In Vivo Microscopy of Targeted Vessel Occlusion Employing Acoustic Droplet Vaporization

AbstractNanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides distinct advantages, including in situ activation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilizing an expanding gas surface by employing the lung surfactant replacement, Beractant. Lung surfactant contains a suite of lipids and surfactant proteins that provides efficient shuttling of material from bilayer folds to the monolayer surface. We therefore hypothesized that Beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized Beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading and re-solidification. We then harnessed this unique spreading capability to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization for in vivo ultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy.Graphical Abstract

Download Full-text

Acoustic Droplet Vaporization in Biology and Medicine

BioMed Research International ◽

10.1155/2013/404361 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 34

Author(s):

Chung-Yin Lin ◽

William G. Pitt

Keyword(s):

Drug Delivery ◽

Contrast Agent ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound ◽

Superheated Liquid ◽

Clinical Use ◽

Vessel Occlusion ◽

Acoustic Droplet Vaporization ◽

Droplet Vaporization ◽

Preclinical Trials

This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, and high intensity focused ultrasound (HIFU) sensitization. Vessel occlusion via ADV has been explored in rodents and dogs and may be approaching clinical use. ADV for drug delivery is still in preclinical stages with initial applications to treat tumors in mice. Other techniques are still in preclinical studies but have potential for clinical use in specialty applications. Overall, ADV has a bright future in clinical application because the small size of nanodroplets greatly reduces the rate of clearance compared to larger contrast agent bubbles and yet provides the advantages of ultrasonographic contrast, acoustic cavitation, and nontoxicity of conventional perfluorocarbon contrast agent bubbles.

Download Full-text

Use of pulse repetition frequency to augment acoustic droplet vaporization in vivo

The Journal of the Acoustical Society of America ◽

10.1121/1.4969388 ◽

2016 ◽

Vol 140 (4) ◽

pp. 3026-3026 ◽

Cited By ~ 2

Author(s):

Robinson Seda ◽

Jonah Harmon ◽

Jeffrey B. Fowlkes ◽

Joseph Bull

Keyword(s):

Pulse Repetition Frequency ◽

Repetition Frequency ◽

Pulse Repetition ◽

Acoustic Droplet Vaporization ◽

Droplet Vaporization

Download Full-text

Studies on Chick Embryo Thrombocytes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654983 ◽

1963 ◽

Vol 09 (02) ◽

pp. 291-299 ◽

Cited By ~ 9

Author(s):

Helge Stalsberg ◽

Hans Prydz

Keyword(s):

Chick Embryo ◽

Bleeding Time ◽

In Vivo Microscopy ◽

Cut Edge ◽

Vessel Lumen ◽

Cellular Constituent

SummaryThe formation of hemostatic plugs were studied in the chick embryo through in vivo microscopy, in sections of hemostatic plugs and by measurements of primary bleeding time. Thrombocytes were found to be their only cellular constituent. Ability to form adequate hemostatic plugs appeared rather abruptly in embryos of stages 16-17 and coincided with an increase in thrombocyte precursors (stages III and IV).The thrombocytes initially adhere to the cut edge of the vessel. The extension of the hemostatic plug into the vessel lumen is a secondary step in plug development.

Download Full-text

A New Model for Quantitative In Vivo Microscopic Analysis of Thrombus Formation and Vascular Recanalisation: The Ear of the Hairless (hr/hr) Mouse

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665420 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1408-1414 ◽

Cited By ~ 25

Author(s):

Frank Roesken ◽

Martin Ruecker ◽

Brigitte Vollmar ◽

Nicole Boeckel ◽

Eberhard Morgenstern ◽

...

Keyword(s):

Endothelial Cell ◽

Light Exposure ◽

Thrombus Formation ◽

Microscopic Analysis ◽

Cell Interaction ◽

Vascular Perfusion ◽

Vessel Occlusion ◽

Endothelial Cell Interaction ◽

Platelet Deposition

SummaryThe alteration of rheological blood properties as well as deterioration of vascular perfusion conditions and cell-cell interactions are major determinants of thrombus formation. Herein, we present an experimental model which allows for quantitative in vivo microscopic analysis of these determinants during both thrombus formation and vascular recanalisation. The model does not require surgical preparation procedures, and enables for repeated analysis of identical microvessels over time periods of days or months, respectively. After i.v. administration of FITC-dextran thrombus formation was induced photochemically by light exposure to individual arterioles and venules of the ear of ten anaesthetised hairless mice. In venules, epiillumination induced rapid thrombus formation with first platelet deposition after 0.59 ± 0.04 min and complete vessel occlusion within 7.48 ±1.31 min. After a 24-h time period, 75% of the thrombosed venules were found recanalised. Marked leukocyte-endothelial cell interaction in those venules indicated persistent endothelial cell activation and/or injury, even after an observation period of 7 days. In arterioles, epi-illumination provoked vasomotion, while thrombus formation was significantly (p <0.05) delayed with first platelet deposition after 2.32 ± 0.22 min and complete vessel occlusion within 20.07 ±3.84 min. Strikingly, only one of the investigated arterioles was found recanalised after 24 h, which, however, did not show leukocyte-endothelial cell interaction. Heparin (300 U/kg, i.v.) effectively counteracted the process of thrombus formation in this model, including both first platelet deposition and vessel occlusion. We conclude that the model of the ear of the hairless mouse allows for distinct in vivo analysis of arteriolar and venular thrombus formation/ recanalisation, and, thus, represents an interesting tool for the study of novel antithrombotic and thrombolytic strategies, respectively.

Download Full-text