Quantitative high resolution cone beam CT for assessment of bone and joint health

描述（由申请人提供）：骨关节炎（OA）是最常见的退行性关节疾病，困扰着约3000万美国成年人，目前缺乏有效的治疗。使用放射照相术和MRI诊断OA主要依赖于晚期疾病的生物标志物，并且早期检测OA的能力可以使治疗能够防止不可逆的软骨损失。 软骨下骨（SB）结构和骨矿物质密度（BMD）的变化已被确定为早期疾病的可能生物标志物和治疗靶点。然而，由于缺乏结合高水平空间分辨率来表征骨小梁结构的成像技术，OA诊断和治疗的这一潜在进展受到阻碍 （<0.2 mm），具有高定量准确度，能够进行可靠的BMD测量，并能够在体内对大关节进行成像。专用四肢锥束CT（CBCT）是一项最新进展，与传统CT相比，它具有承重成像、减少剂量和上级空间分辨率（~0.3 mm）的能力，如使用我们机构开发的系统进行的临床研究所证明。我们假设，采用新型CMOS探测器、基于模型的图像重建和患者特异性散射校正的肢体CBCT先进系统将提供SB结构、BMD和关节间隙形态的同时体内评估，用于OA的早期诊断和治疗反应评价。支持这一假设的系统的开发和临床转化涉及以下具体目标：1）开发一种先进的肢体CBCT配置，用于体内骨健康评估，该配置采用快速、低噪声、高分辨率CMOS探测器，在针对OA成像任务优化的系统内，并与快速转化为肢体CBCT临床原型兼容; 2）通过结合系统模糊模型、无基准刚性运动校正和感兴趣体积的基于模型的重建，增强CBCT中的空间分辨率超过常规限制，多分辨率对象表示，以产生约0.1 mm的最小可分辨细节尺寸，以促进精确的SB形态测量; 3）提高定量准确度和软组织对比度（例如，软骨和肌腱），使用具有通过迭代去噪加速的蒙特卡罗计算的患者特异性散射校正（预期校正时间~2分钟/扫描），并通过开发一种新型的自动BMD校准系统与扫描仪外壳集成，以产生优于3%的BMD准确度;（4）整合目标1-在临床试点研究中对系统进行评估，以评估SB的潜在诊断性能和再现性骨结构和骨密度测量。该项目将提高CBCT的分辨率和定量准确性，转化为与OA早期检测和分期相关的试点研究，并可能应用于骨健康的其他领域，例如类风湿性关节炎或骨质疏松症。 这项研究是在约翰霍普金斯大学和Carestream Health之间的学术-工业联盟中进行的。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is the most common degenerative joint disease, afflicting ~30 million US adults and currently lacking effective treatment. OA diagnosis with radiography and MRI relies predominantly on biomarkers of late disease, and capability for early detection of OA could enable therapies preventing irreversible cartilage loss. Changes in subchondral bone (SB) architecture and bone mineral density (BMD) have been identified as possible biomarkers of early disease and a target for therapy. However, this potential advance in OA diagnosis and treatment is hampered by the lack of imaging technology that combines the high level of spatial resolution required to characterize trabecular architecture (<0.2 mm) with a high degree of quantitative accuracy enabling reliable BMD measurement and the ability to image large joints in vivo. Dedicated extremity cone-beam CT (CBCT) is a recent advance providing the capability for weight-bearing imaging, reduced dose, and superior spatial resolution (~0.3 mm) compared to conventional CT, as demonstrated in clinical studies using a system developed at our institution. We hypothesize that an advanced system for extremity CBCT utilizing a novel CMOS detector, model-based image reconstruction, and patient-specific scatter correction will provide simultaneous in-vivo assessment of SB architecture, BMD, and joint space morphology for early diagnosis and evaluation of treatment response in OA. The development and clinical translation of the system supporting this hypothesis involve the following Specific Aims: 1) Develop an advanced extremity CBCT configuration for in-vivo assessment of bone health employing a fast, low-noise, high-resolution CMOS detector within a system optimized for OA imaging tasks and compatible with rapid translation to the extremity CBCT clinical prototype; 2) Enhance spatial resolution in CBCT beyond conventional limits with model-based reconstruction incorporating a model of system blur, fiducially-free rigid motion correction, and a volume-of-interest, multi-resolution object representation to yield minimum resolvable detail size of ~0.1 mm to facilitate accurate SB morphometry; 3) Improve quantitative accuracy and soft tissue contrast (e.g., cartilage and tendons) using a patient-specific scatter correction with Monte Carlo calculation accelerated with iterative de-noising (anticipated correction time ~2 min/scan) and by developing a novel, automatic BMD calibration system integrated with the scanner enclosure to yield BMD accuracy better than 3%; and 4) Integrate the systems from Aims 1-3 onto a clinical platform for extremity CBCT and evaluate the system in a clinical pilot study to assess potential diagnostic performance and reproducibility of the SB architecture and BMD measurement. The project will advance the resolution and quantitative accuracy of CBCT translated to pilot studies pertinent to the early detection and staging of OA, with potential application in other areas of bone health e.g. rheumatoid arthritis or osteoporosis. The research is conducted in an academic-industry consortium between Johns Hopkins University and Carestream Health.