefGoogle Scholar
  42. 42.
    Chen YI, Brownell AL, Galpern W et al. (1999) Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment. NeuroReport 10:2881–2886PubMedCrossRefGoogle Scholar
  43. 43.
    Brownell AL, Livni E, Galpern W, Isacson O (1998) In vivo PET imaging in rat of dopamine terminals reveals functional neural transplants. Ann Neurol 43:387–390PubMedCrossRefGoogle Scholar
  44. 44.
    Lindvall O, Bjorklund A (2004) Cell therapy in Parkinson’s disease. NeuroRx 1:382–393PubMedCrossRefGoogle Scholar
  45. 45.
    Doudet DJ, Cornfeldt ML, Honey CR, Schweikert AW, Allen RC (2004) PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson’s disease. Exp Neurol 189:361–368PubMedCrossRefGoogle Scholar
  46. 46.
    Danielsen EH, Cumming P, Andersen F et al. (2000) The DaNeX study of embryonic mesencephalic, dopaminergic tissue grafted to a minipig model of Parkinson’s disease: preliminary findings of effect of MPTP poisoning on striatal dopaminergic markers. Cell Transplant 9:247–259PubMedGoogle Scholar
  47. 47.
    Cumming P, Danielsen EH, Vafaee M et al. (2001) Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. Acta Neurol Scand 103:309–315PubMedCrossRefGoogle Scholar
  48. 48.
    Dall AM, Danielsen EH, Sorensen JC et al. (2002) Quantitative [18F]fluorodopa/PET and histology of fetal mesencephalic dopaminergic grafts to the striatum of MPTP-poisoned minipigs. Cell Transplant 11:733–746PubMedGoogle Scholar
  49. 49.
    Bjorklund LM, Sanchez-Pernaute R, Chung S et al. (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci U S A 99:2344–2349PubMedCrossRefGoogle Scholar
  50. 50.
    Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132PubMedCrossRefGoogle Scholar
  51. 51.
    Kishima H, Poyot T, Bloch J et al (2004) Encapsulated GDNF-producing C2C12 cells for Parkinson’s disease: a pre-clinical study in chronic MPTP-treated baboons. Neurobiol Dis 16:428–439PubMedCrossRefGoogle Scholar
  52. 52.
    Opacka-Juffry J, Ashworth S, Hume SP et al. (1995) GDNF protects against 6-OHDA nigrostriatal lesion: in vivo study with microdialysis and PET. NeuroReport 7:348–352PubMedGoogle Scholar
  53. 53.
    Sullivan AM, Opacka-Juffry J, Blunt SB (1998) Long-term protection of the rat nigrostriatal dopaminergic system by glial cell line-derived neurotrophic factor against 6-hydroxydopamine in vivo. Eur J Neurosci 10:57–63PubMedCrossRefGoogle Scholar
  54. 54.
    Kordower JH, Emborg ME, Bloch J et al. (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290:767–773PubMedCrossRefGoogle Scholar
  55. 55.
    Bankiewicz KS, Eberling JL, Kohutnicka M et al. (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164:2–14PubMedCrossRefGoogle Scholar
  56. 56.
    Emborg ME, Carbon M, Holden JE et al. (2006) Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. J Cereb Blood Flow Metab 27:501–509PubMedCrossRefGoogle Scholar
  57. 57.
    Lee WT, Chang C (2004) Magnetic resonance imaging and spectroscopy in assessing 3-nitropropionic acid-induced brain lesions: an animal model of Huntington’s disease. Prog Neurobiol 72:87–110PubMedCrossRefGoogle Scholar
  58. 58.
    The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983CrossRefGoogle Scholar
  59. 59.
    Rubinsztein DC, Barton DE, Davison BC, Ferguson-Smith MA (1993) Analysis of the huntingtin gene reveals a trinucleotide-length polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington’s disease and CAG repeat number. Hum Mol Genet 2:1713–1715PubMedCrossRefGoogle Scholar
  60. 60.
    Hoogeveen AT, Willemsen R, Meyer N et al. (1993) Characterization and localization of the Huntington disease gene product. Hum Mol Genet 2:2069–2073PubMedCrossRefGoogle Scholar
  61. 61.
    Roitberg BZ, Emborg ME, Sramek JG, Palfi S, Kordower JH (2002) Behavioral and morphological comparison of two nonhuman primate models of Huntington’s disease. Neurosurgery 50:137–145PubMedCrossRefGoogle Scholar
  62. 62.
    Brownell AL, Hantraye P, Wullner U et al. (1994) PET- and MRI-based assessment of glucose utilization, dopamine receptor binding, and hemodynamic changes after lesions to the caudate-putamen in primates. Exp Neurol 125:41–51PubMedCrossRefGoogle Scholar
  63. 63.
    Burns LH, Pakzaban P, Deacon TW et al. (1995) Selective putaminal excitotoxic lesions in non-human primates model the movement disorder of Huntington disease. Neuroscience 64:1007–1017PubMedCrossRefGoogle Scholar
