Non‐Invasive in vivo Imaging in Small Animal Research
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Non‐invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi‐modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.
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In vivo imaging is a critical counterpart to studying molecular processes in cell culture systems.
“In vivo imaging is a critical counterpart to studying molecular processes in cell culture systems (Koo et al., 2006”
From Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis (2008) · cites this paper as Koo et al., 2006
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A clearer vision for in vivo imaging
Weissleder, R. (2001) · Nature Biotechnology · doi:10.1038/86684 · Cited by 3,839 · see citing works
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- [1][1] D. Artemov, N. Mori, R. Ravi and Z.M. Bhujwalla, Magnetic resonance molecular imaging of the HER-2/neu receptor, Cancer Res. 63 (2003), 2723-2727. -
- [2][2] R.S. Balaban and V.A. Hampshire, Challenges in small animal noninvasive imaging, ILAR J . 42 (2001), 248-262. -
- [3][3] B. Ballou, B.C. Lagherholm, L.A. Ernst, M.P. Bruchez and A.S. Waggoner, Noninvasive imaging of quantum dots in mice, Bioconjug. Chem. 15 (2004), 79-86. -
- [4][4] N. Beckmann, C. Cannet, M. Fringeli-Tanner, D. Baumann, C. Pally, C. Bruns, H.G. Zerwes, E. Andriambeloson and M. Bigaud, Macrophage labeling by SPIO as an early marker of allograft chronic rejection in a rat model of kidney transplantation, Magn. Reson. Med. 49 (2003), 459-467. -
- [5][5] F. Berger, Y.P. Lee, A.M. Loening, A. Chatziioannou, S.J. Freedland, R. Leahy, J.R. Lieberman, A.S. Belldegrun, C.L. Sawyers and S.S. Gambhir, 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 (2002), 1225-1236. -
- [6][6] S. Bhaumik, Z. Walls, M. Puttaraju, L.G. Mitchell and S.S. Gambhir, Molecular imaging of gene expression in living subjects by spliceosome-mediated RNA trans-splicing, Proc. Natl. Acad. Sci. USA 101 (2004), 8693-8698. -
- [7][7] C. Bos, Y. Delmas, A. Desmouliere, A. Solanilla, O. Hauger, C. Grosset, I. Dubus, Z. Ivanovic, J. Rosenbaum, P. Charbord, C. Combe, J.W. Bulte, C.T. Moonen, J. Ripoche and N. Grenier, In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver, Radiology 233 (2004), 781-789. -
- [8][8] C. Bremer, V. Ntziachristos and R. Weissleder, Optical-based molecular imaging: contrast agents and potential medical applications, Eur. Radiol. 13 (2003), 231-243. -
- [9][9] A.S. Brown, L. Leamen, V. Cucevic and F.S. Foster, Quantitation of hemodynamic function during developmental vascular regression in the mouse eye, Invest. Ophthalmol. Vis. Sci. 46 (2005), 2231-2237. -
- [10][10] A. Chatziioannou, Y.C. Tai, N. Doshi and S.R. Cherry, Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging, Phys. Med. Biol. 46 (2001), 2899-2910. -
- [11][11] A.F. Chatziioannou, Molecular imaging of small animals with dedicated PET tomographs, Eur. J. Nucl. Med. 29 (2002), 98114. -
- [12][12] X. Chen, S. Liu, Y. Hou, M. Tohme, R. Park, J.R. Bading and P.S. Conti, MicroPET imaging of breast cancer α v-integrin expression with 64 Cu-labelled dimeric RGD peptides, Mol. Imaging Biol . 6 (2004), 350-359. -
- [13][13] S.R. Cherry and S.S. Gambhir, Use of positron emission tomography in animal research, Ilar. J. 42 (2001), 219-232. -
- [14][14] P.L. Chow, D.B. Stout, E. Komisopoulou and A.F. Chatziioannou, A method of image registration for small animal, multimodality imaging, Phys. Med. Biol. 51 (2006), 379-390. -
- [15][15] L.A. Colby and B.J. Morenko, Clinical considerations in rodent bioimaging, Comp. Med . 54 (2004), 623-630. -
- [17][17] M. Doubrovin, V. Ponomarev, T. Beresten, J. Balatoni, W. Bornmann, R. Finn, J. Humm, S. Larson, M. Sadelain, R. Blasberg and J. Gelovani Tjuvajev, Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo , Proc. Natl. Acad. Sci. USA 98 (2001), 93009305. -
