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Validation of Dementia Models Employing Neuroimaging Techniques

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Animal Models of Dementia

Part of the book series: Neuromethods ((NM,volume 48))

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Abstract

Dementia is a clinical diagnosis; however, none of the clinical scales guarantee high sensitivity or specificity. Therefore, neuroimaging is often crucial for proper assessment. The most typical neurological symptoms of dementia are often discerned using computed X-ray tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), single-photon emission computerized tomography (SPECT), and positron-emission tomography (PET) techniques. In general, these different imaging modalities provide different information and can be considered as being complementary rather than competitive. Nowadays, structural neuroimaging is a routine component of the diagnostic evaluation of dementia. Neuroimaging offers promise as a surrogate marker for clinical trials, and new technologies have been developed to provide more molecular and physiological biomarkers such as markers for amyloid plaques, one of the neuropathological hallmarks of AD. The combined use of imaging technology and experimental in vivo animal models for human diseases provides a unique platform to study pathological mechanisms in longitudinal studies, develop accurate and early translational diagnostic tools, and evaluate therapeutic strategies. In this chapter, an overview of how brain imaging can be used to detect both early and late stages of dementia in small animal models is explained. The early stage offers a unique therapeutic window and is diagnostically most challenging.

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References

  1. Lindvall O, Bjorklund A (2004) Cell therapy in Parkinson’s disease. NeuroRx 1:382–393

    PubMed  Google Scholar 

  2. Willner P (2008) Methods for assessing the validity of animal models of human psychopathology. In: Boulton AA, Baker GB, Martin-Iverson MT (eds) Neuromethods, animal models in psychiatry I, 18th edn. Humana, Clifton, NJ

    Google Scholar 

  3. 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: 10598–10606.

    PubMed  CAS  Google Scholar 

  4. Suhara T, Higuchi M, Miyoshi M (2008) Neuroimaging in dementia: In vivo amyloid imaging. Tohoku J Exp Med 215:119–124

    PubMed  Google Scholar 

  5. 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(5):593–600

    PubMed  CAS  Google Scholar 

  6. Lauterbur PC (1980) Progress in n.m.r. zeugmatography imaging. Philos Trans R Soc Lond B Biol Sci 289:483–487

    PubMed  CAS  Google Scholar 

  7. Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intravoxel incoherent motions: Application to diffusion and perfusion in neurologic disorders. Radiology 161:401–407

    PubMed  CAS  Google Scholar 

  8. Gass A, Niendorf T, Hirsch JG (2001) Acute and chronic changes of the apparent diffusion coefficient in neurological disorders-biophysical mechanisms and possible underlying histopathology. J Neurol Sci 186:S15–S23

    PubMed  Google Scholar 

  9. Basser PJ (1995) Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed 8:333–344

    PubMed  CAS  Google Scholar 

  10. Assaf Y, Pasternak O (2008) Diffusion tensor imaging (DTI)-based white matter mapping in brain research: A review. J Mol Neurosci 34(1):51–61

    PubMed  CAS  Google Scholar 

  11. Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A 87(24):9868–9872

    PubMed  CAS  Google Scholar 

  12. Benveniste H, Einstein G, Kim KR, Hulette C, Johnson GA (1999) Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy. Proc Natl Acad Sci U S A 96(24):14079–14084

    PubMed  CAS  Google Scholar 

  13. Ginefri JC, Poirier-Quinot M, Girard O, Darrasse L (2007) Technical aspects: Devel­opment, manufacture and installation of a cryo-cooled HTS coil system for high-resolution in-vivo imaging of the mouse at 1.5 T. Methods 43(1):54–67

    PubMed  CAS  Google Scholar 

  14. Dubowitz DJ, Tyszka JM, Sewry CA, Moats RA, Scadeng M, Dubowitz V (2000) High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy. Neuromuscul Disord 10(4–5):292–298

    PubMed  CAS  Google Scholar 

  15. Hesselbarth D, Franke C, Hata R, Brinker G, Hoehn-Berlage M (1998) High resolution MRI and MRS: A feasibility study for the investigation of focal cerebral ischemia in mice. NMR Biomed 11(8):423–429

    PubMed  CAS  Google Scholar 

  16. Yang QX, Smith MB, Briggs RW, Rycyna RE (1999) Microimaging at 14 tesla using GESEPI for removal of magnetic susceptibility artifacts in T(2)(*)-weighted image contrast. J Magn Reson 141(1):1–6

    PubMed  Google Scholar 

  17. Kooy RF, Reyniers E, Verhoye M, et al. (1999) Neuroanatomy of the fragile X knockout mouse brain studied using in vivo high resolution magnetic resonance imaging. Eur J Hum Genet 7(5):526–532

    PubMed  CAS  Google Scholar 

  18. Van Camp N., Peeters RR, Van der LA (2005) A comparison between blood oxygenation level-dependent and cerebral blood volume contrast in the rat cerebral and cerebellar somatosensoric cortex during electrical paw stimulation. J Magn Reson Imaging 22:483–491

