Quantitative bone radiomics using Ultra-High Resolution CT

项目总结/摘要 骨质疏松症（OP）和骨关节炎（OA）累积影响超过4000万美国人。OP和OA 由于现有诊断工具的准确性有限， 治疗监测。对OP和OA生物标志物的改进的需求激发了定量评估的兴趣 松质骨的纹理特征来自X线、CT和MRI。在这种“骨放射组学”中， 纹理提供了对小梁几何形状（≤100 µm细节尺寸）的间接评估，更适合于 诊断成像模态的分辨率比在例如微型CT中使用的直接测量有限。初始 纹理骨生物标志物的临床验证显示在预测椎体失效方面有前景 和OA的进展。然而，对图像形成过程如何影响纹理的严格调查 生物标志物对于建立骨放射组学成像和分析的标准化方案至关重要- 特别是在高分辨率成像的新兴技术的情况下。最近，新的CT扫描仪具有~2x 与传统CT相比改进的空间分辨率已经由主要制造商引入， 包括将用于本项目的佳能精密系统。新一代超高分辨率 CT（UHR CT）能够显示约150 µm的细节，接近小梁厚度，因此可能 从而在骨微结构的体内评估方面取得突破。我们假设， UHR CT的空间分辨率将导致比正常分辨率更好的骨放射组学定量性能 CT（NR CT）或X线吸收测定法（DXA）。为了建立使用UHR-CT的骨放射组学的临床实用性， 将追求以下目标：1）对基于CT的敏感性进行首次全面评估 骨骼的纹理特征到CT成像链的关键组件（例如，扫描和重建协议） 使用高保真CT模拟器和骨芯样本的实验研究。我们将建立UHR， NR CT特征与骨小梁几何形状相关，并可在体型和剂量方面重现。 2)证明使用UHR CT纹理特征改善了对骨小梁硬度的预测。多元 将对约300个骨进行目标1中研究的刚度和纹理骨特征之间的回归 使用UHR CT和NR CT的核心。我们将证明UHR CT与 NR CT。3)在OP治疗的纵向监测中执行基于UHR CT纹理特征的临床试验。 我们将获得20例接受OP药物治疗的脊柱融合患者的纵向UHR CT和DXA，以优化 他们的骨骼质量。我们将证明UHR CT的放射组学特征检测骨质的变化 比DXA更早。我们还将研究骨放射组学在预测融合结果中的可行性。 目标的成功完成将建立定量UHR CT为基础的骨放射组学作为一种新的工具， OA和OP患者骨健康的体内评估，降低患者发病率和死亡率。

PROJECT SUMMARY / ABSTRACT Osteoporosis (OP) and osteoarthritis (OA) cumulatively affect more than 40 million Americans. Both OP and OA are underdiagnosed and undertreated because of the limited accuracy of existing tools for diagnosis and treatment monitoring. The need for improved biomarkers of OP and OA spurred interest in quantitative evaluation of texture features of cancellous bone derived from radiography, CT, and MRI. In such “bone radiomics”, image texture provides an indirect assessment of the trabecular geometry (≤100 µm detail size) that is better suited to the limited resolution of diagnostic imaging modalities than the direct measurements used in e.g. micro-CT. Initial clinical validation of textural bone biomarkers showed promising performance in prediction of vertebral failure and progression of OA. However, rigorous investigation of how the image formation process affects textural biomarkers is essential to establish standardized protocols for imaging and analysis in bone radiomics – especially in light of emerging technologies for high-resolution imaging. Recently, new CT scanners with ~2x improved spatial resolution compared to conventional CT have been introduced by major manufacturers, including the Canon Precision system that will be used in this project. This new generation of ultra-high resolution CT (UHR CT) is capable of visualizing ~150 µm details, approaching the trabecular thickness and thus potentially enabling a breakthrough in in-vivo evaluation of bone micorarchitecture. We hypothesize that the improved spatial resolution of UHR CT will lead to better quantitative performance of bone radiomics than normal resolution CT (NR CT) or x-ray absorptiometry (DXA). To establish the clinical utility of bone radiomics using UHR-CT, the following Aims will be pursued: 1) Perform the first comprehensive assessment of the sensitivity of CT-based texture features of bone to key components of the CT imaging chain (e.g., scan and reconstruction protocol) using a high-fidelity CT simulator and experimental studies in bone core samples. We will establish UHR and NR CT features that are correlated to trabecular geometry and reproducible with respect to body size and dose. 2) Demonstrate improved prediction of trabecular stiffness using UHR CT texture features. Multivariate regression between stiffness and texture bone features investigated in Aim 1 will be performed for ~300 bone cores using UHR CT and NR CT. We will demonstrate improved stiffness estimates with UHR CT compared to NR CT. 3) Perform a clinical pilot of UHR CT-based texture features in longitudinal monitoring of OP treatment. We will acquire longitudinal UHR CT and DXA of 20 spine fusion patients being treated with OP drug to optimize their bone quality. We will demonstrate that radiomic features from UHR CT detect changes in bone quality earlier than DXA. We will also investigate the feasibility of bone radiomics in prediction of fusion outcomes. Successful completion of the Aims will establish quantitative UHR CT-based bone radiomics as a novel tool for in-vivo assessment of bone health in OA and OP, with downstream reduction of patient morbidity and mortality.