Abstract
Translational medicine, experimental medicine and experimental animal models, in particular mice and rats, represent a multidisciplinary field that has made it possible to achieve, in the last decades, important scientific progress. In this review, we have summarized the most frequently used imaging animal models, such as ultrasound (US), micro-CT, MRI and the optical imaging methods, and their main implications in diagnostic and therapeutic fields, with a particular focus on diabetes mellitus, a multifactorial disease extremely widespread among the general population.
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References
Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553. https://doi.org/10.1002/(SICI)1096-9136(199807)15:7%3c539::AID-DIA668%3e3.0.CO;2-S
Chawla A, Chawla R, Jaggi S (2016) Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocr Metab 20:546. https://doi.org/10.4103/2230-8210.183480
American Diabetes Association (2007) Standards of medical care in diabetes–2007. Diabetes Care 30:S4–S41. https://doi.org/10.2337/dc07-S004
American Diabetes Association (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32:S62–S67. https://doi.org/10.2337/dc09-S062
Woolf SH (2008) The meaning of translational research and why it matters. JAMA. https://doi.org/10.1001/jama.2007.26
Cohrs RJ, Martin T, Ghahramani P et al (2014) Translational medicine definition by the European society for translational medicine. Eur J Mol Clin Med 2:86. https://doi.org/10.1016/j.nhtm.2014.12.002
Sardanelli F (2017) Trends in radiology and experimental research. Eur Radiol Exp 1:1. https://doi.org/10.1186/s41747-017-0006-5
Cossu G, Previtali SC, Napolitano S et al (2016) Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy. EMBO Mol Med 8(12):1470–1471. https://doi.org/10.15252/emmm.201607129
Venturini M, Bergamini A, Perani L et al (2018) Contrast-enhanced ultrasound for ovary assessment in a murine model: preliminary findings on the protective role of a gonadotropin-releasing hormone analogue from chemotherapy-induced ovarian damage. Eur Radiol Exp 2:44. https://doi.org/10.1186/s41747-018-0076-z
Dall’Ara E, Boudiffa M, Taylor C et al (2016) Longitudinal imaging of the ageing mouse. Mech Ageing Dev 160:93–116. https://doi.org/10.1016/j.mad.2016.08.001
Vandamme T (2014) Use of rodents as models of human diseases. J Pharm Bioall Sci 6:2. https://doi.org/10.4103/0975-7406.124301
Ziegler M, Hohmann JD, Searle AK et al (2017) A single-chain antibody-CD39 fusion protein targeting activated platelets protects from cardiac ischaemia/reperfusion injury. Eur Heart J. https://doi.org/10.1093/eurheartj/ehx218
Suresh S, Alvarez JC, Dey S, Noguchi CT (2020) Erythropoietin-induced changes in bone and bone marrow in mouse models of diet-induced obesity. IJMS 21:1657. https://doi.org/10.3390/ijms21051657
Shi T, Lu K, Shen S et al (2017) Fenofibrate decreases the bone quality by down regulating Runx2 in high-fat-diet induced Type 2 diabetes mellitus mouse model. Lipids Health Dis 16:201. https://doi.org/10.1186/s12944-017-0592-5
Salas IH, Weerasekera A, Ahmed T et al (2018) High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease. Neurobiol Dis 113:82–96. https://doi.org/10.1016/j.nbd.2018.02.001
Tuckett AZ, Thornton RH, O’Reilly RJ et al (2017) Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency. J Hematol Oncol 10:109. https://doi.org/10.1186/s13045-017-0478-z
Zou T, Zhu M, Ma Y-C et al (2018) MicroRNA-410-5p exacerbates high-fat diet-induced cardiac remodeling in mice in an endocrine fashion. Sci Rep 8:8780. https://doi.org/10.1038/s41598-018-26646-4
