Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 35, Issue 10, Pages 1722-1736Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2009.04.020
Keywords
Pulsed high-intensity focused ultrasound; Muscle; Extravasation; Interstitial transport; Radiation force displacements; Shear strain
Funding
- NIH, National Institutes of Health [CA114075]
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Pulsed high-intensity focused ultrasound (HIFU) exposures without ultrasound contrast agents have been used for noninvasively enhancing the delivery of various agents to improve their therapeutic efficacy in a variety of tissue models in a nondestructive manner. Despite the versatility of these exposures, little is known about the mechanisms by which their effects are produced. In this study, pulsed-HIFU exposures were given in the calf muscle of mice, followed by the administration of a variety of fluorophores, both soluble and particulate, by local or systemic injection. In vivo imaging (whole animal and microscopic) was used to quantify observations of increased extravasation and interstitial transport of the fluorophores as a result of the exposures. Histological analysis indicated that the exposures caused some structural alterations such as enlarged gaps between muscle fiber bundles. These effects were consistent with increasing the permeability of the tissues; however, they were found to be transient and reversed themselves gradually within 72 h. Simulations of radiation force-induced displacements and the resulting local shear strain they produced were carried out to potentially explain the manner by which these effects occurred. A better understanding of the mechanisms involved with pulsed HIFU exposures for noninvasively enhancing delivery will facilitate the process for optimizing their use. (E-mail: vfrenkel@cc.nih.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.
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