    PubMed  Google Scholar 

  19. Artemov D (2003) Molecular magnetic resonance imaging with targeted contrast agents. J Cell Biochem 90:518–524

    PubMed  CAS  Google Scholar 

  20. Meade TJ, Taylor AK, Bull SR (2003) New magnetic resonance contrast agents as biochemical reporters. Curr Opin Neurobiol 13:597–602

    PubMed  CAS  Google Scholar 

  21. Dzik-Jurasz AS (2003) Molecular imaging in vivo: An introduction. Br J Radiol 76:S98–S109

    PubMed  CAS  Google Scholar 

  22. Pfeuffer J, Tkac I, Provencher SW, Gruetter R (1999) Toward an in vivo neurochemical profile: Quantification of 18 metabolites in short-echo-time (1)H NMR spectra of the rat brain. J Magn Reson 141:104–120

    PubMed  CAS  Google Scholar 

  23. Brown TR, Kincaid BM, Ugurbil K (1982) NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci U S A 79:3523–3526

    PubMed  CAS  Google Scholar 

  24. Maudsley AA, Hilal SK, Perman WH, Simon HE (1983) Spatially resolved high resolution spectroscopy by ‘four dimensional ’ NMR. J Magn Reson 51:147–152

    CAS  Google Scholar 

  25. Moffett JR, Ross B, Arun P, Madhavarao CN, Namboodiri AM (2007) N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology. Prog Neurobiol 81:89–131

    PubMed  CAS  Google Scholar 

  26. Kantarci K, Jack CR, Jr., Xu YC, et al. (2000) Regional metabolic patterns in mild cognitive impairment and Alzheimer’s disease: A 1H MRS study. Neurology 55:210–217

    PubMed  CAS  Google Scholar 

  27. Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD (1993) Alzheimer disease: Depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology 187(2):433–437

    PubMed  CAS  Google Scholar 

  28. Govindaraju V, Young K, Maudsley AA, Proton NMR (2000) Chemical shifts and coupling constants for brain metabolites. NMR Biomed 13(3):129–153

    PubMed  CAS  Google Scholar 

  29. Erecinska M, Silver IA (1990) Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 35(4):245–296

    PubMed  CAS  Google Scholar 

  30. Behar KL, den Hollander JA, Stromski ME, et al. (1983) High-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo. Proc Natl Acad Sci U S A 80(16):4945–4948

    PubMed  CAS  Google Scholar 

  31. Bruhn H, Frahm J, Gyngell ML, Merboldt KD, Hanicke W, Sauter R (1989) Cerebral metabolism in man after acute stroke: New observations using localized proton NMR spectroscopy. Magn Reson Med 9(1):126–131

    PubMed  CAS  Google Scholar 

  32. Bruhn H, Frahm J, Gyngell ML, et al. (1989) Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: Initial experience in patients with cerebral tumors. Radiology 172(2):541–548

    PubMed  CAS  Google Scholar 

  33. Jansen JF, Backes WH, Nicolay K, Kooi ME (2006) 1H MR spectroscopy of the brain: Absolute quantification of metabolites. Radiology 240(2):318–332

    PubMed  Google Scholar 

  34. Brand A, Richter-Landsberg C, Leibfritz D (1993) Multinuclear NMR studies on the energy metabolism of glial and neuronal cells. Dev Neurosci 15(3–5):289–298

    PubMed  CAS  Google Scholar 

  35. Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13(3):981–989

    PubMed  CAS  Google Scholar 

  36. Frisoni GB (2001) Structural imaging in the clinical diagnosis of Alzheimer’s disease: Problems and tools. J Neurol Neurosurg Psychiatr 70:711–718

    PubMed  CAS  Google Scholar 

  37. Rose M, Scharf S (2008) Is there any role for computed tomography measurements of medial temporal lobe atrophy in dementia? A review of the literature and case series from a memory clinic. Intern Med J 38:136–139

    PubMed  CAS  Google Scholar 

  38. Muller R, Gerber SC, Hayes WC (1998) Micro-compression: A novel technique for the nondestructive assessment of local bone failure. Technol Health Care 6:433–444

    PubMed  CAS  Google Scholar 

  39. Barck KH, Lee WP, Diehl LJ, et al. (2004) Quantification of cortical bone loss and repair for therapeutic evaluation in collagen-induced arthritis, by micro-computed tomography and automated image analysis. Arthritis Rheum 50:3377–3386

    PubMed  Google Scholar 

  40. Kennel SJ, Davis IA, Branning J, Pan H, Kabalka GW, Paulus MJ (2000) High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: Correlation with histology. Med Phys 27:1101–1107

