Molecular Diagnosis & Therapy

, Volume 18, Issue 2, pp 153–173 | Cite as

Preclinical Imaging: an Essential Ally in Modern Biosciences

  • Lídia Cunha
  • Ildiko Horvath
  • Sara Ferreira
  • Joana Lemos
  • Pedro Costa
  • Domingos Vieira
  • Dániel S. Veres
  • Krisztián Szigeti
  • Teresa Summavielle
  • Domokos Máthé
  • Luís F. Metello
Review Article

Abstract

Translational research is changing the practice of modern medicine and the way in which health problems are approached and solved. The use of small-animal models in basic and preclinical sciences is a major keystone for these kinds of research and development strategies, representing a bridge between discoveries at the molecular level and clinical implementation in diagnostics and/or therapeutics. The development of high-resolution in vivo imaging technologies provides a unique opportunity for studying disease in real time, in a quantitative way, at the molecular level, along with the ability to repeatedly and non-invasively monitor disease progression or response to treatment. The greatest advantages of preclinical imaging techniques include the reduction of biological variability and the opportunity to acquire, in continuity, an impressive amount of unique information (without interfering with the biological process under study) in distinct forms, repeated or modulated as needed, along with the substantial reduction in the number of animals required for a particular study, fully complying with 3R (Replacement, Reduction and Refinement) policies. The most suitable modalities for small-animal in vivo imaging applications are based on nuclear medicine techniques (essentially, positron emission tomography [PET] and single photon emission computed tomography [SPECT]), optical imaging (OI), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy imaging (MRSI), and ultrasound. Each modality has intrinsic advantages and limitations. More recently, aiming to overcome the inherent limitations of each imaging modality, multimodality devices designed to provide complementary information upon the pathophysiological process under study have gained popularity. The combination of high-resolution modalities, like micro-CT or micro-MRI, with highly sensitive techniques providing functional information, such as micro-PET or micro-SPECT, will continue to broaden the horizons of research in such key areas as infection, oncology, cardiology, and neurology, contributing not only to the understanding of the underlying mechanisms of disease, but also providing efficient and unique tools for evaluating new chemical entities and candidate drugs. The added value of small-animal imaging techniques has driven their increasing use by pharmaceutical companies, contract research organizations, and research institutions.

References

  1. 1.
    Milne CP, Kaitin KI. Translational medicine: an engine of change for bringing new technology to community health. Sci Transl Med. 2009 Nov 4;1(5):5cm5.Google Scholar
  2. 2.
    Lewis JS, Achilefu S, Garbow JR, Laforest R, Welch MJ. Small animal imaging: current technology and perspectives for oncological imaging. Eur J Cancer. 2002;38(16):2173–88.PubMedCrossRefGoogle Scholar
  3. 3.
    Franc BL, Acton PD, Mari C, Hasegawa BH. Small-animal SPECT and SPECT/CT: important tools for preclinical investigation. J Nucl Med. 2008;49(10):1651–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Allport JR, Weissleder R. In vivo imaging of gene and cell therapies. Exp Hematol. 2001;29(11):1237–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Pomper MG, Lee JS. Small animal imaging in drug development. Curr Pharm Des. 2005;11(25):3247–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Deng WP, Wu CC, Lee CC, Yang WK, Wang HE, Liu RS, et al. Serial in vivo imaging of the lung metastases model and gene therapy using HSV1-tk and ganciclovir. J Nucl Med. 2006;47(5):877–84.PubMedGoogle Scholar
  7. 7.
    Turetschek K, Floyd E, Helbich T, Roberts TP, Shames DM, Wendland MF, et al. MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS-325) with correlations to histopathology. J Magn Reson Imaging. 2001;14(3):237–42.PubMedCrossRefGoogle Scholar
  8. 8.
    Cheng Z, Mahmood A, Li H, Davison A, Jones AG. [99mTcOAADT]-(CH2)2-NEt2: a potential small-molecule single-photon emission computed tomography probe for imaging metastatic melanoma. Cancer Res. 2005;65(12):4979–86.PubMedCrossRefGoogle Scholar
  9. 9.
    Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME. A tabulated summary of the FDG PET literature. J Nucl Med. 2001;42(5 Suppl):1S–93S.PubMedGoogle Scholar
  10. 10.
