Advanced Quantitative Magnetic Resonance Imaging Phantoms for Nonalcoholic Fatty Liver Disease

用于非酒精性脂肪肝疾病的先进定量磁共振成像模型

• 批准号: 10698927
• 负责人: Jean H. Brittain
• 金额: $ 28.23万
• 依托单位: CALIMETRIX, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698927
• 关键词: Address; Adoption; Affect; American; Biological Markers; Caring; Chemicals; Cicatrix; Cirrhosis; Clinic; Clinical; Clinical Trials; Collaborations; Consensus; Country; Current Procedural Terminology Codes; Data; Diagnosis; Disease; Emulsions; Ensure; Environment; Evaluation; Failure; Fatty acid glycerol esters; Fibrosis; Formulation; Gel; Goals; Health; Housing; Image; Imaging Phantoms; Incidence; Industrialization; Industry; Inflammation; International; Liver; Liver Failure; Liver Fibrosis; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Market Research; Marketing; Measurement; Measures; Medical Imaging; Methods; Monitor; Non-Invasive Detection; Patients; Phase; Primary carcinoma of the liver cells; Process; Protocols documentation; Protons; Provider; Quantitative Evaluations; Reference Standards; Reproducibility; Research; Research Personnel; Site; Staging; Standardization; System; Technology; Testing; Time; Training; Universities; Validation; Vendor; Wisconsin; clinical care; clinically relevant; cost; density; design; drug discovery; elastography; end stage liver disease; experience; feasibility testing; imaging biomarker; imaging modality; improved; invention; liver injury; liver stiffness; magnetic resonance imaging biomarker; manufacture; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; operation; prototype; quality assurance; quantitative imaging; stability testing; standard of care; stem; tool

PROJECT SUMMARY The overall goal of this Phase I proposal is to design and test the feasibility of novel magnetic resonance imaging (MRI) reference standards (“phantoms”) that are urgently needed for comprehensive and standardized quality assurance (QA) of quantitative MRI biomarkers of non-alcoholic fatty liver disease (NAFLD). We propose to develop 1) a quantitative MR elastography (MRE) stiffness phantom, and 2) a combined quantitative MRE and proton density fat fraction (PDFF) phantom that mimics the simultaneous presence of liver fibrosis and fat. Over the past decade, quantitative MRI methods, including MRE to measure stiffness as a biomarker of liver fibrosis and chemical shift encoded MRI (CSE-MRI) to measure PDFF as a biomarker of liver fat, have emerged as the noninvasive standard of care for assessment of NAFLD. The rapid adoption of MRE and PDFF methods at thousands of sites worldwide has created an urgent need for quantitative MRE and PDFF phantoms that enable robust quantitative QA to ensure unbiased and reproducible measurements. Lack of clinical QA can result in misdiagnosis, and inadequate QA in clinical trials can result in errors and inconsistency in the primary trial endpoints (liver stiffness and PDFF) leading to loss of valuable patient data and potentially a failed trial. Currently available single-stiffness MRE phantoms are insufficient for quantitative QA because they mimic only a single stiffness value which drifts over time. These phantoms also require phantom-specific MRE protocols that differ significantly from clinical MRE protocols, leading to technical failures and a cumbersome QA process. Importantly, most clinical MRI protocols evaluating NAFLD measure both MRE-stiffness and PDFF in the same exam. Through market research, Calimetrix has identified the need for two new quantitative phantoms: 1) a multi-stiffness MRE phantom; and 2) a combined MRE/PDFF phantom. Both phantoms must be stable over time and be designed to simplify QA setup, minimizing user and technical errors. In this proposal, we have assembled a team consisting of the primary inventors of both PDFF and MRE including experts from the University of Wisconsin, Calimetrix, the Mayo Clinic, and Resoundant. We propose to design, develop, and validate chemical formulations for gels of varying stiffnesses that span the clinically relevant range of liver stiffness (Aim 1) and emulsions with simultaneously varying stiffness and PDFF values that span the clinically relevant range of liver stiffness and fat (Aim 2). We also propose to design and validate a phantom housing that facilitates accurate quantitative measurements and is efficient and easy-to-use with separate compartments to contain multiple stiffness and/or PDFF values in a single compact unit (Aim 3), and finally, to demonstrate the feasibility of the MRE and MRE/PDFF phantom prototypes, including ease-of-use, high image quality, and utility for QA of clinical MRE and CSE-MRI protocols (Aim 4). If successful, we will have developed and demonstrated the feasibility of truly quantitative MRE and MRE/PDFF phantoms that are urgently needed for quality assurance of quantitative MRI biomarkers of NAFLD.

项目摘要 第一阶段提案的总体目标是设计和测试新型磁共振的可行性。 成像（MRI）参考标准（“phantom”），迫切需要全面和标准化的 非酒精性脂肪肝（NAFLD）定量MRI生物标志物的质量保证（QA）。我们提出 开发1）定量MR弹性成像（MRE）刚度体模，和2）组合定量MRE 和质子密度脂肪分数（PDFF）体模，其模拟肝纤维化和脂肪的同时存在。 在过去的十年中，定量MRI方法，包括MRE，以测量硬度作为肝脏的生物标志物， 纤维化和化学位移编码MRI（CSE-MRI）测量PDFF作为肝脏脂肪的生物标志物，已经出现 作为评估NAFLD的无创护理标准。快速采用MRE和PDFF方法 在全球数千个地点进行的MRE和PDFF模拟试验迫切需要定量MRE和PDFF模拟试验， 支持强大的定量QA，确保测量结果的无偏性和可重复性。缺乏临床质量保证， 导致误诊，临床试验中的质量保证不足可能导致主要诊断的错误和不一致。 试验终点（肝硬度和PDFF）导致有价值的患者数据丢失，并可能导致试验失败。 目前可用的单刚度MRE体模不足以进行定量QA，因为它们仅模拟 随时间漂移的单个刚度值。这些体模还需要体模特定的MRE协议 这与临床MRE协议有很大不同，导致技术故障和繁琐的QA过程。 重要的是，大多数评估NAFLD的临床MRI方案都测量了MRE硬度和PDFF。 同样的考试。通过市场调查，加州已经确定了两个新的定量幻影的需要：1） 多刚度MRE体模;和2）组合MRE/PDFF体模。两个幻影必须稳定在 时间和旨在简化QA设置，最大限度地减少用户和技术错误。 在这个提议中，我们组建了一个由PDFF和MRE的主要发明者组成的团队 包括来自加利福尼亚州威斯康星州大学、马约诊所和Resoundant的专家。我们建议 设计、开发和验证不同硬度凝胶的化学配方， 肝脏硬度范围（目标1）和同时变化硬度和PDFF值的乳剂， 肝脏硬度和脂肪的临床相关范围（目标2）。我们还建议设计和验证一个幻影 外壳便于精确的定量测量，高效且易于使用， 在单个紧凑单元中包含多个刚度和/或PDFF值（目标3），最后， 证明MRE和MRE/PDFF体模原型的可行性，包括易用性、高图像 质量和实用性，用于临床MRE和CSE-MRI方案的QA（目标4）。如果成功，我们将开发出 并证明了迫切需要的真正定量MRE和MRE/PDFF模型的可行性 用于NAFLD定量MRI生物标志物的质量保证。