小鼠腸胃道組織之三維影像研究｜國立清華大學博碩士論文庫

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研究生：	符雅媛 Fu, Ya-Yuan
論文名稱：	小鼠腸胃道組織之三維影像研究 Three-Dimensional Histology of Mouse Gastrointestinal Tissues
指導教授：	湯學成 Tang, Shiue-Cheng
口試委員:	朱一民湯學成鍾元強陳芸張雍
學位類別：	博士 Doctor
系所名稱：	工學院 - 化學工程學系 Department of Chemical Engineering
論文出版年：	2012
畢業學年度：	100
語文別：	英文
論文頁數：	134
中文關鍵詞：	三維影像、組織透明技術、共軛焦顯微鏡、胃腸組織、胰小島、胰臟、組織微結構、血管網絡、神經網絡
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Seeing the gastrointestinal (GI) microstructure and tissue networks is essential to understand the gut physiology and study its disease mechanism. The intrinsic opacity of the GI tissues, however, limits the optical accessibility for in-depth light microscopy. To increase the light transmittance, investigators routinely use the microtome-based planar microscopy to visualize the tissue structure. Because microtome sectioning creates disconnections between tissue slices as well as distortions and artifacts, a microtome-free, nondestructive imaging approach is preferable to provide an integral view of the tissue structure. In this research, we prepared transparent mouse GI specimens by optical clearing to reveal the tissue microstructure, vasculature, and innervation via 3-dimensional (3-D) microscopy.
Three steps of tissue staining were used to label the structure of interest. First, perfusion of the fluorescent wheat germ agglutinin (or membrane dye, i.e. vessel painting) was used to label the blood vessels in mouse gut. Second, immunostaining of neuronal markers such as PGP9.5 (pan-neuronal marker) and tyrosine hydroxylase (sympathetic marker), was used to reveal the enteric nervous system. Third, nuclear and/or membrane staining was used to reveal the tissue microstructure. Finally, the fluorescently labeled tissues were immersed in the optical-clearing solution FocusClear (Fu and Tang, Gastroenterology, 139:p1100-1105, 2010) to prepare transparent specimens for penetrative confocal imaging.
Treatment of tissues with the optical-clearing solution improved photon penetration, which led to acquisition of images with high definition. Collectively, the acquired image stacks were processed by projection algorithms for 3-D analysis of the spatial relationship between the microstructure, blood vessels, and nerves.
In addition to the normal gut tissues, we provide examples of examining the spatiotemporal changes in colonic crypt morphology after the dextran sulfate sodium-induced ulcerative colitis as well as detection of transgenic fluorescent proteins expressed in the colon and ileum. We also revealed the intestinal neurovascular complex in the submucosal and myenteric plexuses. Examples are given in fours chapters (Chapters C-F) to illustrate the development of our new 3-D histology method.
The optical approach developed in this research for penetrative imaging of mouse GI tissues does not require tissue sectioning and provides a useful tool for 3-D presentation and analysis of normal, diseased and transgenic gut tissues in an integrated fashion.

腸胃道組織具有特殊的立體微結構和血管、神經網絡來消化食物及吸收養分以維持生理機能。在使用光學顯微鏡觀察腸胃道組織時，組織的不透明性往往會阻礙組織內部清晰影像之取得。一般解決此問題的方法是使用切片機將腸胃道組織切成薄片樣本，使光能夠穿透薄片組織再使用光學顯微鏡觀察樣本。然而使用切片機進行組織切片，會造成組織樣本的扭曲變形與切割破壞，導致無法取得精確的樣本影像並且無法完整呈現組織之立體結構。因此我們發展出穿透式共軛焦顯微鏡技術來截取老鼠腸胃道組織之微結構、血管及神經網絡之三維影像。
我們使用三種染色技術來標定組織：(1)螢光染色-標定細胞核和細胞膜以取得腸胃道組織的微結構 (2)血管灌流技術-標定血管網絡 (3)免疫螢光染色-標定神經網絡。接著將螢光染色後的組織浸在組織澄清液中，使組織變透明且增加光子的穿透度以取得高解析度的精確影像。最後再使用軟體將連續二維影像重組成三維立體影像來觀察腸胃道組織中微結構、血管和神經網絡之空間關係。在此論文中，我們觀察了腸道發炎小鼠之大腸結構變化以及轉殖基因螢光鼠其腸道組織的螢光表現，並且同時取得血管和神經網絡在腸道組織中之影像。
我們將『組織透明技術』與『共軛焦顯微鏡技術』結合，針對老鼠的腸胃道組織進行非破壞性的連續光學切片影像截取並且重組成立體三維影像，提供了完整且準確的組織影像來幫助研究腸胃道組織之生理機能和致病機制。

Chapter A. Abstract    8
Abstract    8
中文摘要    10
Chapter B. Introduction    11
B.1. Gastrointestinal tissues    11
      B.1.1. Histology of the GI tract    11
      B.1.2. Histology of pancreas    14
B.2. Biological imaging of the GI tissues    15
      B.2.1. Microtome sectioning    15
      B.2.2. Optical clearing      16
      B.2.3. Confocal microscopy            18
B.3. Objective of research            20
Chapter C. Microtome-free 3-dimensional confocal imaging method