    Bading JR, Shields AF. Imaging of cell proliferation: status and prospects. J Nucl Med. 2008;49(Suppl 2):64S–80S.PubMedCrossRefGoogle Scholar
  11. 11.
    Blasberg R. PET imaging of gene expression. Eur J Cancer. 2002;38(16):2137–46.PubMedCrossRefGoogle Scholar
  12. 12.
    Gambhir SS, Herschman HR, Cherry SR, Barrio JR, Satyamurthy N, Toyokuni T, et al. Imaging transgene expression with radionuclide imaging technologies. Neoplasia. 2000;2(1–2):118–38.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Orlova A, Nilsson FY, Wikman M, Widstrom C, Stahl S, Carlsson J, et al. Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors. J Nucl Med. 2006;47(3):512–9.PubMedGoogle Scholar
  14. 14.
    Foss CA, Mease RC, Fan H, Wang Y, Ravert HT, Dannals RF, et al. Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer. Clin Cancer Res. 2005;11(11):4022–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Haubner RH, Wester HJ, Weber WA, Schwaiger M. Radiotracer-based strategies to image angiogenesis. Q J Nucl Med. 2003;47(3):189–99.PubMedGoogle Scholar
  16. 16.
    Jia B, Shi J, Yang Z, Xu B, Liu Z, Zhao H, et al. 99mTc-labeled cyclic RGDfK dimer: initial evaluation for SPECT imaging of glioma integrin alphavbeta3 expression. Bioconjugate Chem. 2006;17(4):1069–76.CrossRefGoogle Scholar
  17. 17.
    Niu G, Chen X. PET imaging of angiogenesis. PET Clin. 2009;4(1):17–38.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Holland JP, Lewis JS, Dehdashti F. Assessing tumor hypoxia by positron emission tomography with Cu-ATSM. Q J Nucl Med Mol Imag. 2009;53(2):193–200.Google Scholar
  19. 19.
    Madar I, Huang Y, Ravert H, Dalrymple SL, Davidson NE, Isaacs JT, et al. Detection and quantification of the evolution dynamics of apoptosis using the PET voltage sensor 18F-fluorobenzyl triphenyl phosphonium. J Nucl Med. 2009;50(5):774–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Murakami Y, Takamatsu H, Taki J, Tatsumi M, Noda A, Ichise R, et al. 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur J Nucl Med Mol Imag. 2004;31(4):469–74.CrossRefGoogle Scholar
  21. 21.
    Jaffer FA, Weissleder R. Seeing within: molecular imaging of the cardiovascular system. Circ Res. 2004;94(4):433–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Lamb HJ, van der Meer RW, de Roos A, Bax JJ. Cardiovascular molecular MR imaging. Eur J Nucl Med Mol Imag. 2007;34(Suppl 1):S99–104.CrossRefGoogle Scholar
  23. 23.
    Hua J, Dobrucki LW, Sadeghi MM, Zhang J, Bourke BN, Cavaliere P, et al. Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia. Circulation. 2005;111(24):3255–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Khaw BA, Tekabe Y, Johnson LL. Imaging experimental atherosclerotic lesions in ApoE knockout mice: enhanced targeting with Z2D3-anti-DTPA bispecific antibody and 99mTc-labeled negatively charged polymers. J Nucl Med. 2006;47(5):868–76.PubMedGoogle Scholar
  25. 25.
    Kolodgie FD, Petrov A, Virmani R, Narula N, Verjans JW, Weber DK, et al. Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation. 2003;108(25):3134–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Schafers M, Riemann B, Kopka K, Breyholz HJ, Wagner S, Schafers KP, et al. Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation. 2004;109(21):2554–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Acton PD, Kung HF. Small animal imaging with high resolution single photon emission tomography. Nucl Med Biol. 2003;30(8):889–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Lancelot S, Zimmer L. Small-animal positron emission tomography as a tool for neuropharmacology. Trend Pharmacol Sci. 2010;31(9):411–7.CrossRefGoogle Scholar
  29. 29.
    Zanzonico P. Noninvasive imaging for supporting basic research. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 3–16.CrossRefGoogle Scholar
  30. 30.
