SBIR Phase I: Digitization of Skeletal Evaluations for Developmental and Reproductive Toxicology (DART) Studies.

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是为生殖毒理学研究开发一个数字骨骼评估工作流程，这将更好地确保具有致畸作用的潜在治疗方法不会进入市场，并减少时间和成本。目前表征新疗法和化学物质对骨骼发育影响的方法依赖于基于人类的定性表征，而这种数字和定量方法的目标将是更准确地表征疗法的效果。在这个价值25亿美元的毒理学市场中，改进的骨骼表征工作流程也将减少动物的使用。通过该项目开发的成像和表征平台将作为一种服务商业化，合同研究机构或制药公司可能会将胎儿骨骼送到分析中心。或者，客户可以购买该平台。这种双阶段的商业模式将允许小型合同研究机构外包劳动密集型特征，而大型合同研究机构将转向这种新的数字方法。SBIR第一期项目提出优化原型光学相干断层扫描（CT）扫描仪，用于高分辨率啮齿动物骨骼的3D数字化。使用该系统，啮齿动物骨骼将被转换成三维数据矩阵，可以由胎儿病理学家进行数字评估或通过计算机定量表征缺陷。光学扫描仪的照明和成像参数将被系统优化，以减少噪声，并使不同骨骼特征之间的清晰区分。一旦啮齿类动物骨骼可以以可重复的方式成像以创建三维数据集，这些数据集将与使用更昂贵的x射线CT成像从同一动物获得的数据集进行定量并排比较。在成像优化和验证之后，将开发一个数字分析程序，以确定啮齿动物模型中的骨骼是否偏离对照样本。该计划将开始允许对发育和生殖毒理学研究的啮齿动物骨骼进行完整的数字评估。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of a digital skeletal evaluation workflow for reproductive toxicology studies that will better ensure that potential therapeutics with teratogenic effects will not make it to the marketplace, and at reduced time and cost. The current approach for characterizing the impact of new therapeutics and chemicals on skeletal development relies upon human-based qualitative characterization, while the goal for this digital and quantitative approach will be to more accurately characterize the effect of therapeutics. An improved skeletal characterization workflow in this $2.5 billion toxicology market also will allow for the reduced usage of animals. The imaging and characterization platform developed through this project will be commercialized as a service where contract research organizations or pharmaceutical companies may send fetal skeletons for analysis. Alternatively, customers may purchase the platform. This biphasic business model will allow small contract research organizations to outsource labor intensive characterization and large contract research organizations to switch to this new digital approach. This SBIR Phase I project proposes to optimize a prototype optical coherence tomography (CT) scanner for the 3D digitization of rodent skeletons at high resolution. Using this system, rodent skeletons will be transformed into three-dimensional data matrices that can be evaluated digitally by a fetal pathologist or characterized quantitively by a computer for defects. The illumination and imaging parameters of the optical scanner will be systematically optimized to reduce noise and to enable the clear differentiation between different skeletal features. Once rodent skeletons can be imaged in a reproducible manner to create three-dimensional data sets, these data sets will be compared quantitatively side-by-side to data sets acquired from the same animals using more expensive X-ray CT imaging. Following imaging optimization and validation, a digital analysis program will be developed that will determine if bones in a rodent model deviate from control samples. This program will begin to allow for the complete digital evaluation of rodent skeletons for developmental and reproductive toxicology studies.