Effect of anesthesia carrier gas on in vivo circulation times of ultrasound microbubble contrast agents in rats

Abstract

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents.

Targeted ultrasound contrast agents for ultrasound molecular imaging and therapy

“…In such methods the quantification of bound tMBs strongly depends on the injected dose, imaging system gain, and local perfusion [137]. In addition, the influence of inhaled gases in the anaesthetic protocols influences the MBs longevity [148][149][150][151]. These studies confirmed longer circulation times of in-house lipid-shell decafluorobutane-filled UCAs and commercially available UCAs such as Definity and Albunex when animals breathe medical air instead of pure oxygen as the carrier gas for the isoflurane anaesthetic.…”

“…This is perhaps due to a reduced ventilation/perfusion mismatch and classical diffusion between the blood gases and the gas inside the MBs (e.g. perfluorobutane), in which nitrogen plays a role by increasing the volume of the MBs and diluting other gas species in the MBs gas core [151].…”

Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos

“…It is expected that changes in oxygenation and physiology will occur, although we do not anticipate these to dramatically affect microbubble performance [68]. It may, however, influence expression levels, as endoglin is upregulated under hypoxic conditions and is transcriptionally modulated by HIF-1a [32].…”

Enhanced in vivo and in vitro high intensity focused ultrasound ablation via phase-shift nanodroplets compared to microbubbles

“…Originally developed as ultrasound contrast agents, these micron-sized, lipid-shelled gas bubbles are limited to the vasculature due to their size. They have a relatively short half-life in vivo [5] rendering them insufficiently stable for an entire HIFU surgery, which can last several hours. Nano-sized bubbles are particularly challenging to produce, and exhibit resonance beyond HIFU frequencies.…”