Simulations and Inversions in Photoacoustic Tomography for High Resolution Quantitative Biomedical Imaging

根据英国国家统计局的数据，在英国，每三个人中就有一个人在一生中的某个阶段患上癌症，四分之一的人死于癌症。众所周知，癌症的早期发现可以提高存活的机会。例如，恶性黑色素瘤是一种皮肤癌，在英国每天导致5人死亡，但在治疗更有效的早期阶段被诊断出来的患者预后良好，五年存活率超过95%。因此，一种实用而廉价的技术，可以很容易地部署到诊所和医院，在比目前可能的阶段更早地发现癌症，因此将立即提高存活率。从长远来看，更好地了解导致癌症的过程和途径将有助于开发新的治疗方法和药物。了解人体疾病最成功的方法之一就是在老鼠等小动物身上研究类似的疾病。小鼠和人类的生理学有足够的相似性，比如在免疫系统的工作方式上，“小鼠模型”已经成为医学研究的支柱。近年来，用于识别疾病机制中涉及的基因和蛋白质的技术的进步，以及转基因小鼠的增加，导致了对高分辨率、活体小动物成像方式的需求，这些小动物成像方式可以揭示特定基因或蛋白质在哪里以及在什么水平上表达，或者其他生物分子或药物正在积累。光声断层成像是一种新的、廉价的成像技术，可以提供生物软组织的3D图像，并有可能解析组织内窄至人类头发(100微米)的结构。通过检测新生肿瘤中的小毛细血管的存在，它可能能够在比目前可能的更早阶段发现癌症。例如，使用这种方法可以检测到早期的皮肤和乳房肿瘤。此外，通过使用造影剂、分子标记或报告基因，小动物的3D活体图像可以显示几个细胞内感兴趣的生物分子的浓度。光声断层成像可以区分不同的生物分子或组织，因为它们的光学吸收光谱不同，即。他们的颜色。当组织中的光被例如血液或分子标记物吸收时，产生小的超声波脉冲。通过用只被所需目标吸收的颜色的光照射组织，那么只有该目标才会产生超声波。通过在几个探测器上记录超声波，可以计算出它的来源，就像我们通过声音到达我们两只耳朵的不同时间来确定汽车喇叭的位置一样。通过这种方式，可以形成目标吸收体的3D图像。光声断层扫描显然有很大的前景，对患者、临床医生和研究人员的好处可能是巨大的。然而，在充分实现所有潜在好处之前，必须克服一些剩余的技术障碍。例如，超声波在组织中传播的速度在所有地方都不一样，因此会导致图像模糊。也许最重要的突出问题是当两种或两种以上的吸收物质(比如血液和造影剂)同时存在于组织中时，产生不同的图像。这里提出的研究将探索一些不同的方法来克服剩余的挑战，从而充分发挥光声断层成像作为生物医学和生命科学的临床诊断和高分辨率成像工具的潜力。

One out of every three people in the UK develops cancer at some stage in their life, and one in four die from it, according to the Office for National Statistics.It is well known that the early detection of cancer improves the chances of survival. For instance, malignant melanoma is a type of skin cancer that causes five deaths per day in the UK, but patients diagnosed at an early stage, when the treatments are much more effective, have an excellent prognosis with a five-year survival rate greater than 95%. A practical and inexpensive technique that could easily be deployed in clinics and hospitals to detect cancers at an earlier stage than is currently possible would therefore immediately improve survival rates.In the longer term, a better understanding of the processes and pathways that lead to cancerous tumours would aid in the development of new treatments and drugs. One of the most successful approaches to understanding disease in the human body has been to study similar diseases in small animals such as mice. There is sufficient similarity between murine and human physiology, such as in the way the immune system works, that 'mouse models' have become a mainstay of medical research. In recent years, advances in the techniques used to identify genes and proteins involved in disease mechanisms, and the increased availability of transgenic mice, have led to a demand for high-resolution, in vivo, small animal imaging modalities that can reveal where, and at what level, specific genes or proteins are being expressed, or other biomolecules or drugs are accumulating.Photoacoustic tomography is a new, inexpensive imaging technique that can provide 3D images of biological soft tissue, and has the potential to resolve structures within the tissue as narrow as a human hair (< 100 microns). By detecting the presence of small capillaries within nascent tumours, it may be able to detect cancers at an earlier stage than is currently possible. Early skin and breast tumours, for example, may be detectable using this approach. Furthermore, by using contrast agents, molecular markers or 'reporter' genes, 3D in vivo images of small animals showing the concentrations of the biomolecules of interest to within a few cells could become a realistic possibility.Photoacoustic tomography can distinguish between different biomolecules or tissues because of differences in their optical absorption spectra, ie. their colour. Small ultrasonic pulses are generated when light is absorbed in the tissue by, for instance, blood or a molecular marker. By illuminating the tissue with a colour of light that is absorbed only by the desired target, then only that target will generate ultrasound. By recording the ultrasound over several detectors, its origin can be calculated, in much the same way as we determine the location of a car horn by the difference in the time of arrival of the sound at our two ears. In this way a 3D image of the target absorber can be formed.Photoacoustic tomography clearly has great promise and the benefits to patients, clinicians and researchers could be enormous. However, some remaining technical hurdles must be overcome before all the potential benefits can be fully realised. For example, the speed at which the ultrasound travels through the tissue is not the same everywhere and so results in blurred images. Perhaps the most important outstanding problem is that of producing separate images of two or more absorbing substances (blood and a contrast agent, say) when they are simultaneously present in the tissue.The research proposed here will investigate a number of different ways to overcome the remaining challenges and so realize the full potential of photoacoustic tomography as a tool both for clinical diagnosis and high resolution imaging in biomedicine and the life sciences.