    PubMed  CAS  Google Scholar 

  41. Paulus MJ, Gleason SS, Kennel SJ, Hunsicker PR, Johnson DK (2000) High resolution X-ray computed tomography: An emerging tool for small animal cancer research. Neoplasia 2:62–70

    PubMed  CAS  Google Scholar 

  42. Noda-Saita K, Yoneyama A, Shitaka Y, et al. (2006) Quantitative analysis of amyloid plaques in a mouse model of Alzheimer’s disease by phase-contrast X-ray computed tomography. Neuroscience 138:1205–1213

    PubMed  CAS  Google Scholar 

  43. Seo Y, Hashimoto T, Nuki Y, Hasegawa BH (2008) In vivo microCT imaging of rodent cerebral vasculature. Phys Med Biol 53:N99–N107

    PubMed  Google Scholar 

  44. Pichler BJ, Judenhofer MS, Wehrl HF (2008) PET/MRI hybrid imaging: Devices and initial results. Eur Radiol 18(6):1077–1086

    PubMed  Google Scholar 

  45. Goetz C, Breton E, Choquet P, Israel-Jost V, Constantinesco A (2008) SPECT low-field MRI system for small-animal imaging. J Nucl Med 49(1):88–93

    PubMed  Google Scholar 

  46. Klerk CP, Overmeer RM, Niers TM, et al. (2007) Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals. Biotechniques 43(1 Suppl):7–13, 30

    PubMed  Google Scholar 

  47. Bacskai BJ, Kajdasz ST, Christie RH, et al. (2001) Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat Med 7(3):369–372

    PubMed  CAS  Google Scholar 

  48. Carson JP, Ju T, Thaller C, et al. (2004) Automated characterization of gene expression patterns with an atlas of the mouse brain. Conf Proc IEEE Eng Med Biol Soc 4:2917–2920

    PubMed  CAS  Google Scholar 

  49. Dhenain M, Ruffins SW, Jacobs RE (2001) Three-dimensional digital mouse atlas using high-resolution MRI. Dev Biol 232(2):458–470

    PubMed  CAS  Google Scholar 

  50. Kenzie-Graham A, Jones ES, Shattuck DW, Dinov ID, Bota M, Toga AW (2003) The informatics of a C57BL/6J mouse brain atlas. Neuroinformatics 1(4):397–410

    Google Scholar 

  51. Kenzie-Graham A, Boline J, Toga AW (2007) Brain atlases and neuroanatomic imaging. Methods Mol Biol 401:183–194

    Google Scholar 

  52. Kovacevic N, Henderson JT, Chan Eet al., (2005) A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability. Cereb Cortex 15(5):639–645

    PubMed  CAS  Google Scholar 

  53. Lein ES, Hawrylycz MJ, Ao N, et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124): 168–176

    PubMed  CAS  Google Scholar 

  54. Ma Y, Hof PR, Grant SC, et al. (2005) A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 135:1203–1215

    PubMed  CAS  Google Scholar 

  55. Paxinos GaFKB (2001) The mouse brain in stereotaxic coordinates. Elsevier, San Diego, CA

    Google Scholar 

  56. Paxinos GaWC (2005) The rat brain in stereotaxic coordinates. Elsevier, San Diego, CA

    Google Scholar 

  57. Hjornevik T, Leergaard T, Dariune D, et al. (2007) Three-dimensional atlas system for mouse and rat brain imaging data. Front NeuroInformatics1:1–4

    Google Scholar 

  58. Casteels C, Vermaelen P, Nuyts J, et al. (2006) Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain. J Nucl Med 47:1858–1866

    PubMed  Google Scholar 

  59. Talairach JaTP (1988) Co-planar stereotaxic atlas of the human brain. Thieme Medical Publishers, New York

    Google Scholar 

  60. Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: Gain- and loss-of-function in neurodegenerative diseases. EMBO J 27:336–349

    PubMed  CAS  Google Scholar 

  61. Ho LW, Carmichael J, Swartz J, Wyttenbach A, Rankin J, Rubinsztein DC (2001) The molecular biology of Huntington’s disease. Psychol Med 31:3–14

    PubMed  CAS  Google Scholar 

  62. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 297:353–356

    PubMed  CAS  Google Scholar 

  63. Oakley H, Cole SL, Logan S, et al. (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: Potential factors in amyloid plaque formation. J Neurosci 26:10129–10140

    PubMed  CAS  Google Scholar 

  64. Bruijn LI, Houseweart MK, Kato S, et al. (1998) Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281(5384):1851–1854

    PubMed  CAS  Google Scholar 

  65. Ma J, Wollmann R, Lindquist S (2002) Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol. Science 298(5599):1781–1785

    PubMed  CAS  Google Scholar 

  66. Dawson TM, Dawson VL (2003) Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J Clin Invest 111(2):145–151

    PubMed  CAS  Google Scholar 

  67. Majocha RE, Reno JM, Friedland RP, VanHaight C, Lyle LR, Marotta CA (1992) Development of a monoclonal antibody specific for beta/A4 amyloid in Alzheimer’s disease brain for application to in vivo imaging of amyloid angiopathy. J Nucl Med 33(12):2184–2189