Zhang G, Li H, Zhao W et al (2020) miR-205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2. Exp Ther Med 20:1557–1565. https://doi.org/10.3892/etm.2020.8867
Perlman RL (2016) Mouse models of human disease: an evolutionary perspective. EMPH. https://doi.org/10.1093/emph/eow014
Zheng X, Soroush F, Long J et al (2017) Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy. PLoS ONE 12:e0185250. https://doi.org/10.1371/journal.pone.0185250
Senchenkova EY, Ansari J, Becker F et al (2019) Novel role for the AnxA1-Fpr2/ALX signaling axis as a key regulator of platelet function to promote resolution of inflammation. Circulation 140:319–335. https://doi.org/10.1161/CIRCULATIONAHA.118.039345
Singh SP, Schragenheim J, Cao J et al (2016) PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: role of epoxyeicosatrienoic acid. Prostaglandins Other Lipid Mediat 125:8–18. https://doi.org/10.1016/j.prostaglandins.2016.07.004
Sebo ZL, Rodeheffer MS (2021) Testosterone metabolites differentially regulate obesogenesis and fat distribution. Mol Metab 44:101141. https://doi.org/10.1016/j.molmet.2020.101141
Lieschke GJ, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nat Rev Genet 8:353–367. https://doi.org/10.1038/nrg2091
Wang M, Sun Y, Cao X et al (2018) Graphene quantum dots against human IAPP aggregation and toxicity in vivo. Nanoscale 10:19995–20006. https://doi.org/10.1039/C8NR07180B
Oka T, Nishimura Y, Zang L et al (2010) Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity. BMC Physiol 10:21. https://doi.org/10.1186/1472-6793-10-21
Taveau C, Chollet C, Bichet DG et al (2017) Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V 1A receptors. Am J Physiol-Endocrinol Metab 312:E127–E135. https://doi.org/10.1152/ajpendo.00269.2016
Zhang M, Yu W-Z, Shen X-T et al (2016) Advanced interfere treatment of diabetic cardiomyopathy rats by aFGF-loaded heparin-modified microbubbles and UTMD technique. Cardiovasc Drugs Ther 30:247–261. https://doi.org/10.1007/s10557-016-6639-4
Yang Y, Wang Y, Kong Y et al (2018) Carnosine prevents type 2 diabetes-induced osteoarthritis through the ROS/NF-κB pathway. Front Pharmacol 9:598. https://doi.org/10.3389/fphar.2018.00598
Zheng W, Li D, Gao X et al (2018) Carvedilol alleviates diabetic cardiomyopathy in diabetic rats. Exp Ther Med. https://doi.org/10.3892/etm.2018.6954
Vicente A, Bravo-González L-A, Navarro JA et al (2021) Effects of diabetes on oxidative stress, periodontal ligament fiber orientation, and matrix metalloproteinase 8 and 9 expressions during orthodontic tooth movement. Clin Oral Invest 25:1383–1394. https://doi.org/10.1007/s00784-020-03446-7
Serizawa K, Yogo K, Tashiro Y et al (2017) Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats. Cardiovasc Ther 35:e12250. https://doi.org/10.1111/1755-5922.12250
Rong L, Sun S, Zhu F et al (2020) Expression of NLRP1 inflammasomes in myocardial tissue of diabetic rats. Nan Fang Yi Ke Da Xue Xue Bao 40:87–92. https://doi.org/10.12122/j.issn.1673-4254.2020.01.14
Jacob HJ (1999) Functional genomics and rat models. Genome Res 9:1013–1016. https://doi.org/10.1101/gr.9.11.1013
Yue G, Edani H, Sullivan A et al (2020) Is maxillary diastema an appropriate site for implantation in rats? Int J Implant Dent 6:8. https://doi.org/10.1186/s40729-019-0203-5
Xu X, Fang K, Wang L et al (2019) Local application of semaphorin 3A combined with adipose-derived stem cell sheet and anorganic bovine bone granules enhances bone regeneration in type 2 diabetes mellitus rats. Stem Cells Int 2019:1–14. https://doi.org/10.1155/2019/2506463
