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. 2011 Aug;16(8):086004.
doi: 10.1117/1.3606565.

Ultrahigh sensitive optical microangiography reveals depth-resolved microcirculation and its longitudinal response to prolonged ischemic event within skeletal muscles in mice

Yali Jia  1 , Jia Qin, Zhongwei Zhi, Ruikang K Wang
Affiliations

Ultrahigh sensitive optical microangiography reveals depth-resolved microcirculation and its longitudinal response to prolonged ischemic event within skeletal muscles in mice

Yali Jia et al. J Biomed Opt. 2011 Aug.

Abstract

The primary pathophysiology of peripheral arterial disease is associated with impaired perfusion to the muscle tissue in the lower extremities. The lack of effective pharmacologic treatments that stimulate vessel collateralization emphasizes the need for an imaging method that can be used to dynamically visualize depth-resolved microcirculation within muscle tissues. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing three-dimensional images of dynamic blood perfusion within microcirculatory tissue beds at an imaging depth of up to ∼2 mm, with an unprecedented imaging sensitivity of blood flow at ∼4 μm∕s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary-level resolution, within skeletal muscles of mice. By use of the mouse model of hind-limb ischemia, we show that OMAG can assess the time-dependent changes in muscle perfusion and perfusion restoration along tissue depth. These findings indicate that OMAG can represent a sensitive, consistent technique to effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.

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Figures

Figure 1
Figure 1
Schematic diagram illustrating the occlusion site and imaging site for unilateral hind-limb ischemia. UHS-OMAG C-scan (2.5×2.5 mm2) and B-scan are shown by solid line box and dashed line, respectively.
Figure 2
Figure 2
Typical in vivo UHS-OMAG images of detailed microcirculation within skeletal muscle in mice are compared with the typical schematic obtained from histological work. (a) is one UHS-OMAG cross-sectional image (B-scan) of microstructures, and (b) is the corresponding blood flow image where the capillary flows in a layer shown by a bar are readily apparent. (c) shows 3D volumetric rendering of blood perfusion within scanned muscle tissue volume. After segmentation, the 2D x-y projection views of muscle blood microflows in three layers [(d)–(f)] are in agreement with the vascular network described in schematic (g). Venule (V); arteriole (A); collecting venule (CV), and transverse arteriole (TA).
Figure 3
Figure 3
Representative functional microcirculation network in the muscle in response to femoral artery ligation. (a)–(d) show time course of perfusion changes before ligation (a), at 5 min, (b) 48 h and, (c) 1 week (d) after ligation. Acute perfusion reduction and restoration can be observed. The brighter microvessels observed in (c) are indicative of increased blood flow associated with collateral perfusion. In (d), arrows indicate that new patterns of collateral vessels are developed during perfusion recovery. Cross-sectional images (e)–(h) detect the variation of blood perfusion before ligation (e) at 5 min, (f) 48 h and, (g) 1 week (h) after ligation along tissue depth.
Figure 4
Figure 4
Representative flow responses within 1 min after femoral artery ligation. (a) is a representative cross-sectional B-scan at baseline, showing the microcirculation involved in the quantification analysis. (b) and (c) show the fractional flow signal changes in each B-scan collected from two individual vessels pointed by arrows in (a) along with the fitted curves to show quantified flow response after acute artery ligation. (d) is the averaged time-course for flow change over the region denoted by a dashed box in (a).
Figure 5
Figure 5
Mapping blood perfusion after femoral artery ligation using LSI. (a)–(d) show LSI blood perfusion maps before, during, 5 min and 48 h after ligation. It is noteworthy that a rapid flow reduction initiated during ligation (b) and continuously developed immediately after ligation (c) and persisted at 48 h after onset (d) by use of LSI where the sensitive analysis of the capillary flow is currently difficult.
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References

    1. Weitz J. I., Byrne J., Clagett G. P., Farkouh M. E., Porter J. M., Sackett D. L., Strandness D. E., and Taylor L. M., “Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review,” Circulation 94, 3026–3049 (1996). - PubMed
    1. Cook J. P., “The pathophysiology of peripheral arterial disease: rational targets for drug intervention,” Vasc. Med. 2, 227–230 (1997). - PubMed
    1. Rey S., Lee K., Semenza G. L., Wang C. J., Gupta K., Chen S., McMillan A., Bhise N., Levchenko A., and Semenza G. L., “Synergistic effect of HIF-1alpha gene therapy and HIF-1-activated bone marrow-derived angiogenic cells in a mouse model of limb ischemia,” Proc. Natl. Acad. Sci. U.S.A. 106(48), 20399–20404 (2009).10.1073/pnas.0911921106 - DOI - PMC - PubMed
    1. Emanueli C., Minasi A., Zacheo A., Chao J., Chao L., Salis M. B., Straino S., Tozzi M. G., Smith R., Gaspa L., Bianchini G., Stillo F., Capogrossi M. C., and Madeddu P., “Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia,” Circulation 103(1), 125–32 (2001). - PubMed
    1. Limbourg A., Korff T., Napp L. C., Schaper W., Drexler H., and Limbourg F. P., “Evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia,” Nat. Protoc. 4(12), 1737–1746 (2009).10.1038/nprot.2009.185 - DOI - PubMed

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