  64. 64.
    Hantraye P, Loc’h C, Maziere B et al. (1992) 6-[18F]fluoro-L-dopa uptake and [76Br]bromolisuride binding in the excitotoxically lesioned caudate-putamen of nonhuman primates studied using positron emission tomography. Exp Neurol 115:218–227PubMedCrossRefGoogle Scholar
  65. 65.
    Hantraye P, Leroy-Willig A, Denys A et al. (1992) Magnetic resonance imaging to monitor pathology of caudate-putamen after excitotoxin-induced neuronal loss in the nonhuman primate brain. Exp Neurol 118:18–23PubMedCrossRefGoogle Scholar
  66. 66.
    Hantraye P, Riche D, Maziere M et al. (1989) Anatomical, behavioral and positron emission tomography studies of unilateral excitotoxic lesions of the baboon caudate-putamen as a primate model of Huntington’s disease. In: Crossman AR, Sambrook MA (eds) Neural mechanisms in disorders of movement. London: LibbeyGoogle Scholar
  67. 67.
    Araujo DM, Cherry SR, Tatsukawa KJ, Toyokuni T, Kornblum HI (2000) Deficits in striatal dopamine D(2) receptors and energy metabolism detected by in vivo microPET imaging in a rat model of Huntington’s disease. Exp Neurol 166:287–297PubMedCrossRefGoogle Scholar
  68. 68.
    Ishiwata K, Ogi N, Hayakawa N et al. (2002) Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: comparison with the dopamine receptor imaging. Ann Nucl Med 16:467–475PubMedCrossRefGoogle Scholar
  69. 69.
    Brownell AL, Chen YI, Yu M et al. (2004) 3-Nitropropionic acid-induced neurotoxicity—assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy. J Neurochem 89:1206–1214PubMedCrossRefGoogle Scholar
  70. 70.
    Jenkins BG, Andreassen OA, Dedeoglu A et al. (2005) Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington’s disease. J Neurochem 95:553–562PubMedCrossRefGoogle Scholar
  71. 71.
    Wang X, Sarkar A, Cicchetti F et al. (2005) Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington’s disease. J Neurol Sci 231:57–66PubMedCrossRefGoogle Scholar
  72. 72.
    Meguro K, Blaizot X, Kondoh Y et al. (1999) Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer’s disease. Brain 122:1519–1531PubMedCrossRefGoogle Scholar
  73. 73.
    Millien I, Blaizot X, Giffard C et al. (2002) Brain glucose hypometabolism after perirhinal lesions in baboons: implications for Alzheimer disease and aging. J Cereb Blood Flow Metab 22:1248–1261PubMedCrossRefGoogle Scholar
  74. 74.
    Noda A, Murakami Y, Tsukada H, Nishimura S (2006) Amyloid imaging in aged and young macaques with PIB and FDDNP. Soc Nucl Med Abstr 34Google Scholar
  75. 75.
    Xiao-Chuan W, Zheng-Hui H, Zheng-Yu F et al. (2004) Correlation of Alzheimer-like tau hyperphosphorylation and fMRI bold intensity. Curr Alzheimer Res 1:143–148PubMedCrossRefGoogle Scholar
  76. 76.
    Bhagat YA, Obenaus A, Richardson JS, Kendall EJ (2002) Evolution of beta-amyloid induced neuropathology: magnetic resonance imaging and anatomical comparisons in the rodent hippocampus. Magma 14:223–232PubMedGoogle Scholar
  77. 77.
    Song Y, Morikawa S, Morita M et al. (2006) Comparison of MR images and histochemical localization of intra-arterially administered microglia surrounding beta-amyloid deposits in the rat brain. Histol Histopathol 21:705–711PubMedGoogle Scholar
  78. 78.
    Codita A, Winblad B, Mohammed AH (2006) Of mice and men: more neurobiology in dementia. Curr Opin Psychiatry 19:555–563PubMedCrossRefGoogle Scholar
  79. 79.
    Klunk WE, Lopresti BJ, Ikonomovic MD et al. (2005) Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci 25:10598–10606PubMedCrossRefGoogle Scholar
  80. 80.
    Toyama H, Ye D, Ichise M et al. (2005) PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 32:593–600PubMedCrossRefGoogle Scholar
  81. 81.
    Valla J, Chen K, Berndt JD et al. (2002) Effects of image resolution on autoradiographic measurements of posterior cingulate activity in PDAPP mice: implications for functional brain imaging studies of transgenic mouse models of Alzheimer’s disease. NeuroImage 16:1–6PubMedCrossRefGoogle Scholar
  82. 82.
    Heneka MT, Ramanathan M, Jacobs AH et al. (2006) Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J Neurosci 26:1343–1354PubMedCrossRefGoogle Scholar
  83. 83.
