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The welfare and scientific advantages of non-invasive imaging of animals used in biomedical research

Published online by Cambridge University Press:  11 January 2023

M Hudson
M Hudson*
Affiliation:
FRAME, Russell and Burch House, 96–98 North Sherwood Street, Nottingham NG1 4EE, UK
*
email: michelle@frame.org.uk
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Abstract

At present, animal experimentation remains central to our understanding of human disease-related processes and of the biological effects of many substances. Traditional experiments have relied heavily on invasive techniques to monitor changes in blood biochemistry, tissue structure or function, or to phenotype or genotype genetically modified animals. In some cases, a proportion or all of the animals used during the course of a study may be sacrificed for histopathological assessment. In most cases, this is to track the progression or regression of a disease over time, or to determine the levels of toxicity evident in specific organs or tissues. However, many of these techniques fail to provide details of how a disease develops or how a substance elicits its effects. In recent years there has been a gradual increase in the application of imaging techniques that were originally developed and used in fundamental research or in medicine. These non-invasive techniques allow diseases, and responses to exogenous substances, to be monitored in a temporal and spatial manner, therefore allowing a greater amount of information to be derived from smaller numbers of animals, which in turn, increases the statistical validity of the data by reducing the level of experimental variation. Non-invasive imaging also allows more informative and humane endpoints to be used and, perhaps most importantly, allows functional details to be studied in the context of a living animal. Some of the recent developments within the field of non-invasive imaging and their significance with respect to animal welfare and the understanding of human physiology are discussed.

Keywords

animal welfarebioluminescencehuman diseaseMRInon-invasive imagingPET
Type
Research Article
Information
Animal Welfare , Volume 14 , Issue 4 , November 2005 , pp. 303 - 317
Copyright
© 2005 Universities Federation for Animal Welfare

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References

Abbey, CK, Borowsky, AD, McGoldrick, ET, Gregg, JP, Maglione, JE, Cardiff, RD and Cherry, SR 2004 In vivo positron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia. Proceedings of the National Academy of Sciences 101: 11438–11443CrossRefGoogle Scholar
Anon 2004 Method to visualize gene activity may provide important insight into normal development and genome function. ScienceDaily. www.sciencedaily.com/releases/2004/08/040806095617.htm (accessed 10 August 2004)Google Scholar
Anon 2005 Lord Dowding Fund for Humane Research 2005: Summary of Research Projects p 11. www.navs.org.uk/download_files/research/LDF%20Summary%2004%20-%2005.pdf%20(17_1_05).pdf (accessed 22 September 2005)Google Scholar
Bakalova, R, Ohba, H, Zhelev, Z, Ishikawa, M and Baba, Y 2004 Quantum dots as photosensitizers? Nature Biotechnology 22: 1360–1361CrossRefGoogle ScholarPubMed
Bangard, C, Gossmann, A, Papyan, A, Tawadros, S, Hellmich, M and Bruns, CJ 2005 Magnetic resonance imaging in an orthotopic rat model: blockade of epidermal growth factor receptor with EMD72000 inhibits human pancreatic carcinoma growth. International Journal of Cancer 114: 131–138CrossRefGoogle Scholar
Benveniste, H and Blackband, S 2002 MR microscopy and high resolution small animal MRI: applications in neuroscience research. Progress in Neurobiology 67: 393–420CrossRefGoogle ScholarPubMed