    PubMed  CAS  Google Scholar 

  68. Agdeppa ED, Kepe V, Liu J, et al. (2003) 2-Dialkylamino-6-acylmalononitrile substituted naphthalenes (DDNP analogs): Novel diagnostic and therapeutic tools in Alzheimer’s disease. Mol Imaging Biol 5(6):404–417

    Google Scholar 

  69. Mathis CA, Wang Y, Holt DP, Huang GF, Debnath ML, Klunk WE (2003) Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. J Med Chem 46(13):2740–2754

    PubMed  CAS  Google Scholar 

  70. Wang Y, Klunk WE, Huang GF, Debnath ML, Holt DP, Mathis CA (2002) Synthesis and evaluation of 2-(3’-iodo-4’-aminophenyl)-6-hydroxybenzothiazole for in vivo quantitation of amyloid deposits in Alzheimer’s disease. J Mol Neurosci 19(1–2):11–16

    PubMed  Google Scholar 

  71. Zhang W, Oya S, Kung MP, Hou C, Maier DL, Kung HF (2005) F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting Abeta aggregates in the brain. Nucl Med Biol 32(8):799–809

    PubMed  CAS  Google Scholar 

  72. Okamura N, Suemoto T, Shiomitsu T, et al. (2004) A novel imaging probe for in vivo detection of neuritic and diffuse amyloid plaques in the brain. J Mol Neurosci 24:247–255

    PubMed  CAS  Google Scholar 

  73. El Tannir El TN, Delatour B, Le CC, Guegan M, Volk A, Dhenain M (2006) Age-related evolution of amyloid burden, iron load, and MR relaxation times in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 22:199–208

    Google Scholar 

  74. 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 30:201–205

    PubMed  CAS  Google Scholar 

  75. Falangola MF, Dyakin VV, Lee SP, et al. (2007) Quantitative MRI reveals aging-associated T2 changes in mouse models of Alzheimer’s disease. NMR Biomed 20:343–351

    PubMed  CAS  Google Scholar 

  76. 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 52:1263–1271

    PubMed  Google Scholar 

  77. Vanhoutte G, Dewachter I, Borghgraef P, Van LF, 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 53:607–613

    PubMed  CAS  Google Scholar 

  78. Zhang J, Yarowsky P, Gordon MN, et al. (2004) Detection of amyloid plaques in mouse models of Alzheimer’s disease by magnetic resonance imaging. Magn Reson Med 51:452–457

    PubMed  Google Scholar 

  79. Wadghiri YZ, Sigurdsson EM, Sadowski M, et al. (2003) Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med 50:293–302

    PubMed  CAS  Google Scholar 

  80. Poduslo JF, Wengenack TM, Curran GL, et al. (2002) Molecular targeting of Alzheimer’s amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiol Dis 11:315–329

    PubMed  CAS  Google Scholar 

  81. Poduslo JF, Ramakrishnan M, Holasek SS, et al. (2007) In vivo targeting of antibody fragments to the nervous system for Alzheimer’s disease immunotherapy and molecular imaging of amyloid plaques. J Neurochem 102:420–433

    PubMed  CAS  Google Scholar 

  82. Bacskai BJ, Skoch J, Hickey GA, Allen R, Hyman BT (2003) Fluorescence resonance energy transfer determinations using multiphoton fluorescence lifetime imaging microscopy to characterize amyloid-beta plaques. J Biomed Opt 8:368–375

    PubMed  CAS  Google Scholar 

  83. Hintersteiner M, Enz A, Frey P, et al. (2005) In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583

    PubMed  CAS  Google Scholar 

  84. Raymond SB, Skoch J, Hills ID, Nesterov EE, Swager TM, Bacskai BJ (2008) Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging 35:S93–S98

    PubMed  Google Scholar 

  85. Mueggler T, Meyer-Luehmann M, Rausch M, Staufenbiel M, Jucker M, Rudin M (2004) Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis. Eur J Neurosci 20:811–817

    PubMed  Google Scholar 

  86. 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 15:640–647

    PubMed  CAS  Google Scholar 

  87. 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

    PubMed  CAS  Google Scholar 

  88. Beckmann N, Schuler A, Mueggler T, et al. (2003) Age-dependent cerebrovascular abnormalities and blood flow disturbances in APP23 mice modeling Alzheimer’s disease. J Neurosci 23:8453–8459

    PubMed  CAS  Google Scholar 

  89. Meyer EP, Ulmann-Schuler A, Staufenbiel M, Krucker T (2008) Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer’s disease. Proc Natl Acad Sci U S A 105:3587–3592

    PubMed  CAS  Google Scholar 

  90. Hooijmans CR, Rutters F, Dederen PJ, et al. (2007) Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched Typical Western Diet (TWD). Neurobiol Dis 28:16–29

