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

摘要 肝纤维化是许多肝脏疾病的标志，每年影响数百万美国人。 每年都有数以万计的患者死亡。尽管有非常积极的研究努力， FDA仍然没有批准特定的抗纤维化药物。肝病和 药物开发社区目前没有经过充分验证的，低成本的，易于使用的， 在临床前啮齿动物模型中研究肝纤维化的非侵入性工具， 进行高质量的纵向研究。 为了解决这一需求，Sonopolitan Inc.提出开发一种新型台式成像系统， 能够提供啮齿类动物肝纤维化的快速、非侵入性测量， 机器人控制的剪切波弹性成像（SWEI）。在SWEI中，超声脉冲是 用于在感兴趣的器官中产生剪切波，并且组织硬度可以通过 监测行波的速度。SWEI技术已经非常成功， 临床试验，并开始被世界各地的腹部放射诊所采用， 替代肝脏活检。虽然目前市场上存在一些临床前SWEI产品， 所有这些都遵循传统的超声数据收集范例-一种经过训练的 超声波检查者使用手持探头并手动选择感兴趣区域以进行询问 瑞典。进行一致和准确的测量需要深入了解探头 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，Sonopolitan将开发一种能够实现全自动、非接触式SWEI的设备， 消除了对受过训练的超声波检查师的需要， 临床前肝病研究领域的强大技术。要验证新的 系统，将评估两种不同的肝纤维化动物模型， 与传统的肝纤维化死后评估相比。这项技术代表了 宽视野3D机器人超声成像系统和非侵入性 剪切波弹性成像此外，该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.