Confounder-Corrected Quantitative MRI Biomarkers of Hepatic

描述（由申请方提供）：这项多中心、多供应商研究将验证基于快速磁共振的混杂因素校正R2* 标测方法作为肝脏铁浓度（LIC）的定量成像生物标志物。铁在各种器官（包括肝脏）中的过度积累影响成人和儿童人群，是有毒的，需要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具有副作用的铁还原螯合剂疗法至关重要。磁共振成像（MRI）是一种广泛可用，可访问和安全的技术，它对组织中铁的存在非常敏感。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、精确、对扫描参数变化具有稳健性、校准至经验证的LIC参考标准，并且在研究中心和制造商之间具有重现性。目前没有满足这些要求的可用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进行，在单次20秒屏气中覆盖整个肝脏3D。过去的工作已经证明了R2* 和LIC之间良好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]噪音和[3]磁场变化。威斯康星州大学开发的定量混杂校正R2*-MRI方法显示出解决当前R2*-MRI方法缺点的巨大前景。通过解决脂肪、噪声和磁场变化的混杂效应，这种单次屏气方法 对协议的变化具有鲁棒性，并且具有多次测量的精确性（可重复性）。混淆校正R2* 方法的初步临床数据证明了与LIC的线性校准具有良好的相关性。初步体模研究显示，各研究中心和MRI制造商之间的再现性极佳。然而，该技术在不同部位和平台上用于体内肝铁定量的性能和重现性尚未得到证实。 验证.因此，本提案的目标是在一项多中心研究（参与研究中心：斯坦福大学、UT-西南大学、约翰霍普金斯和UW-Madison）中，在不同场强（1.5 T和3 T）下，在患有肝铁过载的成人和儿科患者中验证快速混淆校正R2*-MRI作为肝铁过载的生物标志物，包括三家主要MRI供应商（GE、Siemens和Philips）。具体而言，我们的目标是确定混淆校正R2*-MRI的[1]精密度和[2]耐用性，[3]在1.5 T和3.0 T下将R2* MRI校准至LIC，[4]在制造商和研究中心之间确定R2* 的重现性。需要成功验证混淆校正的R2*-MRI，以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，并提供一种通用和标准化的方法来评估具有广泛影响和临床适用性的体内铁含量。

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.