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

移植肝微观和宏观脂肪变性的声学评估

• 批准号: 8769881
• 负责人: Wayne E Kreider
• 金额: $ 21.45万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-16 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769881
• 关键词: Acoustics; Address; Area; Biochemical; Biopsy; Cancerous; Castor Oil; Clinical; Communities; Data; Development; Devices; Diabetes Mellitus; Diagnostic; Diet; Elements; Emulsions; Epidemic; Evaluation; Excision; Family suidae; Fatty Liver; Fatty acid glycerol esters; Frequencies; Functional disorder; Glean; Glycerol; Gold; Human; Human Resources; Laboratories; Lipid Inclusion; Lipids; Liver; Liver diseases; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mechanics; Methodology; Methods; Metric; Modality; Modeling; Obesity; Organ; Organ Donor; Outcome; Pathology; Patients; Performance; Prevalence; Property; Protons; Relative (related person); Research Personnel; Risk Factors; Sampling; Spectrum Analysis; Speed; Staging; Surgeon; System; Techniques; Temperature; Testing; Time; Tissues; Training; Transducers; Transplant Recipients; Transplantation; Ultrasonic wave; Ultrasonics; Ultrasonography; Universities; Waiting Lists; Washington; Water; Work; X-Ray Computed Tomography; attenuation; base; data acquisition; design; high risk; imaging modality; improved; in vivo; liver transplantation; public health relevance; signal processing; sound; tool; transmission process; usability

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.

描述（申请人提供）：肝移植是终末期肝病患者的主要治疗方法，美国每年进行超过 6,000 例肝移植手术。目前有近 16,000 人在等待名单上，尽管这一数字预计还会增加。努力扩大捐助者群体。肥胖和糖尿病的流行导致了这一问题，因为所需肝移植的数量和供体器官的废弃数量都增加了。脂肪肝病（肝脂肪变性）是肝移植中最常见的不良状况，其中脂肪可分为大泡型或微泡型。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使用。历史上，被判定脂肪含量高于 30% 的肝脏会被拒绝移植。然而，由于迫切需要扩大供体库，因此开始使用被认为是中度脂肪（30-60%）的肝脏。为了有效地使用这些肝脏，需要准确量化脂肪含量，以促进肝脏与受体的成功匹配。目前， 肝脂肪变性评估的金标准是活检和组织学评估。然而，这种方法是侵入性的，依赖于训练有素的人员，并且产生主观结果。虽然已经出现了最先进的成像方式来确定脂肪含量，但这些方法成本高昂、耗时，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，超声组织表征方法很有希望。此类方法利用超声波与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来表征肝脏组织的总脂肪含量，但没有一个方法专注于区分微量脂肪。 和大囊泡成分。在这里，我们建议开发、实施和测试这样的方法。我们的方法结合了成熟的技术：声速测量和非线性比 B/A 可以预测总脂肪含量，而作为频率函数的衰减测量将能够估计微泡和大泡的相对组成胖的。第一个和第二个提案旨在构建一个在传输模式下运行的声卡尺装置，实施测量和解释 B/A、声速和衰减的先进方法，并根据脂质乳液体模和肥猪的测量结果完善这些功能肝脏。第三个目标是收集脂肪变性猪肝脏以及拒绝移植的人类供体肝脏的体内和离体声学测量结果。将评估这些测量的结果，以通过与目前用于移植的黄金标准指标进行比较来证明原理验证。我们在华盛顿大学组建了一个由声学、组织评估和肝移植领域的专家组成的团队，以及更广泛的移植界（西北生命中心）的合作伙伴，以实现提案目标并解决肝脏的主要临床需求移植。