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.

项目摘要 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， 非酒精性脂肪性肝病（NAFLD）的定量生物标志物。它采用新颖、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 用于护理点（POC）访问的空间，或者可以在用于移动的诊断递送的小型货车中操作。我们 最近收到了第一阶段SBIR赠款（1 R43 DK 135225 -01），以显示使用LiverScope®的可行性， 估计肝脏PDFF，现在正在重新提交当前的第1阶段SBIR提案，以显示 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 在许多使用情况下的定量生物标志物，包括“有风险的NASH”的诊断，治疗反应， 监测、分层和统计。为LiverScope®增加T1弛豫时间估计功能 有可能使其成为“一站式”测试，大大提高其临床，科学和商业 值证实非侵入性成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）将支持一项后续的全面2期试验，其中这些 可以前瞻性地测试NASH的生物标志物。我们的长期目标是将LiverScope®推向市场。我们 本研究的重点将是开发LiverScope®功能，并建立估计T1弛豫的可行性 时间（T1）。本研究的近期目标是评估两种相同LiverScope®器械的T1精密度， 因此，我们的主要具体目标是估计水T1器械内重复性和器械间 在体模（目标1）和人体（目标2）中的重现性。本文的创新之处在于， 一种新技术，用于估计和验证基于MR的NAFLD定量生物标志物在低 在POC设置中，同时保持全尺寸MRI扫描仪的准确度和精度。临床 这项工作的意义在于，这项技术的广泛实施将使早期诊断成为可能， 更及时地转诊给专家，更容易监测NAFLD。如果这些研究成功， LiverScope®在初级保健、农村、服务不足和第三世界社区的部署将成为可能。 提供实时PDFF和T1估计能力，以及LiverScope未来扩展的潜力 包括评估肝脏疾病活动和损伤的能力，可能会转变为医疗 对已知或疑似NAFLD患者的护理。该技术可支持POC和移动的临床 在许多使用环境中的应用，包括早期检测，诊断，分期，监测， 治疗反应评估;早期干预，以防止下游肝和肝外 NAFLD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、招募和执行临床试验，以加速药物发现。