Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

背景：肝纤维化/肝硬化困扰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，具有侵入性，偶尔可 导致严重并发症，这限制了对高危人群的筛查、治疗监测， 随访目前的血清标志物和经典的医学成像，如超声，CT或MRI， 纤维化评估的足够灵敏度/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。本文提出了一种新的超声检测方法--剪切波超声 色散振动测量法（SDUV），用于无创、活检样的弹性和粘度定量， 肝纤维化分期方法：SDUV使用FDA安全限值内的超声“推”射束刺激 在所研究的组织中形成传播的谐波剪切波。诱导剪切传播速度 波是频率相关的（色散的），并且与组织的机械特性有关。剪切波 多个频率（通常为数百赫兹）下的速度由单独的超声“检测”来测量。 在脉冲回波模式下的波束，并与理论色散模型拟合，以逆解组织弹性， 粘度在仿组织体模和横纹肌方面的初步研究是非常有前途的。一个特殊 已经开发了脉冲序列以便于单个超声阵列换能器用于推和检测 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 已通过使用内部仪器在正常猪肝中进行体内测量进行了验证。目的：1. 在商用超声扫描仪上实现SDUV。2.使用体模校准和优化原型， 体外组织和体内动物实验。3.对怀疑患有 肝纤维化患者计划进行临床指征肝活检。成功完成本 该项目应导致一种新的临床技术，SDUV，为无创，快速，经济和可靠的“虚拟”， 活检”进行纤维化分期。

Background: 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.