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，该小型企业创新研究（SBIR）I期项目的更广泛影响/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年龄、骨关节炎和癌症治疗导致的早期骨病理学的能力。虽然目前的骨骼护理标准依赖于对整体骨密度的测量，但这项新技术评估了骨骼内的微观结构，这一指标与骨折风险和疾病阶段的相关性更强。沿着提供骨折风险的精确测量，该技术将实现敏感测量，以：1）将目标患者纳入治疗试验，以及2）能够监测这些治疗对改善具有可怕预后的极度疼痛的病理的功效（一半的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驱动的商业市场很大。虽然该SBIR项目的重点是开发骨骼疾病的诊断方法，但该开发将为诊断技术在目前没有非侵入性早期诊断的大范围疾病中的未来应用提供信息。拟议项目旨在验证这种新的基于磁共振的诊断方法在临床相关环境中提供骨小梁形态测量参数的灵敏测量的能力。直接测量骨小梁微结构的变化是骨疾病的预兆，这超出了当前磁共振成像的能力，分辨率受到生成图像所需的长时间内患者运动的限制。新的诊断将有能力获得必要的数据与免疫患者的运动，提高分辨率显着，并实现灵敏的测量骨小梁形态参数。这种能力的验证将通过应用于一组纹理复杂性增加的3D打印体模和尸体椎骨，使用能够在数据采集期间诱导临床相关运动曲线的专用设备。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细胞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.