3D Free-Breathing Fat and Iron Corrected T1 Mapping

项目摘要 非酒精性脂肪性肝病（NAFLD）的全球患病率约为25%，是慢性肝病的主要病因。 世界范围内的肝病非酒精性脂肪性肝炎（NASH）作为NAFLD的晚期形式，涉及脂肪变性， 炎症和伴随的肝脏铁沉积。由于慢性细胞损伤，NASH还可引起 肝纤维化是更严重的肝脏并发症如肝硬化，门静脉高压， 或肝细胞癌（HCC）。因此，同时测量这些临床指标对于 更准确、更全面地评估NASH。磁共振成像（MRI）是一种... 由于其出色的软组织对比度分辨率和丰富的对比度，是评价NASH的公认模式 没有辐射暴露的机制，允许对肝脏进行多参数评估。几个核磁共振- 相关的生物标志物，如质子密度脂肪分数（PDFF）、T2*/R2* 和弹性成像衍生的硬度， 已开发并建立了肝脏脂肪，铁和纤维化的定量评估，分别，但没有 已被证明可用于评估炎症，炎症是整个疾病中最重要的临床标志 NASH的过程T1是一个MRI参数，可能是NASH的一个有用的标志物， 一直对使用T1变化来表征肝脏炎症和/或纤维化感兴趣。但现有 当应用于NASH患者时，标准的T1映射方法受到若干限制。首先也是最 重要的是，标准T1标测仅测量肝脏的复合T1（水-脂肪-铁混合T1）， 由于NASH患者肝脏中脂肪和铁含量增加，导致实质性偏倚。这是因为 脂肪和铁都具有短的T1，而相反，炎症/纤维化倾向于延长T1。第二，T1映射 由于呼吸运动和肝脏的缓慢运动， MRI的成像速度，这会降低测量精度和再现性。这些问题代表了 使用T1映射评估脂肪肝疾病和相关疾病异质性的主要障碍。的 本申请的首要目标是提出并测试一种新的3D肝脏T1标测方法， 这些挑战。这种新方法称为磁化制备的狄克逊黄金角稀疏平行 （MP-Dixon-GRASP）MRI，具有自适应反转恢复准备的多回波星状堆叠采集， 结合先进的基于模型的图像重建，这将使自由呼吸的脂肪/铁- 校正T1图以估计潜在肝实质的“真实T1”。我们要验证的主要假设 在这个R21的建议是，通过消除脂肪和铁的影响，更准确的T1可以估计为 更好的肝脏炎症/纤维化标志物。如果成功，这种技术可以进一步结合 伴随T2* 和PDFF量化，最终提供新的自由呼吸3D多参数MRI 用于评估NASH和潜在的具有高临床影响的其他慢性肝病的技术。

Project Summary Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of ~25% and is a leading etiology of chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), as an advanced form of NAFLD, involves steatosis, inflammation and concomitant iron deposition in the liver. Due to chronic cellular injury, NASH can also cause liver fibrosis, which is a common trigger of more severe liver complications such as cirrhosis, portal hypertension, or hepatocellular carcinoma (HCC). As a result, simultaneous measures of these clinical indicators are crucial to provide more accurate and comprehensive assessment of NASH. Magnetic resonance imaging (MRI) is a well- accepted modality for evaluating NASH due to its excellent soft-tissue contrast resolution and abundant contrast mechanisms without radiation exposure, allowing for multiparametric assessment of the liver. Several MRI- related biomarkers, such as proton density fat fraction (PDFF), T2*/R2*, and elastography-derived stiffness, have been developed and established for quantitative assessment of liver fat, iron, and fibrosis, respectively, but none has been demonstrated for evaluating inflammation, the most important clinical hallmark throughout the disease course of NASH. T1 is an MRI parameter that can potentially be a useful marker for NASH, and there has long been an interest in using T1 changes to characterize liver inflammation and/or fibrosis. However, existing standard T1 mapping methods suffer from several limitations when applied to NASH patients. First, and most important, standard T1 mapping only measures composite T1 (water-fat-iron-mixed T1) of the liver, which can result in substantial bias due to the increased fat and iron content in the liver of NASH patients. This is because both fat and iron have short T1, while conversely, inflammation/fibrosis tends to prolong T1. Second, T1 mapping of the liver, particularly with 3D whole-liver coverage, remains challenging due to respiratory motion and the slow imaging speed of MRI, which can reduce measurement accuracy and reproducibility. These problems represent major barriers for evaluating fatty liver diseases and associated disease heterogeneity using T1 mapping. The overarching goal of this application is to propose and test a novel 3D liver T1 mapping method that could address these challenges. The new method, called Magnetization-Prepared Dixon Golden-angle RAdial Sparse Parallel (MP-Dixon-GRASP) MRI, features adaptive inversion recovery-prepared multi-echo stack-of-stars acquisition in combination with advanced model-based image reconstruction, which will enable free-breathing fat/iron- corrected T1 mapping to estimate the “true T1” of underlying liver parenchyma. Our main hypothesis to be tested in this R21 proposal is that by removing the influence of fat and iron, more accurate T1 can be estimated as a better marker of liver inflammation/fibrosis. If successful, this technique can be further combined with concomitant T2* and PDFF quantification to ultimately provide a new free-breathing 3D multiparametric MRI technique for assessment of NASH and potentially other chronic liver diseases of high clinical impact.