Dual-Energy Cone-Beam Tomographic Imaging and Analysis for Rheumatoid Arthritis

描述(申请人提供)：过去十年带来了类风湿性关节炎(RA)治疗的革命，迫切需要可靠的疾病进展和反应测量。尽管诊断成像能力有了长足的进步，但MRI、超声、放射成像和CT的传统方法面临着各种限制，使其不能广泛应用于RA评估--例如，有限的空间和对比度分辨率、量化、重复性和成本/可获得性。CT的一项新进展有望超越风湿学中这种模式的传统局限性-高分辨率锥束CT(CBCT)和双能量(DE)材料分解。我们最近开发了一种新的CBCT平台，专门用于肢体成像，在降低剂量的情况下展示了超出常规CT限制的空间和对比度分辨率。具体地说，该系统通过DE分解提供各向同性、亚毫米空间分辨率和软组织对比度，包括滑膜组织、软骨、肌腱和韧带。由此产生的技术可以通过获得高质量的成像以及与风湿病临床设置相适应的成本、工作流程和地点考虑，为风湿病医生的武器库提供强大的补充。我们假设，高质量的DE-CBCT结合先进的全3D图像分析将提供可靠的RA可视化和定量指标。我们将通过以下具体目标来解决这一假设：1)风湿学成像任务中DE-CBCT图像质量的优化，包括非对比检查(内源性软组织)和对比增强检查(外源性Gd或碘)；开发基于图像的定量指标，利用DE-CBCT优越的空间和对比度分辨率来测量早期-中期RA发现，遵循当前基于图像的评估的黄金标准[RA MRI评分(RAMRIS)]-即滑膜体积(SMV)、骨髓水肿体积(BMEV)和侵蚀体积(EV)-以及已被确定为风湿病潜在新相关性的全3D关节内和软骨下形态的新指标；在原型扫描仪上对20名RA患者进行试点研究，以评估DE-CBCT和相关的基于图像的指标(在配对t检验中分析的1周间隔内的测试-重测)的重复性，以及DE-CBCT指标相对于RAMRIS的有效性(RA病理评分的敏感性/特异性)。为了实现这些目标，组建了一个结合了工程学、放射学、风湿学和生物统计学专业知识的跨学科团队。这项研究的成功完成将为RA的DE-CBCT确定最佳的成像技术，开发基于图像的早期、中期和晚期RA疾病的量化指标(适用于MRI和DE-CT)，并为DE-CBCT在RA评估中的重复性和有效性提供必要的量化，作为应用DE-CBCT定量测量RA进展和治疗反应的第一步。

DESCRIPTION (provided by applicant): The last decade brought a revolution in rheumatoid arthritis (RA) therapies and an immediate need for reliable measurement of disease progression and response. Despite the strides in diagnostic imaging capabilities, conventional approaches in MRI, ultrasound, radiography, and CT face a variety of limitations that do not permit widespread application to RA assessment - e.g., limited spatial and contrast resolution, quantitation, reproducibility, and cost / accessibility. An emerging advance in CT promises to transcend the conventional limitations of this modality in rheumatology - high-resolution cone-beam CT (CBCT) with dual-energy (DE) material decomposition. We have recently developed a novel platform for CBCT dedicated to extremity imaging, demonstrating spatial and contrast resolution beyond the limits of conventional CT at reduced dose. Specifically, the system provides isotropic, sub-millimeter spatial resolution and soft-tissue contrast including synovial tissues, cartilage, tendons, and ligaments through DE decomposition. The resulting technology could provide a powerful addition to the rheumatologist's arsenal through access to high-quality imaging with cost, workflow, and site considerations appropriate to rheumatology clinical settings. We hypothesize that high- quality DE-CBCT combined with advanced, fully 3D image analysis will provide reliable visualization and quantitative metrics of RA. We will address this hypothesis through the following Specific Aims: 1.) Optimization of DE-CBCT image quality in rheumatological imaging tasks, including non-contrast exams (endogenous soft-tissues) and contrast-enhanced exams (exogenous Gd or iodine); 2.) Development of quantitative image-based metrics that leverage the superior spatial and contrast resolution of DE-CBCT for measurement of early-intermediate RA findings following the current gold standard in image-based assessment [the RA MRI score (RAMRIS)] - namely, synovial membrane volume (SMv), bone marrow edema volume (BMEv), and erosion volume (Ev) - as well as novel metrics of fully 3D intra-articular and subchondral morphology that have been identified as potential new correlates of rheumatic disease; and 3.) Translation to a pilot study in 20 RA patients on the prototype scanner to evaluate the reproducibility of DE-CBCT and associated image-based metrics (test-retest within a 1-week interval analyzed in paired t-tests) and the validity of DE-CBCT metrics relative to RAMRIS (sensitivity / specificity in scoring of RA pathology). An interdisciplinary team combining expertise in engineering, radiology, rheumatology, and biostatistics is assembled to accomplish these goals. Successful completion of the research will identify optimal imaging techniques for DE-CBCT of RA, develop quantitative image-based metrics of early, intermediate, and late RA disease (with applicability to MRI and DE-CT), and provide essential quantitation of reproducibility and validity of DE-CBCT in RA assessment as a first step toward applying DE-CBCT for quantitative measurement of RA progression and therapy response.