3D Free-Breathing Fat and Iron Corrected T1 Mapping

项目摘要 非酒精性脂肪性肝病(NAFLD)在全球的患病率约为25%，是慢性脂肪肝的主要病因 全球范围内的肝病。非酒精性脂肪性肝炎(NASH)作为NAFLD的一种高级形式，涉及脂肪变性， 肝脏中的炎症和伴随的铁沉积。由于慢性细胞损伤，NASH也会导致 肝纤维化，这是更严重的肝脏并发症的常见触发因素，如肝硬变、门脉高压、 或肝细胞癌(HCC)。因此，对这些临床指标的同时测量对于 提供更准确、更全面的NASH评估。磁共振成像(MRI)是一个很好的- 由于NASH良好的软组织对比分辨率和丰富的对比度，可以接受NASH的评估方式 没有辐射暴露的机制，允许对肝脏进行多参数评估。几种核磁共振成像- 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，有 已经开发和建立了分别用于肝脏脂肪、铁和纤维化的定量评估，但没有 已被证明用于评估炎症，这是贯穿整个疾病的最重要的临床标志 当然是纳什。T1是一项MRI参数，可能成为NASH的有用标志，而且有很长的 人们对使用T1变化来表征肝脏炎症和/或纤维化很感兴趣。然而，现有的 标准的T1标测方法在应用于NASH患者时受到几个限制。首先，也是大多数 重要的是，标准T1图仅测量肝脏的复合T1(水-脂肪-铁混合T1)，它可以 由于NASH患者肝脏中脂肪和铁含量的增加，导致了实质性的偏差。这是因为 脂肪和铁都有较短的T1，相反，炎症/纤维化倾向于延长T1。第二，T1映射 肝脏的成像，特别是3D全肝覆盖，由于呼吸运动和缓慢的 MRI的成像速度，这会降低测量精度和重复性。这些问题代表了 使用T1图评估脂肪肝疾病和相关疾病异质性的主要障碍。这个 本申请的首要目标是提出并测试一种新的3D肝脏T1映射方法，该方法可以解决 这些挑战。这种新的方法称为磁化制备的Dixon黄金角径向稀疏平行 (MP-Dixon-Graff)MRI，采用自适应反转恢复-准备的多回波叠加星体采集 与先进的基于模型的图像重建相结合，将使脂肪/铁自由呼吸- 修正了T1图，估计了肝实质的“真实T1”。我们的主要假设有待检验 在这个R21建议中，通过去除脂肪和铁的影响，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，这项技术可以进一步结合 伴随T2*和PDFF量化最终提供一种新的自由呼吸3D多参数磁共振成像 评估NASH和其他可能具有较高临床影响的慢性肝病的技术。

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.