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，可用于研究和临床设置以评估 非酒精性脂肪肝病（NAFLD）的定量生物标志物。它使用新颖，无噪音，高级 基于磁共振（MR）的技术，不需要房间屏蔽，并且可以位于标准诊所中 可以访问（POC）的空间，也可以在小型货车中操作以进行移动诊断。我们 最近收到了1阶段SBIR赠款（1 R43 DK135225-01），以显示使用LiversCope®的可行性 估计肝脏PDF，现在正在重新收集此当前阶段1 SBIR提案，以显示可行性 LiversCope®估计肝T1放松时间。新兴数据支持将T1放松时间用作用作 在多种使用情况下进行定量生物标志物 监视，分层和提示。将T1放松时间估计能力添加到LiversCope® 有可能使其成为“一站式”测试，从而大大增强其临床，科学和商业 价值。证明两种肝脂肪变性的非侵入性成像生物标志物评估可行性（通过 PDF）和纤维化/炎症（通过T1）将支持一项随后的全面2期试验，其中这些试验 纳什的生物标志物可以预期测试。我们的长期目标是将LiversCope®推向市场。我们的 这项研究的重点是发展LiversCope®能力并确定可行性以估计T1放松 时间（T1）。我们在这项研究中的直接目标是评估两个相同LiversCope®设备的T1精度，即 因此，我们的主要特定目的是估计水T1内部内在可重复性和设备间 幻影（AIM 1）和人类（AIM 2）的可重复性。这项提议的创新源于 用于估算和验证NAFLD基于MR的定量生物标志物的新技术 成本和POC设置，同时保持全尺寸MRI扫描仪的准确性和精度。临床 这项工作的重要性是，该技术的宽度实施将使早期的诊断， 更及时地转介给专家，并更多地访问NAFLD的监视。如果这些研究成功， LiversCope®在初级保健，水平，服务不足和第三世界社区的部署将是可能的。 提供实时PDF和T1估计能力，并提供LiversCope的未来扩展的潜力 能够包括评估肝脏疾病活动和损害的能力，可以转变为医学 护理已知或疑似NAFLD的患者。该技术可以支持POC和移动临床 在多种使用情况下应用，包括早期检测，诊断，分期，监视和 治疗反应评估；早期干预以防止下游肝和肝外肝 Nafld的并发症；大规模流行病学研究，以更好地了解 nafld;以及更有效的筛查，入学和执行临床试验以加速药物发现。