Hemodynamic and metabolic diffuse optical monitoring in a mouse model of hindlimb ischemia.
Murine hindlimb ischemia is a useful model for investigation of the mechanisms of peripheral arterial disease and for understanding the role of endothelial cells and generic factors affecting vascular regeneration or angiogenesis. To date, important research with these models has explored tissue reperfusion following ischemia with Laser Doppler methods, methods which provide information about superficial (~mm) vascular regeneration. In this work, we employ diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) in mice after hindlimb ischemia. We hypothesize that vascular re-growth is not uniform in tissue, and therefore, since diffuse optical methods are capable of probing deep tissues, that the diffuse optics approach will provide a more complete picture of the angiogenesis process throughout the whole depth profile of the limb. Besides increased depth penetration, the combined measurements of DCS and DOS enable all-optical, noninvasive, longitudinal monitoring of tissue perfusion and oxygenation that reveals the interplay between these hemodynamic parameters during angiogenesis. Control mice were found to reestablish 90% of perfusion and oxygen consumption during this period, but oxygen saturation in the limb only partially recovered to about 30% of its initial value. The vascular recovery of mice with endothelial cell-specific deletion of HIF-2α was found to be significantly impaired relative to control mice, indicating that HIF-2α is important for endothelial cell functions in angiogenesis. Comparison of DOS/DCS measurements to parallel measurements in the murine models using Laser Doppler Flowmetry reveal differences in the reperfusion achieved by superficial versus deep tissue during neoangiogenesis; findings from histological analysis of blood vessel development were further correlated with these differences. In general, the combination of DCS and DOS enables experimenters to obtain useful information about oxygenation, metabolism, and perfusion throughout the limb. The results establish diffuse optics as a practical noninvasive method to evaluate the role of transcription factors, such as the endothelial cell-specific HIF-2α, in genetic ally modified mice.
Rickson C
RC
Mesquita
Nicolas
N
Skuli
Meeri N
MN
Kim
Jiaming
J
Liang
Steve
S
Schenkel
Amar J
AJ
Majmundar
M Celeste
MC
Simon
Arjun G
AG
Yodh
J Biomed Opt. 2010 May-Jun;15(3):037004
20615033
Med Biol Eng Comput. 2002 Nov;40(6):687-97
12507319
Circ Res. 2007 Dec 7;101(12):1310-8
17932327
J Cereb Blood Flow Metab. 2003 Aug;23(8):911-24
12902835
J Cell Mol Med. 2006 Jan-Mar;10(1):45-55
16563221
Curr Top Dev Biol. 2006;76:217-57
17118268
Lab Anim Sci. 1993 Apr;43(2):189-92
8320967
Cancer Res. 2004 Oct 15;64(20):7553-61
15492282
Nat Med. 2000 Apr;6(4):389-95
10742145
Opt Express. 2008 Sep 29;16(20):15514-30
18825190
Cardiovasc Res. 2001 Feb 16;49(3):609-17
11166274
Neurocrit Care. 2010 Apr;12(2):173-80
19908166
J Biomed Opt. 2009 May-Jun;14(3):034015
19566308
J Biomed Opt. 2007 May-Jun;12(3):034023
17614731
Phys Med Biol. 1992 Jul;37(7):1531-60
1631197
Phys Med Biol. 2002 Mar 21;47(6):857-73
11936174
Am J Physiol. 1958 Nov;195(2):424-8
13583188
Nat Protoc. 2009;4(12):1737-46
19893509
J Biol Chem. 1995 Jan 20;270(3):1230-7
7836384
Blood. 2009 Jul 9;114(2):469-77
19439736
Neuroimage. 2001 Jun;13(6 Pt 1):975-87
11352604
J Mol Cell Cardiol. 2002 Jul;34(7):775-87
12099717
Circ Res. 2001 Oct 26;89(9):779-86
11679407
Rep Prog Phys. 2010 Jul;73(7):
26120204
Photochem Photobiol. 2007 Sep-Oct;83(5):1040-8
17880498
Opt Express. 2002 Feb 11;10(3):159-70
19424345
Basic Res Cardiol. 2009 Jan;104(1):5-21
19101749
Oncogene. 2007 Jul 26;26(34):4897-907
17297442
Am J Pathol. 1998 Jun;152(6):1667-79
9626071
Phys Med Biol. 2003 Aug 7;48(15):2405-18
12953906
J Physiol. 1964 Dec;175:161-71
14241160
Phys Rev Lett. 1995 Aug 28;75(9):1855-1858
10060408
Nature. 2005 Dec 15;438(7070):932-6
16355210
Magn Reson Med. 2005 Dec;54(6):1530-5
16276490
Histol Histopathol. 2007 Jun;22(6):677-86
17357097
Opt Express. 2007 Feb 5;15(3):1064-75
19532334
Nat Rev Cancer. 2008 Dec;8(12):967-75
18987634
IEEE Trans Biomed Eng. 1979 Dec;26(12):656-64
544437
Genes Dev. 1997 Jan 1;11(1):72-82
9000051
Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):520-6
16397137
Curr Top Dev Biol. 2004;62:37-54
15522738