- [18][18] P.A. Flecknell, Anaesthesia of animals for biomedical research, Br. J. Anaesth . 71 (1993), 885-894. -
- [19][19] Gassmann, M. and T. Hennet, From genetically altered mice to integrative physiology, News Physiol. Sci. 13 (1998), 53-57. -
- [20][20] O. Gauthier, R. Muller, D. von Stechow, B. Lamy, P. Weiss, J.M. Bouler, E. Aguado and G. Daculsi, In vivo bone regeneration with injectable calcium phosphate biomaterial: a threedimensional micro-computed tomographic, biomechanical and SEM study, Biomaterials 27 (2005), 5444-5453. -
- [21][21] J.L. Griffin and J.P. Shockcor, Metabolic profiles of cancer cells, Nat. Rev. Cancer . 4 (2004), 551-561. -
- [22][22] J.W. Hastings, Chemistries and colors of bioluminescent reactions: a review, Gene 173 (1996), 5-11. -
- [23][23] A. Honigman, E. Zeira, P. Ohana, R. Abramovitz, E. Tavor, I. Bar, Y. Zilberman, R. Rabinovsky, D. Gazit, A. Joseph, A. Panet, E. Shai, A. Palmon, M. Laster and E. Galun, Imaging transgene expression in live animals, Mol. Ther. 4 (2001), 239-249. -
- [24][24] M.L. Janssen, W.J. Oyen, I. Dijkgraaf, L.F. Massuger, C. Frielink, D.S. Edwards, M. Rajopadhye, H. Boonstra, F.H. Corstens and O.C. Boerman, Tumor targeting with radiolabeled α v β 3 integrin binding peptides in a nude mouse model, Cancer Res. 62 (2002), 6146-6151. -
- [25][25] D.E. Jenkins, Y. Oei, Y.S. Hornig, S.F. Yu, J. Dusich, T. Purchio and P.R. Contag, Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis, Clin. Exp. Metastasis 20 (2003), 733-744. -
- [26][26] P. Johnström, T.D. Fryer, H.K. Richards, N.G. Harris, O. Barret, J.C. Clark, J.D. Pickard and A.P. Davenport, Positron emission tomography using 18F-labelled endothelin-1 reveals prevention of binding to cardiac receptors owing to tissue-specific clearance by ET B receptors in vivo , Br. J. Pharmacol. 144 (2005), 115-122. -
- [27][27] K. Kaneko, M. Yano, T. Yamano, T. Tsujinaka, H. Miki, Y. Akiyama, M. Taniguchi, Y. Fujiwara, Y. Doki, M. Inoue et al., Detection of peritoneal micrometastases of gastric carcinoma with green fluorescent protein and carcinoembryonic antigen promoter, Cancer Res. 61 (2001), 5570-5574. -
- [28][28] S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E.M. Sevick-Muraca et al., Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts, Cancer Res. 63 (2003), 7870-7875. -
- [29][29] M.F. Kircher, J.R. Allport, E.E. Graves, V. Love, L. Josephson, A.H. Lichtman and R. Weissleder, In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors, Cancer Res. 63 (2003), 6838-6846. -
- [30][30] J.C. LaManna and S.I. Harik, Regional studies of blood-brain barrier transport of glucose and leucine in awake and anesthetized rats, J. Cereb. Blood Flow Metab. 6 (1986), 717-723. -
- [31][31] Y. Lin, R. Weissleder and C.H. Tung, Novel near-infraredcyanine fluorochromes: Synthesis, properties, and bioconjugation, Bioconjug. Chem. 13 (2002), 605-610. -
- [32][32] S.K. Lyons, Advances in imaging mouse tumour models in vivo , J. Pathol. 205 (2005), 194-205. -
- [33][33] T.F. Massoud and S.S. Gambhir, Molecular imaging in living subjects: seeing fundamental biological processes in a new light, Genes Dev . 17 (2003), 545-580. -
- [34][34] T.F. Massoud, R. Paulmurugan and S.S. Gambhir, Molecular imaging of homodimeric protein-protein interactions in living subjects, FASEB J. 18 (2004), 1105-1107. -
- [35][35] A. Moore, Z. Medarova, A. Potthast and G. Dai, In vivo targeting of underglycosylated MUC-1 tumor antigen using a multimodal imaging probe, Cancer Res. 64 (2004), 1821-1827. -
- [36][36] V. Ntziachristos and R. Weissleder, Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media, Med. Phys. 29 (2002), 803-809. -
- [37][37] V. Ntziachristos, C.H. Tung, C. Bremer and R. Weissleder, Fluorescence molecular tomography resolves protease activity in vivo , Nat. Med. 8 (2002), 757-760. -
