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

用于肝病动态无创评估的临床前多模式系统

• 批准号: 9557233
• 负责人: Tomasz Joseph Czernuszewicz
• 金额: $ 89.63万
• 依托单位: SONOVOL, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-05 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9557233
• 关键词: Acoustics; Address; Adoption; Affect; Alcohol abuse; Algorithms; Americas; Anatomy; Angiography; Animal Model; Animals; Autopsy; Awareness; Biological Markers; Biological Neural Networks; Bolus Infusion; Cardiac; Cessation of life; Cirrhosis; Clinic; Clinical; Communities; Community Developments; Computer software; Contrast Media; Core Facility; Custom; Data; Data Collection; Data Set; Detection; Development; Devices; Disease; Elasticity; Elements; Ensure; FDA approved; Fibrosis; Frequencies; Future; Hand; Histology; Image; Image Enhancement; Imaging Device; Imaging technology; Immunohistochemistry; Inflammation; Injury; Knowledge; Laboratory Research; Left; Lesion; Liver; Liver Fibrosis; Liver diseases; Longitudinal Studies; Malignant Neoplasms; Manuals; Measurement; Methods; Microbubbles; Modality; Modeling; Molecular Target; Morphologic artifacts; Organ; Patients; Penetration; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physics; Physiological Processes; Pilot Projects; Preparation; Primary carcinoma of the liver cells; Protocols documentation; Public Health; Reproducibility; Research; Research Personnel; Respiration; Robotics; Rodent; Rodent Model; Scanning; Sensitivity and Specificity; Serum; Small Business Innovation Research Grant; Staging; System; Techniques; Technology; Testing; Three-Dimensional Image; Time; Tissues; Training; Transducers; Ultrasonography; United States; Viral hepatitis; animal imaging; base; chronic liver disease; contrast enhanced; cost; design; drug development; dynamic system; imaging system; in vivo; innovation; interest; liver injury; models and simulation; molecular imaging; mouse model; non-invasive imaging; nonalcoholic steatohepatitis; novel; pre-clinical; pre-clinical research; prototype; quantitative ultrasound; research and development; response; skills; success; targeted imaging; tool; voltage; western diet

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.

抽象的 慢性肝病 (CLD) 每年影响数百万人，每年导致数十人死亡 成千上万的这样的病人。尽管研究工作非常积极，但仍然没有特异性的抗纤维化药物 FDA批准的药物。肝病和药物开发界目前没有很好的 经验证的、低成本、易于使用的非侵入性工具，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得执行高质量的纵向研究具有挑战性。 为了满足这一需求，SonoVol Inc. 提议开发一种新型多模态台式成像系统 能够对啮齿类动物的肝脏疾病提供快速、无创的测量。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施了 上述技术，都遵循传统的超声数据收集范式——a 训练有素的超声医师使用手持式探头并手动选择要询问的感兴趣区域。制作 一致且准确的测量需要深入了解探头放置和超声检查 学术生物学家或药物研究人员不太可能拥有的技术。 因此，SonoVol 将开发一种能够全自动、非接触式成像的设备，消除 需要训练有素的超声技师，这将使这些强大的技术能够在 临床前肝病研究团体。为了验证新系统，两种不同的动物模型 将评估肝损伤，并将结果与​​传统的死后肝脏评估进行比较 疾病。该技术代表了宽场 3D 机器人超声成像的创新组合 系统和无创 SWEI、QUS 和对比增强成像。此外，该技术还可以 未来应用于许多其他疾病，包括癌症或心脏模型，增加了潜力 市场和对该领域的影响。