    PubMed  CAS  Google Scholar 

  91. Koretsky AP, Silva AC (2004) Manganese-enhanced magnetic resonance imaging (MEMRI). NMR Biomed 17:527–531

    PubMed  CAS  Google Scholar 

  92. Pautler RG, Silva AC, Koretsky AP (1998) In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging. Magn Reson Med 40:740–748

    PubMed  CAS  Google Scholar 

  93. Smith KD, Kallhoff V, Zheng H, Pautler RG (2007) In vivo axonal transport rates decrease in a mouse model of Alzheimer’s disease. Neuroimage 35:1401–1408

    PubMed  Google Scholar 

  94. Pelled G, Bergman H, Ben-Hur T, Goelman G (2007) Manganese-enhanced MRI in a rat model of Parkinson’s disease. J Magn Reson Imaging 26:863–870

    PubMed  Google Scholar 

  95. Thiruvady DR, Georgiou-Karistianis N, Egan GF, et al. (2007) Functional connectivity of the prefrontal cortex in Huntington’s disease. J Neurol Neurosurg Psychiatr 78(2): 127–133

    PubMed  CAS  Google Scholar 

  96. Wang K, Liang M, Wang L, et al. (2007) Altered functional connectivity in early Alzheimer’s disease: A resting-state fMRI study. Hum Brain Mapp 28(10):967–978

    PubMed  Google Scholar 

  97. Zhao F, Zhao T, Zhou L, Wu Q, Hu X (2008) BOLD study of stimulation-induced neural activity and resting-state connectivity in medetomidine-sedated rat. Neuroimage 39(1):248–260

    PubMed  Google Scholar 

  98. Huang J, Friedland RP, Auchus AP (2007) Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: Preliminary evidence of axonal degeneration in the temporal lobe. AJNR Am J Neuroradiol 28(10):1943–1948

    PubMed  CAS  Google Scholar 

  99. Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17(3):1429–1436

    PubMed  Google Scholar 

  100. Song SK, Yoshino J, Le TQ, et al. (2005) Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 26(1):132–140

    PubMed  Google Scholar 

  101. Boska MD, Hasan KM, Kibuule D, et al. (2007) Quantitative diffusion tensor imaging detects dopaminergic neuronal degeneration in a murine model of Parkinson’s disease. Neurobiol Dis 26(3):590–596

    PubMed  CAS  Google Scholar 

  102. Aponso PM, Faull RL, Connor B (2008) Increased progenitor cell proliferation and astrogenesis in the partial progressive 6-hydroxydopamine model of Parkinson’s disease. Neuroscience 151(4):1142–1153

    PubMed  CAS  Google Scholar 

  103. Tattersfield AS, Croon RJ, Liu YW, Kells AP, Faull RL, Connor B (2004) Neurogenesis in the striatum of the quinolinic acid lesion model of Huntington’s disease. Neuroscience 127:319–332

    PubMed  CAS  Google Scholar 

  104. Shapiro EM, Gonzalez-Perez O, Manuel Garcia-Verdugo J, varez-Buylla A, Koretsky AP (2006) Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain. Neuroimage 32:1150–1157

    PubMed  Google Scholar 

  105. Aigner L, Bogdahn U (2008) TGF-beta in neural stem cells and in tumors of the central nervous system. Cell Tissue Res 331:225–241

    PubMed  Google Scholar 

  106. Couillard-Despres S, Finkl R, Winner B, et al. (2008) In vivo optical imaging of neurogenesis: Watching new neurons in the intact brain. Mol Imaging 7:28–34

    PubMed  CAS  Google Scholar 

  107. Geraerts M, Eggermont K, Hernandez-Acosta P, Garcia-Verdugo JM, Baekelandt V, Debyser Z (2006) Lentiviral vectors mediate efficient and stable gene transfer in adult neural stem cells in vivo. Hum Gene Ther 17:635–650

    PubMed  CAS  Google Scholar 

  108. Reumers V, Deroose CM, Krylyshkina O, et al. (2008) Non-invasive and quantitative monitoring of adult neuronal stem cell migration in mouse brain using bioluminescence imaging. Stem Cells 26:2382–2390

    PubMed  Google Scholar 

  109. Jin K, Peel AL, Mao XO, et al. (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci U S A 101:343–347

    PubMed  CAS  Google Scholar 

  110. Zhang C, McNeil E, Dressler L, Siman R (2007) Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer’s disease. Exp Neurol 204:77–87

    PubMed  CAS  Google Scholar 

  111. Louis N, Manganas LN., Zhang X, et al. (2007) Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318:980–985

    Google Scholar 

  112. Van der Linden A., Van CN, Ramos-Cabrer P, Hoehn M (2007) Current status of functional MRI on small animals: Application to physiology, pathophysiology, and cognition. NMR Biomed 20:522–545