Bernardes, R, Dias, J and Cunha-Vaz, J 2005 Mapping the human blood-retinal barrier function. IEEE Transactions on Biomedical Engineering 52: 106–116CrossRefGoogle ScholarPubMed
Bhaumik, S and Gambhir, SS 2002 Optical imaging of Renilla luciferase reporter gene expression in living mice. Proceedings of the National Academy of Sciences 99: 377–382CrossRefGoogle ScholarPubMed
Bhaumik, S, Lewis, XZ and Gambhir, SS 2004 Optical imaging of Renilla luciferase, synthetic Renilla luciferase, and firefly luciferase reporter gene expression in living mice. Journal of Biomedical Optics 9: 578–586CrossRefGoogle ScholarPubMed
Boussaoud, D, Jouffrais, C and Bremmer, F 1998 Eye position effects on the neuronal activity of dorsal premotor cortex in the macaque monkey. Journal of Neurophysiology 80: 1132–1150CrossRefGoogle ScholarPubMed
Chudakov, DM, Verkhusha, VV, Staroverov, DB, Souslova, EA, Lukyanov, S and Lukyanov, KA 2004 Photoswitchable cyan fluorescent protein for protein tracking. Nature Biotechnology 22: 1435–1439CrossRefGoogle ScholarPubMed
Cólon, AL, Madrigal, JLM, Menchén, LA, Moro, MA, Lizasoain, I, Lorenzo, P and Leza, JC 2004 Stress increases susceptibility to oxidative/nitrosative mucosal damage in an experimental model of colitis in rats. Digestive Diseases and Sciences 49: 1713–1721CrossRefGoogle Scholar
Contag, CH, Contag, PR, Mullins, JI, Spilman, SD, Stevenson, DK and Benaron, DA 1995 Photonic detection of bacterial pathogens in living hosts. Molecular Microbiology 18: 593–603CrossRefGoogle ScholarPubMed
Cornelissen, K, Laine, M, Renvall, K, Saarinen, T, Martin, N and Salmelin, R 2004 Learning new names for objects: cortical effects as measured by magnetoencephalography. Brain and Language 89: 617–622CrossRefGoogle ScholarPubMed
Crawford, JD and Guitton, D 1997 Primate head-free saccade generator implements a desired (post-VOR) eye position command by anticipating intended head motion. Journal of Neurophysiology 78: 2811–2816CrossRefGoogle ScholarPubMed
Edinger, M, Cao, YA, Hornig, YS, Jenkins, DE, Verneris, MR, Bachmann, MH, Negrin, RS and Contag, CH 2002 Advancing animal models of neoplasia through in vivo bioluminescence imaging. European Journal of Cancer 38: 2128–2136CrossRefGoogle ScholarPubMed
Fernández, EJ, Unterhuber, A, Prieto, PM, Hermann, B, Drexler, W and Artal, P 2005 Ocular aberrations as a function of wavelength in the near infrared measured with a femtosecond laser. Optics Express 13: 400–409CrossRefGoogle ScholarPubMed
Francis, KP, Joh, D, Bellinger-Kawahara, C, Hawkinson, MJ, Purchio, TF and Contag, PR 2000 Monitoring bioluminescent Staphylococcus aureus infections in living mice using a novel luxABCDE construct. Infection and Immunity 68: 3594–3600CrossRefGoogle ScholarPubMed
Francis, KP, Yu, J, Bellinger-Kawahara, C, Joh, D, Hawkinson, MJ, Xiao, G, Purchio, TF, Caparon, MG, Lipsitch, M and Contag, PR 2001 Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon. Infection and Immunity 69: 3350–3358CrossRefGoogle ScholarPubMed
Funk, T, Sun, M and Hasegawa, BH 2004 Radiation dose estimate in small animal SPECT and PET. Medical Physics 31: 2680–2686CrossRefGoogle ScholarPubMed
Gao, X, Cui, Y, Levenson, RM, Chung, LWK and Nie, S 2004 In vivo cancer targeting and imaging with semiconductor quantum dots. Nature Biotechnology 22: 969–976CrossRefGoogle ScholarPubMed
Giannesini B, Cozzone PJ and Bendahan 2004 In vivo MR investigation of skeletal muscle function in small animals. MAGMA 17: 210–218CrossRefGoogle Scholar
Goertzen, AL, Meadors, AK, Silverman, RW and Cherry, SR 2002 Simultaneous molecular and anatomical imaging of the mouse in vivo. Physics in Medicine and Biology 47: 4315–4328CrossRefGoogle ScholarPubMed
