Noninvasive Assessment of Liver Stiffness with Tagged MRI

描述（由申请人提供）：肝脏疾病是一个主要的和日益增长的公共卫生问题。虽然许多表现为病毒性或酒精性肝炎的患者会很好地恢复，但其他患者的疾病会有显著进展（接触丙型肝炎的患者中超过50%会成为慢性感染），通常最初没有明显的外部症状。这可能导致肝硬化的晚期发展，伴随可能危及生命的并发症，并增加发展为肝细胞癌的风险。虽然许多患者在疾病的早期阶段可以成功治疗，但一旦发展为全面肝硬化，治疗就不那么成功了。然而，现有的治疗方法并非没有成本和潜在风险，也不能在所有患者首次就诊时就常规地给予治疗。因此，在早期阶段检测肝病进展的能力将使更有效的治疗和预防后期并发症，同时避免对那些不需要治疗的患者进行治疗。不幸的是，目前可用的检测疾病早期进展的无创手段在准确性上是有限的，因此经常导致需要反复进行肝活检，以跟踪那些被认为有较高肝硬化风险的患者。本研究的重点是初步开发和测试一种基于标记磁共振成像（tMRI）的无创评估肝脏硬度的新方法，该方法有望为肝纤维化的发展提供一个敏感的早期标志物，肝纤维化是肝硬化进展的一个重要标志。心脏运动在肝脏中产生传递运动，这可以用tMRI观察和测量。在我们的初步结果中，肝纤维化已经被认为在这种肝脏运动中产生定性和定量的变化。拟议的研究将开发改进的工具来研究与肝纤维化相关的这种运动的变化，并将它们与纤维化程度相关联，作为验证结果的手段。这种评估肝脏硬度的新方法产生的图像可以直接直观地理解；它可以在传统的MRI系统上实现，只需要对成像软件进行轻微的修改，并使用合适的软件工具来分析生成的图像；而且可以快速实施。这些特征都使其潜在地适合纳入常规肝脏MRI评估，当有可能增加肝脏僵硬的问题时。因此，这项研究对病人护理有重要的有益影响。

DESCRIPTION (provided by applicant): Liver disease is a major and growing public health concern. While many patients presenting with viral or alcoholic hepatitis will recover well, others will have significant progression of their disease (more than 50% of patients with exposure to hepatitis C become chronically infected), often initially without externally apparent symptoms. This can lead to the late development of frank liver cirrhosis, with its attendant potentially life-threatening complications, and an increased risk of developing hepatocellular carcinoma. While many patients can be successfully treated in the earlier stages of the disease, treatment is much less successful once full-blown cirrhosis has developed. However, the available treatments are not without their own cost and potential risks, and cannot be given routinely to all patients at their initial presentation. Thus, the ability to detect progression of liver disease at an earlier stage would enable more effective treatment and the prevention of later complications, while avoiding treatment of those patients who do not require it. Unfortunately, the currently available noninvasive means of detecting the early progression of the disease are limited in their accuracy, thus often leading to a need for repeated liver biopsies to follow those patients who are felt to be at a higher risk of developing cirrhosis. This proposed research is focused on the initial development and testing of a new method for the noninvasive evaluation of liver stiffness, based on tagged magnetic resonance imaging (tMRI), which is expected to provide a sensitive early marker for the development of liver fibrosis, an important hallmark of the progression toward cirrhosis. Cardiac motion produces transmitted motion in the liver that can be seen and measured with tMRI. Fibrosis of the liver has been seen to produce qualitative and quantitative changes in this liver motion in our initial results. The proposed research will develop improved tools to study the changes in this motion associated with liver fibrosis, and will correlate them with the degree of fibrosis as a means to validate the results. This new method for assessment of liver stiffness produces images that can be directly and intuitively understood; it can be implemented on conventional MRI systems, requiring only minor imaging software modification and the use of suitable software tools for analysis of the resulting images; and it can be rapidly carried out. These features all make it potentially suitable for incorporation in routine liver MRI evaluations when there is a question of possible increased liver stiffness. Thus, there is a significant potential for an important beneficial impact of this research on patient care. PUBLIC HEALTH RELEVANCE: Liver disease is an important and growing public health problem, with there frequently being clinically silent progression to the later serious complications of cirrhosis. However, conventional noninvasive methods of detecting liver fibrosis, a hallmark of developing cirrhosis, are unreliable, often resulting in the need for repeated liver biopsies (with their associated discomfort and risk) to follow patients at risk for progressive liver disease. The overall aim of this project is the development and evaluation of a new method for assessing the stiffness of the liver, specifically, the use of tagged magnetic resonance imaging (tMRI) to measure the motion and deformation induced in the liver by the motion of the heart; if successful, this could provide a way to avoid the need for biopsy in following many patients with liver disease.