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In Vivo Magnetic Resonance Imaging of Amyloid-β Plaques in Mice

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Amyloid Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 849))

Abstract

Transgenic mice are used increasingly to model brain amyloidosis, mimicking the pathogenic processes involved in Alzheimer’s disease (AD). In this chapter, an in vivo strategy is described that has been successfully used to map amyloid-β deposits in transgenic mouse models of AD with magnetic resonance imaging (MRI), utilizing both the endogenous contrast induced by the plaques attributed to their iron content and by selectively enhancing the signal from amyloid-β plaques using molecular-targeting vectors labeled with MRI contrast agents. To obtain sufficient spatial resolution for effective and sensitive mouse brain imaging, magnetic fields of 7-Tesla (T) or more are required. These are higher than the 1.5-T field strength routinely used for human brain imaging. The higher magnetic fields affect contrast agent efficiency and dictate the choice of pulse sequence parameters for in vivo MRI, all addressed in this chapter. Two-dimensional (2D) multi-slice and three-dimensional (3D) MRI acquisitions are described and their advantages and limitations are discussed. The experimental setup required for mouse brain imaging is explained in detail, including anesthesia, immobilization of the mouse’s head to reduce motion artifacts, and anatomical landmarks to use for the slice alignment procedure to improve image co-registration during longitudinal studies and for subsequent matching of MRI with histology.

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References

  1. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science (New York, NY) 1996, 274: 99–102

    Google Scholar 

  2. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, Jantzen P, Wright K, et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 1998, 4: 97–100

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Ashe KH, Zahs KR. Probing the biology of Alzheimer’s disease in mice. Neuron 2010, 66: 631–645

    Google Scholar 

  5. Obulesu M, Rao DM. Animal models of Alzheimer’s disease: an understanding of pathology and therapeutic avenues. The International Journal of Neuroscience 2010, 120: 531–537

    Google Scholar 

  6. Wisniewski T, Sigurdsson EM. Murine models of Alzheimer’s disease and their use in developing immunotherapies. Biochimica et Biophysica Acta 2010, 1802: 847–859

    Google Scholar 

  7. Benveniste H, Einstein G, Kim KR, Hulette C, Johnson GA. Detection of neuritic plaques in Alzheimer’s disease by magnetic resonance microscopy. Proc. Natl. Acad. Sci. of the United States of America 1999, 96: 14079–14084

    Article  PubMed  CAS  Google Scholar 

  8. Dhenain M, Privat N, Duyckaerts C, Jacobs RE. Senile plaques do not induce susceptibility effects in T2*-weighted MR microscopic images. NMR Biomed 2002, 15: 197–203

    Article  PubMed  Google Scholar 

  9. Poduslo JF, Wengenack TM, Curran GL, Wisniewski T, Sigurdsson EM, Macura SI, Borowski BJ, et al. Molecular targeting of Alzheimer’s amyloid plaques for contrast-enhanced magnetic resonance imaging. Neurobiol Dis 2002, 11: 315–329

    Article  PubMed  CAS  Google Scholar 

  10. Helpern JA, Lee SP, Falangola MF, Dyakin VV, Bogart A, Ardekani B, Duff K, et al. MRI assessment of neuropathology in a transgenic mouse model of Alzheimer’s disease. Magn Reson Med 2004, 51: 794–798

    Article  PubMed  Google Scholar 

  11. Lee SP, Falangola MF, Nixon RA, Duff K, Helpern JA. Visualization of beta-amyloid plaques in a transgenic mouse model of Alzheimer’s disease using MR microscopy without contrast reagents. Magn Reson Med 2004, 52: 538–544

    Article  PubMed  Google Scholar 

  12. Zhang J, Yarowsky P, Gordon MN, Di Carlo G, Munireddy S, van Zijl PC, Mori S. Detection of amyloid plaques in mouse models of Alzheimer’s disease by magnetic resonance imaging. Magn Reson Med 2004, 51: 452–457

    Article  PubMed  Google Scholar 

  13. Dhenain M, Delatour B, Walczak C, Volk A. Passive staining: a novel ex vivo MRI protocol to detect amyloid deposits in mouse models of Alzheimer’s disease. Magn Reson Med 2006, 55: 687–693

    Article  PubMed  CAS  Google Scholar 

  14. Sigurdsson EM, Wadghiri YZ, Mosconi L, Blind JA, Knudsen E, Asuni A, Scholtzova H, et al. A non-toxic ligand for voxel-based MRI analysis of plaques in AD transgenic mice. Neurobiol Aging 2008, 29: 836–847

    Article  PubMed  CAS  Google Scholar 

  15. Wadghiri YZ, Sigurdsson EM, Sadowski M, Elliott JI, Li Y, Scholtzova H, Tang CY, et al. Detection of Alzheimer’s amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med 2003, 50: 293–302

