Bubble brilliance - how microbubbles provide contrast in ultrasound imaging

微泡是超声成像的造影剂，当它们循环血液时增强超声信号。最常见的微泡有一个脂质壳和一个重气体核，使它们稳定和生物惰性。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风口浪尖。有了微泡，超声成像的传统局限性正在被新技术所打破，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 Hz的超快成像。这些技术利用微泡的增强信号，提供超声从未想过的令人难以置信的图像。尽管微泡具有令人难以置信的潜力，但微泡如何在人体中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，目前还不清楚微泡增强的图像显示的是什么-临床医生是否看到所有微泡都在循环，或者图像增强一种血管而不是另一种血管是否存在偏差？第二，如果没有更好的理解，就不能开发新的成像技术。尽管微泡在水中的表现已被很好地描述，但它们在血管中的行为却没有。在水中，微泡随着超声脉冲膨胀和收缩，向发射器发射独特的信号。在毛细管中，一些人假设这种信号是阻尼的，因为气泡膨胀的空间较小。这可能导致发射信号的共振、强度和形状发生变化。这些问题具有相反的含义，因为所有微泡信号都来自血管内，并且尚不清楚信号在不同大小的血管中如何不同。到目前为止，所有关于微泡在毛细血管中的行为的假设性解释都还没有得到验证，因为还没有人找到一种方法来观察毛细血管中的微泡振荡。微泡以每秒数百万次的速度振荡，并在嵌入不透明组织的毛细血管中振荡。在拟议的博士项目中，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中的超声造影。学生将开始学习如何提取和保存大鼠大脑切片（离体模型）和在水凝胶中创建微米大小的毛细血管（体外模型）。微泡将暴露于超声波，同时捕获其径向振荡并倾听它们发出的声音。将分析光学和声学数据，以解释微泡如何振荡并在微血管中提供对比度。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。通过提供微泡如何在微血管中提供对比度的第一个机械理解，我们希望激发能够对微血管成像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.