Xing H, Wang X, Xiao S et al (2017) Osseointegration of layer-by-layer polyelectrolyte multilayers loaded with IGF1 and coated on titanium implant under osteoporotic condition. IJN 12:7709–7720. https://doi.org/10.2147/IJN.S148001
Sheng M, Huang Z, Pan L et al (2017) SOCS2 exacerbates myocardial injury induced by ischemia/reperfusion in diabetic mice and H9c2 cells through inhibiting the JAK-STAT-IGF-1 pathway. Life Sci 188:101–109. https://doi.org/10.1016/j.lfs.2017.08.036
Bryda EC (2013) The mighty mouse: the impact of rodents on advances in biomedical research. Mo Med 110:207–211
Xiong Y, Aroor AR, Ramirez-Perez FI et al (2020) Western diet induces renal artery endothelial stiffening that is dependent on the epithelial Na + channel. Am J Physiol-Renal Physiol 318:F1220–F1228. https://doi.org/10.1152/ajprenal.00517.2019
Somashekar ST, Sammour I, Huang J et al (2017) Intra-amniotic soluble endoglin impairs lung development in neonatal rats. Am J Respir Cell Mol Biol 57:468–476. https://doi.org/10.1165/rcmb.2016-0165OC
Dolenšek J, Rupnik MS, Stožer A (2015) Structural similarities and differences between the human and the mouse pancreas. Islets 7:e1024405. https://doi.org/10.1080/19382014.2015.1024405
Kennedy AJ, Ellacott KLJ, King VL, Hasty AH (2010) Mouse models of the metabolic syndrome. Dis Model Mech 3:156–166. https://doi.org/10.1242/dmm.003467
Roth DM, Swaney JS, Dalton ND et al (2002) Impact of anesthesia on cardiac function during echocardiography in mice. Am J Physiol Heart Circ Physiol 282:H2134-2140. https://doi.org/10.1152/ajpheart.00845.2001
Renault G, Bonnin P, Marchiol-Fournigault C et al (2006) L’échographie haute résolution de la souris. J Radiol 87:1937–1945. https://doi.org/10.1016/S0221-0363(06)74179-8
Foster FS, Zhang MY, Zhou YQ et al (2002) A new ultrasound instrument for in vivo microimaging of mice. Ultrasound Med Biol 28:1165–1172. https://doi.org/10.1016/s0301-5629(02)00567-7
Akirav C, Lu Y, Mu J et al (2005) Ultrasonic detection and developmental changes in calcification of the placenta during normal pregnancy in mice. Placenta 26:129–137. https://doi.org/10.1016/j.placenta.2004.05.010
Brown AS, Leamen L, Cucevic V, Foster FS (2005) Quantitation of hemodynamic function during developmental vascular regression in the mouse eye. Invest Ophthalmol Vis Sci 46:2231–2237. https://doi.org/10.1167/iovs.04-0848
Curnis F, Dallatomasina A, Bianco M et al (2016) Regulation of tumor growth by circulating full-length chromogranin A. Oncotarget 7:72716–72732. https://doi.org/10.18632/oncotarget.12237
Catucci M, Zanoni I, Draghici E et al (2014) Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity. Eur J Immunol 44:1039–1045. https://doi.org/10.1002/eji.201343935
Pandit H, Tinney JP, Li Y et al (2019) Utilizing contrast-enhanced ultrasound imaging for evaluating fatty liver disease progression in pre-clinical mouse models. Ultrasound Med Biol 45:549–557. https://doi.org/10.1016/j.ultrasmedbio.2018.10.011
Weissleder R (2002) Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2:11–18. https://doi.org/10.1038/nrc701
Dugnani E, Pasquale V, Marra P et al (2018) Four-class tumor staging for early diagnosis and monitoring of murine pancreatic cancer using magnetic resonance and ultrasound. Carcinogenesis 39:1197–1206. https://doi.org/10.1093/carcin/bgy094
