脂质包膜微泡的壳黏度估计
Shell viscosity estimation of lipid-coated microbubbles
AI总结：
本研究通过超高速显微成像、光镊和宽场荧光技术精细表征脂质包膜微泡的壳黏度，发现其变异性约一个数量级且不依赖气泡尺寸，并证明先前报道的尺寸依赖趋势是气泡光谱法方法学偏差和气泡尺寸测量误差造成的伪影。
摘要：
理解超声造影剂微泡的壳流变学对于预测其在临床实践中的生物效应至关重要。过去利用精密声学和光学技术的研究在这一方向上取得了巨大进展，使得能够建立壳模型，充分再现包膜微泡在声激励下的非线性行为。然而，关于壳黏度对平衡气泡半径的依赖性，仍存在令人困惑的差异和缺失的物理解释，这需要进一步的实验研究。在本研究中，我们旨在通过对壳黏度进行精细表征来揭示这种行为的成因。我们使用超高速显微成像、光镊和宽场荧光技术，在一系列气泡尺寸范围内准确记录单个微泡在超声驱动下的响应。验证并采用了一种先进的气泡动力学模型，从单个气泡的径向时间演化中推断其壳黏度。所得结果揭示了壳黏度约一个数量级的显著变异性，并且不依赖于气泡尺寸，这与先前的研究相反。我们发现，过去被广泛用于确定壳黏度的所谓气泡光谱法对方法学误差高度敏感，并通过解析论证证明先前报道的非物理趋势是这些偏差造成的伪影。我们还展示了正确确定气泡尺寸的重要性，因为当通过气泡时间响应的非线性拟合来估计壳黏度时，这一方面的误差也可能导致非物理趋势。
英文摘要：
Understanding the shell rheology of ultrasound contrast agent microbubbles is vital for anticipating their bioeffects in clinical practice. Past studies using sophisticated acoustic and optical techniques have made enormous progress in this direction, enabling the development of shell models that adequately reproduce the nonlinear behaviour of the coated microbubble under acoustic excitation. However, there have also been puzzling discrepancies and missing physical explanations for the dependency of shell viscosity on the equilibrium bubble radius, which demands further experimental investigations. In this study, we aim to unravel the cause of such behaviour by performing a refined characterisation of the shell viscosity. We use ultra-high-speed microscopy imaging, optical trapping and wide-field fluorescence to accurately record the individual microbubble response upon ultrasound driving across a range of bubble sizes. An advanced model of bubble dynamics is validated and employed to infer the shell viscosity of single bubbles from their radial time evolution. The resulting values reveal a prominent variability of the shell viscosity of about an order of magnitude and no dependency on the bubble size, which is contrary to previous studies. We find that the method called bubble spectroscopy, which has been used extensively in the past to determine the shell viscosity, is highly sensitive to methodology inaccuracies, and we demonstrate through analytical arguments that the previously reported unphysical trends are an artifact of these biases. We also show the importance of correct bubble sizing, as errors in this aspect can also lead to unphysical trends in shell viscosity, when estimated through a nonlinear fitting from the time response of the bubble.
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