    Article  PubMed  CAS  Google Scholar 

  16. Jack CR, Jr., Garwood M, Wengenack TM, Borowski B, Curran GL, Lin J, Adriany G, et al. In vivo visualization of Alzheimer’s amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent. Magn Reson Med 2004, 52: 1263–1271

    Article  PubMed  Google Scholar 

  17. Jack CR, Jr., Wengenack TM, Reyes DA, Garwood M, Curran GL, Borowski BJ, Lin J, et al. In vivo magnetic resonance microimaging of individual amyloid plaques in Alzheimer’s transgenic mice. J Neurosci 2005, 25: 10041–10048

    Article  PubMed  CAS  Google Scholar 

  18. Sigurdsson EM, Wadghiri YZ, Sadowski M, Elliott JI, Li Y, Scholtzova H, Tang CY, et al. In vivo magnetic resonance of amyloid plaques in Alzheimer’s disease model mice. In: Hyman B, Demonet JF, Christen Y eds., The living brain and Alzheimer’s disease. Hardcover ed. Berlin: Springer Verlag 2004: 47–59

    Google Scholar 

  19. Higuchi M, Iwata N, Matsuba Y, Sato K, Sasamoto K, Saido TC. 19F and 1H MRI detection of amyloid beta plaques in vivo. Nat Neurosci 2005, 8: 527–533

    Article  PubMed  CAS  Google Scholar 

  20. Vanhoutte G, Dewachter I, Borghgraef P, Van Leuven F, Van der Linden A. 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 2005, 53: 607–613

    Article  PubMed  CAS  Google Scholar 

  21. Braakman N, Matysik J, van Duinen SG, Verbeek F, Schliebs R, de Groot HJ, Alia A. Longitudinal assessment of Alzheimer’s beta-amyloid plaque development in transgenic mice monitored by in vivo magnetic resonance microimaging. J Magn Reson Imaging 2006, 24: 530–536

    Article  PubMed  Google Scholar 

  22. Borthakur A, Gur T, Wheaton AJ, Corbo M, Trojanowski JQ, Lee VM, Reddy R. In vivo measurement of plaque burden in a mouse model of Alzheimer’s disease. J Magn Reson Imaging 2006, 24: 1011–1017

    Article  PubMed  Google Scholar 

  23. Faber C, Zahneisen B, Tippmann F, Schroeder A, Fahrenholz F. Gradient-echo and CRAZED imaging for minute detection of Alzheimer plaques in an APPV717I x ADAM10-dn mouse model. Magn Reson Med 2007, 57: 696–703

    Article  PubMed  Google Scholar 

  24. Muskulus M, Scheenstra AE, Braakman N, Dijkstra J, Verduyn-Lunel S, Alia A, de Groot HJ, et al. Prospects for early detection of Alzheimer’s disease from serial MR images in transgenic mice. Current Alzheimer Research 2009, 6: 503–518

    Article  PubMed  CAS  Google Scholar 

  25. Scholtzova H, Wadghiri YZ, Douadi M, Sigurdsson EM, Li YS, Quartermain D, Banerjee P, et al. Memantine leads to behavioral improvement and amyloid reduction in Alzheimer’s-disease-model transgenic mice shown as by micromagnetic resonance imaging. Journal of Neuroscience Research 2008, 86: 2784–2791

    Article  PubMed  CAS  Google Scholar 

  26. Yang J, Zaim Wadghiri Y, Minh Hoang D, Tsui W, Sun Y, Chung E, Li Y, et al. Detection of amyloid plaques targeted by USPIO-Abeta1–42 in Alzheimer’s disease transgenic mice using magnetic resonance microimaging. Neuroimage 2011, 55(4): 1600–1609

    Google Scholar 

  27. Weinmann HJ, Brasch RC, Press WR, Wesbey GE. Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR Am J Roentgenol 1984b, 142: 619–624

    PubMed  CAS  Google Scholar 

  28. Weinmann HJ, Laniado M, Mutzel W. Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. Physiological chemistry and physics and medical NMR 1984a, 16: 167–172

    PubMed  CAS  Google Scholar 

  29. Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004, 17: 484–499

    Article  PubMed  CAS  Google Scholar 

  30. Mulder WJ, Griffioen AW, Strijkers GJ, Cormode DP, Nicolay K, Fayad ZA. Magnetic and fluorescent nanoparticles for multimodality imaging. Nanomedicine (London, England) 2007, 2: 307–324

    Google Scholar 

  31. Siddiqui TS, Jani A, Williams F, Muller RN, Vander Elst L, Laurent S, Yao F, et al. Lanthanide complexes on Ag nanoparticles: designing contrast agents for magnetic resonance imaging. Journal of Colloid and Interface Science 2009, 337: 88–96