- [38][38] T. Olafsen, V.E. Kenanova, G. Sundaresan, A.L. Anderson, D. Crow, P.J. Yazaki, L. Li, M.F. Press, S.S. Gambhir, L.E. Williams, J.Y. Wong, A.A. Raubitschek, J.E. Shively and A.M. Wu, Optimizing radiolabelled engineered anti-p185 HER2 antibody fragments for in vivo imaging, Cancer Res. 65 (2005), 5907-5916. -
- [39][39] M.J. Paulus, S.S. Gleason, M.E. Easterly and C.J. Foltz, A review of high-resolution X-ray computed tomography and other imaging modalities for small animal research, Lab. Anim. (NY) 30 (2001), 36-45. -
- [40][40] O. Peyruchaud, B. Winding, I. Pecheur, C.M. Serre, P. Delmas and P. Clezardin, Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions, J. Bone Miner. Res. 16 (2001), 2027-2034. -
- [41][41] R.D. Phair and T. Misteli, Kinetic modelling approaches to in vivo imaging, Nat. Rev. Mol. Cell. Biol. 2 (2001), 898-907. -
- [42][42] A. Pichler, J.L. Prior and D. Piwnica-Worms, Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine, Proc. Natl. Acad. Sci. USA 101 (2004), 1702-1707. -
- [43][43] P.J. Pickhardt, R.B. Halberg, A.J. Taylor, B.Y. Durkee, J. Fine, F.T. Lee, Jr. and J.P. Weichert, Microcomputed tomography colonography for polyp detection in an in vivo mouse tumor model, Proc. Natl. Acad. Sci. USA 102 (2005), 3419-3422. -
- [44][44] V. Ponomarev, M. Doubrovin, I. Serganova, J. Vider, A. Shavrin, T. Beresten, A. Ivanova, L. Ageyeva, V. Tourkova, J. Balatoni, W. Bornmann, R. Blasberg and J. Gelovani Tjuvajev, A novel triple-modality reporter gene for whole-body fluorescent, bioluminescent, and nuclear noninvasive imaging, Eur. J. Nucl. Med. Mol. Imaging 31 (2004), 740-751. -
- [45][45] A. Preda, V. Novikov, M. Moglich, K. Turetschek, D.M. Shames, R.C. Brasch, F.M. Cavagna and T.P. Roberts, MRI monitoring of Avastin antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer, J. Magn. Reson. Imaging 20 (2004), 865-873. -
- [46][46] D.L. Prout, R.W. Silverman and A. Chatziioannou, Detector concept for OPET-A combined PET and optical imaging system, IEEE Trans. Nucl. Sci. 51 (2004), 752-756. -
- [47][47] P. Ray, A.M. Wu and S.S. Gambhir, Optical bioluminescence and positron emission tomography imaging of a novel fusion reporter gene in tumor xenografts of living mice, Cancer Res. 63 (2003), 1160-1165. -
- [48][48] H.L. Rocchetta, C.J. Boylan, J.W. Foley, P.W. Iversen, D.L. LeTourneau, C.L. McMillian, P.R. Contag, D.E. Jenkins and T.R. Parr, Jr., Validation of a noninvasive, real-time imaging technology using bioluminescent Escherichia coli in the neutropenic mouse thigh model of infection, Antimicrob. Agents Chemother. 45 (2001), 129-137. -
- [49][49] D.J. Rowland, J.R. Garbow, R. Laforest and A.Z. Snyder, Registration of [18F]FDG microPET and small-animal MRI, Nucl. Med. Biol. 32 (2005), 567-572. -
- [50][50] E.A. Schellenberger, A. Bogdanov, Jr., D. Hogemann, J. Tait, R. Weissleder and L. Josephson, Annexin V-CLIO: a nanoparticle for detecting apoptosis by MRI, Mol. Imaging 1 (2002), 102-107. -
- [51][51] C.A. Schmitt, J.S. Fridman, M. Yang, S. Lee, E. Baranov, R.M. Hoffman and S.W. Lowe, A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy, Cell 109 (2002), 335-346. -
- [52][52] N.C. Shaner, P.A. Steinbach and R.Y. Tsien, A guide to choosing fluorescent proteins, Nat. Methods 2 (2005), 905-909. -
- [53][53] O. Szentirmai, C.H. Baker, N. Lin, S. Szucs, M. Takahashi, S. Kiryu, A.L. Kung, R.C. Mulligan and B.S. Carter, Nonin- 16. vasive bioluminescence imaging of luciferase expressing intracranial U87 xenografts: correlation with magnetic resonance imaging determined tumor volume and longitudinal use in assessing tumor growth and antiangiogenic treatment effect, Neurosurgery 58 (2006), 365-372. -
