Point-of-Care High Accuracy Fracture Risk Prediction

人口老龄化及其对准确医疗诊断的需求是世界范围内一个重大且不断升级的健康负担。特别令人担忧的是骨质疏松症等骨性疾病，因为这些疾病在老年人群中变得更加明显。不幸的是，目前的诊断方法不能很好地预测病理结果，如骨折风险。因此，挑战是确定和开发可用于准确预后、靶向治疗和治疗评估的增强的和新的骨质量评估方法。已经很好地证明了‘骨质量’(包括诸如胶原/矿物质比率、胶原完整性、矿物微晶大小、微应变等特征)对骨骼的机械性能有显著的影响，并且可能是产生骨折诊断预测模型所需的‘缺失’信息。遗憾的是，目前还没有体内测定它的技术。然而，这些信息包含在传统的X射线散射特征(例如，X射线衍射)中，尽管这些特征很弱并且存在重大的测量困难。我们已经确定了一条在体内测量这些具有临床价值但微弱的信号的潜在途径。这项技术最近才通过(I)X射线产生(平板/芯片上的源)和(Ii)从散射X射线中获得“放大”信息(使用“焦点构建技术”，FCT)的独立创新而可用。重要的是，多发射体平板X射线源将使我们能够精确地设计所需的分析X射线束，以提供增强了几个数量级的散射特征。FCT波束拓扑还能够同时测量被吸收的X射线(以估计骨密度)和那些相干(和非相干)散射的X射线。这种单芯片源技术是作为一种平板设备制造的，能够从非常低的功率源产生X射线。它还有一个额外的优点，那就是它可以被制造成精确地产生FCT所需的几何形状的X射线源。最终，我们设想将这些技术集成到单个成像/DEXA/散射系统中，以提供一个全面的诊断工具。该技术的性质也使得设计能够针对患者点护理的手持便携设备。因此，这项建议主要涉及开发一种新的仪器，随后将用来审查将我们的新技术应用于若干不同领域的可能性，因此它将使新的和令人兴奋的研究能力成为可能。

A significant and escalating worldwide health burden is the aging population and its demand for accurate medical diagnostics. Of particular concern are osteo diseases such as osteoporosis as these become significantly more apparent in elderly populations. Unfortunately, current diagnostic methods are poor predictors of pathology outcomes such as fracture risk. The challenge then is to identify and develop enhanced and new approaches to bone quality appraisal that can be employed for accurate prognosis, targeted therapies and therapy assessment. It has been well demonstrated that 'bone quality' (including characteristics such as collagen/mineral ratio, collagen integrity, mineral crystallite size, microstrain) has a marked affect on a bone's mechanical properties and is probably the 'missing' information required to produce diagnostically predictive models of fracture. Unfortunately there is no current technique for its in vivo determination. However, such information is embodied within conventional X-ray scatter signatures (e.g. X-ray diffraction) although these are weak and present significant measurement difficulties. We have identified a potential route to in vivo measurement of these clinically valuable but weak signals. The technology has only recently become available through independent innovations for (i) X-ray generation (flat panel/source-on-a-chip) and (ii) obtaining 'amplified' information from scattered X-rays (using 'focal construct technology', FCT). Critically, the multi-emitter flat panel X-ray source will enable us to engineer precisely the analytical X-ray beam required to provide scatter signatures enhanced by several orders of magnitude. The FCT beam topology also enables the simultaneous measurement of the absorbed X-rays (to estimate bone mineral density) and those coherently (and incoherently) scattered. The source-on-a-chip technology is manufactured as a flat-panel device capable of generating X-rays from very low-power sources. It has the additional advantage that it may be fabricated to produce an X-ray source of precisely the geoemetric form required for FCT. Ultimately we envisage these techniques being integrated within a single imaging/DEXA/scatter system to provide a comprehensive diagnostic tool. The nature of the techniques also enables design towards hand portable devices for point-of-patient care. Thus this proposal principally concerns the development of a new instrument that will be subsequently used to examine the possibilities of applying our novel technologies to a number of different areas and therefore it will enable a new and exciting research capability.