Hepatic Steatosis Quantification with Ultrasound

项目总结 肝脏脂肪变性的量化在非酒精性脂肪性肝病(A)的治疗中具有重要意义 影响到7500万至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 脂肪变性分期。核磁共振测量质子密度脂肪分数(PDFF)具有较高的准确性，但受到以下因素的限制 可获得性和成本。在这里，我们提出了一种新的超声技术，频谱归一化衰减 成像(SNAI)，以量化超声衰减系数，以准确的肝脏脂肪变性分期。斯奈尔做了 不需要校准模体，对肋骨阴影以及相位像差和混响具有很强的抗干扰性 身体壁上的杂物。SNAI对脂肪变性分期的准确性被一个有希望的相关性所证明。 50例患者MRI-PDFF的相关系数为0.91。在这个项目中，我们将构建、优化和评估SNAI 一种低成本、袖珍无线超声波探头，可方便地用于筛查和 在家庭医生或肝病专科医生的办公室等护理地点进行随访。 具体目标1：技术发展。我们将使用体模和患者研究来推进和优化 SNAI在无线超声探头上。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 对于肝脏中的声速不匹配，以便更准确地量化脂肪变性。 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。 对临床表现为MRI-PDFF的患者，探讨SNAI对脂肪变性量化的效果。 将进行相关分析，以评估SNAI与MRI-PDFF的相关性。脂肪变性也会 根据PDFF分类为S0、S1和S2/S3。接收器操作特性分析将包括 用来评估SNAI检测≥S1和≥S2的性能。SNAI和SNAI之间的协议 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：重复性研究。两名超声师和两名肝病住院医生将反复扫描 在目标2中研究的受试者子集(50名患者)。将使用组内相关系数来评估 关于SNAI测量的运营商间协议。模型中的患者内部方差分量 将提供运算符间方差的估计，该估计表示最小值的下界 纵向随访中可检测到的差异。 该项目的成功完成将带来一种安全、经济、易于获得的超声波 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个非常大的 在诸如肝病专家或家庭医生办公室等医疗场所的病人群体。

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.