                  for visualization of mouse intestine with subcellular-level
                  resolution   22
C.1. Abstract    22
C.2. Introduction    23
C.3. Materials and methods    25
      C.3.1. Animals    25
      C.3.2. Preparation of specimens    26
      C.3.3. Imaging settings    27
      C.3.4. Post-recording image processing and analysis    28
C.4. Results    29
      C.4.1. Optical clearing of the colon and ileum specimens    29
      C.4.2. Optical clearing enables deep-tissue confocal microscopy    30
      C.4.3. Penetrative 3-D imaging of the mouse colon    31
      C.4.4. 3-D microscopy of the mouse ileum       32
      C.4.5. 3-D confocal imaging of dextran sulfate sodium (DSS)-induced
                colitis    33
      C.4.6. Application of transmitted light to characterize crypt structure in
                the DSS-induced colitis    34
      C.4.7. 3-D confocal imaging of transgenic mice carrying fluorescent
                proteins in the intestine    36
C.5. Discussion    37
Chapter D. Optical clearing facilitates integrated 3-D visualization of mouse
                  ileal microstructure and vascular network with high definition  51
D.1. Abstract    51
D.2. Introduction    52
D.3. Materials and methods    53
      D.3.1. Animals    53
      D.3.2. Preparation of ileal specimens    54
      D.3.3. Image acquisition    54
      D.3.4. 3-D image processing and projection    55
D.4. Results    56
      D.4.1. Optical clearing facilitates photon penetration into the mouse
                 small intestine    56
      D.4.2. Vessel painting is compatible with FocusClear-mediated optical
                 clearing    57
      D.4.3. High-resolution, 3-D imaging of the villus microvasculature    58
      D.4.4. 3-D imaging of the microvasculature at the submucosal and
                 muscularis domains      58
      D.4.5. Panoramic visualization of microvasculature: from the luminal to
                 the serosal surface      60
D.5. Discussion         61
Chapter E. The relationship between serotonin cells, blood vessels and nerves
                 as revealed by 3-D imaging of mouse intestine with optical
                 clearing       75
E.1. Abstract    75
E.2. Introduction    76
E.3. Materials and methods    78
      E.3.1. Animals and tissue preparation    78
      E.3.2. Confocal microscopy    80
      E.3.3. 3-D image processing and projection    81
E.4. Results    81
      E.4.1. Optical clearing facilitates 3-D imaging of mouse enteric plexus
                 with μm-level resolution    81
      E.4.2. Features of the TH network: sparse in epithelium, perivascular at
                 the submucosa, and intra-ganglionic at myenteric plexus    83
      E.4.3. Distinct patterns of TH+ perivascular and TH- pericryptic
                innervation at the submucosal-mucosal boundary    84
      E.4.4. The mucosal microvasculature and intrinsic innervation    85
      E.4.5. The relationship between epithelial serotonin cells and the mucosal
                 neurovascular elements    86
      E.4.6. The relationship between blood vessels and the myenteric ganglia
                86
E.5. Discussion    87
Chapter F. Three-dimensional optical method for integrated visualization
                    of mouse islet microstructure and vascular network with
                    subcellular-level resolution    105
F.1. Abstract    105
F.2. Introduction    106
F.3. Materials and methods    108
      F.3.1. Animals    108
      F.3.2. Sample preparation    108
      F.3.3. Imaging settings    109
      F.3.4. Post-recording image processing and projection    110
F.4. Results    111
      F.4.1. Optical clearing of the mouse pancreas    111
      F.4.2. Penetrative confocal imaging of islets of Langerhans in the
                mouse pancreas    112
      F.4.3. High-resolution, 3-D imaging of islet vasculature in the mouse
                pancreas    113
F.5. Discussion    115
F.6. Conclusions    118
Chapter G. Conclusion and Future Work    126
References    128
Publications    134

                                

