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In Vivo Imaging in Humanized Mice

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 324))

The radiological modalities that are currently utilized as critical components in clinical medicine have also been adapted to small-animal imaging, among which are ultrasound imaging, X-ray computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and singlephoton emission computed tomography (SPECT). Optical imaging techniques such as bioluminescence imaging (BLI) and fluorescence imaging (FLI) are approaches that are commonly used in small animals. Longitudinal surveys of living (i.e., nonsacrificed) animal models with these modalities provide some clues for the development of clinical applications. The techniques are absolutely essential for translational research. However, there are currently few tools available with sufficient spatial or temporal resolution ideal for all experimental studies. In this chapter, we provide a rationale and techniques for visualizing target cells in living small animals and an overview of the advantages and limitations of current imaging technology. Finally, we introduce a humanized mouse and a novel in vivo imaging system that we have developed. We also discuss real-time observations of reconstructs and clinical manifestations.

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References

  1. Balaban RS, Hampshire VA (2001) Challenges in small animal noninvasive imaging. ILAR J 42:248–62

    PubMed  CAS  Google Scholar 

  2. Beekman FJ, van der Have F, Vastenhouw B, van der Linden AJ, van Rijk PP, Burbach JP, Smidt MP (2005) U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice. J Nucl Med 46:1194–200

    PubMed  Google Scholar 

  3. Berger F, Lee YP, Loening AM, Chatziioannou A, Freedland SJ, Leahy R, Lieberman JR, Belldegrun AS, Sawyers CL, Gambhir SS (2002) Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone disease. Eur J Nucl Med Mol Imaging 29:1225–36

    Article  PubMed  CAS  Google Scholar 

  4. Bremer C, Ntziachristos V, Weissleder R (2003) Optical-based molecular imaging: contrast agents and potential medical applications. Eur Radiol 13:231–43

    PubMed  Google Scholar 

  5. Cao YA, Wagers AJ, Beilhack A, Dusich J, Bachmann MH, Negrin RS, Weissman IL, Contag CH (2004) Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci USA 101:221–6

    Article  PubMed  CAS  Google Scholar 

  6. Chatziioannou A, Tai YC, Doshi N, Cherry SR (2001) Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging. Phys Med Biol 46:2899–910

    Article  PubMed  CAS  Google Scholar 

  7. Chatziioannou AF (2002) Molecular imaging of small animals with dedicated PET tomographs. Eur J Nucl Med Mol Imaging 29:98–114

    Article  PubMed  Google Scholar 

  8. Cherry SR, Gambhir SS (2001) Use of positron emission tomography in animal research. ILAR J 42:219–32

    PubMed  CAS  Google Scholar 

  9. Coatney RW (2001) Ultrasound imaging: principles and applications in rodent research. ILAR J 42:233–47

    PubMed  CAS  Google Scholar 

  10. Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA (1995) Photonic detection of bacterial pathogens in living hosts. Mol Microbiol 18:593–603

    Article  PubMed  CAS  Google Scholar 

  11. DeYoe EA, Bandettini P, Neitz J, Miller D, Winans P (1994) Functional magnetic resonance imaging (FMRI) of the human brain. J Neurosci Methods 54:171–87

    Article  PubMed  CAS  Google Scholar 

  12. Foster FS, Pavlin CJ, Harasiewicz KA, Christopher DA, Turnbull DH (2000) Advances in ultrasound biomicroscopy. Ultrasound Med Biol 26:1–27

    Article  PubMed  CAS  Google Scholar 

  13. Foster FS, Zhang MY, Zhou YQ, Liu G, Mehi J, Cherin E, Harasiewicz KA, Starkoski BG, Zan L, Knapik DA, Adamson SL (2002) A new ultrasound instrument for in vivo microimaging of mice. Ultrasound Med Biol 28:1165–72

    Article  PubMed  CAS  Google Scholar 

  14. Gao X, Cui Y, Levenson RM, Chung LW, Nie S (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–76

    Article  PubMed  CAS  Google Scholar 

  15. Graves EE, Ripoll J, Weissleder R, Ntziachristos V (2003) A submillimeter resolution fluorescence molecular imaging system for small animal imaging. Med Phys 30:901–11

    Article  PubMed  CAS  Google Scholar 

  16. Green MV, Seidel J, Vaquero JJ, Jagoda E, Lee I, Eckelman WC (2001) High resolution PET, SPECT and projection imaging in small animals. Comput Med Imaging Graph 25:79–86

