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Journal of Biomedical Optics

Endotoxemia increases the clearance of mPEGylated 5000-MW quantum dots as revealed by multiphoton microvascular imaging
Author(s): Ryon M. Bateman; Kevin C. Hodgson; Kapil Kohli; Darryl Knight; Keith R. Walley
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Paper Abstract

Imaging the microcirculation is becoming increasingly important in assessing life-threatening disease states. To address this issue in a highly light absorbing and light scattering tissue, we use laser scanning multiphoton microscopy and fluorescent 655-nm 5000-MW methoxy-PEGylated quantum dots to image the functional microcirculation deep in mouse hind limb skeletal muscle. Using this approach, we are able to minimize in vivo background tissue autofluorescence and visualize complete 3-D microvascular units, including feeding arterioles, capillary networks, and collecting venules to depths of 150 to 200 μm. In CD1 mice treated with lipopolysaccharide to model an endotoxemic response to bacterial infection, we find that these quantum dots accumulate at microvascular bifurcations and extravasate from the microcirculation in addition to accumulating in organs (liver, spleen, lung, and kidney). The quantum dots are cleared from the circulation with a first-order elimination rate constant seven times greater than under normal conditions, 1.6±0.06 compared to 0.23±0.05 h-1, P<0.05, thereby reducing the imaging time window. In vitro experiments using TNFalpha treated isolated leukocytes suggest that circulating monocytes (phagocytes) increased their nonspecific uptake of quantum dots when activated. In combination with multiphoton microscopy, quantum dots provide excellent in vivo imaging contrast of deep microvascular structures.

Paper Details

Date Published: 1 November 2007
PDF: 8 pages
J. Biomed. Opt. 12(6) 064005 doi: 10.1117/1.2822882
Published in: Journal of Biomedical Optics Volume 12, Issue 6
Show Author Affiliations
Ryon M. Bateman, The Univ. of British Columbia (Canada)
Kevin C. Hodgson, The Univ. of British Columbia (Canada)
Kapil Kohli, The Univ. of British Columbia (Canada)
Darryl Knight, The Univ. of British Columbia (Canada)
Keith R. Walley, The Univ. of British Columbia (Canada)


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