    PubMed  CAS  Google Scholar 

  113. Mueggler T, Baumann D, Rausch M, Staufenbiel M, Rudin M (2003) Age-dependent impairment of somatosensory response in the amyloid precursor protein 23 transgenic mouse model of Alzheimer’s disease. J Neurosci 23:8231–8236

    PubMed  CAS  Google Scholar 

  114. Mueggler T, Baumann D, Rausch M, Rudin M (2001) Bicuculline-induced brain activation in mice detected by functional magnetic resonance imaging. Magn Reson Med 46:292–298

    PubMed  CAS  Google Scholar 

  115. Xu F, Liu N, Kida I, Rothman DL, Hyder F, Shepherd GM (2003) Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb. Proc Natl Acad Sci U S A 100:11029–11034

    PubMed  CAS  Google Scholar 

  116. Liang WS, Reiman EM, Valla J, et al. (2008) Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 105:4441–4446

    PubMed  CAS  Google Scholar 

  117. Valla J, Berndt JD, Gonzalez-Lima F (2001) Energy hypometabolism in posterior cingulate cortex of Alzheimer’s patients: Superficial laminar cytochrome oxidase associated with disease duration. J Neurosci 21: 4923–4930

    PubMed  CAS  Google Scholar 

  118. 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 16:1–6

    PubMed  CAS  Google Scholar 

  119. Winkeler A, Waerzeggers Y, Klose A, et al. (2008) Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 35:S107–S113

    PubMed  CAS  Google Scholar 

  120. Heneka MT, Ramanathan M, Jacobs AH (2006) Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice. J Neurosci 26:1343–1354

    PubMed  CAS  Google Scholar 

  121. Browne SE, Bowling AC, MacGarvey U, et al. (1997) Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Ann Neurol 41:646–653

    PubMed  CAS  Google Scholar 

  122. Browne SE, Beal MF (2004) The energetics of Huntington’s disease. Neurochem Res 29:531–546

    PubMed  CAS  Google Scholar 

  123. Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH (1996) Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol 39:385–389

    PubMed  CAS  Google Scholar 

  124. Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR (1993) Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology 43:2689–2695

    PubMed  CAS  Google Scholar 

  125. Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF (1997) Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Ann Neurol 41:160–165

    PubMed  CAS  Google Scholar 

  126. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 321:168–1671

    PubMed  CAS  Google Scholar 

  127. Ferrante RJ, Kowall NW, Cipolloni PB, Storey E, Beal MF (1993) Excitotoxin lesions in primates as a model for Huntington’s disease: Histopathologic and neurochemical characterization. Exp Neurol 119:46–71

    PubMed  CAS  Google Scholar 

  128. Strauss I, Williamson JM, Bertram EH, Lothman EW, Fernandez EJ (1997) Histological and 1H magnetic resonance spectroscopic imaging analysis of quinolinic acid-induced damage to the rat striatum. Magn Reson Med 37:24–33

    PubMed  CAS  Google Scholar 

  129. Tkac I, Keene CD, Pfeuffer J, Low WC, Gruetter R (2001) Metabolic changes in quinolinic acid-lesioned rat striatum detected non-invasively by in vivo (1)H NMR spectroscopy. J Neurosci Res 66:891–898

    PubMed  CAS  Google Scholar 

  130. Beal MF, Brouillet E, Jenkins B, Henshaw R, Rosen B, Hyman BT (1993) Age-dependent striatal excitotoxic lesions produced by the endogenous mitochondrial inhibitor malonate. J Neurochem 61:1147–1150

    PubMed  CAS  Google Scholar 

  131. Beal MF, Brouillet E, Jenkins BG, et al. (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13:4181–4192

    PubMed  CAS  Google Scholar 

  132. Brouillet E, Hantraye P, Ferrante RJ, et al. (1995) Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci U S A 92:7105–7109

    PubMed  CAS  Google Scholar 

  133. Greene JG, Porter RH, Eller RV, Greenamyre JT (1993) Inhibition of succinate dehydrogenase by malonic acid produces an “excitotoxic” lesion in rat striatum. J Neurochem 61:1151–1154

    PubMed  CAS  Google Scholar 

  134. Dautry C, Conde F, Brouillet E, et al. (1999) Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid. Neurobiol Dis 6:259–268

    PubMed  CAS  Google Scholar 

  135. Henry PG (2001) In vivo NMR measurement of TCA cycle rate alteration following 3NP intoxication. Proc Intl Soc Mag Reson Med 9

    Google Scholar 

  136. Jenkins BG, Brouillet E, Chen YC, et al. (1996) Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. J Cereb Blood Flow Metab 16:450–461

    PubMed  CAS  Google Scholar 

  137. Lee WT, Shen YZ, Chang C (2000) Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: Evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy. Neuroscience 95:89–95

