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(Circulation. 2000;102:2745.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Noninvasive Ultrasound Imaging of Inflammation Using Microbubbles Targeted to Activated Leukocytes
From the Cardiovascular Division (J.R.L., F.X., S.K.) and the Department of Biomedical Engineering (J.S., K.S., K.L., S.K.), University of Virginia School of Medicine, Charlottesville; Mallinckrodt Inc (A.L.K.), St Louis, Mo; and the Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin (K.S.), Westfälische Wilhelms-Universität, Münster, Germany.
Correspondence to Jonathan R. Lindner, MD, Box 158, Cardiovascular Division, University of Virginia Medical Center, Charlottesville, VA 22908. E-mail jlindner{at}virginia.edu
Background—Lipid microbubbles used for perfusion imaging with ultrasound are retained within inflamed tissue because of complement-mediated attachment to leukocytes within venules. We hypothesized that incorporation of phosphatidylserine (PS) into the microbubble shell may enhance these interactions by amplifying complement activation and thereby allow ultrasound imaging of inflammation.
Methods and Results—In 6 mice, intravital microscopy of tissue
necrosis factor-
–treated cremaster muscle was performed to assess
the microvascular behavior of fluorescein-labeled lipid
microbubbles with and without PS in the shell. Ten minutes after
intravenous injection, microbubble attachment to leukocytes
within inflamed venules was greater for PS-containing than for standard
lipid microbubbles (20±4 versus 10±3 per 20 optical fields,
P<0.05). The ultrasound signal from retained
microbubbles was assessed in the kidneys of 6 mice undergoing renal
ischemia-reperfusion injury and in 6 control kidneys. The
signal from retained microbubbles in control kidneys was low (<2.5
video intensity units) for both agents. After
ischemia-reperfusion, the signal from retained microbubbles was
2-fold higher for PS-containing than for standard lipid microbubbles
(18±6 versus 8±2 video intensity units, P<0.05). An
excellent relation was found between the ultrasound signal from
retained microbubbles and the degree of renal inflammation, assessed by
tissue myeloperoxidase activity.
Conclusions—We conclude that noninvasive assessment of inflammation is possible by ultrasound imaging of microbubbles targeted to activated leukocytes by the presence of PS in the lipid shell.
Key Words: echocardiography • inflammation • leukocytes
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