Development of a Novel, Safe Method for the Non-invasive Assessment of Human Bone Quality, In Vivo, using spatially offset Raman spectroscopy.

拟议的活动是一项令人兴奋的国际和多学科工作计划的一部分，该计划开发用于临床的骨骼组织的拉曼光谱；首次通过未破裂的皮肤进行测量。我们最初针对的是骨质疏松症患者的骨骼，但这项新技术也适用于其他组织和条件。该项目将通过三个主要的相关开发为我们的工作增加价值：通过皮肤优化骨骼光谱(时间和空间分辨率技术)；识别与骨骼强度相关的主要光谱特征；以及与当前标准的DXA扫描相比，改进骨折风险预测。随着医疗保健的不断进步和财富的增加，我们的社会面临的一个主要问题是预期寿命的延长。因此，享受健康和积极衰老的能力往往会受到肌肉骨骼系统长期痛苦的退行性疾病的影响。事实上，政府热衷于通过早期诊断和改变生活方式进行预防，健康老龄化是国家政府的优先事项。目前用于确定骨关节炎和骨质疏松症等主要退行性骨骼疾病的技术是基于使用X射线辐射的成像(DXA扫描、CT扫描和X光照相)。这些技术是有限的，因为它们依赖于骨组织的矿物成分的成像，然而，骨的机械强度在很大程度上由蛋白质成分决定，主要是I型胶原，这对于X射线技术是不可见的。骨组织是一种复合材料，由无机矿物晶体成分和有机蛋白质纤维成分组成。矿物成分在很大程度上决定了材料的硬度和纤维成分的强度。许多骨骼疾病和与年龄相关的骨骼变化是蛋白质化学变化的结果，要么是个人遗传组成的结果，要么是骨骼本身机械负荷的结果。最近，我们的合作团队开发了一种新的革命性技术，能够通过患者的皮肤非侵入性地确定骨组织组成。空间偏移拉曼光谱(SOR)的概念能够安全地表征几毫米深度的活体组织。这至少比传统的拉曼方法要深一个数量级。我们的突破为开发用于疾病早期诊断的安全技术铺平了道路，其中组织中微妙的分子细节可以提供健康问题的指标，例如，对遗传性骨骼疾病(如脆性骨骼疾病)和退行性疾病(如关节炎)的非侵入性诊断。其他分析应用包括对药品的深度和透过涂层和包装的探测，对涂料、食品和安全筛查的地下探测。该研究项目通过一个强大的跨学科科学组成部分得到加强，开辟了拉曼光谱学的一个新分支，具有强大的研究成果商业开发潜力。我们的研究使我们能够在完全安全的条件下(2 MW)获得第一个活体人骨的拉曼光谱，作为概念的基本证明。尽管尚未得到优化，但现有的信息可以与使用传统X射线技术(如DEXA)获得的信息进行对比，后者只能得出矿物成分的密度。拉曼光谱中包含的额外信息为骨质疏松或脆性骨病等骨骼疾病的特征提供了希望。为了实现这一目标，现在需要进一步的研究来增加穿透深度，并在拉曼光谱和特定骨骼疾病之间建立牢固的联系。这一提议有可能在现代医学中开发一种新的诊断模式。

The proposed activity is part of an exciting programme of international and multi-disciplinary work developing Raman spectroscopy of skeletal tissues for clinical use; measured for the first time through the unbroken skin. We are initially targeting bone in patients with osteoporosis, but this novel technology is applicable to other tissues and conditions. This project will add value to our work with three major associated developments: optimisation of bone spectroscopy through skin (both temporally and spatially-resolved techniques); identification of major spectral features that are associated with bone strength; and improving fracture risk predictions in comparison to the current standard DXA scans. A major problem our Society faces as a consequence of continual advances in healthcare and increasing wealth is enhanced life expectancy. With this the ability to enjoy a healthy and active ageing is often compromised by painful long lasting degenerative diseases of the musculoskeletal system. Indeed the Government is keen on prevention through ealry diagnosis and lifestyle changes, health ageing is a National Government priority.Current techniques used to identify the major degenerative skeletal diseases such as osteoarthritis and osteoporosis are based on imaging using X-ray radiation (DXA scanning, CT scans and Radiography). These technologies are limited as they rely on imaging the mineral component of the bone tissue, the mechanical strength of bone,however, is determined largely by the protein component, predominantly collagen type I and this is invisible to X-ray techniques.Bone tissue is a composite material comprising an inorganic mineral crystal component and an organic proteinaceous fibre component. The mineral fraction largley determines the stiffness of the material and the fibre component the strength.Many bone diseases and age related changes to the skeleton arise as a consequence of changes in the protein chemistry, either as a consequence of the genetic make up of an indivudual or the mechanical loading of the bone itself.Recently our collaborative team has developed a new revolutionary technique capable of determining bone tissue composition non-invasively through patients' skin. The concept, Spatially Offset Raman Spectroscopy (SORS), enables safe characterisation of tissue in vivo at depths of several millimetres. This is by at least an order of magnitude deeper than that possible with conventional Raman methods. Our breakthrough paves the way for the development of safe techniques for the early diagnosis of diseases where subtle molecular details within tissue can provide indicators of health problems, for example, the non-invasive diagnosis of genetic bone disease such as brittle bone disease and degenerative conditions such as arthritis. Other analytical applications include the probing of pharmaceutical products in depth and through coatings and packaging, the subsurface probing of paints, food products and security screening. The research project is enhanced through a strong cross-disciplinary science component opening a new branch of Raman spectroscopy with strong potential for commercial exploitation of research outcomes. Our research has permitted us to obtain the first Raman spectra of human bone in vivo under totally safe conditions (2 mW) as a basic proof of concept. Although as yet unoptimised the available information can be contrasted with that obtainable using conventional X-ray techniques such as DEXA which only yield the density of the mineral component. The extra information contained in Raman spectra holds promise for the characterisation of bone diseases such as osteoporosis or brittle bone disease. To realise this goal, further research is now needed to increase the penetration depth and establish a firm link between Raman spectra and specific bone diseases. This proposal has the potential to develop a new diagnostic modality in modern medicine.