    Falangola MF, Lee SP, Nixon RA, Duff K, Helpern JA (2005) Histological co-localization of iron in Abeta plaques of PS/APP transgenic mice. Neurochem Res 30:201–205PubMedCrossRefGoogle Scholar
  84. 84.
    Jack CR, Jr., Wengenack TM, Reyes DA et al. (2005) In vivo magnetic resonance microimaging of individual amyloid plaques in Alzheimer’s transgenic mice. J Neurosci 25:10041–10048PubMedCrossRefGoogle Scholar
  85. 85.
    Vanhoutte G, Dewachter I, Borghgraef P, Van Leuven F, Van der LA (2005) Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer’s disease. Magn Reson Med 53:607–613PubMedCrossRefGoogle Scholar
  86. 86.
    Jack CR, Jr., Garwood M, Wengenack TM et al. (2004) In vivo visualization of Alzheimer’s amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent. Magn Reson Med 52:1263–1271PubMedCrossRefGoogle Scholar
  87. 87.
    Helpern JA, Lee SP, Falangola MF et al. (2004) MRI assessment of neuropathology in a transgenic mouse model of Alzheimer’s disease. Magn Reson Med 51:794–798PubMedCrossRefGoogle Scholar
  88. 88.
    Wadghiri YZ, Sigurdsson EM, Sadowski M et al. (2003) Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med 50:293–302PubMedCrossRefGoogle Scholar
  89. 89.
    Weiss C, Venkatasubramanian PN, Aguado AS et al (2002) Impaired eyeblink conditioning and decreased hippocampal volume in PDAPP V717F mice. Neurobiol Dis 11:425–433PubMedCrossRefGoogle Scholar
  90. 90.
    Koistinaho M, Kettunen MI, Goldsteins G et al. (2002) Beta-amyloid precursor protein transgenic mice that harbor diffuse A beta deposits but do not form plaques show increased ischemic vulnerability: role of inflammation. Proc Natl Acad Sci U S A 99:1610–1615 PubMedCrossRefGoogle Scholar
  91. 91.
    Sykova E, Vorisek I, Antonova T et al. (2005) Changes in extracellular space size and geometry in APP23 transgenic mice: a model of Alzheimer’s disease. Proc Natl Acad Sci U S A 102:479–484PubMedCrossRefGoogle Scholar
  92. 92.
    Sun SW, Song SK, Harms MP et al (2005) Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer’s disease using magnetic resonance diffusion tensor imaging. Exp Neurol 191:77–85PubMedCrossRefGoogle Scholar
  93. 93.
    Mueggler T, Meyer-Luehmann M, Rausch M et al (2004) Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis. Eur J Neurosci 20:811–817PubMedCrossRefGoogle Scholar
  94. 94.
    Song SK, Kim JH, Lin SJ, Brendza RP, Holtzman DM (2004) Diffusion tensor imaging detects age-dependent white matter changes in a transgenic mouse model with amyloid deposition. Neurobiol Dis 15:640–647PubMedCrossRefGoogle Scholar
  95. 95.
    Krucker T, Schuler A, Meyer EP, Staufenbiel M, Beckmann N (2004) Magnetic resonance angiography and vascular corrosion casting as tools in biomedical research: application to transgenic mice modeling Alzheimer’s disease. Neurol Res 26:507–516PubMedCrossRefGoogle Scholar
  96. 96.
    Higuchi M, Iwata N, Matsuba Y et al. (2005) 19F and 1H MRI detection of amyloid beta plaques in vivo. Nat Neurosci 8:527–533CrossRefGoogle Scholar
  97. 97.
    von Kienlin M, Kunnecke B, Metzger F et al. (2005) Altered metabolic profile in the frontal cortex of PS2APP transgenic mice, monitored throughout their life span. Neurobiol Dis 18:32–39CrossRefGoogle Scholar
  98. 98.
    Dedeoglu A, Choi JK, Cormier K, Kowall NW, Jenkins BG (2004) Magnetic resonance spectroscopic analysis of Alzheimer’s disease mouse brain that express mutant human APP shows altered neurochemical profile. Brain Res 1012:60–65PubMedCrossRefGoogle Scholar
  99. 99.
    Sherer TB, Fiske BK, Svendsen CN, Lang AE, Langston JW (2006) Crossroads in GDNF therapy for Parkinson’s disease. Mov Disord 21:136–141PubMedCrossRefGoogle Scholar
  100. 100.
    Ravina B, Eidelberg D, Ahlskog JE et al. (2005) The role of radiotracer imaging in Parkinson’s disease. Neurology 64:208–215PubMedGoogle Scholar
  101. 101.
    Willner P (1984) The validity of animal models of depression. Psychopharmacology (Berl) 83:1–16CrossRefGoogle Scholar

Copyright information

© Academy of Molecular Imaging 2007

Authors and Affiliations

  1. 1.Pacific Parkinson’s Research CentreUniversity of British ColumbiaVancouverCanada
  2. 2.UBC/TRIUMF PET ProgramUniversity of British ColumbiaVancouverCanada
  3. 3.Basal Ganglia Pathophysiology UnitDepartment of Experimental Medical ScienceLundSweden

Personalised recommendations