Acoustic evaluation of micro- and macro-steatosis in transplant livers

描述（由申请人提供）：肝移植是终末期肝病患者的主要治疗方法，美国每年进行6，000多例肝移植，目前有近16，000人在等待名单上，尽管努力扩大供体库，但这一数字预计还会增加。肥胖和糖尿病的流行增加了肝移植的需求和供体器官的不使用，从而导致了这一问题。脂肪肝疾病（肝脂肪变性）是肝移植物中最普遍的不良状况，其中脂肪可被分类为大泡或微泡。大泡性脂肪变性被认为是移植肝脏原发性无功能和功能障碍的主要危险因素，因此可能导致器官不能使用。从历史上看，被判断为脂肪含量高于30%的肝脏被拒绝移植。然而，由于迫切需要扩大供体库，被认为中度脂肪（30-60%）的肝脏开始被使用。为了有效地使用这些肝脏，需要准确定量脂肪含量，以促进肝脏与受体的成功匹配。目前该 肝脂肪变性评估的金标准是活组织检查和组织学评估。然而，这种方法是侵入性的，依赖于训练有素的人员，并产生主观结果。虽然已经出现了最先进的成像方式来确定脂肪含量，但这些方法成本高，时间密集，并且无法区分大泡性脂肪变性和微泡性脂肪变性。为了填补可用诊断工具的这一空白，超声组织定征方法具有前景。这样的方法利用超声波和组织之间的相互作用来识别机械组织特性。虽然这些方法已被用于在总脂肪含量方面表征肝组织，但没有一种方法专注于区分微脂肪和脂肪酸。 和大泡组分。在这里，我们建议开发，实现和测试这样的方法。我们的方法包括一个成熟的技术相结合：测量声速和非线性比B/A预测总脂肪含量，而衰减作为频率的函数的测量将使微泡和宏泡脂肪的相对组成的估计。第一个和第二个建议旨在寻求建立一个声学卡尺设备在传输模式下运行，实施先进的方法来测量和解释B/A，声速和衰减，并完善这些功能的基础上，从脂肪乳剂幻影和脂肪猪肝的测量。第三个目标是收集来自脂肪变性猪肝脏以及拒绝移植的人类供体肝脏的体内和体外声学测量。将对这些测量结果进行评估，以通过与目前用于移植的金标准指标进行比较来证明原理证明。我们在华盛顿大学组建了一个声学、组织评估和肝移植领域的专家团队，以及更广泛的移植社区（LifeCenter Northwest）的合作伙伴，以实现提案目标并解决肝移植的主要临床需求。

DESCRIPTION (provided by applicant): Liver transplantation is the primary treatment for patients with end-stage liver disease, with over 6,000 liver transplants performed each year in the U.S. There are almost 16,000 people currently on waiting lists and this number is expected to increase despite efforts to expand the donor pool. The epidemic in obesity and diabetes has contributed to the problem by increasing both the number of liver transplants needed and donor organ nonuse. Fatty liver disease (hepatic steatosis) is the most prevalent adverse condition in liver grafts, wherein the fat can be classified as macrovesicular or microvesicular. Macrovesicular steatosis is considered a primary risk factor in transplanted livers for both primary non-function and dysfunction and can therefore result in organ nonuse. Historically, livers judged to have a fat content higher than 30% were rejected for transplantation. However, due to the dire need to expand the donor pool, livers that are considered moderately fatty (30-60%) are starting to be used. To effectively use these livers, an accurate quantification of fat content will be needed to facilitate successful matching of livers with recipients. At present, the gold standard for hepatic steatosis evaluation is biopsy and histological assessment. However, this method is invasive, relies on highly trained personnel, and produces subjective results. While state-of-the-art imaging modalities have emerged to determine fat content, these methods are costly, time intensive, and unable to differentiate between macro- and micro-vesicular steatosis. To fill this gap in available diagnostic tools, ultrasound tissue characterization methods have promise. Such methods utilize the interactions between ultrasound waves and tissue to identify mechanical tissue properties. While such approaches have been used to characterize liver tissue in terms of total fat content, none have focused on distinguishing micro- and macro-vesicular components. Here, we propose to develop, implement, and test such a method. Our approach comprises a combination of well-developed techniques: measurements of sound speed and the nonlinear ratio B/A predict total fat content, while measurements of attenuation as a function of frequency will enable estimates of the relative composition of micro- and macro-vesicular fat. The first and second proposal aims seek to build an acoustic caliper device operating in transmission mode, implement advanced methods for measuring and interpreting B/A, sound speed, and attenuation, and refine these functionalities based on measurements from lipid-emulsion phantoms and fatty pig livers. The third aim seeks to collect in vivo and ex vivo acoustic measurements from steatotic pig livers as well as human donor livers rejected for transplantation. Results of these measurements will be evaluated to demonstrate proof-of-principle by comparison with gold-standard metrics currently used for transplants. We have assembled a team of experts in the areas of acoustics, tissue evaluation, and liver transplantation at the University of Washington, as well as partners in the broader transplant community (LifeCenter Northwest) to accomplish proposal aims and address a major clinical need for liver transplantation.