Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes

J. R. Lindner, J. Song, F. Xu, A. L. Klibanov, Kai Singbartl, K. Ley, S. Kaul

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

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-α-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.

Original languageEnglish (US)
Pages (from-to)2745-2750
Number of pages6
JournalCirculation
Volume102
Issue number22
DOIs
StatePublished - Nov 28 2000

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Microbubbles
Ultrasonography
Leukocytes
Inflammation
Phosphatidylserines
Kidney
Lipids
Venules
Abdominal Muscles
Perfusion Imaging
Complement Activation
Thromboplastin
Reperfusion Injury
Fluorescein
Intravenous Injections
Peroxidase
Reperfusion
Necrosis
Ischemia

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lindner, J. R., Song, J., Xu, F., Klibanov, A. L., Singbartl, K., Ley, K., & Kaul, S. (2000). Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. Circulation, 102(22), 2745-2750. https://doi.org/10.1161/01.CIR.102.22.2745
Lindner, J. R. ; Song, J. ; Xu, F. ; Klibanov, A. L. ; Singbartl, Kai ; Ley, K. ; Kaul, S. / Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. In: Circulation. 2000 ; Vol. 102, No. 22. pp. 2745-2750.
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abstract = "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-α-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.",
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Lindner, JR, Song, J, Xu, F, Klibanov, AL, Singbartl, K, Ley, K & Kaul, S 2000, 'Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes', Circulation, vol. 102, no. 22, pp. 2745-2750. https://doi.org/10.1161/01.CIR.102.22.2745

Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. / Lindner, J. R.; Song, J.; Xu, F.; Klibanov, A. L.; Singbartl, Kai; Ley, K.; Kaul, S.

In: Circulation, Vol. 102, No. 22, 28.11.2000, p. 2745-2750.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes

AU - Lindner, J. R.

AU - Song, J.

AU - Xu, F.

AU - Klibanov, A. L.

AU - Singbartl, Kai

AU - Ley, K.

AU - Kaul, S.

PY - 2000/11/28

Y1 - 2000/11/28

N2 - 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-α-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.

AB - 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-α-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.

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