Wirtzfeld LA, Wu G, Bygrave M et al (2005) A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model. Cancer Res 65:6337–6345. https://doi.org/10.1158/0008-5472.CAN-05-0414
Denis F, Bougnoux P, de Poncheville L et al (2002) In vivo quantitation of tumour vascularisation assessed by Doppler sonography in rat mammary tumours. Ultrasound Med Biol 28:431–437. https://doi.org/10.1016/s0301-5629(02)00478-7
Foster FS, Burns PN, Simpson DH et al (2000) Ultrasound for the visualization and quantification of tumor microcirculation. Cancer Metastasis Rev 19:131–138. https://doi.org/10.1023/a:1026541510549
Xu H, Ma Z, Lu S et al (2017) Renal resistive index as a novel indicator for renal complications in high-fat diet-fed mice. Kidney Blood Press Res 42:1128–1140. https://doi.org/10.1159/000485781
Ramirez DG, Abenojar E, Hernandez C et al (2020) Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes. Nat Commun 11:2238. https://doi.org/10.1038/s41467-020-15957-8
Roberts FR, Hupple C, Norowski E et al (2017) Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model. PLoS ONE 12:e0178641. https://doi.org/10.1371/journal.pone.0178641
Tang Y, Zhao Y, Lin W (2020) Preparation of robust fluorescent probes for tracking endogenous formaldehyde in living cells and mouse tissue slices. Nat Protoc 15:3499–3526. https://doi.org/10.1038/s41596-020-0384-7
Tang A, Destrempes F, Kazemirad S et al (2019) Quantitative ultrasound and machine learning for assessment of steatohepatitis in a rat model. Eur Radiol 29:2175–2184. https://doi.org/10.1007/s00330-018-5915-z
Yue T, Xu H-L, Chen P-P et al (2017) Combination of coenzyme Q10-loaded liposomes with ultrasound targeted microbubbles destruction (UTMD) for early theranostics of diabetic nephropathy. Int J Pharm 528:664–674. https://doi.org/10.1016/j.ijpharm.2017.06.070
Yang X-F, Wang H-Y, Lu W-L et al (2020) Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery. Am J Transl Res 12:7275–7286
Wu K, Chiu Y, Yao C et al (2019) Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat model. J Gastroenterol Hepatol 34:720–727. https://doi.org/10.1111/jgh.14368
Wang X, Searle AK, Hohmann JD et al (2018) Dual-targeted theranostic delivery of miRs arrests abdominal aortic aneurysm development. Mol Ther 26:1056–1065. https://doi.org/10.1016/j.ymthe.2018.02.010
Wang X, Gkanatsas Y, Palasubramaniam J et al (2016) Thrombus-targeted theranostic microbubbles: a new technology towards concurrent rapid ultrasound diagnosis and bleeding-free fibrinolytic treatment of thrombosis. Theranostics 6:726–738. https://doi.org/10.7150/thno.14514
Suarez Castellanos I, Jeremic A, Cohen J, Zderic V (2017) Ultrasound stimulation of insulin release from pancreatic beta cells as a potential novel treatment for type 2 diabetes. Ultrasound Med Biol 43:1210–1222. https://doi.org/10.1016/j.ultrasmedbio.2017.01.007
Clark DP, Badea CT (2014) Micro-CT of rodents: state-of-the-art and future perspectives. Phys Med 30:619–634. https://doi.org/10.1016/j.ejmp.2014.05.011
Badea C, Hedlund LW, Johnson GA (2004) Micro-CT with respiratory and cardiac gating. Med Phys 31:3324–3329. https://doi.org/10.1118/1.1812604
Holdsworth DW, Thornton MM (2002) Micro-CT in small animal and specimen imaging. Trends Biotechnol 20:S34–S39. https://doi.org/10.1016/S0167-7799(02)02004-8
Caro AC, Hankenson FC, Marx JO (2013) Comparison of thermoregulatory devices used during anesthesia of C57BL/6 mice and correlations between body temperature and physiologic parameters. J Am Assoc Lab Anim Sci 52:577–583
