WHOLE-BODY, HIGH RESOLUTION, 3D, SMALL ANIMAL PHOTOACOUSTIC AND ULTRASOUND COMPUTED TOMOGRAPHY SYSTEM

在一种被提议的新药进入临床试验阶段之前——也就是在它被允许用于人类之前——它必须已经经历了大量的测试。试验将主要检查药物的安全性和有效性。在人体试验之前，药物开发过程中最关键的阶段可能是在小鼠身上进行药物测试。使用老鼠的原因有很多，一个关键的原因是它们的遗传和生物学特征与人类非常相似，因此许多人类疾病或医疗状况可以在老鼠身上复制或建模。近年来，随着转基因小鼠的出现及其提供的控制能力的增强，小鼠模型变得更加有用。在这些测试中被问到的一个关键问题是：药物在体内的最终位置？例如，如果药物被设计用来治疗肠道，它最终会进入肠道，还是会在身体的其他地方积累，造成潜在的破坏性后果？这类测试被称为生物分布研究。生物分布研究的理想工具是一种设备，它可以提供整个小鼠的高分辨率3D图像，并可以在图像中找出药物所在的位置。通过探测它独特的光谱特征。如果这种成像技术能用于活体小鼠，而且不会对小鼠造成损伤，那将是有益的。后一点尤其重要，因为这意味着可以在几个时间点对同一只动物进行成像，以观察药物的分布如何变化，或者观察随着时间的推移，老鼠本身发生了什么变化。目前有几种常规使用的小动物成像模式，但没有一种接近于满足这种理想。由于光声层析成像有可能成为一种理想的工具，因此对小动物成像的兴趣迅速增长。光声断层扫描是一种新兴技术，它利用短脉冲光在老鼠体内产生超声波，无论光被吸收到哪里。光声波携带有关组织结构甚至分子含量的空间分辨信息，向外传播到一系列探测器。然后使用数值算法重建鼠标内部的三维体积图像。这项技术是非侵入性的，无害的（因为它使用的是非电离辐射），而且，因为它是基于光学吸收的，它有可能根据它们的光谱（每种类型的分子都是独特的）来识别组织内的成分。有一个因素阻碍了光声断层成像成为世界范围内小动物成像的默认方法：图像质量还没有达到应有的水平。这有三个原因。首先，最容易获得的传感器无法检测光声信号的整个频率带宽，因此无法捕获关键信息；其次，由于所需阵列的制造复杂性和成本，大多数成像系统不能从动物周围进行检测，从而导致图像伪影；第三，由于不同组织类型之间和内部的声速变化引起的光声波畸变导致图像畸变和模糊，特别是在深度处。本文提出的扫描仪将克服当前可用技术的所有这三个限制，通过使用光学检测和超声产生，并通过使用超声计算机断层扫描作为辅助方式，以促进图像重建过程中的像差校正。

Before a proposed new medicine reaches the stage of a clinical trial - so before it is allowed to be used on people - it must have already undergone a great deal of testing. The tests will principally examine the safety of the drug and its efficacy. Perhaps the most crucial stage in the drug development pathway prior to human trials involves testing drugs on mice. There are many reasons why mice are used, a key one being that their genetic and biological characteristics are sufficiently similar to humans that many human diseases or medical conditions can be replicated or modelled in mice. In recent years, with the advent of genetically-altered mice and the increase control it offers, mouse models have become even more useful. One of the key questions that is asked during these tests is: where has the drug ended up in the body? If the drug is designed to treat the gut, for example, does it end up in the gut or does it accumulate elsewhere in the body with potentially damaging consequences? Tests of this sort are called biodistribution studies.The ideal tool for biodistribution studies would be a device that can provide an image of the whole mouse in 3D, in high resolution, and can pick out where in that image the drug is located, eg. by being able to detect its unique spectral signature. It would also be helpful if the imaging technique could be used on a live mouse and, furthermore, did no damage to the mouse. This latter point is especially important as it means that the same animal can be imaged at several points in time to see how the distribution of the drug changes, or see what changes are occurring in the mouse itself over time. There are several small animal imaging modalities that are in routine use today, but none of them come close to meeting this ideal. There is rapidly growing interest in photoacoustic tomography for small animal imaging because it has the potential to become this ideal tool. Photoacoustic tomography is an emerging technique that uses short pulses of light to generate ultrasound waves within the mouse wherever the light is absorbed. The photoacoustic waves, which carry spatially-resolved information about the structure and even the molecular content of the tissue, propagate out to an array of detectors. A numerical algorithm is then used to reconstruct a 3D volumetric image of the interior of the mouse. The technique is non-invasive, harmless (as it uses non-ionising radiation), and, because it is based on optical absorption, it has the potential to identify components within the tissue based on their optical spectra (which are unique to every type of molecule). There is one factor holding photoacoustic tomography back from becoming the default approach for small animal imaging the world over: the image quality is not yet as good as it could be. There are three reasons for this. First, the most readily-available sensors cannot detect the full frequency bandwidth of the photoacoustic signals and so fail to capture key information; second, most imaging systems do not detect from all around the animal due to the fabrication complexity and cost of the arrays that would be needed, resulting in image artefacts; third, distortions of the photoacoustic waves due to sound speed variations between and within the different tissue types leads to aberration and blurring in the image, especially at depth.The scanner proposed here will overcome all three of these limitations of the currently available technologies, through the use of optical detection and generation of ultrasound, and by using ultrasound computed tomography as a adjunct modality to facilitate aberration correction during the image reconstruction.