Accurate Point of Care Liver Disease Diagnostics

项目总结 我们的长期目标是获得FDA 510(K)批准，并将一种低成本、容易- 在研究和临床环境中使用的桌面护理点式设备，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，可以放置在标准的诊所中 有足够的空间进行医疗接诊，也可以在小型货车中操作，以便进行移动诊断。我们最初的 重点是质子密度脂肪分数(PDFF)的估计，这是一种基于MRI的标准化生物标记物 肝脏脂肪变性。我们的直接目标(也是本应用程序的重点)是在 模特儿和人类来验证liverScope®(liverScope®-PDFF)估计的PDFF是否满足 由定量成像生物标记物联盟制定的符合性标准。主要的具体内容 此阶段1提案的目的是验证liverScope®估计的PDFF是否与地面事实相符 幻影PDF值(目标1)，在人体内可重复和可复制(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第二阶段提案，以获得FDA 510(K)批准。发生的可能性 之前与FDA的对话、保护Livivos知识产权的专利以及 支持性的初步数据。在liverScope获得fda批准评估pdff后，我们将调查其 评估NAFLD其他潜在生物标志物的能力，如T1松弛、T2松弛和扩散率 (建议的肝脏疾病活动和损害的生物标志物)。拟议工作的创新之处在于 低成本、准确评估NAFLD磁共振定量生物标记物的新技术的建立 在保持全尺寸核磁共振扫描仪的准确性和精确度的同时，还可以进行紧急护理设置。临床部 拟议工作的意义在于，这项技术的广泛实施将使 诊断，更及时地向专家转介，以及更多地监测非酒精性脂肪肝。如果这件事的目标是 符合第一阶段SBIR建议，如果后续全面的第二阶段SBIR研究结果符合FDA 510(K) 批准liverScope进行初级保健、农村、服务不足和第三方的初级保健- 世界共同体将成为可能。LiverScope功能的未来扩展包括评估 肝脏疾病的活动和损害可能会改变已知或 疑似非酒精性脂肪肝。这项技术可以支持多种医疗保健和移动临床应用 使用情况，包括早期发现、诊断、分期、监测和治疗反应评估； 早期干预预防NAFLD下游肝及肝外并发症；大规模 流行病学研究，以更好地了解非酒精性脂肪肝的患病率和遗传学；以及更有效的筛查， 登记和执行临床试验，以加快药物发现。

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.