La radiologia medica

, Volume 114, Issue 1, pp 152–167 | Cite as

Small animal imaging facility: new perspectives for the radiologist

  • R. Grassi
  • C. Cavaliere
  • S. Cozzolino
  • L. Mansi
  • S. Cirillo
  • G. Tedeschi
  • R. Franchi
  • P. Russo
  • S. Cornacchia
  • A. Rotondo
PET-CT PET-TC

Abstract

In recent years, new technologies have become available for imaging small animals. The use of animal models in basic and preclinical sciences, for example, offers the possibility of testing diagnostic markers and drugs, which is becoming crucial in the success and timeliness of research and is allowing a more efficient approach in defining study objectives and providing many advantages for both clinical research and the pharmaceutical industry. The use of these instruments offers data that are more predictive of the distribution and efficacy of a compound. The mouse, in particular, has become a key animal model system for studying human disease. It offers the possibility of manipulating its genome and producing accurate models for many human disorders, thus resulting in significant progress in understanding pathologenic mechanisms. In neurobiology, the possibility of simulating neurodegenerative diseases has enabled the development and validation of new treatment strategies based on gene therapy or cell grafting. Noninvasive imaging in small living animal models has gained increasing importance in preclinical research, itself becoming an independent specialty. The aim of this article is to review the characteristics of these systems and illustrate their main applications.

Keywords

Molecular imaging Micro-PET Micro-CT Optical imaging Small-animal imaging 

Servizio di imaging su piccoli animali: nuove prospettive per il radiologo

Riassunto

Negli ultimi anni si sono rese disponibili nuove apparecchiature per lo studio di piccoli animali. L’utilizzo di modelli sperimentali nelle scienze di base e pre-cliniche consente di verificare test diagnostici e farmaci, divenendo essenziale per il successo e la tempestività della ricerca, offrendo un approccio più efficace nella definizione degli obiettivi da studiare e notevoli vantaggi sia per la ricerca clinica sia per le industrie farmaceutiche. L’utilizzo di tali tecnologie consente di ottenere informazioni più predittive riguardo alla distribuzione o all’efficacia di una molecola. Il topo, in particolare, è un modello animale insostituibile per lo studio delle malattie umane. Esso offre la possibilità di manipolare il suo genoma e di riprodurre accuratamente malattie umane, consentendo progressi significativi nella comprensione dei meccanismi patogenetici. In neurobiologia, la possibilità di ricreare malattie neurodegenerative ha permesso lo sviluppo e la convalida di nuove strategie terapeutiche basate sulla terapia genica o sul trapianto di cellule. L’imaging non invasivo su piccoli animali in vivo ha acquisito un ruolo sempre maggiore nella ricerca pre-clinica fino a divenire un settore autonomo. Scopo di questo contributo è presentare le caratteristiche di queste apparecchiature illustrandone le principali applicazioni.

