Ultrasound Elastography for Liver Fibrosis Staging

 描述（由申请人提供）：由于肝活检的局限性，非常需要无创性肝纤维化分期。超声弹性成像在无创性肝纤维化分期方面显示出巨大的前景，并且由于其高可及性和低成本，可能具有比磁共振弹性成像（MRE）更高的临床影响。然而，基于超声辐射力的商业弹性成像方法在肥胖患者中具有较高的失败率。考虑到美国一般人群的肥胖患病率（35.7%）以及需要肝纤维化分期且通常肥胖的非酒精性脂肪性肝炎患者数量的增加，这是一个严重的限制。在这个项目中，我们将开发和验证一种新的超声成像技术，称为随机外部振动超声弹性成像（REVUE），具有上级穿透性，可用于肝纤维化分期。REVUE使用外部机械振动来产生穿透整个肝脏的剪切波。采用先进的处理算法将复杂的波场分解为简单的单向波场，用于大视场定量弹性成像的重建。的 研究有三个目的。目标1：在传统超声扫描仪上实现和推进REVUE。我们将在传统的临床扫描仪上实现REVUE，并研究先进的剪切波生成、检测（通过谐波成像和编码激励）和处理方法，以方便肥胖患者的临床使用和可靠的性能。我们将REVUE扩展到3D成像，以更准确和全面地评估肝脏。目标1包括体模和初步人体研究，以验证所开发的技术。目的2：重复性和再现性研究。我们将使用目标1中的REVUE原型来研究45名MRE患者。每例患者将进行3次REVUE成像：每次由3名超声医师进行3次独立扫描（共9次扫描）。前两次会议之间将有10分钟的休息时间，第三次会议将在另一天举行。组内相关系数（ICC）将用于评估重测重复性和评分者间一致性。还将估计REVUE的总体测量方差。目的3：与MRE进行体内比较。我们将使用REVUE研究220例患者，并将结果与MRE和最先进的超声弹性成像仪（Aixplorer（r））的结果进行比较。数据分析包括测量成功率，与MRE结果的相关性，以及ROC（受试者操作特征）评估区分轻度纤维化患者（MRE = 2.9kPa）和晚期纤维化患者（MRE = 5.0kPa）的性能。该项目的成功完成将导致一种快速，低成本的超声弹性成像方法，具有深穿透性，满足肥胖患者肝纤维化分期的重要需求。在本提案中使用传统的临床超声扫描仪为该技术的临床实施提供了明确的途径。

 DESCRIPTION (provided by applicant): Due to limitations of liver biopsy, there is a great need for noninvasive liver fibrosis staging. Ultrasound elastography has shown great promise for noninvasive liver fibrosis staging and may have higher clinical impact than Magnetic Resonance Elastography (MRE) due to its high accessibility and low cost. However, commercial elastography methods based on ultrasound radiation force have high failure rate in obese patients. This is a serious limitation considering the obesity prevalence in the U.S. general population (35.7%) and the increasing number of nonalcoholic steatohepatitis patients who are in need of liver fibrosis staging and are commonly obese. In this project, we will develop and validate a novel ultrasound imaging technology called Random External Vibration Ultrasound Elastography (REVUE) with superior penetration for liver fibrosis staging. REVUE uses external mechanical vibration to produce shear waves that penetrate throughout the liver. Advanced processing algorithms are employed to decompose the complex wave field into simpler unidirectional wave fields for reconstruction of large field-of-view quantitative elastography. The study has 3 aims. Aim 1: Implement and Advance REVUE on a traditional ultrasound scanner. We will implement REVUE on a traditional clinical scanner and investigate advanced shear wave generation, detection (by harmonic imaging and coded excitation), and processing methods to facilitate convenient clinical usage and reliable performance in obese patients. We will extend REVUE to 3D imaging for more accurate and comprehensive evaluation of the liver. Aim 1 includes phantom and preliminary human studies to validate the technologies developed. Aim 2: Repeatability and reproducibility study. We will use REVUE prototyped in Aim 1 to study 45 MRE patients. Each patient will have 3 REVUE imaging sessions: each session has 3 independent scans performed by 3 sonographers (a total of 9 scans). The first two sessions will be separated by a 10-minute break and the third performed on a different day. Intraclass correlation coefficients (ICC) will used to evaluate the test-retest repeatability and inter-rater agreement. The overall measurement variance will also be estimated for REVUE. Aim 3: In Vivo comparison with MRE. We will use REVUE to study 220 patients and compare results with those of MRE and a state-of-art ultrasound elastography machine (Aixplorer(r)). Data analysis includes measurement success rate, correlation with MRE results, and ROC (receiver operating characteristic) evaluation of performance for separating patients with minimum fibrosis (MRE = 2.9kPa) and patients with advanced fibrosis (MRE = 5.0kPa). Successful completion of this project will lead to a fast and low-cost ultrasound elastography method with deep penetration that meets the vital need for liver fibrosis staging in obese patients. The use of a traditional clinical ultrasound scanner in this proposal provides a clear path to clinical implementation of this technology.