Optical and acoustical dynamics of microbubble contrast agents inside neutrophils

被引:110
作者
Dayton, PA
Chomas, JE
Lum, AFH
Allen, JS
Lindner, JR
Simon, SI
Ferrara, KW
机构
[1] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA
[2] Univ Virginia, Div Cardiovasc, Charlottesville, VA 22903 USA
关键词
D O I
10.1016/S0006-3495(01)76127-9
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Acoustically active microbubbles are used for contrast-enhanced ultrasound assessment of organ perfusion. In regions of inflammation, contrast agents are captured and phagocytosed by activated neutrophils adherent to the venular wall. Using direct optical observation with a high-speed camera and acoustical interrogation of individual bubbles and cells, we assessed the physical and acoustical responses of both phagocytosed and free microbubbles. Optical analysis of bubble radial oscillations during insonation demonstrated that phagocytosed microbubbles experience viscous damping within the cytoplasm and yet remain acoustically active and capable of large volumetric oscillations during an acoustic pulse. Fitting a modified Version of the Rayleigh-Plesset equation that describes mechanical properties of thin shells to optical radius-time data of oscillating bubbles provided estimates of the apparent viscosity of the intracellular medium. Phagocytosed microbubbles experienced a viscous damping approximately sevenfold greater than free microbubbles. Acoustical comparison between free and phagocytosed microbubbles indicated that phagocytosed microbubbles produce an echo with a higher mean frequency than free microbubbles in response to a rarefaction-first single-cycle pulse. Moreover, this frequency increase is predicted using the modified Rayleigh-Plesset equation. We conclude that contrast-enhanced ultrasound can detect distinct acoustic signals from microbubbles inside of neutrophils and may provide a unique tool to identify activated neutrophils at sites of inflammation.
引用
收藏
页码:1547 / 1556
页数:10
相关论文
共 19 条
[1]  
Berne R., 1993, PHYSIOLOGY
[2]   APPARENT VISCOSITY AND CORTICAL TENSION OF BLOOD GRANULOCYTES DETERMINED BY MICROPIPET ASPIRATION [J].
EVANS, E ;
YEUNG, A .
BIOPHYSICAL JOURNAL, 1989, 56 (01) :151-160
[3]  
EVANS E, 1984, BLOOD, V64, P1028
[4]  
GAINEY MA, 1988, J NUCL MED, V29, P689
[5]  
Leighton T. G., 1994, ACOUSTIC BUBBLE
[7]  
Lindner JR, 2000, CIRCULATION, V102, P531
[8]   Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes [J].
Lindner, JR ;
Coggins, MP ;
Kaul, S ;
Klibanov, AL ;
Brandenburger, GH ;
Ley, K .
CIRCULATION, 2000, 101 (06) :668-675
[9]  
Morgan KE, 2000, IEEE T ULTRASON FERR, V47, P1494, DOI 10.1109/58.883539
[10]   RAPID FLOW OF PASSIVE NEUTROPHILS INTO A 4 MU-M PIPETTE AND MEASUREMENT OF CYTOPLASMIC VISCOSITY [J].
NEEDHAM, D ;
HOCHMUTH, RM .
JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, 1990, 112 (03) :269-276