A noninvasive method for tissue stiffness quantification in small animals with shear wave elastography

摘要 肝纤维化是许多肝病的标志，每年影响着美国数百万人 一年，每年杀死数万名这样的患者。尽管进行了非常积极的研究， 目前还没有FDA批准的特效抗纤维化药物。肝病和 药物开发社区目前没有经过充分验证的、低成本、易于使用、 在临床前啮齿动物模型中研究肝纤维化的非侵入性工具使其具有挑战性 执行高质量的纵向研究。 为了满足这一需求，SonoVol Inc.提议开发一种新的台式成像系统 能够为啮齿动物的肝纤维化提供快速、非侵入性的测量 机器人控制的剪切波弹性成像(SWI)。在Swei，超声波脉冲是 用来在感兴趣的器官中产生剪切波，组织硬度可以通过 监测行波的速度。Swei技术在以下方面非常成功 临床试验，并开始被世界各地的腹部放射科诊所作为一种 肝活检的替代物。虽然目前市场上存在一些临床前的Swei产品， 他们所有人都遵循传统的超声数据收集范例-训练有素的 超声医师使用手持探头，手动选择要询问的感兴趣区域 好极了。进行一致和准确的测量需要对探头有深入的了解 放置和超声技术，学术生物学家或药物研究人员 不太可能拥有。 因此，SonoVol将开发一种能够实现全自动、非接触式Swei的设备 消除了对训练有素的超声技师的需求，并将使大规模采用此技术成为可能 在临床前肝病研究界拥有强大的技术。要验证新的 系统中，将对两种不同的肝纤维化动物模型进行评估，结果 与传统的肝纤维化尸检评估相比。这项技术代表了 宽视场三维机器人超声成像系统与无创技术的创新结合 剪切波弹性成像。此外，这项技术在未来可以应用于许多 其他疾病，包括癌症或心脏模型，增加了潜在的市场和影响 在球场上。

Abstract Liver fibrosis, a hallmark of many liver diseases, affects millions of people in America every year, and annually kills tens of thousands of these patients. Despite very active research efforts, there still have been no specific antifibrotic drugs approved by the FDA. The liver disease and drug development communities do not currently have well-validated, low-cost, easy to use, noninvasive tools for studying liver fibrosis in preclinical rodent models making it challenging to execute high-quality longitudinal studies. To address this need, SonoVol Inc. proposes to develop a novel benchtop imaging system capable of providing rapid, noninvasive measurements of liver fibrosis in rodents with robotically-controlled shear wave elasticity imaging (SWEI). In SWEI, ultrasound pulses are used to generate shear waves in an organ an interest, and tissue stiffness can be inferred by monitoring the speed of the travelling waves. SWEI technology has been very successful in clinical trials and is starting to be adopted by abdominal radiology clinics around the world as a replacement for liver biopsy. While some preclinical SWEI products exist on the market today, all of them follow the conventional ultrasound paradigm of data collection – a trained sonographer uses a handheld probe and manually selects regions of interest to interrogate with SWEI. Making consistent and accurate measurements requires in depth knowledge of probe placement and sonographic technique, which academic biologists or drug researchers are unlikely to possess. Therefore, SonoVol will develop a device capable of fully-automated, non-contact SWEI that eliminates the need for a trained sonographer and will enable large scale adoption of this powerful technology in the preclinical liver diseases research community. To validate the new system, two different animal models for hepatic fibrosis will be evaluated, and the results compared to conventional postmortem assessments of liver fibrosis. This technology represents an innovative combination of a widefield 3D robotic ultrasound imaging system and noninvasive shear wave elastography. Furthermore, the technology can be applied in the future to many other diseases, including cancer or cardiac models, increasing the potential market and impact on the field.