title: Anatomical and microstructural imaging of angiogenesis.
abstract: OBJECTIVE
  This article reviews and discusses different options for visualizing the microarchitecture of vessels ex vivo and in vivo with respect to reliability, practicability and availability.
  
  
  CONCLUSIONS
  The investigation of angiogenesis by standard histological methods, like microvessel density counts, is limited since the three-dimensional (3-D) architecture and the functionality of vessels cannot be considered properly. Coregistration of immunostained images of vessels may be performed but is time consuming and often not sufficiently accurate. Confocal fluorescence microscopy is an alternative, but only enables 3-D stacks of less than 500 nm in thickness. Multiphoton microscopy and other advanced technologies, such as optical coherence tomography and optical frequency domain imaging, provide a deeper view into tissues and allow for in vivo imaging of microvessels, which is a precondition for longitudinal studies. Besides these microscopic techniques, the vascularization in larger tissue samples can be investigated using corrosion casts in combination with scanning electron microscopy, or microcomputed tomography (microCT). Furthermore, recent improvements in microCT technology open up new perspectives for in vivo scans with high resolution and tolerable X-ray doses. Also 3-D contrast-enhanced high-frequency ultrasound has been shown to be sensitive for angiogenic vessels and even distinguishing between mature and immature vessels appears feasible. Microvessel architecture can also be visualized by MRI. Here, T1-weighted angiography techniques after injection of blood pool contrast agents appear preferable. Optoacoustic tomographic imaging has more recently shown promise for high-resolution in vivo mapping of the microvasculature in rodents using intrinsic haemoglobin-based contrast and exogenous contrast agents.
authors.affiliation: University of Aachen, Germany. fkiessling@ukaachen.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Daniel
authors.initials: D
authors.lastname: Razansky
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
mesh_terms: D000818:Animals; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000473:pathology; D018919:Neovascularization, Physiologic
references.citation: Curr Med Chem. 2009;16(5):627-42
references.pmid: 19199927
references.citation: Exp Cell Res. 2009 Feb 1;315(3):396-410
references.pmid: 19041305
references.citation: Magn Reson Med. 2001 Sep;46(3):579-85
references.pmid: 11550252
references.citation: Nat Nanotechnol. 2008 Sep;3(9):557-62
references.pmid: 18772918
references.citation: Prostate. 1998 Dec 1;37(4):270-7
references.pmid: 9831224
references.citation: Scanning Microsc. 1990 Dec;4(4):889-940; discussion 941
references.pmid: 2094009
references.citation: Radiology. 2000 Nov;217(2):593-6
references.pmid: 11058666
references.citation: Oral Oncol. 2006 Jul;42(6):581-5
references.pmid: 16469530
references.citation: Br J Ophthalmol. 1996 Mar;80(3):246-51
references.pmid: 8703863
references.citation: Acad Radiol. 1999 Jan;6(1):61-5
references.pmid: 9891154
references.citation: JACC Cardiovasc Imaging. 2008 Nov;1(6):752-61
references.pmid: 19356512
references.citation: Nat Med. 2001 Jul;7(7):864-8
references.pmid: 11433354
references.citation: Nat Biotechnol. 2006 Jul;24(7):848-51
references.pmid: 16823374
references.citation: Med Phys. 2008 Nov;35(11):5030-42
references.pmid: 19070237
references.citation: Am J Pathol. 2000 Apr;156(4):1363-80
references.pmid: 10751361
references.citation: Neoplasia. 2009 Jan;11(1):48-56
references.pmid: 19107231
references.citation: Microvasc Res. 2006 Jul-Sep;72(1-2):20-6
references.pmid: 16806289
references.citation: Angiogenesis. 2009;12(2):113-23
references.pmid: 19194777
references.citation: Am J Pathol. 1995 Jul;147(1):9-19
references.pmid: 7541613
references.citation: Nat Med. 2009 Oct;15(10):1219-23
references.pmid: 19749772
references.citation: Am J Ther. 2001 Sep-Oct;8(5):359-65
references.pmid: 11550077
references.citation: Circulation. 2002 Apr 9;105(14):1708-12
references.pmid: 11940551
references.citation: Magn Reson Med. 2001 Mar;45(3):397-408
references.pmid: 11241696
references.citation: Mol Imaging. 2002 Jan-Mar;1(1):9-15
references.pmid: 12920856
references.citation: Scanning. 2007 May-Jun;29(3):128-32
references.pmid: 17477397
references.citation: Acad Radiol. 2003 May;10(5):475-83
references.pmid: 12755534
references.citation: Clin Exp Metastasis. 2009;26(4):357-70
references.pmid: 18766302