1. Tortora GJ, Derrickson B. Principles of anatomy and physiology. Hoboken, N.J.: Wiley, 2009.
2. Furness JB. The enteric nervous system. Malden, Mass.: Blackwell Pub., 2006.
3. Brunicardi FC, Stagner J, Bonner-Weir S, et al. Microcirculation of the islets of Langerhans. Long Beach Veterans Administration Regional Medical Education Center Symposium. Diabetes 1996;45:385-92.
4. Ballian N, Brunicardi FC. Islet vasculature as a regulator of endocrine pancreas function. World J Surg 2007;31:705-714.
5. Kiesslich R, Burg J, Vieth M, et al. Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 2004;127:706-13.
6. Kiesslich R, Canto MI. Confocal laser endomicroscopy. Gastrointest Endosc Clin N Am 2009;19:261-72.
7. Kiesslich R, Goetz M, Angus EM, et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 2007;133:1769-78.
8. Kiesslich R, Goetz M, Burg J, et al. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology 2005;128:2119-23.
9. Kiesslich R, Goetz M, Neurath MF. Confocal laser endomicroscopy for gastrointestinal diseases. Gastrointest Endosc Clin N Am 2008;18:451-66, viii.
10. Kiesslich R, Goetz M, Vieth M, et al. Technology insight: confocal laser endoscopy for in vivo diagnosis of colorectal cancer. Nat Clin Pract Oncol 2007;4:480-90.
11. Brooksby B, Dehghani H, Vishwanath K, et al. Internal refractive index changes affect light transport in tissue. P Soc Photo-Opt Ins 2003;4955:296-304.
12. Wenner M. The most transparent research. Nat Med 2009;15:1106-1109.
13. Tuchin VV. Optical clearing of tissues and blood using the immersion method. J Phys D Appl Phys 2005;38:2497-2518.
14. Moulton K, Lovell F, Williams E, et al. Use of glycerol as an optical clearing agent for enhancing photonic transference and detection of Salmonella typhimurium through porcine skin. J Biomed Opt 2006;11.
15. Plotnikov S, Juneja V, Isaacson AB, et al. Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle. Biophys J 2006;90:328-39.
16. Wang RKK, Xu XQ, He YH, et al. Investigation of optical clearing of gastric tissue immersed with hyperosmotic agents. Ieee J Sel Top Quant 2003;9:234-242.
17. Wen X, Mao Z, Han Z, et al. In vivo skin optical clearing by glycerol solutions: mechanism. J Biophotonics 2010;3:44-52.
18. Bui AK, McClure RA, Chang J, et al. Revisiting optical clearing with dimethyl sulfoxide (DMSO). Lasers Surg Med 2009;41:142-8.
19. Zimmerley M, McClure RA, Choi B, et al. Following dimethyl sulfoxide skin optical clearing dynamics with quantitative nonlinear multimodal microscopy. Appl Opt 2009;48:D79-87.
20. Hama H, Kurokawa H, Kawano H, et al. Scale: a chemical approach for fluorescence imaging and reconstruction of. Nat Neurosci 2011;14:1481-8.
21. Lin HH, Lai JS, Chin AL, et al. A map of olfactory representation in the Drosophila mushroom body. Cell 2007;128:1205-17.
22. Liu YC, Chiang AS. High-resolution confocal imaging and three-dimensional rendering. Methods 2003;30:86-93.
23. Wu CL, Xia S, Fu TF, et al. Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body. Nat Neurosci 2007;10:1578-86.
24. Conchello JA, Lichtman JW. Optical sectioning microscopy. Nat Methods 2005;2:920-31.
25. Helmchen F, Denk W. Deep tissue two-photon microscopy. Nat Methods 2005;2:932-40.
26. Regueiro CR. AGA Future Trends Committee report: Colorectal cancer: a qualitative review of emerging screening and diagnostic technologies. Gastroenterology 2005;129:1083-103.
27. Gordon JI, Hermiston ML. Differentiation and self-renewal in the mouse gastrointestinal epithelium. Curr Opin Cell Biol 1994;6:795-803.
28. Wu ML, Varga VS, Kamaras V, et al. Three-dimensional virtual microscopy of colorectal biopsies. Arch Pathol Lab Med 2005;129:507-10.
