Imaging the 3-D collagen organisation of biological tissues in-vivo using polarisation-sensitive optical coherence tomography.

理解人体的巨大复杂性是科学面临的巨大挑战之一，然而一个主要的简化是将人体分为细胞和细胞外基质。细胞完成生命的基本过程，包括产生能量，运输氧气和制造蛋白质，而细胞外基质为细胞本身提供支架，也为它们的血液和淋巴管网络提供支持。如果把身体比作一个大公司，那么细胞就是工人，细胞外基质就是他们的办公大楼。如果公司的建筑维修不善或有缺陷，那么工人将无法很好地工作。同样，许多使人痛苦和衰弱的疾病的根源不是细胞功能失常，而是细胞外基质的缺陷。细胞外基质主要由胶原蛋白组成，胶原蛋白是人体最丰富的结构蛋白，也是一种非常强的生物聚合物，它能形成长纤维，赋予皮肤和软骨等组织抗拉强度。在健康组织中，它具有明确的结构和组织。当这种结构变得异常时，几乎不可避免地会导致严重的疾病。骨关节炎是由年龄引起的关节软骨磨损，它会使髋关节等主要关节的骨表面无法平滑地相互滑动。极大的疼痛和活动能力的丧失。手术或放疗后形成的疤痕也与胶原结构异常有关。当使用植皮治疗严重烧伤时，一个严重的副作用是植皮后可能会收缩，这被认为是由于胶原蛋白的过量产生。结果是难看、痛苦和虚弱。现代医学有许多治疗这些疾病的策略，但其中最有希望的是组织工程。组织工程包括将病人自己的细胞或供体细胞植入伤口，并试图让这些细胞再生成正常、健康的组织。要做到这一点，它们必须再生正常、健康的细胞外基质。因此，迫切需要能够非破坏性地确定生物组织中胶原蛋白的结构和丰度的工具，无论是天然的还是人工生产的。骨科手术室、皮肤科诊所和组织工程实验室都需要这样的工具，这只是其中的一些应用。偏振敏感光学相干层析成像（PSOCT）是一种新兴的光学成像技术，可以无创地确定生物组织中光学双折射的存在。双折射是一种光学效应，在大多数组织中，其最强的来源是胶原蛋白。PSOCT的典型穿透深度可达1mm，深度分辨率为2-20微米，有潜力成为测定生物组织中胶原结构的理想工具。我们已经在实验室研究这项技术好几年了。在我们的研究过程中，我们发现了解软骨等组织中胶原纤维的完整三维结构是至关重要的，否则PSOCT的结果是模糊的，不能可靠地用于量化胶原结构。我们开创了psot技术的新扩展，可以克服这一限制，但我们以前的工作只是一个起点。我们需要开发新的仪器，最重要的是，新的数据分析算法，以便充分利用这个独特工具可能提供的所有信息。如果我们成功了，那么psot将提供目前任何现有技术都无法获得的临床重要数据。研究结果可能会大大改善骨关节炎和烧伤的治疗方法。

Understanding the enormous complexity of the human body is one of the great challenges facing science however a major simplification is to divide the body into cells and extracellular matrix . Cells perform the basic processes of life including generating energy, transporting oxygen and making proteins whilst the extracellular matrix provides the scaffolding to house the cells themselves and also their support network of blood and lymph vessels. If the body were likened to a large company then the cells are the workers and the extracellular matrix is their office block. If the buildings housing a company are in poor repair or defective then the workers will not be able to perform well. Likewise many painful and debilitating medical conditions have their origin not in a malfunction of the cells but rather in defects of the extracellular matrix. The extracellular matrix is composed chiefly of collagen, the body's most abundant structural protein and a very strong biopolymer which forms long fibres that give tissues such as skin and cartilage their tensile strength. In healthy tissues it has well-defined structure and organisation. When this structure becomes abnormal, a serious medical condition almost inevitably results. Osteoarthritis is age-induced wear of articular cartilage, which stops the bone surfaces at major joints such as the hip from sliding smoothly past each other. Great pain and loss of mobility result. Scar formation following surgery or radiotherapy is also associated with abnormalities in collagen structure. When severe burns are treated using grafted skin, a serious side-effect is that the skin-graft may contract after implantation and this is thought to be due to the excessive production of collagen. The result is unsightly, painful and debilitating. Modern medicine has many strategies for treating these conditions but one of the most promising is tissue engineering . Tissue engineering involves implanting cells, either the patient's own or donor cells, into the sight of a wound and trying to get the cells to regenerate normal, healthy tissue. To do this they must regenerate normal, healthy extracellular matrix. Consequently a pressing need exists for tools that can non-destructively determine the structure and abundance of collagen in biological tissues, both native and artificially produced. Such a tool is needed in the orthopaedic operating theatre, in the dermatology clinic and in the tissue-engineering laboratory to name just some applications. Polarization-sensitive optical coherence tomography (PSOCT) is a newly developed optical imaging technique that can non-invasively determine the presence of optical birefringence in biological tissue. Birefringence is an optical effect the strongest source of which in most tissues is collagen. With a typical depth penetration of up to 1 mm and a depth resolution of 2-20 microns, PSOCT has the potential to be an ideal tool to determine collagen structure in biological tissues. We have been investigating this technique in our lab for several years. In the course of our research we have found that it is vital to know the full 3-dimensional structure of collagen fibres in tissues such as cartilage, otherwise the results from PSOCT are ambiguous and cannot be used reliably to quantify collagen structure. We have pioneered a novel extension to the PSOCT technique which can overcome this limitation however our previous work is only a starting point. We need to develop new instrumentation and, most importantly, new data analysis algorithms in order to fully exploit all the information that this unique tool can potentially offer. If we are successful then PSOCT will deliver clinically vital data that currently is simply not available from any existing technique. The result could be greatly improved treatments for osteoarthritis and burns.