SBIR Phase I: Development of a novel, high-sensitivity diagnostic for bone disease, enabling early-stage diagnosis and precise monitoring of therapy effects.

如果成功，这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力是引入一种新的诊断范式，可以显著提高临床医生诊断由年龄、骨关节炎和癌症治疗引起的早期骨病理的能力。虽然目前的骨护理标准依赖于测量整体骨密度，但这项新技术评估骨内的微观结构，这一测量与骨折风险和疾病阶段的相关性更强。除了提供骨折风险的精确测量外，该技术还将实现以下敏感测量：1)将目标患者纳入治疗试验；2)监测这些治疗方法的疗效，以改善预后糟糕的痛苦病理（一半髋部骨折患者无法恢复独立生活的能力，并且进一步骨折的风险显著增加）。因此，由制药公司和诊断设备制造商推动的商业市场是巨大的。虽然这个SBIR项目的重点是开发一种骨骼疾病的诊断方法，但这一发展将为诊断技术在未来的广泛应用提供信息，这些疾病目前还没有无创的早期诊断方法。该项目旨在验证这种新的基于磁共振的诊断能力，在临床相关环境中提供小梁骨形态测量参数的敏感测量。直接测量骨小梁微结构的变化是骨病的先兆，目前的磁共振成像技术无法做到这一点，因为成像所需的患者长时间运动限制了分辨率。新的诊断将能够获得对患者运动免疫的必要数据，显着提高分辨率，并能够对小梁骨形态测量参数进行敏感测量。这种能力的验证将通过应用于一组纹理复杂性不断增加的3d打印模型和尸体椎骨，并使用能够在数据采集过程中诱导临床相关运动轮廓的专用设备。这项工作的主要重点是优化采集和分析软件，以达到测量骨质疏松骨小梁元素宽度所需的高分辨率。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase l Project, if successful, is the introduction of a new diagnostic paradigm that can significantly increase the ability of clinicians to diagnose early stage bone pathology resulting from age, osteoarthritis, and cancer therapy. While the current standard of bone care relies on a measurement of overall bone density, this new technology assesses the microstructure within bone, a measure that correlates much more strongly with fracture risk and disease stage. Along with providing an accurate measure of fracture risk, this technology will enable sensitive measure to: 1) target patients for inclusion in therapy trials, and 2) enable monitoring of the efficacy of these therapies towards amelioration of an excruciatingly painful pathology with a dire prognosis (half of people suffering hip fracture never regain their ability to live independently, and are at significantly increased risk of further fractures). As such, the commercial market, driven by pharmaceutical companies and diagnostic equipment manufacturers, is large. While the focus of this SBIR project is to develop a diagnostic for bone disease, the development will inform future application of the diagnostic technology to a large range of diseases for which no non-invasive, early-stage diagnostic currently exists. The proposed project is designed to validate the ability of this new magnetic-resonance based diagnostic to provide a sensitive measure of trabecular bone morphometry parameters, in a clinically relevant environment. Direct measurement of the changes in trabecular bone microarchitecture that are the harbinger of bone disease is outside the capability of current magnetic resonance imaging, resolution being limited by patient motion over the long times needed to generate an image. The new diagnostic will have the ability to acquire the requisite data with immunity to patient motion, increasing resolution significantly, and enabling sensitive measurement of trabecular bone morphometry parameters. Validation of this ability will be through application to a set of 3D-printed phantoms of increasing textural complexity and cadaver vertebrae, with use of a purpose-built apparatus capable of inducing clinically relevant motion profiles during data acquisition. The major focus of this effort is optimization of the acquisition and analysis software so as to achieve the high resolution needed to measure trabecular element width in osteoporotic bone.