29. Nathanson MH. Confocal colonoscopy: more than skin deep. Gastroenterology 2004;127:987-9.
30. Xia S, Miyashita T, Fu TF, et al. NMDA receptors mediate olfactory learning and memory in Drosophila. Curr Biol 2005;15:603-15.
31. Wang Y, Mamiya A, Chiang AS, et al. Imaging of an early memory trace in the Drosophila mushroom body. J Neurosci 2008;28:4368-76.
32. Okayasu I, Hatakeyama S, Yamada M, et al. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990;98:694-702.
33. Wirtz S, Neufert C, Weigmann B, et al. Chemically induced mouse models of intestinal inflammation. Nat Protoc 2007;2:541-6.
34. Mignone JL, Kukekov V, Chiang AS, et al. Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol 2004;469:311-24.
35. Choi B, Tsu L, Chen E, et al. Determination of chemical agent optical clearing potential using in vitro human skin. Lasers Surg Med 2005;36:72-75.
36. Khan MH, Choi B, Chess S, et al. Optical clearing of in vivo human skin: Implications for light-based diagnostic imaging and therapeutics. Lasers Surg Med 2004;34:83-85.
37. Tessner TG, Cohn SM, Schloemann S, et al. Prostaglandins prevent decreased epithelial cell proliferation associated with dextran sodium sulfate injury in mice. Gastroenterology 1998;115:874-882.
38. Amoh Y, Li L, Yang M, et al. Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. P Natl Acad Sci USA 2004;101:13291-13295.
39. Amoh Y, Yang M, Li L, et al. Nestin-linked green fluorescent protein transgenic nude mouse for imaging human tumor angiogenesis. Cancer Res 2005;65:5352-7.
40. Hayashi K, Yamauchi K, Yamamoto N, et al. Dual-color imaging of angiogenesis and its inhibition in bone and soft tissue sarcoma. J Surg Res 2007;140:165-170.
41. Ravnic DJ, Jiang X, Wolloscheck T, et al. Vessel painting of the microcirculation using fluorescent lipophilic tracers. Microvasc Res 2005;70:90-6.
42. Goldstein NS, Soman A, Sacksner J. Disparate surgical margin lengths of colorectal resection specimens between in vivo and in vitro measurements. The effects of surgical resection and formalin fixation on organ shrinkage. Am J Clin Pathol 1999;111:349-51.
43. Paddock SW. Confocal microscopy methods and protocols. Totowa, N.J.: Humana Press, 1999.
44. Lametschwandtner A, Lametschwandtner U, Weiger T. Scanning electron microscopy of vascular corrosion casts--technique and applications: updated review. Scanning Microsc 1990;4:889-940; discussion 941.
45. Djonov V, Burri PH. Corrosion cast analysis of blood vessels. Methods in endothelial cell biology. Berlin ; New York: Springer, 2004:pp. 357-369.
46. Ravnic DJ, Konerding MA, Tsuda A, et al. Structural adaptations in the murine colon microcirculation associated with hapten-induced inflammation. Gut 2007;56:518-523.
47. Filipovic N, Tsuda A, Lee GS, et al. Computational flow dynamics in a geometric model of intussusceptive angiogenesis. Microvasc Res 2009;78:286-293.
48. Folarin AA, Konerding MA, Timonen J, et al. Three-dimensional analysis of tumour vascular corrosion casts using stereoimaging and micro-computed tomography. Microvasc Res 2010;80:89-98.
49. Xu X, Wang RK. Synergistic effect of hyperosmotic agents of dimethyl sulfoxide and glycerol on optical clearing of gastric tissue studied with near infrared spectroscopy. Phys Med Biol 2004;49:457-68.
50. Genina EA, Bashkatov AN, Korobko AA, et al. Optical clearing of human skin: comparative study of permeability and dehydration of intact and photothermally perforated skin. J Biomed Opt 2008;13:021102.
51. Tseng SJ, Lee YH, Chen ZH, et al. Integration of optical clearing and optical sectioning microscopy for three-dimensional imaging of natural biomaterial scaffolds in thin sections. J Biomed Opt 2009;14:044004.
52. Tuchin VV, Wang RK, Yeh AT. Optical clearing of tissues and cells. J Biomed Opt 2008;13:021101.
53. Hirshburg J, Choi B, Nelson JS, et al. Correlation between collagen solubility and skin optical clearing using sugars. Lasers Surg Med 2007;39:140-144.
