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一种基于混杂校正的快速磁共振R2*制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度积累对成人和儿童都有影响，这是有毒的，需要针对减少体内铁储存进行治疗。LIC的测量对于铁超载的检测和分期，以及监测价格昂贵且有副作用的铁还原螯合剂治疗至关重要。磁共振成像（MRI）是一种广泛可用、易于获取和安全的技术，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它在临床上是可行的，精确的，对扫描参数变化的鲁棒性，校准为经过验证的LIC参考标准，并且在各个部位和制造商之间是可重复的。目前还没有可用的MRI方法满足这些要求。R2*-MRI最有希望满足这些要求。R2*映射可以非常快速地进行全肝脏3D覆盖，只需20秒的屏气。过去的工作已经证明R2*和LIC之间具有良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淆效应，这种单一的屏气方法是

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.