de Lin M, Ning L, Badea CT et al (2008) A high-precision contrast injector for small animal x-ray digital subtraction angiography. IEEE Trans Biomed Eng 55:1082–1091. https://doi.org/10.1109/TBME.2007.909541
Feldkamp LA, Goldstein SA, Parfitt AM et al (1989) The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res 4:3–11. https://doi.org/10.1002/jbmr.5650040103
Rüegsegger P, Koller B, Müller R (1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int 58:24–29. https://doi.org/10.1007/BF02509542
Zhang H, Liu J, Qin G et al (2017) Melanocortin 4 receptor activation attenuates mitochondrial dysfunction in skeletal muscle of diabetic rats. J Cell Biochem 118:4072–4079. https://doi.org/10.1002/jcb.26062
Zhang W-L, Meng H-Z, Yang R-F et al (2016) Melatonin suppresses autophagy in type 2 diabetic osteoporosis. Oncotarget 7:52179–52194. https://doi.org/10.18632/oncotarget.10538
Yang L, Zheng L-L, Chen Y et al (2016) Study on the characteristics of bone in type-2 diabetic rats by micro-CT. Sichuan Da Xue Xue Bao Yi Xue Ban 47:727–731
Mohsin S, Kaimala S, Sunny JJ et al (2019) Type 2 diabetes mellitus increases the risk to hip fracture in postmenopausal osteoporosis by deteriorating the trabecular bone microarchitecture and bone mass. J Diabetes Res 2019:1–10. https://doi.org/10.1155/2019/3876957
Mujica LKS, Glanzner WG, Prante AL et al (2020) Trabecular bone is increased in a rat model of polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. https://doi.org/10.1055/a-1284-5491
Votava L, Schwartz AG, Harasymowicz NS et al (2019) Effects of dietary fatty acid content on humeral cartilage and bone structure in a mouse model of diet-induced obesity. J Orthop Res 37:779–788. https://doi.org/10.1002/jor.24219
Phongkitkarun S, Kobayashi S, Kan Z et al (2004) Quantification of angiogenesis by functional computed tomography in a Matrigel model in rats. Acad Radiol 11:573–582. https://doi.org/10.1016/S1076-6332(03)00728-1
Toyota E, Ogasawara Y, Fujimoto K et al (2004) Global heterogeneity of glomerular volume distribution in early diabetic nephropathy. Kidney Int 66:855–861. https://doi.org/10.1111/j.1523-1755.2004.00816.x
Turnbull DH, Mori S (2007) MRI in mouse developmental biology. NMR Biomed 20:265–274. https://doi.org/10.1002/nbm.1146
von Morze C, Chang G-Y, Larson PEZ et al (2017) Detection of localized changes in the metabolism of hyperpolarized gluconeogenic precursors 13 C-lactate and 13 C-pyruvate in kidney and liver: Localized Changes in Hyperpolarized Lactate Metabolism. Magn Reson Med 77:1429–1437. https://doi.org/10.1002/mrm.26245
Zhou Y, van Zijl PCM, Xu X et al (2020) Magnetic resonance imaging of glycogen using its magnetic coupling with water. Proc Natl Acad Sci USA 117:3144–3149. https://doi.org/10.1073/pnas.1909921117
Thaiss WM, Gatidis S, Sartorius T et al (2021) Noninvasive, longitudinal imaging-based analysis of body adipose tissue and water composition in a melanoma mouse model and in immune checkpoint inhibitor-treated metastatic melanoma patients. Cancer Immunol Immunother 70:1263–1275. https://doi.org/10.1007/s00262-020-02765-8
Mustafi D, Fernandez S, Markiewicz E et al (2017) MRI reveals increased tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer. NMR Biomed 30:e3758. https://doi.org/10.1002/nbm.3758
Mustafi D, Valek R, Fitch M et al (2020) Magnetic resonance angiography reveals increased arterial blood supply and tumorigenesis following high fat feeding in a mouse model of triple-negative breast cancer. NMR Biomed. https://doi.org/10.1002/nbm.4363