Parole chiave

Imaging molecolare Micro-PET Micro-TC Imaging ottico Imaging per piccoli animali 

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References/Bibliografia

  1. 1.
    Poltorak A, He X, Smirnova I et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088PubMedCrossRefGoogle Scholar
  2. 2.
    Gu L, Tseng S, Horner RM et al (2000) Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411PubMedCrossRefGoogle Scholar
  3. 3.
    Hantraye P (1998) Modeling dopamine system dysfunction in experimental animals. Nucl Med Biol 25:721–728PubMedCrossRefGoogle Scholar
  4. 4.
    Brouillet E, Condé F, Beal MF et al (1999) Replicating Huntington’s disease phenotype in experimental animals. Prog Neurobiol 59:427–468PubMedCrossRefGoogle Scholar
  5. 5.
    Williams RW, Rakic P (1988) 3-Dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. J Comp Neurol 278:344–352PubMedCrossRefGoogle Scholar
  6. 6.
    Kanekal S, Sahai A, Jones RE et al (1995) Storage-phosphor autoradiography: a rapid and highly sensitive method for spatial imaging and quantitation of radioisotopes. J Pharmacol Toxicol Methods 33:171–178PubMedCrossRefGoogle Scholar
  7. 7.
    Wu S, Ying G, Wu Q et al (2007) Toward simpler and faster genome-wide mutagenesis in mice. Nat Genet 39:922–930PubMedCrossRefGoogle Scholar
  8. 8.
    Campbell RE, Tour O, Palmer AE et al (2002) A monomeric red fluorescent protein Proc Natl Acad Sci U S A 99:7877–7882PubMedCrossRefGoogle Scholar
  9. 9.
    Contag CH, Bachmann MH (2002) Advances in in vivo bioluminescence imaging of gene expression Annu Rev Biomed Eng 4:235–260PubMedCrossRefGoogle Scholar
  10. 10.
    Hastings JW (1996) Chemistries and colors of bioluminescent reactions: a review. Gene 173:5–11PubMedCrossRefGoogle Scholar
  11. 11.
    Morgan NY, English S, Chen W et al (2005) Real-time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots. Acad Radiol 12:313–323PubMedCrossRefGoogle Scholar
  12. 12.
    Gratton E, Breusegem S, Sutin J et al (2003) Fluorescence lifetime imaging for the two-photon microscopy: TD and frequency domain methods. J Biomed Opt 8:381–390PubMedCrossRefGoogle Scholar
  13. 13.
    Montet X, Ntziachristos V, Grimm J et al (2005) Tomographic fluorescence mapping of tumor targets. Cancer Res 65:6330–6336PubMedCrossRefGoogle Scholar
  14. 14.
    Kelly KA, Carson J, McCarthy JR et al (2007) Novel peptide sequence (“IQ-tag”) with high affinity for NIR fluorochromes allows protein and cell specific labeling for in vivo imaging. PLoS ONE 2:e665PubMedCrossRefGoogle Scholar
  15. 15.
    Lipscomb IP, Hervé R, Harris K et al (2007) Amyloid-specific fluorophores for the rapid, sensitive in situ detection of prion contamination on surgical instruments. J Gen Virol 88:2619–2626PubMedCrossRefGoogle Scholar
  16. 16.
    Medarova Z, Pham W, Kim Y et al (2006) In vivo imaging of tumor response to therapy using a dual-modality imaging strategy. Int J Cancer 118:2796–2802PubMedCrossRefGoogle Scholar
  17. 17.
    Prout DL, Silverman RW, Chatziioannou A (2004) Detector concept for OPET—A combined PET and optical imaging system. IEEE Trans Nucl Sci 51:752–756PubMedCrossRefGoogle Scholar
  18. 18.
    Benaron DA, Contag PR, Contag CH (1997) Imaging brain structure and function, infection and gene expression in the body using light. Philos Trans R Soc Lond B Biol Sci 352:755–761PubMedCrossRefGoogle Scholar
  19. 19.
    Sadikot RT, Wudel LJ, Jansen DE et al (2002) Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF-kappaB activation in a transgenic mouse model. J Gstrointest Surg 6:264–270CrossRefGoogle Scholar
  20. 20.
    Ray P, De A, Min JJ et al (2004) Imaging tri-fusion multimodality reporter gene expression in living subjects. Cancer Res 64:1323–1330PubMedCrossRefGoogle Scholar
  21. 21.
    Francis KP, Yu J, Bellinger-Kawahara C et al (2001) Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon. Infect Immun 69:3350–3358PubMedCrossRefGoogle Scholar
  22. 22.
    Edinger M, Cao YA, Hornig YS et al (2002) Advancing animal models of neoplasia through in vivo bioluminescence imaging. Eur J Cancer 38:2128–2136PubMedCrossRefGoogle Scholar
  23. 23.
    Koransky ML, Ip TK, Wu S et al (2001) In vivo monitoring of myoblast transplantation into rat myocardium. J Heart Lung Transplant 20:188–189PubMedCrossRefGoogle Scholar
  24. 24.
    Ritman EL (2002) Molecular imaging in small animals-roles for micro-CT. J Cell Biochem 39:116–124CrossRefGoogle Scholar
  25. 25.
    Goertzen AL, Meadors AK, Silverman RW et al (2002) Simultaneous molecular and anatomical imaging of the mouse in vivo. Phys Med Biol 47:4315–4328PubMedCrossRefGoogle Scholar