    PubMed  CAS  Google Scholar 

  138. Lee WT, Lee CS, Pan YL, Chang C (2000) Temporal changes of cerebral metabolites and striatal lesions in acute 3-nitropropionic acid intoxication in the rat. Magn Reson Med 44:29–34

    PubMed  CAS  Google Scholar 

  139. 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 72:87–110

    PubMed  CAS  Google Scholar 

  140. Beal MF, Henshaw DR, Jenkins BG, Rosen BR, Schulz JB (1994) Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol 36:882–888

    PubMed  CAS  Google Scholar 

  141. Henshaw R, Jenkins BG, Schulz JB, et al. (1994) Malonate produces striatal lesions by indirect NMDA receptor activation. Brain Res 647:161–166

    PubMed  CAS  Google Scholar 

  142. Matthews RT, Yang L, Jenkins BG, et al. (1998) Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. J Neurosci 18: 156–163

    PubMed  CAS  Google Scholar 

  143. Chou SY, Lee YC, Chen HM et al. (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320

    PubMed  CAS  Google Scholar 

  144. Ferrante RJ, Andreassen OA, Jenkins BG, et al. (2000) Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 20:4389–4397

    PubMed  CAS  Google Scholar 

  145. Ferrante RJ, Andreassen OA, Dedeoglu A, et al. (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci 22(5):1592–1599

    PubMed  CAS  Google Scholar 

  146. Jenkins BG, Klivenyi P, Kustermann E, et al. (2000) Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington’s disease mice. J Neurochem 74(5):2108–2119

    PubMed  CAS  Google Scholar 

  147. 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(2):553–562

    PubMed  CAS  Google Scholar 

  148. Tkac I, Dubinsky JM, Keene CD, Gruetter R, Low WC (2007) Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H NMR spectroscopy. J Neurochem 100(5):1397–1406

    PubMed  CAS  Google Scholar 

  149. McGowan E, Eriksen J, Hutton M (2006) A decade of modeling Alzheimer’s disease in transgenic mice. Trends Genet 22(5):281–289

    PubMed  CAS  Google Scholar 

  150. 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(1–2):60–65

    PubMed  CAS  Google Scholar 

  151. Marjanska M, Curran GL, Wengenack TM, et al. (2005) Monitoring disease progression in transgenic mouse models of Alzheimer’s disease with proton magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 102(33):11906–11910

    PubMed  CAS  Google Scholar 

  152. 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 18:32–39

    PubMed  CAS  Google Scholar 

  153. Marsden CD (1994) Parkinson’s disease. J Neurol Neurosurg Psychiatr 57:672–681

    PubMed  CAS  Google Scholar 

  154. Tipton KF, Singer TP (1993) Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. J Neurochem 61:1191–1206

    PubMed  CAS  Google Scholar 

  155. Hadjiconstantinou M, Cavalla D, Anthoupoulou E, Laird HE, Neff NH (1985) N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine increases acetylcholine and decreases dopamine in mouse striatum: Both responses are blocked by anticholinergic drugs. J Neurochem 45:1957–1959

    PubMed  CAS  Google Scholar 

  156. Heikkila RE, Hess A, Duvoisin RC (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice. Science 224:1451–1453

    PubMed  CAS  Google Scholar 

  157. Schneider JS, Markham CH (1986) Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry. Brain Res 373:258–267

    PubMed  CAS  Google Scholar 

  158. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 80:4546–4550

    PubMed  CAS  Google Scholar 

  159. Betarbet R, Sherer TB, Di Monte DA, Greenamyre JT (2002) Mechanistic approaches to Parkinson’s disease pathogenesis. Brain Pathol 12:499–510

    PubMed  CAS  Google Scholar 

  160. Boska MD, Lewis TB, Destache CJ, et al. (2005) Quantitative 1H magnetic resonance spectroscopic imaging determines therapeutic immunization efficacy in an animal model of Parkinson’s disease. J Neurosci 25(7): 1691–1700

    PubMed  CAS  Google Scholar 

  161. Brownell AL, Jenkins BG, Elmaleh DR, Deacon TW, Spealman RD, Isacson O (1998) Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease. Nat Med 4(11):1308–1312

    PubMed  CAS  Google Scholar 

  162. Chassain C, Bielicki G, Durand E, et al. (2008) Metabolic changes detected by proton magnetic resonance spectroscopy in vivo and in vitro in a murin model of Parkinson’s disease, the MPTP-intoxicated mouse. J Neurochem 105(3):874–882

    PubMed  CAS  Google Scholar 

  163. Koga K, Mori A, Ohashi S, et al. (2006) H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice. Eur J Neurosci 23(4):1077–1081

    PubMed  Google Scholar 

  164. Podell M, Hadjiconstantinou M, Smith MA, Neff NH (2003) Proton magnetic resonance imaging and spectroscopy identify metabolic changes in the striatum in the MPTP feline model of parkinsonism. Exp Neurol 179(2):159–166

