Ultrasensitive Doppler Ultrasound for Evaluation of Rheumatoid Arthritis

项目概要 类风湿性关节炎 (RA) 是一种关节自身免疫性疾病，影响着 130 万美国人，其中 据估计，美国每年的护理费用为 416 亿美元。 RA 的临床管理需要定期评估 滑膜炎症的情况来指导治疗。 RA、放射线照相和对比增强 MRI 的临床评分为 分别受到低灵敏度、辐射安全性和成本的限制。多普勒超声在临床上用于 滑膜炎评估，但微血管检测灵敏度较低（可能导致漏诊）和 取决于操作员。因此，迫切需要更先进的超声多普勒技术 安全、经济、准确的 RA 评估。 在这里，我们提出了一种新颖的 3D 高灵敏度超声微血管成像 (HUMI) 技术，用于更多 准确、全面的滑膜炎评估，减少对操作者的依赖。高频（14-39 MHz）平面波成像与先进的处理算法相结合，可检测具有高频率的微血管 敏感性。 3D 成像是通过 1D 线性阵列换能器在其高度上的自动平移来实现的。 使用紧凑型步进电机进行方向控制。初步体内研究表明 HUMI 比 最先进的商用多普勒仪，可以清晰地检测 3D 滑膜微血管。 目标 1：开发和优化用于联合成像的 HUMI。我们将进一步开发和优化3D-HUMI 使用模型和患者研究进行体内关节成像的几种换能器。采集参数如 超声波频率、脉冲重复频率 (PRF)、多普勒数据包大小和步进电机运动 3D 成像方案将得到优化，以最大限度地提高微血管成像灵敏度和穿透力。 包括局部SVD和相干SVD在内的先进信号处理算法将用于改善 微血管成像对比并抑制噪声和伪影。 3.3 目标 2：患者研究。目标 1 中优化的 HUMI 将用于对 40 名 RA 患者进行成像，以研究其 评估滑膜炎的疗效。两名超声医师将使用 3D-HUMI 扫描手关节，以研究其 再现性。相同的关节将使用多普勒和微血管成像模式在 用于基准测试的 GE Logiq E10。对比增强 MRI 将用作参考标准。常见 RA 的临床评分将用作辅助验证。每个关节的滑膜炎评分为0（正常）， 1（轻度）、2（中度）和 3（重度）用于 MRI 和超声图像。组内相关系数 (ICC) 将用于评估超声医师之间的再现性以及每个超声检查之间的一致性 MRI 方法。还将进行皮尔逊相关性来评估超声评分的关联 与 RA 临床评分。将进行类似的分析来评估定量超声的关联 MRI 和临床评分的参数（例如微血管总面积和血管密度）。

PROJECT SUMMARY Rheumatoid arthritis (RA) is an autoimmune disorder of the joint affecting 1.3 million Americans, with an estimated annual care cost of 41.6 billion in the USA. Clinical management of RA requires regular assessment of synovial inflammation to guide therapy. Clinical scores of RA, radiography, and contrast-enhanced MRI are limited by low sensitivity, radiation safety, and cost, respectively. Doppler ultrasound is used clinically for synovitis evaluation, but has low sensitivity for microvessel detection (which may lead to underdiagnosis) and is operator dependent. Therefore, more advanced ultrasound Doppler technologies are critically needed for safe, cost-effective, and accurate evaluation of RA. Here we propose a novel 3D High-sensitivity Ultrasound Microvessel Imaging (HUMI) technology for more accurate and comprehensive evaluation of synovitis with less operator dependency. High frequency (14-39 MHz) plane wave imaging is combined with advanced processing algorithms to detect microvessels with high sensitivity. 3D imaging is achieved by automatic translation of the 1D linear array transducer in its elevational direction using a compact step motor. Preliminary in vivo studies show that HUMI is much more sensitive than state-of-the-art commercial Doppler and can clearly detect synovial microvessels in 3D. Aim 1: Develop and optimize HUMI for joint imaging. We will further develop and optimize 3D-HUMI on several transducers for in vivo joint imaging using phantom and patient studies. Acquisition parameters such as ultrasound frequency, pulse repetition frequency (PRF), Doppler packet size, and step motor movement scheme for 3D imaging will be optimized to maximize microvessel imaging sensitivity and penetration. Advanced signal processing algorithms including local SVD and coherent SVD will be used to improves microvessel imaging contrast and suppress noise and artifacts. 3.3 Aim 2: Patient study. The HUMI optimized in Aim 1 will be used to image 40 RA patients to study its efficacy for synovitis evaluation. Hand joints will be scanned with 3D-HUMI by two sonographers to study its reproducibility. The same joints will be imaged using both Doppler and Micro Vascular Imaging mode on the GE Logiq E10 for benchmarking. Contrast-enhanced MRI will be used as the reference standard. Common clinical scores of RA will be used as secondary validations. Synovitis of each joint will be scored as 0 (normal), 1 (mild), 2 (moderate), and 3 (severe) for MRI and ultrasound images. Intraclass correlation coefficients (ICC) will be used to evaluate inter-sonographer reproducibility and the agreement between each of the ultrasound methods with MRI. Pearson correlation will also be performed to assess the association of ultrasound scores with RA clinical scores. Similar analyses will be performed to assess the association of quantitative ultrasound parameters (such as total area of microvessels and vessel density) with MRI and clinical scores.