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

项目总结 LiverScope®是一种低成本、易于使用的桌面设备，用于研究和临床环境中的评估 非酒精性脂肪性肝病(NAFLD)的定量生物标志物它采用了新颖、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 医疗点(POC)通道的空间或可在小型货车中操作，以提供移动诊断服务。我们 最近获得了第一阶段SBIR资助(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一阶段SBIR提案，以显示 LiverScope®用于评估肝脏T1弛豫时间。新兴数据支持将T1松弛时间用作 定量生物标记物在多种使用环境中的应用，包括对“风险NASH”的诊断、治疗反应、 监测、分层和预测。为liverScope®添加T1松弛时间估计功能 有可能使其成为一站式测试，大大增强其临床、科学和商业价值 价值。非侵入性成像生物标记物评估两种肝脏脂肪变性的可行性论证(通过 和纤维化/炎症(到T1)将支持后续的综合2期试验，在该试验中， NASH的生物标志物可以进行前瞻性的检测。我们的长期目标是将liverScope®推向市场。我们的 这项研究的重点将是开发liverScope®功能，并建立评估T1松弛的可行性 时间(T1)。我们在这项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，我们的主要特定目标是评估设备内部的重复性和设备间的水T1 在幻影(目标1)和人类(目标2)中的重复性。这一建议的创新之处来自于 用于评估和验证NAFLD磁共振定量生物标志物有效性的新技术 成本和POC设置，同时保持全尺寸核磁共振扫描仪的准确性和精确度。临床部 这项工作的意义在于，这项技术的广泛应用将使早期诊断成为可能， 更及时地向专家转介，以及更多地监测非酒精性脂肪肝。如果这些研究成功， 在初级保健、农村、服务不足和第三世界社区部署liverScope®将是可能的。 提供实时的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害的能力，可能会对医疗 护理已确诊或疑似NAFLD的患者。这项技术可以支持PoC和移动临床 在多种使用环境中的应用，包括早期检测、诊断、分阶段、监测和 治疗反应评估；早期干预以预防下游肝和肝外 NAFLD的并发症；大规模流行病学研究，以更好地了解NFLD的患病率和遗传学 NAFLD；以及更有效的筛查、登记和临床试验的执行，以加快药物发现。

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.