Hepatic Steatosis Quantification with Ultrasound

超声定量肝脏脂肪变性

• 批准号: 10436480
• 负责人: Shigao Chen
• 金额: $ 57.66万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436480
• 关键词: Affect; Agreement; Algorithms; American; Benchmarking; Biological Markers; Calibration; Cardiovascular Diseases; Classification; Clinical; Detection; Development; Diabetes Mellitus; Diagnosis; Evaluation; Family; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Frequencies; Guidelines; Hepatology; Image; Intervention; Lead; Liver; Liver Cirrhosis; Liver Fibrosis; Magnetic Resonance Elastography; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Modernization; Noise; Outcome; Patients; Penetration; Performance; Phase; Populations at Risk; Protons; ROC Curve; Reference Standards; Regression Analysis; Reproducibility; Risk; Scanning; Serum; Signal Transduction; Specificity; Speed; Staging; Technology; Testing; Time; X-Ray Computed Tomography; attenuation; cost; cost effective; density; diabetes management; fatty liver disease; follow-up; improved; new technology; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; patient population; point of care; prototype; rib bone structure; screening; serial imaging; signal processing; sound; ultrasound; wireless

PROJECT SUMMARY Quantification of liver steatosis has weighty implications in management of Nonalcoholic Fatty Liver Disease (a condition affecting 75-100 million Americans), diabetes mellitus, and cardiovascular disease. Serum biomarkers, computed tomography, and existing ultrasound methods have low sensitivity or specificity for steatosis staging. Proton Density Fat Fraction (PDFF) measured by MRI has high accuracy, but is limited by accessibility and cost. Here we propose a novel ultrasound technology, Spectrum Normalization Attenuation Imaging (SNAI), to quantify ultrasound attenuation coefficient for accurate liver steatosis staging. SNAI does not require a calibration phantom, and is robust to rib shadowing as well as phase aberration and reverberation clutter from the body wall. Accuracy of SNAI for steatosis staging is demonstrated by a promising correlation coefficient of 0.91 with MRI-PDFF in 50 patients. In this project, we will prototype, optimize, and evaluate SNAI on a low-cost, pocket-sized, wireless ultrasound probe, which can be conveniently used for screening and follow-up at the point-of-care setting such as the office of a family doctor or hepatologist. Specific Aim 1: Technical Development. We will use phantom and patient studies to advance and optimize SNAI on the the wireless ultrasound probe. Acquisition parameters and post processing algorithms will be optimized for both fundamental and harmonic SNAI imaging. We will suppress reverberation clutter and correct for sound speed mismatch in liver for more accurate steatosis quantification. Specific Aim 2: Patient study. We will use the SNAI prototypes optimized in Aim 1 to study 250 steatosis patients with clinically indicated MRI-PDFF to investigate the efficacy of SNAI for steatosis quantification. Correlation analysis will be performed to assess the association of SNAI with MRI-PDFF. Steatosis will also be categorized as S0, S1, and S2/S3 according to PDFF. Receiver operating characteristic analyses will be performed to evaluate performance of SNAI for detecting ≥S1 and ≥S2. The agreement between SNAI and PDFF classification will be evaluated using the Kappa statistic. Fibroscan CAP will be used for benchmarking. Specific Aim 3: Reproducibility study. Two sonographers and two hepatology residents will repeatedly scan a subset of subjects (50 patients) studied in Aim 2. Intraclass correlation coefficients will be used to evaluate the inter-operator agreement for SNAI measurements. The within patient variance component from the model will provide an estimate of the inter-operator variance, which represents a lower bound for the minimum detectable difference for longitudinal follow-ups. Successful completion of this project will result in a safe, cost-effective, and easily accessible ultrasound solution for accurate quantification of liver steatosis for diagnosis and frequent follow-up of this very large patient population at point-of-care settings such as the office of a hepatologist or family doctor.

项目概要 肝脏脂肪变性的量化对于非酒精性脂肪肝病的治疗具有重要意义（a 影响 75-1 亿美国人的疾病）、糖尿病和心血管疾病。血清 生物标志物、计算机断层扫描和现有的超声方法对于以下疾病的敏感性或特异性较低 脂肪变性分期。通过 MRI 测量的质子密度脂肪分数 (PDFF) 具有较高的准确性，但受到以下因素的限制 可达性和成本。在这里，我们提出了一种新颖的超声技术，频谱归一化衰减 成像 (SNAI)，量化超声衰减系数，以实现准确的肝脏脂肪变性分期。 SNAI 确实 不需要校准模型，并且对肋骨阴影以及相位畸变和混响具有鲁棒性 来自体壁的杂乱。 SNAI 对脂肪变性分期的准确性通过有希望的相关性得到证明 50 名患者的 MRI-PDFF 系数为 0.91。在这个项目中，我们将对 SNAI 进行原型设计、优化和评估 低成本、袖珍型、无线超声探头，可方便地用于筛查和 在家庭医生或肝病专家办公室等护理点进行随访。 具体目标 1：技术开发。我们将利用模型和患者研究来推进和优化 SNAI上的无线超声探头。采集参数和后处理算法将 针对基波和谐波 SNAI 成像进行了优化。我们将抑制混响杂波并纠正 针对肝脏中的声速不匹配，以实现更准确的脂肪变性量化。 具体目标 2：患者研究。我们将使用目标 1 中优化的 SNAI 原型来研究 250 脂肪变性 对具有临床指示的 MRI-PDFF 患者进行研究，以研究 SNAI 对脂肪变性定量的功效。 将进行相关分析以评估 SNAI 与 MRI-PDFF 的关联。也会出现脂肪变性 根据 PDFF 分为 S0、S1 和 S2/S3。接收器工作特性分析将是 评估 SNAI 检测 ≥S1 和 ≥S2 的性能。 SNAI 与 PDFF 分类将使用 Kappa 统计量进行评估。 Fibroscan CAP 将用于基准测试。 具体目标 3：再现性研究。两名超声医师和两名肝病住院医生将反复扫描 目标 2 中研究的受试者子集（50 名患者）。组内相关系数将用于评估 SNAI 测量的运营商间协议。模型中患者内部方差分量 将提供操作员间方差的估计，它代表最小值的下限 纵向随访可检测到的差异。 该项目的成功完成将带来安全、具有成本效益且易于获取的超声波 准确量化肝脏脂肪变性的解决方案，用于诊断和频繁随访这一非常大的疾病 肝病专家或家庭医生办公室等护理点的患者群体。