Accurate Point of Care Liver Disease Diagnostics

项目摘要 我们的长期目标是获得FDA 510（k）许可，并将LiverScope®推向市场，这是一种低成本，简单， 在研究和临床环境中使用的台式床旁设备，用于评估定量 非酒精性脂肪性肝病（NAFLD）的生物标志物。LiverScope®采用新颖、无噪音、先进的 基于磁共振（MR）的技术，不需要房间屏蔽，可以放置在标准诊所中 或者可以在小型货车中操作，用于移动的诊断递送。我们最初 重点是质子密度脂肪分数（PDFF）的估计，PDFF是一种标准化的基于MRI的生物标志物， 肝脂肪变性我们的近期目标（以及本申请的重点）是在以下方面进行I期研究： 验证LiverScope®估计的PDFF（LiverScope®-PDFF）符合 由定量成像生物标志物联盟制定的一致性标准。主要具体 本阶段1提案的目的是验证LiverScope®估计的PDFF与地面实况一致 体模PDFF值（目标1），并且在人体中可重复和再现（目标2）。成功 目标1和目标2中成功的量化里程碑的演示将支持设计、规划和 执行未来更大规模的多中心II期提案，以获得FDA 510（k）批准。可能性 与FDA的事先对话、保护Livivos知识产权的专利以及 初步数据支持。在LiverScope获得FDA批准估计PDFF后，我们将调查其 能够评估NAFLD的其他潜在生物标志物，如T1弛豫、T2弛豫和扩散率 （提出的肝病活动和损伤的生物标志物）。所提出的工作的创新在于 创建新技术，以低成本和准确的方式估计NAFLD的基于MR的定量生物标志物， 同时保持全尺寸MRI扫描仪的准确性和精度。临床 拟议工作的意义在于，广泛实施这项技术将使更早 诊断，更及时地转诊给专家，更容易监测NAFLD。如果这件事的目的 满足1期SBIR提案，如果后续全面的2期SBIR研究导致FDA 510（k） 为PDFF估计、初级保健、农村、服务不足和第三医疗领域的部署清除LiverScope 世界社区将成为可能。LiverScope的未来扩展能力包括评估 肝病活动和损害可能会转化为已知或 疑似NAFLD。该技术可以在许多医疗应用中支持即时和移动的临床应用。 使用背景，包括早期检测、诊断、分期、监测和治疗反应评估; 早期干预以预防NAFLD的下游肝和肝外并发症;大规模 流行病学研究，以更好地了解NAFLD的患病率和遗传学;以及更有效的筛查， 招募和执行临床试验，以加速药物发现。

PROJECT SUMMARY Our long-term goal is to obtain FDA 510(k) clearance and to bring to market LiverScope®, a low cost, easy- to-use, table-top, point-of-care device for use in research and clinical settings to assess quantitative biomarkers of nonalcoholic fatty liver disease (NAFLD). LiverScope® uses novel, noise-free, advanced magnetic resonance (MR)-based technology, requires no room shielding, and can be sited in a standard clinic room for point-of-care access or can be operated in a small van for mobile diagnostic delivery. Our initial focus is on the estimation of proton-density fat fraction (PDFF), a standardized MRI-based biomarker of hepatic steatosis. Our immediate goal (and the focus of this application) is to perform Phase 1 studies in phantoms and humans to verify that PDFF estimated by LiverScope® (LiverScope®-PDFF) meets conformance standards developed by the Quantitative Imaging Biomarkers Alliance. The primary specific aims of this Phase 1 proposal are to verify that PDFF estimated by LiverScope® agrees with ground-truth phantom PDFF values (Aim 1) and is repeatable and reproducible in humans (Aim 2). Successful demonstration of quantitative milestones of success in Aims 1 and 2 will support the design, planning, and execution of a future, larger, multi-center Phase 2 proposal to obtain FDA 510(k) clearance. Likelihood of success is leveraged by prior conversations with FDA, patents to protect Livivos’ intellectual property, and supportive preliminary data. After LiverScope is FDA cleared to estimate PDFF, we will investigate its capability to assess other potential biomarkers of NAFLD, such as T1 relaxation, T2 relaxation, and diffusivity (proposed biomarkers of liver disease activity and damage).The innovation of the proposed work resides in the creation of novel technology to estimate MR-based quantitative biomarkers of NAFLD at low cost and in point- of-care settings while maintaining the accuracy and precision of full-size MRI scanners. The clinical significance of the proposed work is that widespread implementation of this technology will enable earlier diagnosis, more timely referral to specialists, and greater access to monitoring of NAFLD. If the goals of this Phase 1 SBIR proposal are met, and if a follow-on comprehensive Phase 2 SBIR studies result in FDA 510(k) clearance of LiverScope for PDFF estimation, deployment in primary care, rural, underserved, and third- world communities will be possible. Future expansions of LiverScope capability to include assessment of liver disease activity and damage could be transformational to the medical care of patients with known or suspected NAFLD. This technology could support point-of-care and mobile clinical application in numerous contexts of use, including early detection, diagnosis, staging, monitoring, and treatment response assessment; early intervention to prevent downstream hepatic and extrahepatic complications of NAFLD; large-scale epidemiology studies to better understand the prevalence and genetics NAFLD; and more efficient screening, enrollment, and execution of clinical trials to accelerate drug discovery.