Multiparametric diagnosis of fatty liver disease with magnetic resonance fingerprinting

在这项提议中，我们的目标是开发、实施和验证一种新的完全共同注册的多参数定量图谱方法，该方法通过一次有效的MR指纹扫描来实现对非酒精性脂肪肝的全面诊断，非酒精性脂肪肝是世界上最常见的慢性肝病。该项目的具体目标是：开发2D肝脏磁共振指纹(MRF)方法，用于同时进行T1、T2、T2*和脂肪部分成像，以便在小动物模型和人类中进行肝脏成像。将MRF技术扩展到3D，以实现全肝覆盖和更高的空间分辨率，结合基于自主导航的呼吸运动校正。在小鼠脂肪肝疾病模型和治疗反应中验证新的2D和3D MRF技术的敏感性和准确性。如果时间允许，非酒精性脂肪性肝病(NAFLD)是世界上最常见的慢性肝病，在普通成年人(美国约8000万人)中的患病率为30%-40%。它主要发现于高脂肪饮食和不活跃的生活方式的肥胖者。有效的NAFLD风险分层需要评估肝脏脂肪含量、炎症和纤维化，肝活检仍是目前的参考标准，尽管更先进的无创成像技术正在迅速涌现，包括定量超声、MR弹性成像和最新的多参数MRI，涉及T1图、脂肪分数和铁(T2*MAP)定量。虽然包括常规T1、T2*和脂肪比例成像在内的定量MR成像技术在纤维化、含铁血黄素沉着症和肝脏脂肪量化方面的发展显示出有希望的结果，但它们是以不同的空间分辨率顺序获得的，并且由于这些扫描之间的呼吸或大块运动，可能处于不同的呼吸位置。在这里，我们建议在临床前和临床环境中开发和验证一种新的肝脏磁共振指纹(MRF)方法，该方法可以在一次扫描中(与多次顺序扫描相比)实现NAFLD不同阶段的多参数映射(T1、T2、T2*和脂肪分数)。更具体地说，我们建议1)扩展我们先前开发的用于心脏成像的2D Dixon MRF(T1、T2和脂肪分数)技术，以提供同时的水-脂肪T1、T2、T2*和脂肪分数(FF)图，由于不同图的内在共配准，这可能有助于图像分析和诊断。此外，2)考虑到全肝覆盖和提高空间分辨率，我们将2D肝脏MRF框架扩展到自由呼吸运动校正的3D肝脏MRF协议。脂肪肝病动物模型的使用将允许3)研究2D和3D肝脏MRF在脂肪肝疾病的准确分期和治疗反应监测中的应用。与传统的参数肝图相比，建议的方法还将提供共同注册的T2图，以便于区分纤维化和水肿病，而目前使用的临床方法缺乏这一点。最后，4)新的肝脏2D MRF技术将在脂肪肝疾病不同阶段的一小部分患者中得到验证。

In this proposal we aim to develop, implement and validate a novel fully co-registered multiparametric quantitative mapping approach from a single and efficient MR fingerprinting scan, to enable comprehensive diagnosis of non-alcoholic fatty liver disease, the most common chronic liver disease world-wide. The specific aims of the project are to:Develop 2D liver Magnetic Resonance Fingerprinting (MRF) approach for simultaneous T1, T2, T2* and fat-fraction mapping to enable liver imaging in small animal models and humans.Extend the MRF technique to 3D for whole liver coverage and higher spatial resolution, incorporating respiratory motion correction based on self-navigation.Validate the sensitivity and accuracy of the novel 2D and 3D MRF techniques in a mouse model of fatty liver disease and in response to treatment.If time permits, validate the proposed 2D liver MRF approach in a small cohort of patients at different stages of fatty liver disease.Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world with a prevalence of 30%-40% in the general adult population (~80M people in US). It is found predominantly in obese people with high-fat diets and inactive lifestyles. Effective risk stratification of NAFLD requires evaluation of hepatic fat content, inflammation and fibrosis, with liver biopsy remaining the current reference standard although more advanced non-invasive imaging techniques are rapidly emerging including quantitative ultrasound, MR elastography and most recently multiparametric MRI involving T1 mapping, fat fraction and iron (T2* map) quantification. While the development of quantitative MR mapping techniques including conventional T1, T2* and fat fraction mapping for fibrosis, hemosiderosis and liver fat quantification have shown promising results, they are acquired sequentially with different spatial resolution and potentially at different respiratory positions due to respiration or bulk motion in-between those scans. Here we propose to develop and validate in pre-clinical and clinical settings a novel liver Magnetic Resonance Fingerprinting (MRF) approach which may enable multiparametric mapping (T1, T2, T2* and fat fraction) of the different stages of NAFLD in a single scan (compared to multiple sequential scans). More specifically, we propose 1) to extend a 2D Dixon MRF (T1, T2 and fat fraction) technique that we have previously developed for cardiac imaging to provide simultaneous water-fat T1, T2, T2* and fat fraction (FF) maps which may facilitate image analysis and diagnosis due to intrinsic co-registration of the different maps. Furthermore, 2) to allow for whole liver coverage and improve spatial resolution we will extend the 2D liver MRF framework to a free-breathing motion corrected 3D liver MRF protocol. The use of an animal model of fatty liver disease will allow to 3) investigate the utility of 2D and 3D liver MRF for accurate staging of fatty liver disease and monitoring of treatment response. Compared to conventional parametric liver mapping the proposed approach will also provide co-registered T2 maps to facilitate differentiation between fibrosis and oedema, which the currently used clinical approach lacks. Finally, 4) the novel liver 2D MRF technique will be validated in a small cohort of patients at the different stages of fatty liver disease.