González Trotter, DE, Manjeshwar, RM, Doss, M, Shaller, C, Robinson, MK, Tandon, R, Adams, GP and Adler, LP 2004 Quantitation of small-animal 124I activity distributions using a clinical PET/CT scanner. Journal of Nuclear Medicine 45: 1237–1244Google ScholarPubMed
Groot-Wassink, T, Aboagye, EO, Wang, Y, Lemoine, NR, Reader, AJ and Vassuax, G 2004 Quantitative imaging of NA/I symporter transgene expression using positron emission tomography in the living animal. Molecular Therapy 9: 436–442CrossRefGoogle ScholarPubMed
Haller, J 2001 The link between stress and the efficacy of anxiolytics: a new avenue of research. Physiology & Behavior 73: 337–342CrossRefGoogle ScholarPubMed
Hoffman, RM 2004 Images tumor angiogenesis with fluorescent proteins. APMIS 112: 441–449Google ScholarPubMed
Hollingshead, MG, Bonomi, CA, Borgel, SD, Carter, JP, Shoemaker, R, Melillo, G and Sausville, EA 2004 A potential role for imaging technology in anticancer efficacy evaluations. European Journal of Cancer 40: 890–898CrossRefGoogle ScholarPubMed
Huang, Q, Shan, S, Braun, RD, Lanzen, J, Anyrhambatla, G, Kong, G, Borelli, M, Corry, P, Dewhirst, MW and Li, CY 1999 Noninvasive visualization of tumours in rodent dorsal skin window chambers. Nature Biotechnology 17: 1033–1035CrossRefGoogle ScholarPubMed
Irving, EL, Zacher, JE, Allison, RS and Callender, MG 2003 Effects of scleral search coil wear on visual function. Investigative Ophthalmology & Visual Science 44: 1933–1938CrossRefGoogle ScholarPubMed
Jaiswal, JK, Goldman, ER, Mattoussi, H and Simon, SM 2004 Use of quantum dots for live cell imaging. Nature Methods 1: 73–78CrossRefGoogle ScholarPubMed
Jen, PHS and Zhou, X 2003 Corticofugal modulation of amplitude domain processing in the midbrain of the big brown bat, Eptesicus fuscus. Hearing Research 184: 91–106CrossRefGoogle ScholarPubMed
Jenkins, DE, Oei, Y, Hornig, YS, Yu, S-F, Dusich, J, Purchio, T and Contag, PR 2003 Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumour growth and metastasis. Clinical and Experimental Metastasis 20: 733–744CrossRefGoogle Scholar
Judge, SJ, Richmond, BJ and Chu, FC 1980 Implantation of magnetic search coils for measurement of eye position: an improved method. Vision Research 20: 535–538CrossRefGoogle ScholarPubMed
Kale, A, Amende, I, Piskorski, K, Chu, V, Otero, JM, Mueller, P and Hampton, TG 2004 Non-invasive physiology in conscious mice. ATLA 32, Suppl 1: 195–201Google Scholar
Klarreich, E 2001 Biologists join the dots. Nature 413: 450–452CrossRefGoogle ScholarPubMed
Kortekaas, R, van Waarde, A, Maguire, RP, Leenders, KL and Elsinga, PH 2004 Development of an inexpensive, low attenuation styrofoam primate chair for use in a PET scanner. Journal of Medical Primatology 33: 78–82CrossRefGoogle Scholar
Kosman, D, Mizutani, CM, Lemons, D, Cox, WG, McGinnin, W and Bier, E 2004 Multiplex detection of RNA expression in Drosophila embryos. Science 305: 846CrossRefGoogle ScholarPubMed
Lacreuse, A, Diehl, MM, Goh, MY, Hall, MJ, Volk, AM, Chhabra, RK and Herndon, JG 2005 Sex differences in age-related motor slowing in the rhesus monkey: behavioural and neuroimaging data. Neurobiology of Ageing 26: 543–551CrossRefGoogle ScholarPubMed
Larson, DR, Zipfel, WR, Williams, RM, Clark, SW, Bruchez, MP, Wise, FW and Webb, WW 2003 Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300: 1434–1436Google ScholarPubMed
Le Bihan, D, Breton, E, Lallemand, D, Grenier, P, Cabanis, E and Laval-Jeantet, M 1986 MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology 161: 401–407CrossRefGoogle ScholarPubMed
