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; 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）每年都会影响美国数百万的人，每年杀人数十名 这些患者中有成千上万。尽管研究工作非常积极，但仍然没有特定的抗纤维化 FDA批准的药物。肝病和药物开发社区目前没有很好的 经过验证，低成本，易于使用的无创工具，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执行高质量纵向研究的挑战。 为了满足这一需求，Sonovol Inc.提出开发新型多模式台式成像系统的提议 能够对啮齿动物的肝病进行快速的无创测量。该平台将使用四个 核心成像技术：定量超声（QU），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，所有这些都遵循传统的数据收集超声范式 - 一个 受过训练的超声师使用手持式探测器，并手动选择感兴趣的区域进行询问。制作 一致，准确的测量需要深入了解探针放置和超声检查 技术，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将开发一种能够完全自动化的非接触成像的设备，以消除 需要训练有素的超声师，并将大规模采用这些强大的技术 临床前肝病研究界。为了验证新系统，两个不同的动物模型 将评估肝炎损伤，与肝后常规验尸评估相比，结果 疾病。这项技术代表了广场3D机器人超声成像的创新组合 系统和无创的SWEI，QUS和对比度增强成像。此外，该技术可能是 将来应用于许多其他疾病，包括癌症或心脏模型，增加了潜力 市场和对现场的影响。