Virtual Biopsy with Ultrasound for Liver Fibrosis Staging

超声虚拟活检用于肝纤维化分期

• 批准号: 7726313
• 负责人: Shigao Chen
• 金额: $ 33.81万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726313
• 关键词: Address; American; Animal Experiments; Biopsy; Cardiovascular system; Chronic; Cirrhosis; Clinical; Clinical Management; Clinical Research; Computer software; Data; Detection; Diagnosis; Elasticity; Evaluation; Family suidae; Fibrosis; Frequencies; Generations; Goals; Gold; Health; Histocompatibility Testing; Housing; Human; In Vitro; Literature; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Imaging; Manufacturer Name; Measurement; Measures; Mechanics; Medical; Medical Imaging; Methods; Modeling; Modification; Monitor; Motion; Obesity; Pathology; Patients; Penetration; Performance; Physiologic pulse; Populations at Risk; Property; Reporting; Research; Research Proposals; Safety; Schedule; Screening procedure; Sensitivity and Specificity; Serum Markers; Speed; Staging; Striated Muscles; Surrogate Markers; Techniques; Testing; Tissues; Transducers; Ultrasonography; Viscosity; diagnosis standard; drug development; follow-up; human study; in vivo; indexing; instrumentation; liver biopsy; meetings; novel; prototype; public health relevance; research study; respiratory; soft tissue; vibration; virtual

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.

描述（由申请人提供）：肝纤维化/肝硬化困扰着全球数亿患者和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，偶尔可能引起严重并发症，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的医学成像如超声、CT或MRI对于纤维化评价没有足够的灵敏度/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。在这里，我们提出了一种新的超声方法，剪切波超声色散振动测量法（SDUV），用于无创，活检样量化的弹性以及粘度肝纤维化分期。方法：SDUV使用FDA安全限值内的超声“推”射束，刺激研究组织中传播谐波剪切波的形成。诱导的剪切波的传播速度是频率相关的（色散的），并且与组织的机械特性有关。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，并与理论色散模型拟合以逆解组织弹性和粘度。在仿组织体模和横纹肌方面的初步研究是非常有前途的。一种特殊的脉冲序列已被开发出来，以促进一个单一的超声阵列换能器的推动和检测功能，这使得SDUV与目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的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、体外组织和体内动物实验校准和优化原型。3.对计划进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产生一种新的临床技术，SDUV用于无创，快速，经济和可靠的纤维化分期“虚拟活检”。公共卫生相关性：该项目的成功完成将导致一种新的超声技术，用于肝纤维化/肝硬化的安全，快速，经济和可靠的分期，这困扰着全球数亿患者和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。