    Article  PubMed  CAS  Google Scholar 

  32. Wadghiri YZ, Briley-Saebo K. Nanobiomaterials for Preclinical Studies and Clinical Diagnostic. In: Sitharaman B ed., Nanobiomaterials Handbook. Hardback ed. New York: CRC Press. 2011: 1–24

    Google Scholar 

  33. Johnson G, Zaim Wadghiri Y, Turnbull DH. Sensitivity in 2D multislice and 3D MR imaging. Magn Reson Med 2003, 49(5): 848–855

    Google Scholar 

  34. Hoult DI, Richards RE. The signal-to-noise ratio of the nuclear magnetic resonance experiment. J Magn Reson 1976: 71–85

    Google Scholar 

  35. Hayes CE, Edelstein WA, Schenck JF, O.M. M, Eash M. An efficient, highly homogeneous radiofrequency coil for whole-body NMR imaging at 1.5T. J Mag Reson 1985, 63: 622–628

    Google Scholar 

  36. Glover GH, Hayes CE, Pelc NJ, Edelstein WA, Mueller OM, Hart HR, O’Donnell M, et al. Comparison of linear and circular polarization for magnetic resonance imaging. J Mag Reson 1985, 64: 255–270

    Article  CAS  Google Scholar 

  37. Doty FD, Entzminger G, Jr., Hauck CD. Error-tolerant RF litz coils for NMR/MRI. J Magn Reson 1999, 140: 17–31

    Article  PubMed  CAS  Google Scholar 

  38. Crooks LE, Ortendahl DA, Kaufman L, Hoenninger J, Arakawa M, Watts J, Cannon CR, et al. Clinical efficiency of nuclear magnetic resonance imaging. Radiology 1983, 146: 123–128

    PubMed  CAS  Google Scholar 

  39. Crooks L, Arakawa M, Hoenninger J, Watts J, McRee R, Kaufman L, Davis PL, et al. Nuclear magnetic resonance whole-body imager operating at 3.5 KGauss. Radiology 1982, 143: 169–174

    PubMed  CAS  Google Scholar 

  40. Brunner P, Ernst RR. Sensitivity and performance time in NMR imaging. J Magn Reson 1979: 83–106

    Google Scholar 

  41. Johnson G, Wadghiri YZ, Turnbull DH. 2D multislice and 3D MRI sequences are often equally sensitive. Magn Reson Med 1999, 41: 824–828

    Article  PubMed  CAS  Google Scholar 

  42. Jack CR, Jr., Marjanska M, Wengenack TM, Reyes DA, Curran GL, Lin J, Preboske GM, et al. Magnetic resonance imaging of Alzheimer’s pathology in the brains of living transgenic mice: a new tool in Alzheimer’s disease research. Neuroscientist 2007, 13: 38–48

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The research described in this chapter was supported by grants from the NIH (AG020197 and AG032611 to EMS; AG20245, and AG008051 to TW, the Alzheimer’s Association (IIRG-08-91618 to YZW, ZEN-08-91006 to EMS), the American Health Assistance Foundation (ADR-A2008-155 to YZW). We thank Yongsheng, Li and Jeffrey A. Blind and Amr Morsi for assistance with the surgical protocols. We also thank Dr Florence Janody for artistic help with Fig. 2.

Author information

Authors and Affiliations

  1. Department of Radiology, Center for Biomedical Imaging New York University School of Medicine, New York, NY, USA

    Youssef Zaim Wadghiri & Dung Minh Hoang

  2. Departments of Neurology, Pathology and Psychiatry, New York University School of Medicine, New York, NY, USA

    Thomas Wisniewski

  3. Departments of Physiology and Neuroscience, and Psychiatry, New York University School of Medicine, New York, NY, USA

    Einar M. Sigurdsson

Authors
  1. Youssef Zaim Wadghiri
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  2. Dung Minh Hoang
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  3. Thomas Wisniewski
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  4. Einar M. Sigurdsson
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Corresponding author

Correspondence to Youssef Zaim Wadghiri .

Editor information

Editors and Affiliations

  1. School of Medicine, Dept. Psychiatry, New York University, First Ave. 550, New York, 10016, New York, USA

    Einar M. Sigurdsson

  2. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo Km 2, Madrid, 28220, Spain

    Miguel Calero

  3. Inst. Química Física, Rocasolano, CSIC Madrid, C/ Serrano 119, Madrid, 28006, Spain

    María Gasset

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Wadghiri, Y.Z., Hoang, D.M., Wisniewski, T., Sigurdsson, E.M. (2012). In Vivo Magnetic Resonance Imaging of Amyloid-β Plaques in Mice. In: Sigurdsson, E., Calero, M., Gasset, M. (eds) Amyloid Proteins. Methods in Molecular Biology, vol 849. Humana Press. https://doi.org/10.1007/978-1-61779-551-0_30

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  • DOI: https://doi.org/10.1007/978-1-61779-551-0_30

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-550-3

  • Online ISBN: 978-1-61779-551-0

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