Lester, DS, Lyon, RC, McGregor, GN, Englehardt, RT, Schmued, LC, Johnson, GA and Johannessen, JN 1999 3–Dimensional visualization of lesions in rat brain using magnetic resonance imaging microscopy. NeuroReport 10: 737–741CrossRefGoogle ScholarPubMed
Luker, GD, Bardill, JP, Prior, JL, Pica, CM, Piwnica-Worms, D and Leib, DA 2002 Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice. Journal of Virology 76: 12149–12161CrossRefGoogle ScholarPubMed
Luker, KE, Smith, MCP, Luker, G, Gammon, ST, Piwnica-Worms, H and Piwnica-Worms, D 2004 Kinetics of regulated protein-protein interactions revealed with firefly luciferase complementation imaging in cells in living animals. Proceedings of the National Academy of Sciences 101: 12288–12293CrossRefGoogle ScholarPubMed
Lyons, SK 2005 Advances in imaging mouse tumour models in vivo. Journal of Pathology 205: 194–205CrossRefGoogle ScholarPubMed
MatTek The epiocular model. http://www.mattek.com/epiocular.html (accessed 12 March 2005)Google Scholar
May, BJ 2000 Role of the dorsal cochlear nucleus in the sound localization behaviour of cats. Hearing Research 148: 74–87CrossRefGoogle ScholarPubMed
Mazer, JA and Gallant, JL 2003 Goal-related activity in V4 during free viewing visual search: evidence for a ventral stream visual salience map. Neuron 40: 1241–1250CrossRefGoogle ScholarPubMed
Miyawaki, A 2004 Fluorescent proteins in a new light. Nature Biotechnology 22: 1374–1376CrossRefGoogle Scholar
Moseley, ME, Cohen, Y, Kucharczyk, J, Mintorovitch, J, Asgari, HS, Wendland, MF, Tsuruda, J and Norman, D 1990 Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 176: 439–445CrossRefGoogle ScholarPubMed
Myers, R and Hume, S 2002 Small animal PET. European Neuropsychopharmacology 12: 545–555CrossRefGoogle ScholarPubMed
Neeman, M 2002 Functional and molecular MR imaging of angiogenesis: seeing the target, seeing it work. Journal of Cellular Biochemistry 39, Suppl: 11-17CrossRefGoogle Scholar
Pammer, K, Hansen, PC, Kringelbach, ML, Holliday, I, Barnes, G, Hillebrand, A, Singh, KD and Cornelissen, PL 2004 Visual word recognition: the first half second. NeuroImage 22: 1819–1825CrossRefGoogle ScholarPubMed
Peiffer, AM, Rosen, GD and Fitch, RH 2004 Sex differences in rapid auditory processing deficits in microgyric rats. Developmental Brain Research 148: 53–57CrossRefGoogle ScholarPubMed
Perkel, JM 2004 Don't fret, gold quantum dots are here. The Scientist 18: 32Google Scholar
Pogge, A and Slikker, W Jr 2004 Neuroimaging: new approaches for neurotoxicology. Neurotoxicology 25: 525–531CrossRefGoogle ScholarPubMed
Rehemtulla, A, Hall, DE, Stegman, LD, Prasad, U, Chen, G, Bhojani, MS, Chenevert, TL and Ross, BD 2002 Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumour therapy. Molecular Imaging 1: 43–55CrossRefGoogle Scholar
Robinson, V, Morton, DB, Anderson, D, Carver, JFA, Francis, RJ, Hubrecht, R, Jenkins, E, Mathers, KE, Raymond, R, Rosewell, I, Wallace, J and Wells, DJ 2003 Refinement and reduction in production of genetically modified mice. Laboratory Animals 37, Suppl 1: 1–51Google Scholar
Ross, BD, Moffat, BA, Lawrence, TS, Mukherji, SK, Gebarski, SS, Quint, DJ, Johnson, TD, Junck, L, Robertson, PL, Muraszko, KM, Dong, Q, Meyer, CR, Bland, PH, McConville, P, Geng, H, Rehemtulla, A and Chenevert, TL 2003 Evaluation of cancer therapy using diffusion magnetic resonance imaging. Molecular Cancer Therapeutics 2: 581–587Google ScholarPubMed
Schmidt, M 1996 Neurons in the cat pretectum that project to the dorsal lateral geniculate nucleus are activated during saccades. Journal of Neurophysiology 76: 2907–2918CrossRefGoogle Scholar
Sherwin, CM 2004 The influences of standard laboratory cages on rodents and the validity of research data. Animal Welfare 13, Suppl: S9-S15Google Scholar