54. Dickie R, Bachoo RM, Rupnick MA, et al. Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy. Microvasc Res 2006;72:20-6.
55. Fu YY, Lin CW, Enikolopov G, et al. Microtome-free 3-dimensional confocal imaging method for visualization of mouse intestine with subcellular-level resolution. Gastroenterology 2009;137:453-65.
56. Li Y, Song Y, Zhao L, et al. Direct labeling and visualization of blood vessels with lipophilic carbocyanine dye DiI. Nat Protoc 2008;3:1703-8.
57. Ma B, Zimmermann T, Rohde M, et al. Use of Autostitch for automatic stitching of microscope images. Micron 2007;38:492-499.
58. Brown M, Lowe DG. Automatic panoramic image stitching using invariant features. Int J Comput Vision 2007;74:59-73.
59. Vanner S, Surprenant A. Neural reflexes controlling intestinal microcirculation. Am J Physiol 1996;271:G223-30.
60. Lomax AE, Sharkey KA, Furness JB. The participation of the sympathetic innervation of the gastrointestinal tract in disease states. Neurogastroenterol Motil 2010;22:7-18.
61. Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology 2009;136:1979-88.
62. Denis B, Peters C, Chapelain C, et al. Diagnostic accuracy of community pathologists in the interpretation of colorectal polyps. Eur J Gastroenterol Hepatol 2009;21:1153-60.
63. Calhoun BC, Gomes F, Robert ME, et al. Sampling error in the standard evaluation of endoscopic colonic biopsies. Am J Surg Pathol 2003;27:254-7.
64. Tang SC, Fu YY, Lo WF, et al. Vascular labeling of luminescent gold nanorods enables 3-D microscopy of mouse intestinal capillaries. ACS Nano 2010;4:6278-84.
65. Fu YY, Tang SC. Optical clearing facilitates integrated 3D visualization of mouse ileal microstructure and vascular network with high definition. Microvasc Res 2010;80:512-21.
66. Fu YY, Tang SC. At the Movies: 3-Dimensional Technology and Gastrointestinal Histology. Gastroenterology 2010;139:1100-1105.
67. Hanani M, Ermilov LG, Schmalz PF, et al. The three-dimensional structure of myenteric neurons in the guinea-pig ileum. J Auton Nerv Syst 1998;71:1-9.
68. Birch D, Knight GE, Boulos PB, et al. Analysis of innervation of human mesenteric vessels in non-inflamed and inflamed bowel--a confocal and functional study. Neurogastroenterol Motil 2008;20:660-70.
69. Nemeth L, Yoneda A, Kader M, et al. Three-dimensional morphology of gut innervation in total intestinal aganglionosis using whole-mount preparation. J Pediatr Surg 2001;36:291-294.
70. Selim MM, Wendelschafer-Crabb G, Redmon JB, et al. Gastric mucosal nerve density: a biomarker for diabetic autonomic neuropathy? Neurology 2010;75:973-81.
71. Pasricha PJ, Pehlivanov ND, Gomez G, et al. Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis. BMC Gastroenterol 2008;8:21.
72. Korenaga K, Micci MA, Taglialatela G, et al. Suppression of nNOS expression in rat enteric neurones by the receptor for advanced glycation end-products. Neurogastroenterol Motil 2006;18:392-400.
73. Karsenty G, Gershon MD. The importance of the gastrointestinal tract in the control of bone mass accrual. Gastroenterology 2011;141:439-42.
74. Mayer EA, Tillisch K, Bradesi S. Review article: modulation of the brain-gut axis as a therapeutic approach in gastrointestinal disease. Aliment Pharmacol Ther 2006;24:919-933.
75. Mayer EA. Gut feelings: the emerging biology of gut-brain communication. Nat Rev Neurosci 2011;12:453-66.
76. Carl Zeiss Microimaging GmbH. Visualizing the architecture of cells and tissues: Brochures for Laser Scanning Microscopy. Available at: http://www.zeiss.de/micro, 2009.
77. Nishida S, Akai F, Hiruma S, et al. Experimental study of WGA binding on the endothelial cell surface in cerebral ischemia. Histol Histopathol 1986;1:69-74.
78. Wood JD. Application of classification schemes to the enteric nervous system. J Auton Nerv Syst 1994;48:17-29.
79. Spiller RC. Role of nerves in enteric infection. Gut 2002;51:759-62.
80. Sharkey KA, Kroese AB. Consequences of intestinal inflammation on the enteric nervous system: neuronal activation induced by inflammatory mediators. Anat Rec 2001;262:79-90.