    Kagadis GC, Loudos G, Katsanos K, Langer SG, Nikiforidis GC. In vivo small animal imaging: current status and future prospects. Med Phys. 2010;37(12):6421–42.PubMedCrossRefGoogle Scholar
  31. 31.
    Weissleder R, Mahmood U. Molecular imaging. Radiology. 2001;219(2):316–33.PubMedCrossRefGoogle Scholar
  32. 32.
    Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev. 2003;17(5):545–80.PubMedCrossRefGoogle Scholar
  33. 33.
    Grassi R, Lagalla R, Rotondo A. Genomics, proteomics, MEMS and SAIF: which role for diagnostic imaging? La Radiologia medica. 2008;113(6):775–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Alberti C. From molecular imaging in preclinical/clinical oncology to theranostic applications in targeted tumor therapy. Eur Rev Med Pharmacol Sci. 2012;16(14):1925–33.PubMedGoogle Scholar
  35. 35.
    Meikle SR, Kench P, Kassiou M, Banati RB. Small animal SPECT and its place in the matrix of molecular imaging technologies. Phys Med Biol. 2005;50(22):R45–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Peterson TE, Shokouhi S. Advances in preclinical SPECT instrumentation. J Nucl Med. 2012;53(6):841–4.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Khalil MM, Tremoleda JL, Bayomy TB, Gsell W. Molecular SPECT imaging: an overview. Int J Mol Imaging. 2011;2011:796025.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Peterson TE, Furenlid LR. SPECT detectors: the Anger Camera and beyond. Phys Med Biol. 2011;56(17):R145–82.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Kim H, Furenlid LR, Crawford MJ, Wilson DW, Barber HB, Peterson TE, et al. SemiSPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays. Med Phys. 2006;33(2):465–74.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Nat Acad Sci USA. 2000;97(16):9226–33.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Phelps ME. PET: the merging of biology and imaging into molecular imaging. J Nucl Med. 2000;41(4):661–81.PubMedGoogle Scholar
  42. 42.
    Kowalski J, Henze M, Schuhmacher J, Mäcke HR, Hofmann M, Haberkorn U. Evaluation of Positron Emission Tomography Imaging Using [68 Ga]-DOTA-D Phe1-Tyr3-Octreotide in Comparison to [111In]-DTPAOC SPECT. First Results in Patients with Neuroendocrine Tumors. Mol Imaging Biol. 2003;5(1):42–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Holland JP, Sheh Y, Lewis JS. Standardized methods for the production of high specific-activity zirconium-89. Nucl Med Biol. 2009;36(7):729–39.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Basu S, Urhan M, Rosenbaum J, Alavi A. PET and PET/CT in the management of thyroid cancer. Method Mol Biol. 2011;727:205–24.CrossRefGoogle Scholar
  45. 45.
    Fass L. Imaging and cancer: a review. Mol Oncol. 2008;2(2):115–52.PubMedCrossRefGoogle Scholar
  46. 46.
    Levin CS, Zaidi H. Current trends in preclinical PET system design. PET Clin. 2007;2(2):125–60.CrossRefGoogle Scholar
  47. 47.
    Yao R, Lecomte R, Crawford ES. Small-animal PET: what is it, and why do we need it? J Nucl Med Technol. 2012 Sep;40(3):157-65.Google Scholar
  48. 48.
    Hutchins GD, Miller MA, Soon VC, Receveur T. Small animal PET imaging. ILAR J. 2008;49(1):54–65.PubMedCrossRefGoogle Scholar
  49. 49.
    Lecomte R. Technology challenges in small animal PET imaging. Nucl Instrum Methods Phys Res A. 2004;527(1–2):157–65.CrossRefGoogle Scholar
  50. 50.
    Comley J. In vivo preclinical imaging: an essential tool in translational research. Drug Discovery World. 2011:58–71.Google Scholar
  51. 51.
    Beekman F, van der Have F. The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging. Eur J Nucl Med Mol Imaging. 2007;34(2):151–61.PubMedCrossRefGoogle Scholar
  52. 52.
    Shao Y, Cherry SR, Farahani K, Slates R, Silverman RW, Meadors K, et al. Development of a PET detector system compatible with MRI/NMR systems. IEEE Trans Nucl Sci. 1997;44(3):1167–71.CrossRefGoogle Scholar
  53. 53.
