Use of Intravital Microscopy to Study the Microvascular Behavior of Microbubble‐Based Ultrasound Contrast Agents

Schneider, Michel; Broillet, Anne; Tardy, Isabelle; Pochon, Sibylle; Bussat, Philippe; Bettinger, Thierry; Helbert, Alexandre; Costa, Maria Célia Pires; Tranquart, F.

doi:10.1111/j.1549-8719.2011.00152.x

Cited by 22 publications

(14 citation statements)

References 60 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, reliable models for studying the mechanism and efficacy of sonoporation are a prerequisite. currently, intravital in vivo models exist for studying microbubble rheology and adherence of targeted microbubbles in, for example, rat or mouse cremaster muscle and dorsal skinfold chamber, and hamster cheek pouch [16]- [18], which potentially can be used for studying sonoporation. However, these models are complicated and also fall under strict animal experiment legislation regulations.…”

Section: Introductionmentioning

confidence: 99%

Targeted microbubble mediated sonoporation of endothelial cells in vivo

Skachkov

Luan

Steen

et al. 2014

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

View full text Add to dashboard Cite

Ultrasound contrast agents as drug-delivery systems are an emerging field. Recently, we reported that targeted microbubbles are able to sonoporate endothelial cells in vitro. In this study, we investigated whether targeted microbubbles can also induce sonoporation of endothelial cells in vivo, thereby making it possible to combine molecular imaging and drug delivery. Live chicken embryos were chosen as the in vivo model. αvß3-targeted microbubbles attached to the vessel wall of the chicken embryo were insonified at 1 MHz at 150 kPa (1 × 10,000 cycles) and at 200 kPa (1 × 1000 cycles) peak negative acoustic pressure. Sonoporation was studied by intravital microscopy using the model drug propidium iodide (PI). Endothelial cell PI uptake was observed in 48% of microbubble-vessel-wall complexes at 150 kPa (n = 140) and in 33% at 200 kPa (n = 140). Efficiency of PI uptake depended on the local targeted microbubble concentration and increased up to 80% for clusters of 10 to 16 targeted microbubbles. Ultrasound or targeted microbubbles alone did not induce PI uptake. This intravital microscopy study reveals that sonoporation can be visualized and induced in vivo using targeted microbubbles.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeted microbubble mediated sonoporation of endothelial cells in vivo

Skachkov

Luan

Steen

et al. 2014

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

View full text Add to dashboard Cite

show abstract

“…Their passage into the PV or HA, through the parenchyma, and into the hepatic veins enabled visualization of the extent of perfusion throughout the microvasculature. As the microbubbles flowed into the capillary bed, trace amounts were left behind because they were captured by endothelial receptors, primarily on Kupffer cells and leukocytes; they temporarily highlighted the perfused liver vasculature without affecting the flow or causing air embolisms themselves . Two groups of perfusion images were subsequently captured with a Philips iU22 ultrasound scanner (Philips Healthcare, Bothell, WA).…”

Section: Methodsmentioning

confidence: 99%

“…As the microbubbles flowed into the capillary bed, trace amounts were left behind because they were captured by endothelial receptors, primarily on Kupffer cells and leukocytes; they temporarily highlighted the perfused liver vasculature without affecting the flow or causing air embolisms themselves. 22 Two groups of perfusion images were subsequently captured with a Philips iU22 ultrasound scanner (Philips Healthcare, Bothell, WA). The first images were taken with an L9-3 linear array probe, which was held in a fixed position on overlapping left lateral lobes (LLLs) and left medial lobes (LMLs) with a Fisso mechanical articulated arm (Baitella AG, Zurich, Switzerland).…”

Section: Dceus Assessment Of Perfusion Qualitymentioning

confidence: 99%

Effects of air embolism size and location on porcine hepatic microcirculation in machine perfusion

et al. 2014

View full text Add to dashboard Cite

The handling of donor organs frequently introduces air into the microvasculature, but little is known about the extent of the damage caused as a function of the embolism size and distribution. Here we introduced embolisms of different sizes into the portal vein, the hepatic artery, or both during the flushing stage of porcine liver procurement. The outcomes were evaluated during 3 hours of machine perfusion and were compared to the outcomes of livers with no embolisms. Dynamic contrast-enhanced ultrasound (DCEUS) was used to assess the perfusion quality, and it demonstrated that embolisms tended to flow mostly into the left lobe, occasionally into the right lobe, and rarely into the caudate lobe. Major embolisms could disrupt the flow entirely, whereas minor embolisms resulted in reduced or heterogeneous flow. Embolisms occasionally migrated to different regions of the same lobe and, regardless of their size, caused a general deterioration in the flow over time. Histological damage resulted primarily when both vessels of the liver were compromised, whereas bile production was diminished in livers that had arterial embolisms. Air embolisms produced a dose-dependent increase in vascular resistance and a decline in oxygen consumption. This is the first article to quantify the impact of air embolisms on microcirculation in an experimental model, and it demonstrates that air embolisms have the capacity to degrade the integrity of donor organs. The extent of organ damage is strongly dependent on the size and distribution of air embolisms. The diagnosis of embolism severity can be safely and easily made with DCEUS. Liver Transpl 20:601-611, 2014. V C 2014 AASLD.Received October 12, 2013; accepted January 5, 2014.Air embolisms in donor organs are a well-known occurrence. Wolf et al. 1 demonstrated that before transplantation, one-third of donor livers contain intrahepatic air, whereas Liu et al. 2 showed that embolisms occur largely as a result of the routine handling of donor organs. Air can be actively perfused into the donor organ's vasculature during the delivery of the cold flush at the time of procurement, 3,4 during a venovenous bypass, 5-7 and, as machine perfusion (MP) gains popularity, at the time of the connection and during dynamic donor organ preservation. 8 The passive introduction of air can occur when subatmospheric pressures are generated in the vasculature, such as when the organ is suspended above the fluid line and drained, the vasculature is perforated, or air is encapsulated during an anastomosis.2,4,9 Air embolisms are Abbreviations: ALT, alanine aminotransferase; CL, caudate lobe; DCEUS, dynamic contrast-enhanced ultrasound; HA, hepatic artery; LLL, left lateral lobe; LML, left medial lobe; MP, machine perfusion; PV, portal vein.

show abstract

“…Initial bubble size depends on the size of the emulsion particles but, theoretically, the bubbles undergo size variations as they exchange O 2 , nitrogen and CO 2 by diffusion in the lungs and the tissues. 228-231 …”

Section: Oxygen Transport With Perfluorocarbon Microbubblesmentioning

confidence: 99%

Blood Substitutes

Cabrales¹,

Intaglietta²

2013

ASAIO Journal

View full text Add to dashboard Cite

The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity.

show abstract

Use of Intravital Microscopy to Study the Microvascular Behavior of Microbubble‐Based Ultrasound Contrast Agents

Cited by 22 publications

References 60 publications

Targeted microbubble mediated sonoporation of endothelial cells in vivo

Targeted microbubble mediated sonoporation of endothelial cells in vivo

Effects of air embolism size and location on porcine hepatic microcirculation in machine perfusion

Blood Substitutes

Contact Info

Product

Resources

About