Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

描述(由申请人提供)：肝纤维化/肝硬变困扰着全球数亿患者和90万美国患者。肝活检是目前诊断肝纤维化的金标准，它是有创的，有时可能会导致严重的并发症，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影像如超声、CT或MRI对纤维化评估的敏感性/特异性还不够。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)，用于无创性、活检式量化弹性和粘度，用于肝纤维化分期。方法：SDUV使用FDA安全范围内的超声“推动”波束来刺激在研究组织中传播的谐波横波的形成。诱导横波的传播速度与频率有关(色散)，并与组织的力学性质有关。多个频率(通常为数百赫兹)下的剪切波速度由脉冲回波模式下的单独超声“检测”波束测量，并符合理论弥散模型，从而反向求解组织弹性和粘度。在组织模体和横纹肌方面的初步研究非常有前途。开发了一种特殊的脉冲序列，使单个超声阵列换能器同时具有推送和检测功能，使SDUV与现有的超声扫描仪兼容。这种脉冲序列的可行性已经通过使用内部仪器在正常猪肝脏中的活体测量得到了验证。目标：1.在商用超声扫描仪上实现SDUV。2.用体模、体外组织和活体动物实验对样机进行标定和优化。3.对临床指征为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--SDUV，用于无创、快速、经济和可靠的纤维化分期的“虚拟活检”。与公共卫生相关：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、经济和可靠地对肝纤维化/肝硬变进行分期，这种疾病正困扰着全球数亿患者和90万美国人。这项技术可以作为肝脏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.