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一个重大的和不断升级的全球卫生负担。特别值得关注的是骨质疏松症等骨骼疾病，因为这些疾病在老年人中变得更加明显。不幸的是，目前的诊断方法不能很好地预测骨折风险等病理结果。接下来的挑战是确定和开发增强的和新的骨质量评估方法，可以用于准确的预后，靶向治疗和治疗评估。研究充分证明，“骨质量”（包括胶原蛋白/矿物质比例、胶原蛋白完整性、矿物晶体大小、微应变等特征）对骨骼的机械性能有显著影响，并且可能是产生骨折诊断预测模型所需的“缺失”信息。不幸的是，目前还没有在体内测定其含量的技术。然而，这些信息体现在传统的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显著的测量困难。我们已经确定了一种潜在的途径，可以在体内测量这些有临床价值但微弱的信号。该技术直到最近才通过独立创新(i) x射线产生（平板/芯片源）和（ii）从散射x射线中获得“放大”信息（使用“焦点构建技术”，FCT）。关键的是，多发射器平板x射线源将使我们能够精确地设计所需的分析x射线束，以提供提高几个数量级的散射特征。FCT光束拓扑结构还可以同时测量吸收的x射线（以估计骨矿物质密度）和相干（和非相干）散射的x射线。芯片源技术是一种能够从极低功率源产生x射线的平板设备。它还有一个额外的优点，即它可以制造出精确的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一个成像/DEXA/散射系统中，以提供一个全面的诊断工具。该技术的性质也使设计朝着手持便携式设备的点病人护理。因此，这项建议主要涉及一种新仪器的开发，该仪器随后将用于研究将我们的新技术应用于许多不同领域的可能性，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.