    Tsui BM, Kraitchman DL. Recent advances in small-animal cardiovascular imaging. J Nucl Med. 2009;50(5):667–70.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    de Kemp RA, Epstein FH, Catana C, Tsui BM, Ritman EL. Small-animal molecular imaging methods. J Nucl Med. 2010;1(51 Suppl 1):18S–32S.CrossRefGoogle Scholar
  55. 55.
    Fleming JS, Alaamer AS. Influence of collimator characteristics on quantification in SPECT. J Nucl Med. 1996;37(11):1832–6.PubMedGoogle Scholar
  56. 56.
    Chatziioannou AF, Cherry SR, Shao Y, Silverman RW, Meadors K, Farquhar TH, et al. Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. J Nucl Med. 1999;40(7):1164–75.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Levin CS, Hoffman EJ. Calculation of positron range and its effect on the fundamental limit of positron emission tomography system spatial resolution. Phys Med Biol. 1999;44(3):781.PubMedCrossRefGoogle Scholar
  58. 58.
    Tai YC, Ruangma A, Rowland D, Siegel S, Newport DF, Chow PL, et al. Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging. J Nucl Med. 2005;46(3):455–63.PubMedGoogle Scholar
  59. 59.
    Beekman FJ, van der Have F, Vastenhouw B, van der Linden AJ, van Rijk PP, Burbach JP, et al. U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice. J Nucl Med. 2005;46(7):1194–200.PubMedGoogle Scholar
  60. 60.
    Vastenhouw B, Beekman F. Submillimeter total-body murine imaging with U-SPECT-I. J Nucl Med. 2007;48(3):487–93.PubMedGoogle Scholar
  61. 61.
    Chatziioannou AF. Instrumentation for molecular imaging in preclinical research: Micro-PET and Micro-SPECT. Proc Am Thorac Soc. 2005;2(6):533-6, 10-11.Google Scholar
  62. 62.
    Henriksen G, Drzezga A. Imaging in neurology research II: PET imaging in CNS disorders. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 499–513.CrossRefGoogle Scholar
  63. 63.
    Hume SP, Gunn RN, Jones T. Pharmacological constraints associated with positron emission tomographic scanning of small laboratory animals. Eur J Nucl Med. 1998;25(2):173–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Judenhofer MS, Wiehr S, Kukuk D, Fischer K, Pichler BJ. Guidelines for nuclear image analysis. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 379–86.CrossRefGoogle Scholar
  65. 65.
    Cavanaugh D, Johnson E, Price RE, Kurie J, Travis EL, Cody DD. In vivo respiratory-gated micro-CT imaging in small-animal oncology models. Mol Imaging. 2004;3(1):55–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Ritman EL. Current status of developments and applications of micro-CT. Annu Rev Biomed Eng. 2011;15(13):531–52.CrossRefGoogle Scholar
  67. 67.
    Badea CT, Drangova M, Holdsworth DW, Johnson GA. In vivo small-animal imaging using micro-CT and digital subtraction angiography. Phys Med Biol. 2008;53(19):R319–50.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Lee N, Choi SH, Hyeon T. Nano-sized CT contrast agents. Adv Mater. 2013;25(19):2641–60.PubMedCrossRefGoogle Scholar
  69. 69.
    Pietsch H. CT contrast agents. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 141–9.CrossRefGoogle Scholar
  70. 70.
    Kalender WA, Deak P, Engelke K, Karolczak M. X-ray and X-ray CT. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 125–39.CrossRefGoogle Scholar
  71. 71.
    Dufort S, Sancey L, Wenk C, Josserand V, Coll JL. Optical small animal imaging in the drug discovery process. Biochim Biophys Acta. 2010;1798(12):2266–73.PubMedCrossRefGoogle Scholar
  72. 72.
    Tremoleda JL, Khalil M, Gompels LL, Wylezinska-Arridge M, Vincent T, Gsell W. Imaging technologies for preclinical models of bone and joint disorders. EJNMMI Res. 2011;1(1):11.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Koba W, Kim K, Lipton ML, Jelicks L, Das B, Herbst L, et al. Imaging devices for use in small animals. Semin Nucl Med. 2011;41(3):151–65.PubMedCrossRefGoogle Scholar
  74. 74.
    Jakob P. Small animal magnetic resonance imaging: basic principles, instrumentation and practical issues. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 151–64.CrossRefGoogle Scholar
  75. 75.
