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，每年导致数十人死亡。 成千上万的病人。尽管非常积极的研究努力，仍然没有具体的抗纤维化 FDA批准的药物。肝病和药物开发社区目前还没有很好的- 经验证的，低成本，易于使用，非侵入性的工具，用于研究肝纤维化，脂肪变性， 临床前啮齿动物模型中的炎症使得执行高质量的纵向研究具有挑战性。 为了解决这一需求，Sonopolitan Inc.建议开发一种新型的多模态台式成像系统 能够提供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（SWEI）、声学 血管造影（AA）和靶向分子成像（MI）。虽然一些临床前产品实现了 虽然上述技术都遵循传统的超声数据收集范例， 受过训练的超声波检查者使用手持探头并手动选择要询问的感兴趣区域。使 一致和准确的测量需要深入了解探头放置和超声检查 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，Sonopolitan将开发一种能够全自动、非接触式成像的设备， 需要一个训练有素的超声医师，并将使这些强大的技术在大规模采用 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， 将对肝损伤进行评价，并将结果与常规的肝脏死后评估进行比较。 疾病该技术代表了宽场3D机器人超声成像的创新组合， 系统和非侵入性SWEI、QUS和对比增强成像。此外，该技术可以 在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 市场和对该领域的影响。

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.