    Article  PubMed  CAS  Google Scholar 

  17. Griffin JL, Shockcor JP (2004) Metabolic profiles of cancer cells. Nat Rev Cancer 4:551–61

    Article  PubMed  CAS  Google Scholar 

  18. Hasegawa BH, Iwata K, Wong KH, Wu MC, Da Silva AJ, Tang HR, Barber WC, Hwang AH, Sakdinawat AE (2002) Dual-modality imaging of function and physiology. Acad Radiol 9:1305–21

    Article  PubMed  Google Scholar 

  19. Hastings JW (1996) Chemistries and colors of bioluminescent reactions: a review. Gene 173:5–11

    Article  PubMed  CAS  Google Scholar 

  20. Herschman HR (2003) Micro-PET imaging and small animal models of disease. Curr Opin Immunol 15:378–84

    Article  PubMed  CAS  Google Scholar 

  21. Honigman A, Zeira E, Ohana P, Abramovitz R, Tavor E, Bar I, Zilberman Y, Rabinovsky R, Gazit D, Joseph A, Panet A, Shai E, Palmon A, Laster M, Galun E (2001) Imaging transgene expression in live animals. Mol Ther 4:239–49

    Article  PubMed  CAS  Google Scholar 

  22. Ishizu K, Mukai T, Yonekura Y, Pagani M, Fujita T, Magata Y, Nishizawa S, Tamaki N, Shibasaki H, Konishi J (1995) Ultra-high resolution SPECT system using four pinhole collimators for small animal studies. J Nucl Med 36:2282–7

    PubMed  CAS  Google Scholar 

  23. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, Ueyama Y, Koyanagi Y, Sugamura K, Tsuji K, Heike T, Nakahata T (2002) NOD/SCID/γc null mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175–82

    Article  PubMed  CAS  Google Scholar 

  24. Kaneko K, Yano M, Yamano T, Tsujinaka T, Miki H, Akiyama Y, Taniguchi M, Fujiwara Y, Doki Y, Inoue M, Shiozaki H, Kaneda Y, Monden M (2001) Detection of peritoneal micrometastases of gastric carcinoma with green fluorescent protein and carcinoembryonic antigen promoter. Cancer Res 61:5570–4

    PubMed  CAS  Google Scholar 

  25. Koo V, Hamilton PW, Williamson K (2006) Non-invasive in vivo imaging in small animal research. Cell Oncol 28:127–39

    PubMed  CAS  Google Scholar 

  26. Levenson RM, Mansfield JR (2006) Multispectral imaging in biology and medicine: slices of life. Cytometry A69:748–58

    Article  Google Scholar 

  27. Levin CS (2005) Primer on molecular imaging technology. Eur J Nucl Med Mol Imaging 32 Suppl 2: S325–45.

    Article  PubMed  Google Scholar 

  28. Liang HD, Blomley MJ (2003) The role of ultrasound in molecular imaging. Br J Radiol 76 Spec No 2: S140–50.

    Article  PubMed  CAS  Google Scholar 

  29. Lin Y, Weissleder R, Tung CH (2002) Novel near-infrared cyanine fluorochromes: synthesis, properties, and bioconjugation. Bioconjug Chem 13:605–10

    Article  PubMed  Google Scholar 

  30. Mansfield JR, Gossage KW, Hoyt CC, Levenson RM (2005) Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging. J Biomed Opt 10:41207

    Article  PubMed  Google Scholar 

  31. Massoud TF, Paulmurugan R, Gambhir SS (2004) Molecular imaging of homodimeric protein-protein interactions in living subjects. FASEB J 18:1105–7

    PubMed  CAS  Google Scholar 

  32. Masuda H, Maruyama T, Hiratsu E, Yamane J, Iwanami A, Nagashima T, Ono M, Miyoshi H, Okano HJ, Ito M, Tamaoki N, Nomura T, Okano H, Matsuzaki Y, Yoshimura Y (2007) Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gamma cnull immunodeficient mice. Proc Natl Acad Sci USA 104:1925–30

    Article  PubMed  CAS  Google Scholar 

  33. Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–44

    Article  PubMed  CAS  Google Scholar 

  34. Miyoshi H, Blomer U, Takahashi M, Gage FH, Verma IM (1998) Development of a self-inactivating lentivirus vector. J Virol 72:8150–7