    Brockmann MA. Use of clinical MR scanners for small rodent imaging. Methods. 2007;43(1):1.PubMedCrossRefGoogle Scholar
  76. 76.
    Leroy-Willig A, Geldwerth-Feniger G. Nuclear magnetic resonance imaging and spectroscopy. In: Ntziachristos V, Leroy-Willig A, Tavitian B, editors. Textbook of in vivo imaging in vertebrates. UK: Wiley; 2007. p. 1–56.Google Scholar
  77. 77.
    Weber WA, Kiessling F. Imaging in oncology research. In: Kiessling F, Pichler BJ, editors. Small animal imaging—basics and practical guide. Heidelberg: Springer; 2011. p. 543–64.CrossRefGoogle Scholar
  78. 78.
    Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology. 2000;217(2):331–45.PubMedCrossRefGoogle Scholar
  79. 79.
    Heeger DJ, Ress D. What does fMRI tell us about neuronal activity? Nat Rev Neurosci. 2002;3(2):142–51.PubMedCrossRefGoogle Scholar
  80. 80.
    Goetti R, O’Gorman R, Khan N, Kellenberger CJ, Scheer I. Arterial spin labelling MRI for assessment of cerebral perfusion in children with moyamoya disease: comparison with dynamic susceptibility contrast MRI. Neuroradiology. 2013;55(5):639–47.PubMedCrossRefGoogle Scholar
  81. 81.
    Cutajar M, Thomas DL, Banks T, Clark CA, Golay X, Gordon I. Repeatability of renal arterial spin labelling MRI in healthy subjects. MAGMA. 2012;25(2):145–53.PubMedCrossRefGoogle Scholar
  82. 82.
    Thomas D, Wells J. MR angiography and arterial spin labelling. Method Mol Biol. 2011;711:327–45.CrossRefGoogle Scholar
  83. 83.
    Kazan SM, Chappell MA, Payne SJ. Modelling the effects of cardiac pulsations in arterial spin labelling. Phys Med Biol. 2010;55(3):799–816.PubMedCrossRefGoogle Scholar
  84. 84.
    Richards TL. Multinuclear Magnetic Resonance Spectroscopic Imaging. Encyclopedia of Analytical Chemistry. New York: Wiley; 2006.Google Scholar
  85. 85.
    Rudin M. Imaging techniques. Molecular imaging: basic principles and applications in biomedical research. London: Imperial College Press; 2005. p. 45–140.Google Scholar
  86. 86.
    Rosen Y, Lenkinski RE. Recent advances in magnetic resonance neurospectroscopy. Neurotherapeutics. 2007;4(3):330–45.PubMedCrossRefGoogle Scholar
  87. 87.
    Gujar SK, Maheshwari S, Bjorkman-Burtscher I, Sundgren PC. Magnetic resonance spectroscopy. J Neuroophthalmol. 2005;25(3):217–26.PubMedCrossRefGoogle Scholar
  88. 88.
    van der Graaf M. In vivo magnetic resonance spectroscopy: basic methodology and clinical applications. Eur Biophys J. 2010;39(4):527–40.PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Zhu H, Barker PB. MR spectroscopy and spectroscopic imaging of the brain. Methods Mol Biol. 2011;711:203–26.PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Forster D, Davies K, Williams S. Magnetic resonance spectroscopy in vivo of neurochemicals in a transgenic model of Alzheimer’s disease: a longitudinal study of metabolites, relaxation time, and behavioral analysis in TASTPM and wild-type mice. Magn Reson Med. 2013;69(4):944–55.Google Scholar
  91. 91.
    He Q, Xu RZ, Shkarin P, Pizzorno G, Lee-French CH, Rothman DL, et al. Magnetic resonance spectroscopic imaging of tumor metabolic markers for cancer diagnosis, metabolic phenotyping, and characterization of tumor microenvironment. Dis Markers. 2003;19(2–3):69–94.PubMedGoogle Scholar
  92. 92.
    Bremer C, Ntziachristos V, Weissleder R. Optical-based molecular imaging: contrast agents and potential medical applications. Eur Radiol. 2003;13(2):231–43.PubMedGoogle Scholar
  93. 93.