Shin, JH, Chung, JK, Kang, JH, Lee, YJ, Kim, KI, Kim, CW, Jeong, JM, Lee, DS and Lee, MC 2004 Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV-tk. European Journal of Nuclear Medicine and Molecular Imaging 31: 425–432Google ScholarPubMed
Sibson, NR, Blamire, AM, Bernades-Silva, M, Laurent, S, Boutry, S, Muller, RN, Styles, P and Anthony, DC 2004 MRI detection of early endothelial activation in brain inflammation. Magnetic Resonance in Medicine 51: 248–252CrossRefGoogle ScholarPubMed
Spinney, L 2005 Optical topography and the color of blood. The Scientist 19: 25–27Google Scholar
Stathopoulos, E, Schlageter, V, Meyrat, B, De Ribaupierre, Y and Kucera, P 2005 Magnetic pill tracking: a novel non-invasive tool for investigation of human digestive motility. Neurogastroenterology and Motility 17: 148–154CrossRefGoogle ScholarPubMed
Super, H and Roelfsema, PR 2005 Chronic multiunit recordings in behaving animals: advantages and limitations. Development, Dynamics and Pathology of Neuronal Networks: From Molecules to Functional Circuits 147: 263–282Google ScholarPubMed
Sweeney, TJ, Mailänder, V, Tucker, AA, Olomu, AB, Zhang, W, Cao, Y, Negrin, RS and Contag, CH 1999 Visualizing the kinetics of tumor-cell clearance in living animals. Proceedings of the National Academy of Sciences USA 96: 12044–12049CrossRefGoogle ScholarPubMed
Tanahashi, A, Horikawa, J and Suga, N 1997 NMDA-mediated facilitation in the echo-delay tuned areas of the auditory cortex of the mustached bat. Hearing Research 110: 219–228CrossRefGoogle ScholarPubMed
Trakic, A, Crozier, S and Liu, F 2004 Numerical modelling of thermal effects in rats due to high-field magnetic resonance imaging (0.5–1.0 GHz). Physics in Medicine and Biology 49: 5547–5558CrossRefGoogle Scholar
Turner, R and Jones, T 2003 Techniques for imaging neuroscience. British Medical Bulletin 65: 3–20CrossRefGoogle ScholarPubMed
Tyas, DA, Pratt, T, Simpson, TI, Mason, JO and Price, DJ 2003 Identifying GFP-transgenic animals by flashlight. BioTechniques 34: 474–476CrossRefGoogle ScholarPubMed
van Furth, WR, Laughlin, S, Taylor, MD, Salhia, B, Mainprize, T, Henkelman, M, Cuismano, MD, Ackerley, C and Rutka, JT 2003 Imaging of murine brain tumours using a 1.5 telsa clinical MRI system. Canadian Journal of Neurological Sciences 30: 326–332CrossRefGoogle Scholar
Vogelstein, JT, Snyder, LH and Angelaki, DE 2003 Accuracy of saccades to remembered targets as a function of body orientation in space. Journal of Neurophysiology 90: 521–524CrossRefGoogle ScholarPubMed
Vooijs, M, Jonkers, J, Lyons, S and Berns, A 2002 Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Research 62: 1862–1867Google ScholarPubMed
Voura, EB, Jaiswal, JK, Mattoussi, H and Simon, SM 2004 Tracking metastatic tumour cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nature Medicine 10: 993–998CrossRefGoogle ScholarPubMed
Weiskopf, N, Klose, U, Birbaumer, N and Mathiak, K 2005 Single-shot compensation of image distortions and BOLD contrast optimization using multi-echo EPI for real-time fMRI. NeuroImage 24: 1068–1079CrossRefGoogle ScholarPubMed
Wilhelmus, KR 2001 The Draize eye test. Survey of Ophthalmology 45: 493–515CrossRefGoogle ScholarPubMed
Zhang, J, Campbell, RE, Ting, AY and Tsien, RY 2002 Creating new fluorescent probes for cell biology. Nature Reviews Molecular Cell Biology 3: 906–918CrossRefGoogle ScholarPubMed
Zhao, M, Yang, M, Baranov, E, Wang, X, Penman, S, Moossa, AR and Hoffman, RM 2001 Spatial-temporal imaging of bacterial infection and antibiotic response in intact animals. Proceedings of the National Academy of Sciences 98: 9814–9818CrossRefGoogle ScholarPubMed