Confounder-Corrected Quantitative MRI Biomarkers of Hepatic

肝脏的混杂校正定量 MRI 生物标志物

• 批准号: 8614921
• 负责人: Scott B. Reeder
• 金额: $ 69.84万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614921
• 关键词: Address; Adult; Adverse effects; Affect; Air; Biological Markers; Biopsy; Blood; Calibration; Chelating Agents; Child; Childhood; Clinical; Clinical Data; Collaborations; Data; Detection; Development; Diagnosis; Fatty acid glycerol esters; Ferritin; Goals; Hemorrhage; Hemosiderosis; Hepatic; Hereditary Disease; Hereditary hemochromatosis; Image; Institution; Intestinal Absorption; Ionizing radiation; Iron; Iron Overload; Life; Liver; Magnetic Resonance; Magnetic Resonance Imaging; Manufacturer Name; Maps; Measurement; Measures; Methods; Microscopic; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Noise; Organ; Patients; Pediatrics; Performance; Physicians; Pilot Projects; Population; Protocols documentation; Reference Standards; Reproducibility; Research; Risk; Sampling; Scanning; Serum; Side; Signal Transduction; Site; Staging; Techniques; Technology; Testing; Tissues; Translating; Translations; Universities; Validation; Variant; Vendor; Wisconsin; Work; base; clinical application; clinical practice; cost effective; imaging modality; in vivo; magnetic field; meetings; novel; performance tests; public health relevance

DESCRIPTION (provided by applicant): This multi-center, multi-vendor study will validate a rapid magnetic resonance-based confounder- corrected R2* mapping method as a quantitative imaging biomarker of liver iron concentration (LIC). Excessive accumulation of iron in various organs, including the liver, which affects both adult and pediatric populations, is toxic and requires treatment aimed at reducing body iron stores. Measurement of LIC is critical for detection and staging of iron overload, and for monitoring iron-reducing chelator therapies that are expensive and have side effects. Magnetic Resonance Imaging (MRI) is a widely available, accessible, and safe technology, and it is very sensitive to the presence of iron in tissue. Translation of an MRI biomarker of liver iron concentration into broad clinical use requires that i is clinically feasible, precise, robust to changes in scan parameters, calibrated to a validated reference standard of LIC, and is reproducible across sites and manufacturers. There are currently no available MRI methods that meet these requirements. R2*-MRI holds the greatest promise to meet these requirements. R2* mapping can be performed very rapidly with whole-liver 3D coverage in a single 20s breath-hold. Past work has demonstrated excellent correlation and linear calibration between R2* and LIC. However, current R2*-MRI methods are affected by three key confounding factors: [1] fat, [2] noise, and [3] magnetic field variations. A quantitativ confounder- corrected R2*-MRI method developed at the University of Wisconsin shows great promise to address the shortcomings of current R2*-MRI methods. By addressing the confounding effects of fat, noise, and magnetic field variations, this single breath-hold method is robust to changes in protocol and is precise (repeatable) with multiple measurements. Preliminary clinical data of the confounder-corrected R2* method demonstrates linear calibration with LIC with excellent correlation. Preliminary phantom studies show excellent reproducibility across sites and MRI manufacturers. However, the performance and reproducibility of this technique for in vivo liver iron quantification across different sites and platforms have yet to be validated. Therefore, the goal of this proposal is to validate rapid confounder-corrected R2*-MRI as a biomarker for liver iron overload in a multi-center study (participating sites: Stanford, UT-Southwestern, Johns Hopkins and UW-Madison), including the three main MRI vendors (GE, Siemens and Philips) at different field strengths (1.5T and 3T), in adults and pediatrics with live iron overload. Specifically, we aim to establish the [1] precision and [2] robustness of confounder-corrected R2*-MRI, [3] to calibrate R2* MRI to LIC at 1.5T and 3.0T, and [4] to establish the reproducibility of R2* across manufacturer and site. Successful validation of confounder-corrected R2*-MRI is needed to translate this method into a biomarker that is independent of site, platform, and scan parameters, and would provide a universal and standardized method to assess body iron content with widespread impact and clinical applicability.

描述（由申请人提供）：这项多中心、多供应商研究将验证基于快速磁共振的混杂校正 R2* 绘图方法作为肝铁浓度 (LIC) 的定量成像生物标志物。包括肝脏在内的各个器官中铁的过量积累会影响成人和儿童，并且具有毒性，需要进行旨在减少体内铁储存的治疗。 LIC 的测量对于铁过载的检测和分期以及监测昂贵且有副作用的铁还原螯合剂疗法至关重要。磁共振成像 (MRI) 是一种广泛使用、易于使用且安全的技术，它对组织中铁的存在非常敏感。将肝铁浓度的 MRI 生物标志物转化为广泛的临床应用需要临床上可行、精确、对扫描参数的变化稳健、根据经过验证的 LIC 参考标准进行校准，并且在不同地点和制造商之间可重复。目前没有可用的 MRI 方法可以满足这些要求。 R2*-MRI 最有希望满足这些要求。 R2* 映射可以非常快速地进行，只需 20 秒屏气即可覆盖整个肝脏 3D。过去的工作已证明 R2* 和 LIC 之间具有出色的相关性和线性校准。然而，当前的 R2*-MRI 方法受到三个关键混杂因素的影响：[1] 脂肪、[2] 噪声和 [3] 磁场变化。威斯康星大学开发的定量混杂校正 R2*-MRI 方法显示出解决当前 R2*-MRI 方法缺点的巨大希望。通过解决脂肪、噪音和磁场变化的混杂影响，这种单一屏气方法 对协议的变化具有鲁棒性，并且通过多次测量是精确的（可重复的）。混杂校正 R2* 方法的初步临床数据表明，与 LIC 的线性校准具有良好的相关性。初步的模型研究表明，跨站点和 MRI 制造商具有出色的可重复性。然而，该技术在不同位点和平台上体内肝铁定量的性能和重现性尚未得到证实。 已验证。因此，本提案的目标是在成人和儿科的多中心研究（参与地点：斯坦福大学、德克萨斯大学西南分校、约翰霍普金斯大学和威斯康星大学麦迪逊分校）中验证快速混杂校正 R2*-MRI 作为肝脏铁超载的生物标志物，其中包括三个主要 MRI 供应商（GE、西门子和飞利浦）在不同场强（1.5T 和 3T）下的成人和儿科研究 带电铁过载。具体来说，我们的目标是建立混杂校正 R2*-MRI 的 [1] 精度和 [2] 稳健性，[3] 在 1.5T 和 3.0T 下将 R2* MRI 校准到 LIC，以及 [4] 建立 R2* 跨制造商和站点的再现性。需要成功验证混杂校正的 R2*-MRI，才能将该方法转化为独立于部位、平台和扫描参数的生物标志物，并提供一种通用且标准化的方法来评估具有广泛影响和临床适用性的身体铁含量。