references.citation: Opt Lett. 2007 Oct 1;32(19):2891-3
references.pmid: 17909608
references.citation: Arch Ophthalmol. 1998 Jan;116(1):31-9
references.pmid: 9445206
references.citation: J Magn Reson Imaging. 2003 Jul;18(1):59-65
references.pmid: 12815640
references.citation: J Vasc Res. 2004 Sep-Oct;41(5):400-11
references.pmid: 15467299
references.citation: J Hepatol. 2008 Jan;48(1):91-7
references.pmid: 18022725
references.citation: Science. 2005 Jan 7;307(5706):58-62
references.pmid: 15637262
references.citation: Micron. 2006;37(2):134-8
references.pmid: 16242938
references.citation: J Gastroenterol Hepatol. 2008 Jan;23(1):56-61
references.pmid: 18028347
references.citation: Opt Express. 2007 May 28;15(11):6583-8
references.pmid: 19546967
references.citation: Acad Radiol. 1995 Oct;2(10):851-8
references.pmid: 9419650
references.citation: Microvasc Res. 2004 May;67(3):215-7
references.pmid: 15121445
references.citation: Cancer Lett. 2007 Sep 8;254(2):157-64
references.pmid: 17306454
references.citation: Appl Opt. 2005 Feb 10;44(5):770-5
references.pmid: 15751858
references.citation: IEEE Trans Med Imaging. 2005 Apr;24(4):436-40
references.pmid: 15822801
references.citation: Clin Exp Metastasis. 2009;26(4):329-44
references.pmid: 19190882
references.citation: Radiology. 2000 Sep;216(3):865-71
references.pmid: 10966724
references.citation: Thyroid. 1999 Sep;9(9):927-32
references.pmid: 10524572
references.citation: Neoplasia. 2005 Aug;7(8):730-40
references.pmid: 16207475
references.citation: Neuroimage. 2009 Apr 15;45(3):824-31
references.pmid: 19154792
references.citation: Science. 1991 Nov 22;254(5035):1178-81
references.pmid: 1957169
references.citation: Acad Radiol. 2002 Jul;9(7):784-92
references.pmid: 12139092
references.citation: Microsc Res Tech. 2006 Feb;69(2):138-47
references.pmid: 16456839
references.citation: Nature. 2005 Dec 15;438(7070):932-6
references.pmid: 16355210
references.citation: Bone. 2008 Jul;43(1):195-202
references.pmid: 18424249
references.citation: Scanning. 1997 Aug;19(5):361-7
references.pmid: 9262021
references.citation: Ital J Anat Embryol. 2001;106(2 Suppl 1):213-20
references.pmid: 11729958
references.citation: Ann N Y Acad Sci. 2008;1131:1-12
references.pmid: 18519955
references.citation: Eur J Surg Oncol. 2005 Dec;31(10):1198-205
references.pmid: 15993027
references.citation: Med Phys. 2004 Feb;31(2):305-13
references.pmid: 15000616
references.citation: J Magn Reson Imaging. 2001 Dec;14(6):705-13
references.pmid: 11747027
references.citation: Phys Med Biol. 2008 Jan 21;53(2):505-13
references.pmid: 18185002
references.citation: Prostate. 2005 Feb 1;62(2):123-32
references.pmid: 15389798
references.citation: Arch Dermatol. 2007 Nov;143(11):1468-9
references.pmid: 18025387
references.citation: Cancer Res. 2006 Dec 15;66(24):11517-9
references.pmid: 17178842
references.citation: Semin Oncol. 2001 Dec;28(6):536-42
references.pmid: 11740806
references.citation: Lab Invest. 2006 Apr;86(4):409-16
references.pmid: 16518405
references.citation: Microvasc Res. 1976 Mar;11(2):175-80
references.pmid: 1272078
references.citation: Nat Biotechnol. 2003 Jul;21(7):803-6
references.pmid: 12808463
references.citation: Opt Express. 2005 Jan 10;13(1):89-95
references.pmid: 19488331
references.citation: Eur Radiol. 2003 Jul;13(7):1559-65
references.pmid: 12835967
references.citation: Neoplasia. 2008 May;10(5):511-20
references.pmid: 18472968
references.citation: Opt Express. 2007 Sep 17;15(19):12277-85
references.pmid: 19547596
references.citation: Phys Med Biol. 2009 Feb 21;54(4):1035-46
references.pmid: 19168938
references.citation: J Magn Reson Imaging. 2009 May;29(5):1125-33
references.pmid: 19388117
references.citation: Exp Mol Pathol. 2007 Apr;82(2):110-20
references.pmid: 17320863
references.citation: J Biomed Opt. 2009 Jul-Aug;14(4):040505
references.pmid: 19725710
references.citation: Conf Proc IEEE Eng Med Biol Soc. 2006;2006:2345-8
references.pmid: 17946107
references.citation: Nat Med. 2003 Jun;9(6):713-25
references.pmid: 12778170
references.citation: Opt Express. 2009 Apr 27;17(9):7688-93
references.pmid: 19399148
references.citation: Angiogenesis. 2005;8(4):297-305
references.pmid: 16328157
references.citation: Cancer Res. 2008 Sep 1;68(17):7042-9
references.pmid: 18757418
references.citation: Nat Med. 2004 Oct;10(10):1133-8
references.pmid: 15361864
references.citation: Phys Med Biol. 2008 Aug 7;53(15):4203-12
references.pmid: 18635896
references.citation: Cancer Res. 2005 Jun 15;65(12):5352-7
references.pmid: 15958583
references.citation: Eur Radiol. 2005 Jun;15(6):1079-86
references.pmid: 15747142