- [54][54] K.M. Thrailkill, L. Liu, E.C. Wahl, R.C. Bunn, D.S. Perrien, G.E. Cockrell, R.A. Skinner, W.R. Hogue, A.A. Carver, J.L. Fowlkes, J. Aronson and C.K. Lumpkin, Jr., Bone formation is impaired in a model of type 1 diabetes, Diabetes 54 (2005), 2875-2881. -
- [55][55] D.W. Townsend, A combined PET/CT scanner: The choices, J. Nucl. Med. 42 (2001), 533-534. -
- [56][56] D.W. Townsend and S.R. Cherry, Combining anatomy and function: The path to true image fusion, Eur. Radiol. 11 (2001), 1968-1974. -
- [57][57] T. Troy, D. Jekic-McMullen, L. Sambucetti and B. Rice, Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models, Mol. Imaging 3 (2004), 9-23. -
- [58][58] S.M. Weber, K.A. Peterson, B. Durkee, C. Qi, M. Longino, T. Warner, F.T. Lee, Jr. and J.P. Weichert, Imaging of murine liver tumor using microCT with a hepatocyte-selective contrast agent: accuracy is dependent on adequate contrast enhancement, J. Surg. Res. 119 (2004), 41-45. -
- [60][60] R. Weissleder, Scaling down imaging: molecular mapping of cancer in mice, Nat. Rev. Cancer 2 (2002), 11-18. -
- [61][61] R. Weissleder and U. Mahmood, Molecular imaging, Radiology 219 (2001), 316-333. -
- [62][62] T. Wilson and J.W. Hastings, Bioluminescence, Annu. Rev. Cell. Dev. Biol. 14 (1998), 197-230. -
- [63][63] P.M. Winter, S.D. Caruthers, A. Kassner, T.D. Harris, L.K. Chinen, J.S. Allen, E.K. Lacy, H. Zhang, J.D. Robertson, S.A. Wickline and G.M. Lanza, Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel α v β 3 targeted nanoparticle and 1.5 tesla magnetic resonance imaging, Cancer Res. 63 (2003), 5838-5843. -
- [64][64] Y. Wu, X. Zhang, Z. Xiong, Z. Cheng, D.R. Fisher, S. Liu, S.S. Gambhir and X. Chen, MicroPET imaging of glioma integrin α V β 3 expression using 64 Cu-labeled tetrameric RGD peptide, J. Nucl. Med. 46 (2005), 1707-1718. -
- [65][65] M. Yang, L. Li, P. Jiang, A.R. Moossa, S. Penman and R.M. Hoffman, Dual-color fluorescence imaging distinguishes tumor cells from induced hostangiogenic vessels and stromal cells, Proc. Natl. Acad. Sci. USA 100 (2003), 14259-14262. -
- [66][66] M. Yang, P. Jiang, N. Yamamoto, L. Li, J. Geller, A.R. Moossa and R.M. Hoffman, Real-time whole-body imaging of an orthotopic metastatic prostate cancer model expressing red fluorescent protein, Prostate 62 (2005), 374-379. -
- [67][67] H. Zaidi and B. Hasegawa, Determination of the attenuation map in emission tomography, J. Nucl. Med. 44 (2003), 291315. -
- [68][68] S.I. Ziegler, Instrumentation and data acquisition, in: Diagnostic Nuclear Medicine , C. Schiepers, ed., Springer Verlag, Berlin, 2000, pp. 221-236.
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- Authors
- Koo, V., Hamilton, P. W., & Williamson, K.
- Affiliations
- Queen's University Belfast (GB)
- Corresponding author
- Koo, V.
- Venue
- Analytical Cellular Pathology
- Publisher
- Wiley
- Published
- 2006-01
- Volume
- 28
- Issue
- 4
- Pages
- 127-139
- ISSN
- 0921-8912 (ISSN-L)
- 2210-7177
- 2210-7185
- PMC
- PMC4617494
- OpenAlex
- W1587690368
- Cited by
- 145
- References
- 1
- Citations by year
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- FWCI
- 7.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Analytical Cellular Pathology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Physical Sciences › Engineering › Biomedical Engineering › Photoacoustic and Ultrasonic Imaging
- Keywords
- in vivo molecular imaging, small animal models, cancer research, tumour modelling, metastasis detection, longitudinal imaging, translational drug development, magnetic resonance imaging, computed tomography, positron emission tomography, bioluminescence imaging, fluorescence imaging, multimodal imaging
- MeSH terms
- Animals, Diagnostic Imaging, Fluorescent Dyes, Magnetic Resonance Imaging, Tomography, Emission-Computed, Single-Photon, Models, Animal, Positron-Emission Tomography
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