    Chin PT, Welling MM, Meskers SC, Valdes Olmos RA, Tanke H, van Leeuwen FW. Optical imaging as an expansion of nuclear medicine: Cerenkov-based luminescence vs fluorescence-based luminescence. Eur J Nucl Med Mol Imaging. 2013;40(8):1283–91.PubMedCrossRefGoogle Scholar
  94. 94.
    Wilson T, Hastings J. Bioluminescence. Annu Rev Cell Dev Biol. 1988;14:197–230.CrossRefGoogle Scholar
  95. 95.
    Greer LF III, Szalay AA. Imaging of light emission from the expression of luciferases in living cells and organisms: a review. Luminescence. 2002;17(1):43-74.Google Scholar
  96. 96.
    Weissleder R. Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer. 2002;2(1):11–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Culver J, Akers W, Achilefu S. Multimodality molecular imaging with combined optical and SPECT/PET modalities. J Nucl Med. 2008;49(2):169–72.PubMedCrossRefGoogle Scholar
  98. 98.
    Ntziachristos V, Bremer C, Weissleder R. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol. 2003;13(1):195–208.PubMedGoogle Scholar
  99. 99.
    Kruger RA. Photoacoustic ultrasound. Med Phys. 1994;21(1):127–31.PubMedCrossRefGoogle Scholar
  100. 100.
    Wang LV, Hu S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science. 2012;335(6075):1458–62.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Robertson R, Germanos MS, Li C, Mitchell GS, Cherry SR, Silva MD. Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol. 2009;54(16):N355–65.PubMedCentralPubMedCrossRefGoogle Scholar
  102. 102.
    Liu H, Ren G, Miao Z, Zhang X, Tang X, Han P, et al. Molecular optical imaging with radioactive probes. PloS One. 2010;5(3):e9470.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Spinelli AE, Ferdeghini M, Cavedon C, Zivelonghi E, Calandrino R, Fenzi A, et al. First human Cerenkography. J Biomed Opt. 2013;18(2):20502.PubMedCrossRefGoogle Scholar
  104. 104.
    Vooijs M, Jonkers J, Lyons S, Berns A. Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res. 2002;62(6):1862–7.PubMedGoogle Scholar
  105. 105.
    Liang HD, Blomley MJ. The role of ultrasound in molecular imaging. British J Radiol. 2003;76 Spec No 2:S140–50.Google Scholar
  106. 106.
    Coatney RW. Ultrasound imaging: principles and applications in rodent research. ILAR J. 2001;42(3):233–47.PubMedCrossRefGoogle Scholar
  107. 107.
    Tremoleda JL, Kerton A, Gsell W. Anaesthesia and physiological monitoring during in vivo imaging of laboratory rodents: considerations on experimental outcomes and animal welfare. EJNMMI Res. 2012;2(1):44.PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Skresanova IV, Barannik EA. Correlation functions and power spectra of Doppler response signals in ultrasonic medical applications. Ultrasonics. 2012;52(5):676–84.PubMedCrossRefGoogle Scholar
  109. 109.
    Deshpande N, Needles A, Willmann JK. Molecular ultrasound imaging: current status and future directions. Clin Radiol. 2010;65(7):567–81.PubMedCentralPubMedCrossRefGoogle Scholar
  110. 110.
    Greco A, Mancini M, Gargiulo S, Gramanzini M, Claudio PP, Brunetti A, et al. Ultrasound biomicroscopy in small animal research: applications in molecular and preclinical imaging. J Biomed Biotechnol. 2012;2012:519238.PubMedCentralPubMedCrossRefGoogle Scholar
  111. 111.
    Golden HB, Sunder S, Liu Y, Peng X, Dostal DE. In utero assessment of cardiovascular function in the embryonic mouse heart using high-resolution ultrasound biomicroscopy. Method Mol Biol. 2012;843:245–63.CrossRefGoogle Scholar
  112. 112.
    Cheung AM, Brown AS, Cucevic V, Roy M, Needles A, Yang V, et al. Detecting vascular changes in tumour xenografts using micro-ultrasound and micro-ct following treatment with VEGFR-2 blocking antibodies. Ultrasound Med Biol. 2007;33(8):1259–68.PubMedCrossRefGoogle Scholar
  113. 113.