Toma I, Kim PJ, Dash R et al (2016) Telmisartan in the diabetic murine model of acute myocardial infarction: dual contrast manganese-enhanced and delayed enhancement MRI evaluation of the peri-infarct region. Cardiovasc Diabetol 15:24. https://doi.org/10.1186/s12933-016-0348-y
Qi H, Nielsen PM, Schroeder M et al (2018) Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats. Diabetologia 61:445–454. https://doi.org/10.1007/s00125-017-4445-6
Yan YY, Hartono S, Hennedige T et al (2017) Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes. Magn Reson Imaging 38:71–76. https://doi.org/10.1016/j.mri.2016.12.023
Wang Q, Guo C, Zhang L et al (2018) BOLD MRI to evaluate early development of renal injury in a rat model of diabetes. J Int Med Res 46:1391–1403. https://doi.org/10.1177/0300060517743826
Tristão Pereira C, Diao Y, Yin T et al (2021) Synchronous nonmonotonic changes in functional connectivity and white matter integrity in a rat model of sporadic Alzheimer’s disease. Neuroimage 225:117498. https://doi.org/10.1016/j.neuroimage.2020.117498
Wang S, Hua Z, Fan D et al (2019) Gadolinium retention and clearance in the diabetic brain after administrations of gadodiamide, gadopentetate dimeglumine, and gadoterate meglumine in a rat model. Biomed Res Int 2019:1–12. https://doi.org/10.1155/2019/3901907
Younis FM, Blumenthal-Katzir T, Hollander K et al (2016) Telmisartan-mediated metabolic profile conferred brain protection in diabetic hypertensive rats as evidenced by magnetic resonance imaging, behavioral studies and histology. Eur J Pharmacol 789:88–97. https://doi.org/10.1016/j.ejphar.2016.07.021
Qiao J, Lawson CM, Rentrup KFG et al (2020) Evaluating blood–brain barrier permeability in a rat model of type 2 diabetes. J Transl Med 18:256. https://doi.org/10.1186/s12967-020-02428-3
Wang P, Goodwill PW, Pandit P et al (2018) Magnetic particle imaging of islet transplantation in the liver and under the kidney capsule in mouse models. Quant Imaging Med Surg 8:114–122. https://doi.org/10.21037/qims.2018.02.06
Wang P, Liu Q, Zhao H et al (2020) miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model. Sci Rep 10:5302. https://doi.org/10.1038/s41598-020-62269-4
Shuboni-Mulligan DD, Parys M, Blanco-Fernandez B et al (2019) Dynamic contrast-enhanced MRI of OATP dysfunction in diabetes. Diabetes 68:271–280. https://doi.org/10.2337/db18-0525
Ollinger JM, Fessler JA (1997) Positron-emission tomography. IEEE Signal Process Mag 14:43–55. https://doi.org/10.1109/79.560323
Phelps ME (2000) Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci 97:9226–9233. https://doi.org/10.1073/pnas.97.16.9226
Zhao Q, Zhou J, Pan Y et al (2020) The difference between steroid diabetes mellitus and type 2 diabetes mellitus: a whole-body 18F-FDG PET/CT study. Acta Diabetol 57:1383–1393. https://doi.org/10.1007/s00592-020-01566-w
Virta J, Hellberg S, Liljenbäck H et al (2020) Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis: a 18F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes. Atherosclerosis 305:64–72. https://doi.org/10.1016/j.atherosclerosis.2020.03.029
Zhang Y, Song K, Qi G et al (2020) Adipose-derived exosomal miR-210/92a cluster inhibits adipose browning via the FGFR-1 signaling pathway in high-altitude hypoxia. Sci Rep 10:14390. https://doi.org/10.1038/s41598-020-71345-8
Wang Z, Xu X, Liu Y et al (2018) Assessment of the aging of the brown adipose tissue by 1 8 F-FDG PET/CT imaging in the progeria mouse model Lmna −/−. Contrast Media Mol Imaging 2018:1–9. https://doi.org/10.1155/2018/8327089
