Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

描述（由申请人提供）：肝纤维化/肝硬化折磨着全世界数亿患者和90万美国人。肝活检是目前诊断肝纤维化的金标准，它是侵入性的，有时可能导致严重的并发症，这限制了高危人群的筛查、治疗监测和随访。目前的血清标志物和经典医学成像如超声、CT或MRI对纤维化评估没有足够的敏感性/特异性。最近的研究表明，组织弹性（即硬度）可用于肝纤维化分期。在此，我们提出了一种新的超声方法，剪切波超声弥散振动法（SDUV），用于无创，活检样定量肝纤维化分期的弹性和粘度。方法：SDUV使用在FDA安全限制范围内的超声波“推动”光束来刺激在所研究组织中传播的谐波剪切波的形成。诱导剪切波的传播速度与频率相关（色散），并与组织的力学性能有关。多个频率（通常是数百赫兹）的横波速度由脉冲回波模式下的单独超声“检测”光束测量，并与理论色散模型拟合，以反求解组织弹性和粘度。组织模拟幻肌和横纹肌的初步研究是很有前景的。开发了一种特殊的脉冲序列，以促进单个超声阵列换能器的推动和检测功能，这使得SDUV与当前的超声扫描仪兼容。该脉冲序列的可行性已通过内部仪器在正常猪肝中进行体内测量验证。目的:1。在商用超声扫描仪上实现SDUV。2. 用模型、体外组织和体内动物实验校准和优化原型。3. 对拟行临床指征肝活检的疑似肝纤维化患者进行临床研究。该项目的成功完成将带来一种新的临床技术，即SDUV，用于无创、快速、经济、可靠的纤维化分期“虚拟活检”。公共卫生相关性：该项目的成功完成将带来一种新的超声技术，用于安全、快速、经济和可靠的肝纤维化/肝硬化分期。肝纤维化/肝硬化折磨着全世界数亿患者和90万美国人。该技术可作为肝活检的非侵入性替代方法，用于筛查高危人群、治疗监测和慢性肝病患者的随访。

DESCRIPTION (provided by applicant): Liver fibrosis/cirrhosis afflicts hundreds of millions of patients worldwide and 900,000 Americans. Liver biopsy, currently the gold standard for the diagnosis of liver fibrosis, is invasive and may occasionally cause significant complications, which limits the screening of at-risk populations, treatment monitoring, and follow-up. Current serum markers and classic medical imaging such as ultrasound, CT, or MRI do not have sufficient sensitivity/specificity for fibrosis evaluation. Recent studies show that tissue elasticity (i.e. stiffness) may be used for liver fibrosis staging. Herein we propose a novel ultrasound method, Shearwave Ultrasound Dispersion Vibrometry (SDUV), for noninvasive, biopsy-like quantification of elasticity as well as viscosity for liver fibrosis staging. Method: SDUV uses an ultrasound "push" beam within FDA safety limits to stimulate formation of propagating harmonic shear waves in the studied tissue. The propagation speed of induced shear waves is frequency dependent (dispersive) and relates to the tissue's mechanical properties. Shear wave speeds at multiple frequencies (typically hundreds of Hertz) are measured by a separate ultrasound "detect" beam in pulse echo mode and fit with a theoretical dispersion model to inversely solve for tissue elasticity and viscosity. Preliminary studies in tissue-mimicking phantom and striated muscle are very promising. A special pulse sequence has been developed to facilitate a single ultrasound array transducer for both push and detect function, which makes SDUV compatible with current ultrasound scanners. Feasibility of this pulse sequence has been validated with in vivo measurements in normal porcine liver using in-house instrumentation. Aims: 1. Implement SDUV on a commercial ultrasound scanner. 2. Calibrate and optimize the prototype with phantom, in vitro tissue, and in vivo animal experiments. 3. Conduct a clinical research on patients with suspected hepatic fibrosis who are scheduled to have a clinically indicated liver biopsy. Successful completion of this project should result in a new clinical technique, SDUV for noninvasive, fast, economical, and reliable "virtual biopsy" for fibrosis staging. PUBLIC HEALTH RELEVANCE: Successful completion of this project should result in a new ultrasound technique for safe, fast, economical, and reliable staging of liver fibrosis/cirrhosis, which afflicts hundreds of millions of patients worldwide and 900,000 Americans. This technique can be used as a noninvasive alternative to liver biopsy for the screening of at-risk populations, treatment monitoring, and follow-up of patients with chronic liver diseases.