    Kaufmann BA, Lankford M, Behm CZ, French BA, Klibanov AL, Xu Y, et al. High-resolution myocardial perfusion imaging in mice with high-frequency echocardiographic detection of a depot contrast agent. J Am Soc Echocardiogr. 2007;20(2):136–43.PubMedCrossRefGoogle Scholar
  114. 114.
    Alves KZ, Soletti RC, de Britto MA, de Matos DG, Soldan M, Borges HL, et al. In Vivo endoluminal ultrasound biomicroscopic imaging in a mouse model of colorectal cancer. Acad Radiol. 2013;20(1):90–8.PubMedCrossRefGoogle Scholar
  115. 115.
    Alexandrakis G, Rannou FR, Chatziioannou AF. Effect of optical property estimation accuracy on tomographic bioluminescence imaging: simulation of a combined optical-PET (OPET) system. Phys Med Biol. 2006;51(8):2045–53.PubMedCentralPubMedCrossRefGoogle Scholar
  116. 116.
    Peter J, Ruehle H, Stamm V, Schulz RB, Smith MF, Welch B, et al. Development and initial results of a dual-modality SPECT/optical small animal imager. Nuclear Science Symposium Conference Record; 2005 IEEE; 2005 23–29 Oct: p. 4.Google Scholar
  117. 117.
    Hyde D, de Kleine R, MacLaurin SA, Miller E, Brooks DH, Krucker T, et al. Hybrid FMT-CT imaging of amyloid-beta plaques in a murine Alzheimer’s disease model. Neuroimage. 2009;44(4):1304–11.PubMedCrossRefGoogle Scholar
  118. 118.
    Wen Z, Fahrig R, Williams ST, Pelc NJ. Shimming with permanent magnets for the x-ray detector in a hybrid x-ray/ MR system. Med Phys. 2008;35(9):3895–902.PubMedCentralPubMedCrossRefGoogle Scholar
  119. 119.
    Gulsen G, Birgul O, Unlu MB, Shafiiha R, Nalcioglu O. Combined diffuse optical tomography (DOT) and MRI system for cancer imaging in small animals. Technol Cancer Res Treat. 2006;5(4):351–63.PubMedGoogle Scholar
  120. 120.
    Kundu BK, Stolin AV, Pole J, Baumgart L, Fontaine M, Wojcik R, et al. Tri-modality small animal imaging system. IEEE Trans Nucl Sci. 2006;53(1):66–70.CrossRefGoogle Scholar
  121. 121.
    Veit-Haibach P, Kuhn FP, Wiesinger F, Delso G, von Schulthess G. PET-MR imaging using a tri-modality PET/CT-MR system with a dedicated shuttle in clinical routine. MAGMA. 2013;26(1):25–35.Google Scholar
  122. 122.
    Tsukamoto E, Ochi S. PET/CT today: system and its impact on cancer diagnosis. Ann Nucl Med. 2006;20(4):255–67.PubMedCrossRefGoogle Scholar
  123. 123.
    Bergeron M, Cadorette J, Beaudoin JF, Lepage MD, Robert G, Selivanov V, et al. Performance evaluation of the LabPET APD-based digital PET scanner. IEEE Trans Nucl Sci. 2009;56(1):10–6.CrossRefGoogle Scholar
  124. 124.
    Levin Klausen T, Hogild Keller S, Vinter Olesen O, Aznar M, Andersen FL. Innovations in PET/CT. Q J Nucl Med Mol Imaging. 2012;56(3):268–79.PubMedGoogle Scholar
  125. 125.
    Beyer T, Freudenberg LS, Townsend DW, Czernin J. The future of hybrid imaging-part 1: hybrid imaging technologies and SPECT/CT. Insight Imaging. 2011;2(2):161–9.CrossRefGoogle Scholar
  126. 126.
    Hammer BE, Christensen NL, Heil BG. Use of a magnetic field to increase the spatial resolution of positron emission tomography. Med Phys. 1994;21(12):1917–20.PubMedCrossRefGoogle Scholar
  127. 127.
    Beyer T, Freudenberg LS, Czernin J, Townsend DW. The future of hybrid imaging-part 3: PET/MR, small-animal imaging and beyond. Insight Imaging. 2011;2(3):235–46.CrossRefGoogle Scholar
  128. 128.
