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

英国国家统计局（Office for National Statistics）的数据显示，英国每3个人中就有1人在人生的某个阶段患上癌症，每4个人中就有1人死于癌症。众所周知，癌症的早期发现可以提高生存的机会。例如，恶性黑色素瘤是一种皮肤癌，在英国每天导致五人死亡，但早期诊断的患者预后良好，治疗效果更好，五年生存率超过95%。因此，一种实用而廉价的技术可以很容易地应用于诊所和医院，在目前可能的早期阶段检测癌症，从而立即提高生存率。从长远来看，更好地了解导致癌性肿瘤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是研究小动物（如老鼠）的类似疾病。老鼠和人类的生理机能有足够的相似之处，比如免疫系统的工作方式，因此“老鼠模型”已经成为医学研究的支柱。近年来，用于识别参与疾病机制的基因和蛋白质的技术取得进展，以及转基因小鼠的可用性增加，导致对高分辨率、体内小动物成像模式的需求，这些模式可以揭示特定基因或蛋白质在何处、以何种水平表达，或其他生物分子或药物正在积聚。光声断层扫描是一种新的、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的结构，如人类头发（< 100微米）。通过检测新生肿瘤中小毛细血管的存在，它可能能够在比目前可能的更早的阶段发现癌症。例如，早期皮肤和乳腺肿瘤可以通过这种方法检测出来。此外，通过使用造影剂、分子标记或“报告”基因，小动物体内3D图像显示几个细胞内感兴趣的生物分子浓度可能成为现实的可能性。光声层析成像可以区分不同的生物分子或组织，因为它们的光吸收光谱不同。他们的颜色。当光在组织中被血液或分子标记物吸收时，就会产生小的超声波脉冲。用一种颜色的光照亮组织，这种光只被想要的目标所吸收，然后只有那个目标才会产生超声波。通过在几个探测器上记录超声波，就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时间差来确定汽车喇叭的位置一样。用这种方法可以形成目标吸收器的三维图像。光声断层扫描显然有很大的前景，对病人、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利益之前，必须克服一些剩余的技术障碍。例如，超声波在组织中的传播速度并不相同，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，如何产生单独的图像。本文提出的研究将探讨许多不同的方法来克服剩下的挑战，从而实现光声断层成像作为临床诊断和生物医学和生命科学高分辨率成像工具的全部潜力。

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.