Confounder-Corrected Quantitative MRI Biomarkers of Hepatic

描述(由申请人提供)：这项多中心、多供应商的研究将验证基于磁共振的混杂校正R2*映射方法作为肝脏铁浓度(LIC)的定量成像生物标记物的有效性。铁在各种器官中的过度积累，包括肝脏，对成人和儿童都有影响，是有毒的，需要进行旨在减少体内铁储存的治疗。LIC的测量对于铁超载的检测和分期以及对昂贵且有副作用的铁还原螯合疗法的监测至关重要。磁共振成像(MRI)是一种广泛可用的、可获得的、安全的技术，它对组织中是否存在铁非常敏感。要将肝脏铁浓度的MRI生物标志物转化为广泛的临床应用，需要I在临床上可行、准确、对扫描参数的变化具有健壮性、经过LIC验证的参考标准校准，并且可跨地点和制造商重现。目前还没有满足这些要求的可用的MRI方法。R2*-MRI最有希望满足这些要求。R2*标测可以非常快速地完成全肝3D覆盖，只需屏气20s即可。过去的工作已经证明R2*和LIC之间有很好的相关性和线性校准。然而，目前的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一种定量混杂校正的R2*-MRI方法显示出解决当前R2*-MRI方法的缺点的巨大希望。通过解决脂肪、噪声和磁场变化的混杂影响，这种单一的屏息方法是 对协议的更改具有很强的耐受性，并且可通过多次测量实现精确(可重复)。混杂校正R2*法的初步临床数据表明，线性校正与LIC具有良好的相关性。初步的模体研究表明，跨站点和MRI制造商的重复性极佳。然而，这种跨不同部位和平台的体内肝铁定量技术的性能和重复性尚未得到证实。 已验证。因此，这项建议的目标是在一项多中心研究(参与点：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)，包括三家主要的MRI供应商(通用电气、西门子和飞利浦)在不同场强(1.5T和3T)下，在成人和患有活体铁超载的儿科患者中验证混杂校正R2*-MRI作为肝铁超载生物标志物的有效性。具体地说，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将R2*MRI校准为LIC，以及[4]建立R2*在制造商和地点之间的重复性。要将这一方法转化为独立于部位、平台和扫描参数的生物标志物，需要成功验证混杂校正的R2*-MRI，并将提供一种具有广泛影响和临床适用性的通用和标准化方法来评估体内铁含量。

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.