    Wirrwar A, Vosberg H, Herzog H, Halling H, Weber S, MullerGartner HW. 4.5 Tesla magnetic field reduces range of high-energy positrons—potential implications for positron emission tomography. IEEE Trans Nucl Sci. 1997;44(2):184–9.CrossRefGoogle Scholar
  129. 129.
    Cherry SR. Multimodality imaging: beyond PET/CT and SPECT/CT. Semin Nucl Med. 2009;39(5):348–53.PubMedCentralPubMedCrossRefGoogle Scholar
  130. 130.
    Wagenknecht G, Kaiser HJ, Mottaghy FM, Herzog H. MRI for attenuation correction in PET: methods and challenges. MAGMA. 2013;26(1):99–113.Google Scholar
  131. 131.
    Tartis MS, Kruse DE, Zheng H, Zhang H, Kheirolomoom A, Marik J, et al. Dynamic microPET imaging of ultrasound contrast agents and lipid delivery. J Controlled Release. 2008;131(3):160–6.CrossRefGoogle Scholar
  132. 132.
    Markets, Markets. Small Animal Imaging (In Vivo) Market: Competitive Analysis & Global Forecasts to 2017. 2012 [cited 16 Feb 2013]. http://www.companiesandmarkets.com/Market/Healthcare-and-Medical/Market-Research/Small-Animal-Imaging-In-Vivo-Market-Competitive-Analysis-Global-Forecasts-to-2017/RPT1134167.
  133. 133.
    Balcerzyk M, Kontaxakis G, Delgado M, Garcia-Garcia L, Correcher C, Gonzalez AJ, et al. Initial performance evaluation of a high resolution Albira small animal positron emission tomography scanner with monolithic crystals and depth-of-interaction encoding from a user’s perspective. Measurement Sci Technol. 2009;20(10).Google Scholar
  134. 134.
    Szanda I, Mackewn J, Patay G, Major P, Sunassee K, Mullen GE, et al. National electrical manufacturers association NU-4 performance evaluation of the PET component of the NanoPET/CT preclinical PET/CT Scanner. J Nucl Med. 2011;52(11):1741–7.Google Scholar
  135. 135.
    Goorden MC, van der Have F, Kreuger R, Ramakers RM, Vastenhouw B, Burbach JP, et al. VECTor: a preclinical imaging system for simultaneous submillimeter SPECT and PET. J Nucl Med. 2013;54(2):306–12.Google Scholar
  136. 136.
    Goertzen AL, Bao QN, Bergeron M, Blankemeyer E, Blinder S, Canadas M, et al. NEMA NU 4-2008 comparison of preclinical PET imaging systems. J Nucl Med. 2012;53(8):1300–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Bao Q, Newport D, Chen M, Stout DB, Chatziioannou AF. Performance evaluation of the inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med. 2009;50(3):401–8.PubMedCentralPubMedCrossRefGoogle Scholar
  138. 138.
    Herrmann K, Dahlbom M, Nathanson D, Wei L, Radu C, Chatziioannou A, et al. Evaluation of the Genisys4, a bench-top preclinical PET scanner. J Nucl Med. 2013;54(7):1162–7.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Lídia Cunha
    • 1
    • 2
    • 3
  • Ildiko Horvath
    • 4
  • Sara Ferreira
    • 1
  • Joana Lemos
    • 1
  • Pedro Costa
    • 1
  • Domingos Vieira
    • 1
  • Dániel S. Veres
    • 4
  • Krisztián Szigeti
    • 4
  • Teresa Summavielle
    • 2
  • Domokos Máthé
    • 5
  • Luís F. Metello
    • 1
    • 6
  1. 1.Nuclear Medicine DepartmentHigh Institute for Allied Health Technologies, Polytechnic Institute of Porto (ESTSP.IPP)Vila Nova de GaiaPortugal
  2. 2.Neuroprotection Lab, Institute for Molecular and Cell Biology (IBMC)University of PortoPortoPortugal
  3. 3.Institute of Biomedical Sciences Abel Salazar (ICBAS)University of PortoPortoPortugal
  4. 4.Institute of Biophysics and Radiation Biology, Faculty of MedicineSemmelweis UniversityBudapestHungary
  5. 5.CROmed LtdBudapestHungary
  6. 6.IsoPor, SAPortoPortugal

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