  26. 26.
    Suckow C, Stout D (2008) MicroCT liver contrast agent enhancement over time, dose, and mouse strain. Mol Imaging Biol 10:114–120PubMedCrossRefGoogle Scholar
  27. 27.
    Savai R, Wolf JC, Greschus S et al (2005) Analysis of tumor vessel supply in Lewis lung carcinoma in mice by fluorescent microsphere distribution and imaging with micro- and flat-panel computed tomography. Am J Pathol 167:937–946PubMedGoogle Scholar
  28. 28.
    Marxen M, Thornton MM, Chiarot CB et al (2004) MicroCT scanner performance and considerations for vascular specimen imaging. Med Phys 31:305–313PubMedCrossRefGoogle Scholar
  29. 29.
    Bhattacharjee D, Ito A (2001) Deceleration of carcinogenic potential by adaptation with low dose gamma irradiation. In Vivo 15:87–92PubMedGoogle Scholar
  30. 30.
    Borah B, Gross GJ, Dufresne TE et al (2001) Three-dimensional microimaging (MRmicroI and microCT), finite element modelling and rapid prototyping provide unique insights into bone architecture in osteoporosis. Anat Rec 265:101–110PubMedCrossRefGoogle Scholar
  31. 31.
    Rietbergen van B, Majumdar S, Pistoia W et al (1998) Assessment of cancellous bone mechanical properties from micro-FE models based on micro-CT, pQCT and MR images. Technol Health Care 6:413–420PubMedGoogle Scholar
  32. 32.
    Ruegsegger P, Koller B, Muller R (1996) A microtomographic system for the non-destructive evaluation of bone architecture. Calcif Tissue Int 58:24–29PubMedCrossRefGoogle Scholar
  33. 33.
    Kennel SJ, Davis IA, Branning J et al (2000) High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmuntherapy: correlation with histology. Med Phys 27:1101–1107PubMedCrossRefGoogle Scholar
  34. 34.
    Paulus MJ, Gleason SS, Sari-Sarraf H et al (2000) High-resolution X-ray CT screening of mutant mouse models. Proc SPIE 3921:270–279CrossRefGoogle Scholar
  35. 35.
    Larobina M, Brunetti A, Salvatore M (2006) Small animal PET: a review of commercially available imaging systems. Curr Med Imaging Rev 2:187–192CrossRefGoogle Scholar
  36. 36.
    Chatziioannou AF (2005) Instrumentation for molecular imaging in preclinical research: micro-PET and micro-SPECT. Proc Am Thorac Soc 2:533–536PubMedCrossRefGoogle Scholar
  37. 37.
    Qi J, Leahy RM, Cherry SR et al (1998) High-resolution 3D bayesian image reconstruction using the microPET small-animal scanner. Phys Med Biol 43:1001–1013PubMedCrossRefGoogle Scholar
  38. 38.
    Wang Y, Seidel J, Tsui BMW et al (2006) Performance Evaluation of the GE Healthcare eXplore VISTA Dual-Ring Small-Animal PET. J Nucl Med 47:1891–900PubMedGoogle Scholar
  39. 39.
    Jones T (1996) The role of positron emission tomography within the spectrum of medical imaging. Eur J Nucl Med 23:2207–2211Google Scholar
  40. 40.
    Cherry SR, Gambhir SS (2001) Use of positron emission tomography in animal research. ILAR J 42:219–232PubMedGoogle Scholar
  41. 41.
    Kornblum H, Araujo D, Annala A et al (2000) In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat Biotechnol 18:655–660PubMedCrossRefGoogle Scholar
  42. 42.
    Wu AM, Yazaki P, Tsai S et al (2000) High-resolution microPET imaging of carcino-embryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc Natl Acad Sci U S A 97:8495–8500PubMedCrossRefGoogle Scholar
  43. 43.
    Guilloteau D, Emond P, Baulieu JL et al (1998) Exploration of the dopamine transporter: In vitro and In vivo characterisation of a high-affinity and high-specificity iodinated tropane detivative (E)-N-(3-iodoprop-2-enyl)-2b-carbomethoxy-3b(4’-methylphenyl) nortropane (PE2I). Nucl Med Biol 25:331–337PubMedCrossRefGoogle Scholar
  44. 44.
    Hume SP (1992) Quantification of carbon-11-labeled raclopride in rat striatum using PET. Synapse 12:47–54PubMedCrossRefGoogle Scholar
  45. 45.
    Ogawa O, Umegaki H, Ishiwata K et al (2000) In vivo imaging of adenovirsu - mediated over expression of dopamine D2 receptors in rat striatum by positron emission tomography. Neuroreport 11:743–748PubMedCrossRefGoogle Scholar
  46. 46.
    Mandl S, Schimmelpfennig C, Edinger M et al (2002) Understanding immune cell trafficking patterns via in vivo bioluminescence imaging. J Cell Biochem 39:239–248CrossRefGoogle Scholar
  47. 47.
    Beekman FJ, Van der Have F, Vastenhouw B et al (2005) U-SPECT-I: a novel system for submillimeter resolution tomography with radiolabeled molecules in mice. J Nucl Med 46:1194–1200PubMedGoogle Scholar
  48. 48.
