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

使用偏振敏感光学相干断层扫描对体内生物组织的 3D 胶原蛋白组织进行成像。

基本信息

批准号：
EP/F020422/1
负责人：
Stephen Matcher
金额：
$ 51.14万
依托单位：
University of Sheffield
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FF020422%2F1
关键词：
Imaging collagen organisation biological tissues

项目摘要

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.

了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身体分为细胞和细胞外基质。细胞执行生命的基本过程，包括产生能量，运输氧气和制造蛋白质，而细胞外基质提供支架来容纳细胞本身及其血管和淋巴管的支持网络。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室。如果公司所在的建筑物维修不良或有缺陷，那么工人将无法很好地工作。同样，许多疼痛和衰弱的医学状况的起源不是细胞的功能障碍，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，它形成长纤维，使皮肤和软骨等组织具有拉伸强度。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医疗状况。骨关节炎是年龄引起的关节软骨磨损，它阻止了主要关节（如髋关节）的骨表面相互平滑滑动。结果是巨大的疼痛和行动能力的丧失。手术或放疗后的瘢痕形成也与胶原结构异常有关。当使用移植皮肤治疗严重烧伤时，一个严重的副作用是皮肤移植物在植入后可能收缩，这被认为是由于胶原蛋白的过度产生。结果是难看的，痛苦的和衰弱的。现代医学有许多治疗这些疾病的策略，但其中最有前途的是组织工程。组织工程包括将细胞（患者自身或供体细胞）植入伤口，并试图让细胞再生正常健康的组织。要做到这一点，他们必须再生正常，健康的细胞外基质。因此，迫切需要能够非破坏性地确定天然和人工产生的生物组织中胶原蛋白的结构和丰度的工具。在整形外科手术室、皮肤科诊所和组织工程实验室中需要这样的工具，仅举一些应用。偏振敏感光学相干层析成像（PSOCT）是一种新发展的光学成像技术，可以无创地确定生物组织中是否存在光学双折射。胶原蛋白是一种光学效应，其在大多数组织中的最强来源是胶原蛋白。PSOCT的典型穿透深度可达1 mm，深度分辨率为2-20微米，有可能成为确定生物组织中胶原蛋白结构的理想工具。多年来，我们一直在实验室研究这项技术。在我们的研究过程中，我们发现了解组织（如软骨）中胶原纤维的完整三维结构至关重要，否则PSOCT的结果是模糊的，不能可靠地用于量化胶原结构。我们开创了一种新的扩展PSOCT技术，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，以充分利用这个独特的工具可能提供的所有信息。如果我们成功了，那么PSOCT将提供目前任何现有技术都无法提供的临床重要数据。其结果可能会大大改善骨关节炎和烧伤的治疗。