    PubMed  CAS  Google Scholar 

  165. Choi JK, Dedeoglu A, Jenkins BG (2007) Application of MRS to mouse models of neurodegenerative illness. NMR Biomed 20(3):216–237

    PubMed  Google Scholar 

  166. Groves PM, Linder JC (1994) Young SJ. 5-hydroxydopamine-labeled dopaminergic axons: three-dimensional reconstructions of axons, synapses and postsynaptic targets in rat neostriatum. Neuroscience 58(3):593–604

    PubMed  CAS  Google Scholar 

  167. Storey E, Hyman BT, Jenkins B, et al. (1992) 1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J Neurochem 58(5):1975–1978

    PubMed  CAS  Google Scholar 

  168. Chassain C, Bielicki G, Donnat JP, Renou JP, Eschalier A, Durif F (2005) Cerebral glutamate metabolism in Parkinson’s disease: An in vivo dynamic (13)C NMS study in the rat. Exp Neurol 191:276–284

    PubMed  CAS  Google Scholar 

  169. Moussa CE, Rusnak M, Hailu A, Sidhu A, Fricke ST (2008) Alterations of striatal glutamate transmission in rotenone-treated mice: MRI/MRS in vivo studies. Exp Neurol 209:224–233

    PubMed  CAS  Google Scholar 

  170. Kooy RF, Verhoye M, Lemmon V, Van der LA (2001) Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI). Eur J Hum Genet 9:153–159

    PubMed  CAS  Google Scholar 

  171. Redwine JM, Kosofsky B, Jacobs RE, et al. (2003) Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis. Proc Natl Acad Sci U S A 100:1381–1386

    PubMed  CAS  Google Scholar 

  172. Van Broeck B., Vanhoutte G., Pirici D, et al. (2008) Intraneuronal amyloid beta and reduced brain volume in a novel APP T714I mouse model for Alzheimer’s disease. Neurobiol Aging 29:241–252

    PubMed  CAS  Google Scholar 

  173. Fransen E, D’Hooge R, Van CG, et al. (1998) L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns. Hum Mol Genet 7:999–1009

    PubMed  CAS  Google Scholar 

  174. Ferrarini L, Palm WM, Olofsen H, et al. (2008) Ventricular shape biomarkers for Alzheimer’s disease in clinical MR images. Magn Reson Med 59:260–267

    PubMed  Google Scholar 

  175. Angenstein F, Niessen HG, Goldschmidt J, Vielhaber S, Ludolph AC, Scheich H (2004) Age-dependent changes in MRI of motor brain stem nuclei in a mouse model of ALS. Neuroreport 15:2271–2274

    PubMed  Google Scholar 

  176. Niessen HG, Angenstein F, Sander K, et al. (2006) In vivo quantification of spinal and bulbar motor neuron degeneration in the G93A-SOD1 transgenic mouse model of ALS by T2 relaxation time and apparent diffusion coefficient. Exp Neurol 201:293–300

    PubMed  CAS  Google Scholar 

  177. Revuelta GJ, Rosso A, Lippa CF (2008) Neuritic pathology as a correlate of synaptic loss in dementia with lewy bodies. Am J Alzheimers Dis Other Demen 23:97–102

    PubMed  Google Scholar 

  178. Sorrentino G, Bonavita V (2007) Neurodegen­eration and Alzheimer’s disease: The lesson from tauopathies. Neurol Sci 28:63–71

    PubMed  CAS  Google Scholar 

  179. Ferrer I, Puig B, Blanco R, Marti E (2000) Prion protein deposition and abnormal synaptic protein expression in the cerebellum in Creutzfeldt-Jakob disease. Neuroscience 97: 715–726

    PubMed  CAS  Google Scholar 

  180. Rapoport SI (1999) In vivo PET imaging and postmortem studies suggest potentially reversible and irreversible stages of brain metabolic failure in Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 249:46–55

    PubMed  Google Scholar 

  181. Rapoport SI (2005) In vivo imaging for evaluating synaptic integrity in Alzheimer disease. Psychol Neuropsychiatr Vieil 3:97–106

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Bio-Imaging Lab, Department of Biomedical Sciences, University of Antwerp, Wilrijk, Belgium

    Greet Vanhoutte, Adriaan Campo & Annemie Van der Linden

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  1. Greet Vanhoutte
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  2. Adriaan Campo
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  3. Annemie Van der Linden
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  1. Institute Born-Bunge, Lab of Neurochemistry & Behaviour, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

    Peter Paul De Deyn

  2. Institute Born-Bunge, Lab of Neurochemistry & Behaviour, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

    Debby Van Dam

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Vanhoutte, G., Campo, A., Van der Linden, A. (2011). Validation of Dementia Models Employing Neuroimaging Techniques. In: De Deyn, P., Van Dam, D. (eds) Animal Models of Dementia. Neuromethods, vol 48. Humana Press. https://doi.org/10.1007/978-1-60761-898-0_11

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