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Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model.

Abstract：

PURPOSE:To characterize the effect of low-frequency contrast material-enhanced ultrasound on the vascular endothelium and to determine the parameters and techniques required to deliver a therapeutic agent by using the chorioallantoic membrane (CAM) model. MATERIALS AND METHODS:All in vivo animal procedures were conducted with institutional Animal Care and Use Committee approval. Extravasation of 8.5-nm-diameter fluorescein isothiocyanate-labeled dextran was evaluated in the vasculature of a chick CAM model. Intravital microscopy was performed during contrast-enhanced ultrasound exposure (1.00 or 2.25 MHz); results were compared with results of electron microscopy of the insonated regions. Data acquired after insonation with greater mechanical stress (n = 30 animals) (mechanical index [MI] > 1.3) and with lower mechanical stress (n = 86 animals) (MI < 1.13) were compared with measurements in control conditions (n = 46 animals). The diameter of affected vessels; number of extravasation sites; extravasation rate, area, and location; and changes in endothelial cells and basement membrane were evaluated. Differences were tested with analysis of variance or the Student t test. RESULTS:After ultrasound application, convective transport of the model drug was observed through micron-sized openings with a mean fluid velocity of 188.6 microm/sec in the low-stress class and 362.5 microm/sec in the high-stress class. Electron microscopy revealed micron-sized focal endothelial gaps and disseminated blebs, vacuoles, and filopodia extending across tens of microns. The threshold pressure for extravasation was 0.5 MPa for a transmitted center frequency of 1.00 MHz (MI = 0.5) and 1.6 MPa for a frequency of 2.25 MHz (MI = 1.06); thus, the frequency dependence of the threshold was not predicted simply by the MI. CONCLUSION:Low-frequency contrast-enhanced ultrasound can increase vascular permeability and result in convective extravasation of an 8.5-nm-diameter model drug.

journal_name

Radiology

journal_title

Radiology

authors

Stieger SM,Caskey CF,Adamson RH,Qin S,Curry FR,Wisner ER,Ferrara KW

doi

10.1148/radiol.2431060167

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

112-21

issue

eissn

0033-8419

issn

1527-1315

pii

243/1/112

journal_volume

243

pub_type

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Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model.