Bubble brilliance - how microbubbles provide contrast in ultrasound imaging

微泡是超声成像的造影剂，当它们在血液中循环时，会增强超声信号。最常见的微泡有一个脂质外壳和一个沉重的气体核心，这使得它们很稳定，在生物上是惰性的。它们主要用于诊断肝脏和心脏疾病；但它们的使用正处于快速扩张的尖端。有了微泡，超声成像的传统限制正在被新技术打破，例如空间分辨率低于50微米的超分辨率成像和帧速率超过1,000赫兹的超快成像。这些技术使用微泡的增强信号来提供超声波无法想象的令人难以置信的图像。尽管微泡的潜力令人难以置信，但微泡如何在人体内提供对比度仍然存在巨大的不确定性，这导致了两个问题：首先，尚不清楚微泡增强图像显示的是什么--临床医生看到的是所有微泡在哪里循环，还是图像增强一种血管而不是另一种血管存在偏见？其次，如果没有更好的理解，就无法开发新的成像技术。尽管微泡在水中得到了很好的描述，但它们在血管中的行为却不是这样。在水中，微泡根据超声波脉冲膨胀和收缩，向发射器发出独特的信号。在毛细管中，一些人假设这一信号受到了抑制，因为气泡膨胀的空间较小。这可能会导致发射信号的共振、强度和形状发生变化。相反，这些问题有一定的影响，因为所有的微泡信号都来自血管内部，而且目前还不清楚不同大小的血管中的信号有何不同。到目前为止，所有关于微气泡在毛细血管中的行为的假设解释都没有得到检验；因为还没有人找到一种方法来观察毛细血管中的微气泡振荡。微泡以每秒数百万次的速度振荡，并且在嵌入不透明组织的毛细血管中振荡。在建议的博士项目中，学生将使用我们独特的实验平台来研究毛细血管和其他微血管的超声造影剂。学生将首先学习如何提取和保存大鼠脑片(体外模型)，并在水凝胶中创建微米大小的毛细血管(体外模型)。微泡将暴露在超声波下，同时捕捉其径向振荡并聆听它们发出的声音。光学和声学数据将被分析，以解释微泡是如何振荡的，并在微血管中提供对比。然后，我们将开发一种微血管成像算法，增强来自微血管的信号。通过提供对微泡如何在微血管中提供对比的第一个机制的理解，我们希望启发能够成像微血管并区分其许多部分的技术。

Microbubbles are the contrast agents of ultrasound imaging, enhancing the ultrasound signals as they circulate the blood. The most common microbubbles have a lipid shell and a heavy gas core, making them stable and biologically inert. They are primarily used to diagnose diseases in the liver and heart; but their use is at the cusp of rapid expansion. With microbubbles, traditional limitations with ultrasound imaging are being dismantled by new technologies, such as super-resolution imaging with spatial resolutions below 50 microm and ultrafast imaging with frame rates over 1,000 Hz. These technologies use the enhanced signal of microbubbles to provide incredible images never thought possible by ultrasound. Despite the incredible potential of microbubbles, there remains huge uncertainty with how microbubbles provide contrast in the human body, leading to two problems: First, it is unclear what microbubble-enhanced images are displaying - are clinicians seeing where all the microbubbles are circulating, or is there a bias with images enhancing one kind of vessel over another? Second, new technologies for imaging cannot be developed without a better understanding. Although microbubbles are well-described in water their behaviours in blood vessels are not. In water, microbubbles expand and contract to the ultrasound pulse, emitting a unique signal back to the emitter. In a capillary, some hypothesise that this signal is damped, because the bubble has less space to expand into. This could lead to changes in the resonance, strength, and shape of the emitted signal. These questions have implications in contrast as all microbubble signals comes from within vessels, and it is unclear how the signal differs in different sized vessels. So far, all hypothetical explanations for how microbubbles behave in capillaries have been untested; because no one has found a way to observe microbubble oscillations in capillaries. Microbubbles oscillate at millions of times per second and in capillaries that are embedded in opaque tissue. In the proposed PhD project, the student will use our unique experimental platform to study ultrasound contrast in capillaries and other microvessels. The student will begin by learning how to extract and preserve slices of rat brains (ex vivo model) and create micron-sized capillaries in hydrogels (in vitro model). The microbubbles will be exposed to ultrasound while capturing its radial oscillations and listening to the sound that they emit. The optical and acoustic data will be analysed to explain how microbubbles oscillate and provide contrast in microvessels. We will then develop a microvascular imaging algorithm that boosts signals from microvessels. By providing the first mechanistic understanding of how microbubbles provide contrast in microvessels, we hope to inspire technologies that will can image the microvasculature and differentiate its many parts.