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

在一种拟议的新药进入临床试验阶段之前--也就是在它被允许在人体上使用之前--它必须已经经历了大量的测试。这些测试将主要检查该药物的安全性和有效性。也许在人类试验之前，药物开发过程中最关键的阶段是在老鼠身上测试药物。使用老鼠的原因有很多，其中一个关键原因是它们的遗传和生物学特征与人类足够相似，以至于许多人类疾病或医疗条件可以在老鼠身上复制或模拟。近年来，随着转基因小鼠的出现和它提供的更多控制，小鼠模型变得更加有用。在这些测试过程中被问到的一个关键问题是：药物最终在体内的哪里？例如，如果这种药物是为治疗肠道而设计的，它是最终在肠道中，还是在身体的其他地方蓄积，产生潜在的破坏性后果？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，它可以提供整个老鼠的3D高分辨率图像，并可以找出药物在图像中的位置，例如。通过能够检测到它独特的光谱特征。如果成像技术可以在活着的老鼠身上使用，而且不会对老鼠造成损害，那也会很有帮助。后一点尤其重要，因为它意味着可以在几个时间点对同一动物进行成像，以了解药物的分布如何变化，或者了解随着时间的推移，老鼠本身发生了什么变化。今天有几种常规使用的小动物成像方式，但没有一种接近于达到这一理想。人们对用于小动物成像的光声断层扫描的兴趣迅速增长，因为它有可能成为这一理想的工具。光声断层成像是一种新兴的技术，它使用短脉冲光在老鼠体内产生超声波，无论光线被吸收到哪里。光声波携带有关组织结构甚至分子含量的空间分辨率信息，传播到一系列探测器。然后使用数值算法重建鼠标内部的3D体积图像。这项技术是非侵入性的、无害的(因为它使用非电离辐射)，而且因为它是基于光学吸收的，它有可能根据组织中的成分的光学光谱(对于每种类型的分子是唯一的)来识别它们。有一个因素阻碍了光声断层扫描成为世界上小动物成像的默认方法：图像质量还没有达到应有的水平。造成这种情况的原因有三个。首先，最容易获得的传感器无法检测光声信号的全部频带，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的所有位置进行检测，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导致光声波的失真，导致图像中的像差和模糊，特别是在深度上。这里提出的扫描仪将通过使用光学检测和产生超声波，并通过使用超声计算机断层扫描作为辅助手段来帮助图像重建过程中的像差校正，来克服当前现有技术的所有这三个限制。

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.