81. Knowles CH, De Giorgio R, Kapur RP, et al. Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group. Acta Neuropathol 2009;118:271-301.
82. Fu YY, Lu CH, Lin CW, et al. Three-dimensional optical method for integrated visualization of mouse islet microstructure and vascular network with subcellular-level resolution. J Biomed Opt 2010;15:046018.
83. Jacobs JM. Penetration of Systemically Injected Horseradish-Peroxidase into Ganglia and Nerves of Autonomic Nervous-System. J Neurocytol 1977;6:607-618.
84. Allen DT, Kiernan JA. A circulating exogenous protein can enter enteric nervous tissue in the rat. Neuroreport 1990;1:33-6.
85. Gershon MD, Bursztajn S. Properties of the enteric nervous system: limitation of access of intravascular macromolecules to the myenteric plexus and muscularis externa. J Comp Neurol 1978;180:467-88.
86. Cabrera O, Berman DM, Kenyon NS, et al. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A 2006;103:2334-9.
87. Gromada J, Franklin I, Wollheim CB. Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 2007;28:84-116.
88. Tuchin VV. A clear vision for laser diagnostics (review). Ieee J Sel Top Quant 2007;13:1621-1628.
89. Wang RKK, Xu XQ, Tuchin VV, et al. Concurrent enhancement of imaging depth and contrast for optical coherence tomography by hyperosmotic agents. J Opt Soc Am B 2001;18:948-953.
90. Ghosn MG, Carbajal EF, Befrui NA, et al. Differential permeability rate and percent clearing of glucose in different regions in rabbit sclera. J Biomed Opt 2008;13:021110.
91. Yeh AT, Hirshburg J. Molecular interactions of exogenous chemical agents with collagen--implications for tissue optical clearing. J Biomed Opt 2006;11:014003.
92. Jiang J, Boese M, Turner P, et al. Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging. J Biomed Opt 2008;13:021105.
93. Hara M, Dizon RF, Glick BS, et al. Imaging pancreatic beta-cells in the intact pancreas. Am J Physiol Endocrinol Metab 2006;290:E1041-7.
94. Alanentalo T, Loren CE, Larefalk A, et al. High-resolution three-dimensional imaging of islet-infiltrate interactions based on optical projection tomography assessments of the intact adult mouse pancreas. J Biomed Opt 2008;13:054070.
95. Delacour A, Nepote V, Trumpp A, et al. Nestin expression in pancreatic exocrine cell lineages. Mech Dev 2004;121:3-14.
96. Holmberg D, Ahlgren U. Imaging the pancreas: from ex vivo to non-invasive technology. Diabetologia 2008;51:2148-54.
97. Virostko J, Powers AC. Molecular imaging of the pancreas in small animal models. Gastroenterology 2009;136:407-9.
98. Nyman LR, Wells KS, Head WS, et al. Real-time, multidimensional in vivo imaging used to investigate blood flow in mouse pancreatic islets. J Clin Invest 2008;118:3790-3797.
99. Speier S, Nyqvist D, Cabrera O, et al. Noninvasive in vivo imaging of pancreatic islet cell biology. Nat Med 2008;14:574-8.
100. Denis MC, Mahmood U, Benoist C, et al. Imaging inflammation of the pancreatic islets in type 1 diabetes. Proc Natl Acad Sci U S A 2004;101:12634-9.
101. Turvey SE, Swart E, Denis MC, et al. Noninvasive imaging of pancreatic inflammation and its reversal in type 1 diabetes. J Clin Invest 2005;115:2454-61.
102. Medarova Z, Castillo G, Dai G, et al. Noninvasive magnetic resonance imaging of microvascular changes in type 1 diabetes. Diabetes 2007;56:2677-82.
103. Souza F, Freeby M, Hultman K, et al. Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas. Curr Med Chem 2006;13:2761-73.
104. Martinic MM, von Herrath MG. Real-time imaging of the pancreas during development of diabetes. Immunol Rev 2008;221:200-13.
105. Villiger M, Goulley J, Friedrich M, et al. In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy. Diabetologia 2009;52:1599-607.
106. Malaisse WJ, Louchami K, Sener A. Noninvasive imaging of pancreatic beta cells. Nat Rev Endocrinol 2009;5:394-400.

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