Ultrasensitive Doppler Ultrasound for Evaluation of Rheumatoid Arthritis

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.