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

描述（由申请人提供）：过去十年来，类风湿性关节炎（RA）治疗发生了革命，迫切需要可靠的疾病进展和反应测量。尽管在诊断成像能力方面取得了长足的进步，但MRI、超声、放射照相和CT中的常规方法面临着各种限制，这些限制不允许广泛应用于RA评估-例如，有限的空间和对比度分辨率、定量、再现性和成本/可达性。CT的一个新进展有望超越这种模式在流变学中的传统局限性-具有双能量（DE）材料分解的高分辨率锥形束CT（CBCT）。我们最近开发了一种用于CBCT的新型平台，专门用于肢体成像，在降低剂量的情况下展示了超出传统CT极限的空间和对比度分辨率。具体而言，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提供一个强大的除了风湿病学家的武器库，通过访问高质量的成像与成本，工作流程，并适当的风湿病临床设置的网站考虑。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个假设：1。在血流成像任务中优化DE-CBCT图像质量，包括非造影检查（内源性软组织）和造影增强检查（外源性Gd或碘）; 2.）开发基于图像的定量指标，利用DE-CBCT的上级空间和对比度分辨率，根据基于图像的评估[RA MRI评分（RAMRIS）]的当前金标准测量早期-中期RA结果-即滑膜体积（SMv）、骨髓水肿体积（BMEv），和侵蚀体积（Ev）-以及已被鉴定为风湿性疾病的潜在新相关物的全3D关节内和软骨下形态的新度量;和3.）转化为在原型扫描仪上对20名RA患者进行的试点研究，以评价DE-CBCT和相关基于图像的指标的再现性（在配对t检验中分析的1周间隔内的重测）以及DE-CBCT指标相对于RAMRIS的有效性（RA病理学评分的灵敏度/特异性）。一个跨学科的团队，结合工程，放射学，流变学和生物统计学的专业知识组装，以实现这些目标。该研究的成功完成将确定用于RA DE-CBCT的最佳成像技术，开发早期，中期和晚期RA疾病的定量图像指标（适用于MRI和DE-CT），并提供DE-CBCT在RA评估中的重现性和有效性的基本定量，作为将DE-CBCT应用于定量测量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.