Werner RA, Eissler C, Hayakawa N et al (2018) Left ventricular diastolic dysfunction in a rat model of diabetic cardiomyopathy using ECG-gated 18F-FDG PET. Sci Rep 8:17631. https://doi.org/10.1038/s41598-018-35986-0
Wang P, Su C, Feng H et al (2017) Curcumin regulates insulin pathways and glucose metabolism in the brains of APPswe/PS1dE9 mice. Int J Immunopathol Pharmacol 30:25–43. https://doi.org/10.1177/0394632016688025
Templin AT, Meier DT, Willard JR et al (2018) Use of the PET ligand florbetapir for in vivo imaging of pancreatic islet amyloid deposits in hIAPP transgenic mice. Diabetologia 61:2215–2224. https://doi.org/10.1007/s00125-018-4695-y
Velikyan I, Haack T, Bossart M et al (2019) First-in-class positron emission tomography tracer for the glucagon receptor. EJNMMI Res 9:17. https://doi.org/10.1186/s13550-019-0482-0
Son N-H, Basu D, Samovski D et al (2018) Endothelial cell CD36 optimizes tissue fatty acid uptake. J Clin Investig 128:4329–4342. https://doi.org/10.1172/JCI99315
Holly TA, Abbott BG, Al-Mallah M et al (2010) Single photon-emission computed tomography. J Nucl Cardiol 17:941–973. https://doi.org/10.1007/s12350-010-9246-y
Willekens SMA, van der Kroon I, Joosten L et al (2016) SPECT of Transplanted islets of langerhans by dopamine 2 receptor targeting in a rat model. Mol Pharm 13:85–91. https://doi.org/10.1021/acs.molpharmaceut.5b00518
Wall JS, Williams A, Richey T et al (2017) Specific amyloid binding of polybasic peptides in vivo is retained by β-sheet conformers but lost in the disrupted coil and all D-amino acid variants. Mol Imaging Biol 19:714–722. https://doi.org/10.1007/s11307-017-1063-0
Murakami T, Fujimoto H, Fujita N et al (2019) Noninvasive evaluation of GPR119 agonist effects on β-cell mass in diabetic male mice using 111In-exendin-4 SPECT/CT. Endocrinology 160:2959–2968. https://doi.org/10.1210/en.2019-00556
Sharpe J (2003) Optical projection tomography as a new tool for studying embryo anatomy. J Anatomy 202:175–181. https://doi.org/10.1046/j.1469-7580.2003.00155.x
Mezzanotte L, van’t Root M, Karatas H et al (2017) In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol 35:640–652. https://doi.org/10.1016/j.tibtech.2017.03.012
Mezzapelle R, Rrapaj E, Gatti E et al (2016) Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells. Sci Rep 6:22850. https://doi.org/10.1038/srep22850
Stacer AC, Nyati S, Moudgil P et al (2013) NanoLuc reporter for dual luciferase imaging in living animals. Mol Imaging 12:1–13
Darne C, Lu Y, Sevick-Muraca EM (2014) Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update. Phys Med Biol 59:R1-64. https://doi.org/10.1088/0031-9155/59/1/R1
Saif M, Kwanten WJ, Carr JA et al (2020) Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin. Nat Biomed Eng 4:801–813. https://doi.org/10.1038/s41551-020-0569-y
Qiao Q, Song YL, Li FL (2018) Semaphorin 3A-stimulated bone marrow mesenchymal stem cells sheets promotes osteogenesis of type 2 diabetic rat. Zhonghua Kou Qiang Yi Xue Za Zhi 53:333–338. https://doi.org/10.3760/cma.j.issn.1002-0098.2018.05.009
Virostko J, Radhika A, Poffenberger G et al (2013) Bioluminescence imaging reveals dynamics of beta cell loss in the non-obese diabetic (NOD) mouse model. PLoS ONE 8:e57784. https://doi.org/10.1371/journal.pone.0057784
Virostko J, Radhika A, Poffenberger G et al (2010) Bioluminescence imaging in mouse models quantifies beta cell mass in the pancreas and after islet transplantation. Mol Imaging Biol 12:42–53. https://doi.org/10.1007/s11307-009-0240-1
