Noninvasive fat quantification of liver using ultrasound thermal strain imaging

描述（由申请人提供）：在本提案中，我们建议证明新型超声诱导热应变成像（US-TSI）作为临床有用工具的可行性 用于定量评估肝脏中的脂肪，这对于非酒精性脂肪性肝病（NAFLD）的发病率增长至关重要。NAFLD是儿童和成人中最常见的慢性肝病形式，已成为严重的公共卫生问题，影响美国人口的30%。NAFLD被认为是一种良性疾病，但现在越来越多地被认为是肝脏相关发病率和死亡率的主要原因，进展为肝硬化，肝衰竭和肝细胞癌。脂肪变性是肝细胞内含脂肪空泡的积累，是脂肪肝疾病的一个关键组织学特征。如果在早期发现，简单的脂肪变性可以通过适当的治疗逆转，但是中度至重度脂肪变性发生慢性肝脏并发症的风险更大。因此，一种具有成本效益的非侵入性成像方式，可以以高灵敏度和特异性检测和定量肝脏中的脂肪，将在早期提供准确的诊断。 NAFLD的分期和治疗评价。目前NAFLD的诊断方法是侵入性的、昂贵的、电离的或不太敏感的。针吸活检是侵入性的，不适合作为诊断测试在这样一个普遍的条件，因为它的费用和并发症的风险，特别是对儿童。超声（US）B-扫描是目前临床上最常见的非侵入性诊断成像，不能提供脂质蓄积程度的定量信息，也不足以检测早期脂肪变性。CT和MR扫描是量化脂肪变性的更敏感的技术。然而，它们是电离的或昂贵的，不适合儿童。US-TSI可以无创地识别组织中的脂质含量。我们之前已经开发了US-TSI，使用US进行成像和加热（<3 oC），用于动脉粥样硬化斑块中的脂质检测。在本申请中，我们建议评估US-TSI用于肝脏脂肪定量的灵敏度和特异性。本研究计划的长期目标是开发一种新的非侵入性临床成像模式，用于脂肪肝疾病的诊断和治疗评价。拟定研究范围内的目标是开发和评价US-TSI作为评估啮齿动物肝脏脂肪的无创成像工具。将通过计算机模拟、使用组织模拟体模和离体肝脏的实验以及体内小鼠模型系统地进行评价。如果成功，该项目可以相对容易地转化为使用商业超声扫描仪结合安全的US热源的人体受试者研究，这是该研究计划的长期目标。US-TSI将对NAFLD产生高度影响，允许准确的疾病分期，从而改善治疗结果，防止其进展为慢性肝脏并发症。这也将减少MR或CT等扩展测试的医疗费用，这些测试不适合儿童。

DESCRIPTION (provided by applicant): In this proposal, we propose to demonstrate the feasibility of a novel ultrasound-induced thermal strain imaging (US-TSI) as clinically useful tool for quantitative assessment of fat in liver, which is critically important with growing prevalence f nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease in both children and adults and has become a serious public health problem, affecting up to 30% in the United States population. NAFLD was thought to be a benign condition but is now increasingly recognized as a major cause of liver-related morbidity and mortality, progressing to cirrhosis, liver failure, and hepatocellular carcinoma. Steatosis, the accumulation of fat-containing vacuoles within hepatocytes, is a key histological feature of fatty liver disease A simple steatosis can be reversed with proper treatments if found at early stage, however moderate to severe steatosis are at greater risk of developing chronic liver complications. A cost-effective, noninvasive imaging modality, which allows detection and quantification of fat in the liver with high sensitivity and specificity, will therefore provide accurate diagnosis at early stage and evaluation of the treatments of NAFLD longitudinally. Current diagnosis methods for NAFLD are invasive, expensive, ionizing, or less sensitive. A needle biopsy is invasive and poorly suited as a diagnostic test in such a prevalent condition because of its expense and risks of complications, especially for children. Ultrasound (US) B-scan, the most common noninvasive diagnostic imaging in current clinics, does not provide quantitative information of the degree of lipid accumulation, and is not sensitive enough to detect early steatosis. Both CT and MR scanning are more sensitive techniques for quantification of steatosis. However, they are ionizing or expensive, not suitable for children. US-TSI can noninvasively identify lipid contents in tissue. We have previously developed US-TSI using US for both imaging and heating (<3oC) for lipid detection in atherosclerotic plaques. In this application, we propose to evaluate the sensitivity and specificity of US-TSI for fat quantification in liver. The long term goal of this research program is to develop a novel noninvasive clinical imaging modality for diagnosis and treatment evaluation of fatty liver diseases. The objective within the scope of the proposed study is to develop and evaluate US-TSI as noninvasive imaging tool to assess liver fat in rodents. The evaluation will be performed systematically by computer simulation, experiments using tissue mimicking phantoms and excised liver, and in vivo mouse models. If successful, this project can be translated relatively easily into the human subject study using a commercial ultrasound scanner combined with a safe US heating source, which is the long-term goal of this research program. US-TSI will bring a highly influential impact on NAFLD, allowing an accurate disease staging, which will lead to improved treatment outcomes, preventing it from the progression to chronic liver complications. This will also lessens the medical expenses of the extended tests like MR or CT, which are not anyway suitable for children.