    Ochoa AV, Ploux L, Mastrippolito R et al (1997) An original emission tomograph for in vivo brain imaging of small animals. IEEE Trans Nucl Sci 44:1533–1537CrossRefGoogle Scholar
  49. 49.
    Liu Z, Kastis GA, Stevenson GD et al (2002) Quantitative analysis of acute myocardial infarct in rat hearts with ischemia-reperfusion using a high-resolution stationary SPECT system. J Nucl Med 43:933–939PubMedGoogle Scholar
  50. 50.
    Sharma V, Luker GD, Piwnica-Worms D (2002) Molecular imaging of gene expression and protein function in vivo with PET and SPECT. J Magn Reson Imaging 16:336–351PubMedCrossRefGoogle Scholar
  51. 51.
    Beck B, Plant DH, Grant SC et al (2002) Progress in high field MRI at the University of Florida. Magn Reson Mater Phys Biol Med 13:152–157CrossRefGoogle Scholar
  52. 52.
    Slates RB, Farahani K, Shao Y et al (1999) A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner. Phys Med Biol 44:2015–2027PubMedCrossRefGoogle Scholar
  53. 53.
    Faccioli N, Marzola P, Boschi F et al (2007) Pathological animal models in the experimental evaluation of tumour microvasculature with magnetic resonance imaging. Radiol Med 112:319–328PubMedCrossRefGoogle Scholar
  54. 54.
    Menon RS, Kim SG (1999) Spatial and temporal limits in cognitive neuroimaging with fMRI. Trends Cogn Sci 3:207–216PubMedCrossRefGoogle Scholar
  55. 55.
    Weissleder R, Moore A, Mahmood U et al (2000) In vivo magnetic resonance imaging of transgene expression. Nat Med 6:351–355PubMedCrossRefGoogle Scholar
  56. 56.
    Lanza GM, Wickline SA (2001) Targeted ultrasonic contrast agents for molecular imaging and therapy. Prog Cardiovasc Dis 44:13–31PubMedCrossRefGoogle Scholar
  57. 57.
    Dayton PA, Ferrara KW (2002) Targeted imaging using ultrasound. J Magn Reson Imaging 16:362–377PubMedCrossRefGoogle Scholar
  58. 58.
    Rooks V, Beecken WD, Iordanescu I et al (2001) Sonographic evaluation of orthotopic bladder tumors in mice treated with TNP-470 an angiogenic inhibitor. Acad Radiol 8:121–127PubMedCrossRefGoogle Scholar
  59. 59.
    Leong-Poi H, Christiansen J, Klibanov AL et al (2003) Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 107:455–460PubMedCrossRefGoogle Scholar
  60. 60.
    Turnbull DH (1999) In utero ultrasound backscatter microscopy of early stage mouse embryos. Comput Med Imaging Graph 23:25–31PubMedCrossRefGoogle Scholar
  61. 61.
    Lukasik VM, Gillies RJ (2003) Animal anaesthesia for in vivo magnetic resonance. NMR Biomed 16:459–467PubMedCrossRefGoogle Scholar
  62. 62.
    Fricke ST, Vink R, Chiodo C et al (2004) Consistent and reproducible slice selection in rodent brain using a novel stereotaxic device for MRI. J Neurosci Methods 136:99–102PubMedCrossRefGoogle Scholar
  63. 63.
    Robb RA (2002) The virtualization of medicine: a decade of pitfalls and progress. Stud Health Technol Inform 85:1–7PubMedGoogle Scholar
  64. 64.
    Turner R, Howseman A, Rees GE et al (1998) Functional magnetic resonance imaging of the human brain: data acquisition and analysis. Exp Brain Res 123:5–12PubMedCrossRefGoogle Scholar
  65. 65.
    Huang SC, Wu HM, Shoghi-Jadid K et al (2004) Investigation of a new input function validation approach for dynamic mouse microPET studies. Mol Imaging Biol 6:34–46PubMedCrossRefGoogle Scholar
  66. 66.
    Kircher MF, Mahmood U, King RS et al (2003) A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res 63:8122–8125PubMedGoogle Scholar
  67. 67.
    Talanov VS, Regino CAS, Kobayashi H et al (2006) Dendrimer-based nanoprobe for dual modality magnetic resonance and fluorescence imaging. Nano Lett 6:1459–1463PubMedCrossRefGoogle Scholar
  68. 68.
    Lewis JL, Achilefu S, Garbow JR et al (2002) Small animal imaging. current technology and perspectives for oncological imaging. Eur J Cancer 38:2173–2188PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2008

Authors and Affiliations

  • R. Grassi
    • 1
  • C. Cavaliere
    • 1
  • S. Cozzolino
    • 2
  • L. Mansi
    • 1
  • S. Cirillo
    • 3
  • G. Tedeschi
    • 3
  • R. Franchi
    • 4
  • P. Russo
    • 5
  • S. Cornacchia
    • 6
  • A. Rotondo
    • 1
  1. 1.Institute of RadiologySecond University of NaplesNaplesItaly
  2. 2.Biotechnology CenterA.O.R.N. CardarelliNapoliItaly
  3. 3.Neurological Sciences DepartmentSecond University of NaplesNaplesItaly
  4. 4.Nuclear Medicine, PET Unit, Policlinico S. Orsola-MalpighiBologna UniversityBolognaItaly
  5. 5.Dipartimento di Scienze FisicheUniversità Federico II, and INFN, Sezione di NapoliNapoliItaly
  6. 6.Physics DepartmentUniversity of Bologna and INFNBolognaItaly

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