Quantitative bone radiomics using Ultra-High Resolution CT

项目摘要/摘要 骨质疏松症(OP)和骨性关节炎(OA)累计影响着4000多万美国人。OP和OA都是 由于现有诊断和治疗工具的准确性有限，诊断和治疗不足 治疗监测。对改进的OP和OA生物标记物的需求激发了对定量评估的兴趣 从X线片、CT和MRI获得的松质骨的纹理特征。在这样的“骨放射组学”中，图像 纹理提供对骨小梁几何形状(≤100µm细节大小)的间接评估，它更适合于 与微型CT等使用的直接测量相比，诊断成像方式的分辨率有限。首字母 骨组织生物标志物的临床验证在预测椎体衰竭方面显示出良好的性能 和骨性关节炎的进展。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是必不可少的- 特别是在新兴的高分辨率成像技术的背景下。最近，新的CT扫描仪具有~2倍的 与传统CT相比，主要制造商已经引入了更高的空间分辨率， 包括佳能精密系统，将在这个项目中使用。这款新一代的超高分辨率 CT(UHR CT)能够显示~150微米的细节，接近骨小梁厚度，因此有可能 使在体骨微结构评估方面取得突破。我们假设改进后的 UHR CT的空间分辨率将带来比正常分辨率更好的骨放射组学定量性能 CT(NR CT)或X线骨密度仪(DXA)。为了建立使用UHR-CT的骨放射组学的临床实用价值， 将追求以下目标：1)进行第一次基于CT的敏感性的全面评估 骨骼纹理特征到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，对骨芯标本进行实验研究。我们将建立UHR和 与骨小梁几何形状相关的CT征象，在身体大小和剂量方面是可重复的。 2)利用超高分辨率CT纹理特征对骨小梁硬度进行了改进的预测。多变量 将对~300个骨骼进行目标1中研究的硬度和质地骨骼特征之间的回归 使用UHR CT和NR CT的岩心。我们将演示与UHR CT相比，改进的刚度估计 NRCT。3)临床应用UHR CT纹理特征对OP治疗进行纵向监测。 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。我们将演示UHR CT的放射学特征可以检测骨骼质量的变化 比DXA更早。我们还将研究骨放射组学在预测融合结果方面的可行性。 AIMS的成功完成将建立基于UHR CT的定量骨放射学作为一种新的工具 对骨性关节炎和骨质疏松症患者的骨健康进行体内评估，降低患者的发病率和死亡率。

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.