Point-of Care MR Device to Estimate T1 Relaxation Time as a Biomarker of Liver Disease (resubmission)

用于估计 T1 弛豫时间作为肝病生物标志物的护理点 MR 设备（重新提交）

• 批准号: 10760778
• 负责人: PABLO J PRADO
• 金额: $ 31万
• 依托单位: LIVIVOS INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760778
• 关键词: Acceleration; Address; Affect; Agreement; Back; Biological Markers; Caring; Characteristics; Clinic; Clinical; Clinical Trials; Communities; Compensation; Dangerousness; Data; Devices; Diagnosis; Diagnostic; Early Diagnosis; Early Intervention; Enrollment; Extrahepatic; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Future; Genetic; Genetic study; Goals; Grant; Health Services Accessibility; Hepatic; Human; Inflammation; Intervention; Iron; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Marketing; Measures; Medical; Methods; Monitor; Noise; Patient Care; Patients; Performance; Phase; Prevalence; Primary Care; Protons; Quality Control; Relaxation; Reporting; Reproducibility; Research; Risk; Rural; Sample Size; Site; Small Business Innovation Research Grant; Specialist; Staging; Stratification; System; Technology; Testing; Time; Water; Work; clinical application; clinical care; clinically significant; commercialization; cost; density; design; diagnostic biomarker; drug discovery; epidemiology study; imaging biomarker; improved; innovation; liver inflammation; new technology; non-alcoholic fatty liver disease; non-invasive imaging; nonalcoholic steatohepatitis; novel; phase 1 study; phase 2 study; phase II trial; point of care; portability; prevent; prognostication; prospective test; quantitative imaging; screening; success; technology validation; treatment response

PROJECT SUMMARY LiverScope® is a low cost, easy-to-use, table-top device for use in research and clinical settings to assess quantitative biomarkers of nonalcoholic fatty liver disease (NAFLD). It 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 (POC) access or can be operated in a small van for mobile diagnostic delivery. We recently received a Phase 1 SBIR grant (1 R43 DK135225-01) to show feasibility of using LiverScope® to estimate liver PDFF, and are now re-submitting this current Phase 1 SBIR proposal to show feasibility of LiverScope® to estimate liver T1 relaxation times. Emerging data support use of T1 relaxation time as a quantitative biomarker in numerous contexts of use, including diagnosis of ‘at risk NASH’, treatment response, monitoring, stratification, and prognostication. Adding T1 relaxation time estimation capability to LiverScope® has the potential to make it a ‘one-stop’ test, substantially enhancing its clinical, scientific, and commercial value. Demonstration of non-invasive imaging biomarker assessment feasibility of both hepatic steatosis (by PDFF) and fibrosis/inflammation (by T1) will support a follow-on comprehensive Phase 2 trial in which these biomarkers of NASH can be tested prospectively. Our long-term goal is to bring LiverScope® to market. Our focus in this study will be to develop LiverScope® capability and establish feasibility to estimate T1 relaxation time (T1). Our immediate goal in this study is to evaluate T1 precision for two identical LiverScope® devices, and so our primary specific aims are to estimate water T1 intra-device repeatability and inter-device reproducibility in phantoms (Aim 1) and humans (Aim 2). The innovation of this proposed derives from the novel technology used to estimate and verify validity for MR-based quantitative biomarkers of NAFLD at low cost and in POC settings while maintaining the accuracy and precision of full-size MRI scanners. The clinical significance of this 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 these studies are successful, deployment of LiverScope® in primary care, rural, underserved, and third-world communities will be possible. Offering real-time PDFF and T1 estimation capability, and the potential for 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 POC 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 of NAFLD; and more efficient screening, enrollment, and execution of clinical trials to accelerate drug discovery.

项目概要 LiverScope® 是一种低成本、易于使用的台式设备，用于研究和临床环境中进行评估 非酒精性脂肪性肝病 (NAFLD) 的定量生物标志物它采用新型、无噪音、先进的技术。 基于磁共振 (MR) 的技术，不需要房间屏蔽，并且可以放置在标准诊所中 我们可以在小型货车中进行操作以进行现场护理 (POC) 访问，以进行移动诊断。 最近获得了第一阶段 SBIR 拨款 (1 R43 DK135225-01)，以展示使用 LiverScope® 的可行性 估计肝脏 PDFF，现在重新提交当前的第 1 阶段 SBIR 提案以证明可行性 LiverScope® 用于估计肝脏 T1 弛豫时间 新出现的数据支持使用 T1 弛豫时间作为指标。 生物标志物在多种使用环境中的应用，包括“NASH 风险”的诊断、治疗反应、 为 LiverScope® 添加 T1 弛豫时间估计功能。 有潜力使其成为“一站式”测试，从而大大增强其临床、科学和商业性 证明非侵入性影像生物标志物评估肝脂肪变性的可行性（通过 PDFF）和纤维化/炎症（T1）将支持后续全面的 2 期试验，其中这些 我们的长期目标是将 LiverScope® 推向市场。 本研究的重点是开发 LiverScope® 功能并建立估计 T1 松弛的可行性 我们在本研究中的直接目标是评估两个相同的 LiverScope® 设备的 T1 精度， 因此我们的主要具体目标是估计水 T1 设备内可重复性和设备间 模型（目标 1）和人类（目标 2）的可重复性这一提议的创新源于 用于估计和验证基于 MR 的 NAFLD 定量生物标志物的有效性的新技术 成本和 POC 设置，同时保持全尺寸 MRI 扫描仪的准确性和精度。 这项工作的意义在于广泛实施这项技术将能够实现早期诊断， 如果这些研究成功，可以更及时地转诊给专家，并有更多机会监测 NAFLD。 LiverScope® 在初级保健、农村、服务欠缺和第三世界社区的部署将成为可能。 提供实时 PDFF 和 T1 估计功能，以及 LiverScope 未来扩展的潜力 包括评估肝病活动和损害的能力可能会改变医学 该技术可以支持 POC 和移动临床。 在许多使用环境中的应用，包括早期检测、诊断、分期、监测和 治疗反应评估；早期干预以预防下游肝脏和肝外疾病 NAFLD 的并发症；大规模流行病学研究，以更好地了解 NAFLD 的患病率和遗传学 NAFLD；以及更有效的筛选、登记和临床试验执行，以加速药物发现。