Nishimura W, Sakaue-Sawano A, Takahashi S et al (2018) Optical clearing of the pancreas for visualization of mature β-cells and vessels in mice. Islets 10:e1451282. https://doi.org/10.1080/19382014.2018.1451282
Williams IM, Valenzuela FA, Kahl SD et al (2018) Insulin exits skeletal muscle capillaries by fluid-phase transport. J Clin Investig 128:699–714. https://doi.org/10.1172/JCI94053
Reissaus CA, Piñeros AR, Twigg AN et al (2019) A versatile, portable intravital microscopy platform for studying beta-cell biology in vivo. Sci Rep 9:8449. https://doi.org/10.1038/s41598-019-44777-0
Taghian T, Metelev VG, Zhang S, Bogdanov AA (2020) Imaging NF-κB activity in a murine model of early stage diabetes. FASEB j 34:1198–1210. https://doi.org/10.1096/fj.201801147R
Taylor S, Mehina E, White E et al (2018) Suppressing interferon-γ stimulates microglial responses and repair of microbleeds in the diabetic brain. J Neurosci 38:8707–8722. https://doi.org/10.1523/JNEUROSCI.0734-18.2018
Dabbah MA, Graham J, Petropoulos IN et al (2011) Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Med Image Anal 15:738–747. https://doi.org/10.1016/j.media.2011.05.016
Bond J, Green C, Donaldson P, Kistler J (1996) Liquefaction of cortical tissue in diabetic and galactosemic rat lenses defined by confocal laser scanning microscopy. Invest Ophthalmol Vis Sci 37:1557–1565
Papanas N, Ziegler D (2015) Corneal confocal microscopy: recent progress in the evaluation of diabetic neuropathy. J Diabetes Invest 6:381–389. https://doi.org/10.1111/jdi.12335
Ahlgren U, Gotthardt M (2010) Approaches for imaging islets: recent advances and future prospects. In: Islam MdS (ed) The islets of langerhans. Springer Netherlands, Dordrecht, pp 39–57
Yadav SPS, Sandoval RM, Zhao J et al (2021) Mechanism of how carbamylation reduces albumin binding to FcRn contributing to increased vascular clearance. Am J Physiol-Renal Physiol 320:F114–F129. https://doi.org/10.1152/ajprenal.00428.2020
Yang S-N, Berggren P-O (2019) The eye as a novel imaging site in diabetes research. Pharmacol Ther 197:103–121. https://doi.org/10.1016/j.pharmthera.2019.01.005
De Dominicis C, Perrotta P, Dall’Angelo S et al (2020) [18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging. ACS Med Chem Lett 11:933–939. https://doi.org/10.1021/acsmedchemlett.9b00677
Festing MFW (2004) Refinement and reduction through the control of variation. Altern Lab Anim 32(Suppl 1A):259–263. https://doi.org/10.1177/026119290403201s43
Parker RMA, Browne WJ (2014) The place of experimental design and statistics in the 3Rs. ILAR J 55:477–485. https://doi.org/10.1093/ilar/ilu044
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592_2021_1826_MOESM1_ESM.gif
Supplementary Animated Figure S1. Ultrasound imaging of the pancreas of a RIP-Tag transgenic mouse expressing the oncogenic SV40 large T antigen (Tag) under the transcriptional control of the insulin promoter, obtained with a 40 MHz probe. Multiple round hypoechoic pancreatic lesions (annotations) can be seen, consistent with pancreatic cancer (β-islet tumors) (GIF 47 kb)
Supplementary Video S2. Ultrasound imaging of the right kidney in a diabetic murine model. The kidney cortex is markedly hyperechoic if compared to hepatic parenchyma (mov 4721 kb)
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Coppola, A., Zorzetto, G., Piacentino, F. et al. Imaging in experimental models of diabetes. Acta Diabetol 59, 147–161 (2022). https://doi.org/10.1007/s00592-021-01826-3
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DOI: https://doi.org/10.1007/s00592-021-01826-3