    PubMed  CAS  Google Scholar 

  35. Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, Miyawaki A (2002) A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol 20:87–90

    Article  PubMed  CAS  Google Scholar 

  36. Nasir K, Budoff MJ, Post WS, Fishman EK, Mahesh M, Lima JA, Blumenthal RS (2003) Electron beam CT versus helical CT scans for assessing coronary calcification: current utility and future directions. Am Heart J 146:969–77

    Article  PubMed  Google Scholar 

  37. Natt O, Watanabe T, Boretius S, Radulovic J, Frahm J, Michaelis T (2002) High-resolution 3D MRI of mouse brain reveals small cerebral structures in vivo. J Neurosci Methods 120:203–9

    Article  PubMed  CAS  Google Scholar 

  38. Negrin RS, Contag CH (2006) In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease. Nat Rev Immunol 6:484–90

    Article  PubMed  CAS  Google Scholar 

  39. Ntziachristos V, Tung CH, Bremer C, Weissleder R (2002) Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 8:757–60

    Article  PubMed  CAS  Google Scholar 

  40. Ntziachristos V, Weissleder R (2002) Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media. Med Phys 29:803–9

    Article  PubMed  Google Scholar 

  41. Paulus MJ, Gleason SS, Easterly ME, Foltz CJ (2001) A review of high-resolution X-ray computed tomography and other imaging modalities for small animal research. Lab Anim (NY) 30:36–45

    CAS  Google Scholar 

  42. Phoon CK (2006) Imaging tools for the developmental biologist: ultrasound biomicroscopy of mouse embryonic development. Pediatr Res 60:14–21

    Article  PubMed  Google Scholar 

  43. Prout DL, Silverman RW, Chatziioannou A (2004) Detector concept for OPET-A combined PET and optical imaging system. IEEE Trans Nucl Sci 51:752–756

    Article  PubMed  Google Scholar 

  44. Rice BW, Cable MD, Nelson MB (2001) In vivo imaging of light-emitting probes. J Biomed Opt 6:432–40

    Article  PubMed  CAS  Google Scholar 

  45. Shah K, Jacobs A, Breakefield XO, Weissleder R (2004) Molecular imaging of gene therapy for cancer. Gene Ther 11:1175–87

    Article  PubMed  CAS  Google Scholar 

  46. Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–9

    Article  PubMed  CAS  Google Scholar 

  47. Sweeney TJ, Mailander V, Tucker AA, Olomu AB, Zhang W, Cao Y, Negrin RS, Contag CH (1999) Visualizing the kinetics of tumor-cell clearance in living animals. Proc Natl Acad Sci USA 96:12044–9

    Article  PubMed  CAS  Google Scholar 

  48. Townsend DW (2001) A combined PET/CT scanner: the choices. J Nucl Med 42:533–4

    PubMed  CAS  Google Scholar 

  49. Townsend DW, Cherry SR (2001) Combining anatomy and function: the path to true image fusion. Eur Radiol 11:1968–74

    Article  PubMed  CAS  Google Scholar 

  50. Troy T, Jekic-McMullen D, Sambucetti L, Rice B (2004) Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging 3:9–23

    Article  PubMed  CAS  Google Scholar 

  51. Wakeling AE, Dukes M, Bowler J (1991) A potent specific pure antiestrogen with clinical potential. Cancer Res 51: 3867–73

    PubMed  CAS  Google Scholar 

  52. Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–7

    Article  PubMed  CAS  Google Scholar 

  53. Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–8

    Article  PubMed  CAS  Google Scholar 

  54. Wilson T, Hastings JW (1998) Bioluminescence. Annu Rev Cell Dev Biol 14:197–230

    Article  PubMed  CAS  Google Scholar 

  55. Zhao H, Doyle TC, Coquoz O, Kalish F, Rice BW, Contag CH (2005) Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. J Biomed Opt 10:41210

    Article  PubMed  Google Scholar 

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Masuda, H., Okano, H.J., Maruyama, T., Yoshimura, Y., Okano, H., Matsuzaki, Y. (2008). In Vivo Imaging in Humanized Mice. In: Nomura, T., Watanabe, T., Habu, S. (eds) Humanized Mice. Current Topics in Microbiology and Immunology, vol 324. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75647-7_12

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