A preclinical multi-modal system for dynamic noninvasive assessment of liver disease

摘要 慢性肝病(CLD)每年影响美国数百万人，每年导致数千万人死亡 数以千计的这种病人。尽管进行了非常积极的研究，但仍然没有特效的抗纤维化药物。 FDA批准的药物。肝病和药物开发界目前没有很好的- 经过验证的、低成本、易用、非侵入性的工具，用于研究肝纤维化、脂肪变性和 临床前啮齿动物模型中的炎症使高质量的纵向研究具有挑战性。 为了满足这一需求，SonoVol Inc.提议开发一种新型的多模式台式成像系统 能够提供对啮齿动物肝脏疾病的快速、非侵入性测量。该平台将利用四个 核心成像技术：定量超声(QUS)、剪切波弹性成像(SWII)、声学 血管造影术(AA)和靶向分子成像(MI)。虽然一些临床前产品实现了 上述技术，所有这些技术都遵循传统的超声数据收集范例-a 训练有素的超声师使用手持探头，手动选择感兴趣的区域进行讯问。制做 一致和准确的测量需要对探头放置和超声检查有深入了解 技术，这是学术生物学家或药物研究人员不太可能拥有的。 因此，SonoVol将开发一种能够实现全自动、非接触式成像的设备，从而消除 需要训练有素的超声技师，并将使这些强大的技术能够在 临床前肝病研究社区。为了验证新系统，两种不同的动物模型 将对肝脏损伤进行评估，并将结果与传统的肝脏尸检评估进行比较 疾病。这项技术代表了宽视场3D机器人超声成像的创新组合 系统和非侵入性SWI、QUS和对比度增强成像。此外，这项技术可以 未来应用于许多其他疾病，包括癌症或心脏模型，增加了潜在的 市场和对赛场的影响。

Abstract Chronic liver disease (CLD) 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 the progression of liver fibrosis, steatosis, and inflammation in preclinical rodent models making it challenging to execute high-quality longitudinal studies. To address this need, SonoVol Inc. proposes to develop a novel multi-modal benchtop imaging system capable of providing rapid, noninvasive measurements of liver disease in rodents. The platform will utilize four core imaging technologies: quantitative ultrasound (QUS), shear wave elasticity imaging (SWEI), acoustic angiography (AA), and targeted molecular imaging (MI). While some preclinical products implement the abovementioned technologies, 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. 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 imaging that eliminates the need for a trained sonographer and will enable large scale adoption of these powerful technologies in the preclinical liver diseases research community. To validate the new system, two different animal models for hepatic injury will be evaluated, and the results compared to conventional postmortem assessments of liver disease. This technology represents an innovative combination of a widefield 3D robotic ultrasound imaging system and noninvasive SWEI, QUS, and contrast-enhanced imaging. 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.