Multiparametric diagnosis of fatty liver disease with magnetic resonance fingerprinting

在本提案中，我们的目标是开发，实施和验证一种新颖的全共登记多参数定量制图方法，从单一和高效的MR指纹扫描，以实现非酒精性脂肪性肝病的全面诊断，这是世界范围内最常见的慢性肝病。该项目的具体目标是：开发二维肝脏磁共振指纹（MRF）方法，用于同时进行T1， T2， T2*和脂肪分数测绘，以实现小动物模型和人类的肝脏成像。将MRF技术扩展到3D，以实现全肝脏覆盖和更高的空间分辨率，并结合基于自我导航的呼吸运动校正。验证新型二维和三维磁共振成像技术在脂肪性肝病小鼠模型中的敏感性和准确性以及对治疗的反应。如果时间允许，在一组不同阶段的脂肪肝患者中验证所提出的2D肝脏MRF方法。非酒精性脂肪性肝病（NAFLD）是世界上最常见的慢性肝病，在普通成年人中患病率为30%-40%（美国约8000万人）。它主要发生在高脂肪饮食和不活跃生活方式的肥胖人群中。NAFLD的有效风险分层需要评估肝脏脂肪含量、炎症和纤维化，肝活检仍然是目前的参考标准，尽管更先进的非侵入性成像技术正在迅速出现，包括定量超声、MR弹性成像和最近涉及T1制图、脂肪分数和铁（T2*图）量化的多参数MRI。虽然定量磁共振成像技术的发展，包括用于纤维化、含铁血黄素症和肝脏脂肪定量的传统T1、T2*和脂肪部分成像，已经显示出有希望的结果，但它们是顺序获得的，具有不同的空间分辨率，并且由于这些扫描之间的呼吸或大块运动，可能在不同的呼吸位置获得。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，该方法可以在单次扫描（与多次顺序扫描相比）中实现NAFLD不同阶段的多参数映射（T1, T2， T2*和脂肪部分）。更具体地说，我们建议1)扩展我们之前为心脏成像开发的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)为了覆盖整个肝脏并提高空间分辨率，我们将把2D肝脏MRF框架扩展到自由呼吸运动校正的3D肝脏MRF协议。脂肪肝动物模型的使用将允许3)研究二维和三维肝脏磁共振成像在脂肪肝疾病准确分期和治疗反应监测方面的效用。与传统的参数化肝脏制图相比，该方法还将提供共同注册的T2图，以促进纤维化和水肿的区分，这是目前临床使用的方法所缺乏的。最后，4)新的肝脏二维磁共振成像技术将在一组不同阶段的脂肪肝患者中进行验证。

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.