Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

无创次谐波辅助门脉高压压力估计

• 批准号: 10672450
• 负责人: Flemming Forsberg
• 金额: $ 59.54万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672450
• 关键词: Academia; Adrenergic beta-Antagonists; Adult; Algorithms; Ascites; Blood Platelets; Catheters; Cirrhosis; Clinical; Clinical Trials; Compensation; Confidence Intervals; Contrast Media; Development; Diagnosis; Early Diagnosis; Encephalopathies; Esophagus; Evaluation; Event; Grant; Healthcare; Hemorrhage; Hepatic; Human; Incidence; Industry; Liver; Liver diseases; Logic; Manufacturer; Measurement; Methods; Monitor; Morbidity - disease rate; Multicenter Trials; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Pennsylvania; Physicians; Pilot Projects; Portal Hypertension; Portal Pressure; Portal vein structure; Positioning Attribute; Primary carcinoma of the liver cells; Reproducibility; Research Personnel; Risk; Schedule; Scientist; Site; Specificity; Symptoms; System; Techniques; Technology; Therapeutic Intervention; Transjugular intrahepatic portosystemic shunt procedure; Transplantation; Treatment Efficacy; Triage; Universities; University Hospitals; Varicosity; Venous Pressure level; accurate diagnosis; chronic liver disease; clinically significant; contrast enhanced; cost; data acquisition; diagnostic accuracy; elastography; first-in-human; hepatic vein; improved; indexing; innovation; liver biopsy; mortality; mortality risk; novel; pressure; response; screening; treatment response; ultrasound

Common complications of portal hypertension include gastroesophageal varices, ascites, and portasystemic encephalopathy. Patients with cirrhosis have a 5-10% yearly incidence of variceal formation, and a 4-15% yearly incidence of bleeding. Each bleeding episode carries up to a 20% risk of death. Consequently, the development of an accurate and noninvasive technique for measurement of portal venous pressure would represent a major advance in the diagnosis and management of portal hypertension. Currently, clinicians evaluate portal hypertension invasively through the hepatic venous pressure gradient (HVPG) determined by the gradient in pressure readings between wedged and free hepatic vein catheter positions via a transjugular approach. Our group developed the fundamental concept of contrast-enhanced subharmonic-aided pressure estimation (SHAPE). We conducted a first-in-humans pilot study of this technique’s ability to estimate portal pressures in 45 adult patients with HVPG measurements supported by an NIDDK Challenge Grant (RC1 DK087365), which showed significantly higher SHAPE gradients between the portal and hepatic veins in subjects with clinically significant portal hypertension (CSPH; HVPG>10 mmHg) than in those with lower HVPGs (1.37±0.59 dB vs. - 1.68±0.27 dB, p<0.001). Recently, we expanded on the concept of using SHAPE for portal pressure estimation in a larger multi-center trial (supported by this grant i.e., R01 DK098526). Results from 178 subjects across two sites using modified GE Logic 9 systems were very encouraging with an accuracy for diagnosing CSPH of 95% (with a 95% confidence interval (CI): 89%-99%, p<0.001) and achieving a sensitivity of 91% (95% CI: 88%-93%) and a specificity of 82% (95% CI: 75%-85%). The development of SHAPE as an accurate noninvasive technique for measurement of portal venous pressure represents a major advance in the diagnosis and management of portal hypertension. This has encouraged us to bring together researchers and clinicians from Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB) with a premier manufacturer of ultrasound scanners (GE) in order to expand on the clinical utility of SHAPE for the management of portal hypertension. We will conduct large-scale clinical trials of SHAPE in patients with compensated cirrhosis undergoing routine hepatocellular carcinoma surveillance (N=210) as well as in patients (N=276) treated for portal hypertension (in particular with non-selective beta blockers) and (as a secondary aim) in patients (N=96) that may need to undergo screening of varices using a state-of-the-art ultrasound scanner (Logiq E10, GE Healthcare, Waukesha, WI). Finally, we will study 78 subjects with CSPH scheduled for transjugular HVPG measurements using two different ultrasound contrast agents in the same subjects to determine the reproducibility of SHAPE. Hence, this renewal study aims to further develop a novel, shareable and innovative ultrasound based technology (i.e., SHAPE) for the noninvasive evaluation of portal hypertension and to establish the clinical utility of SHAPE for the management of portal hypertension.

门静脉高压症的常见并发症包括胃食管静脉曲张、腹水和门体静脉曲张 脑病。肝硬化患者每年发生静脉曲张的几率为 5-10%，每年发生静脉曲张的几率为 4-15% 出血的发生率。每次出血都会带来高达 20% 的死亡风险。因此，发展 一种准确且无创的门静脉压力测量技术将成为一项重要的技术 门静脉高压症的诊断和治疗进展。目前，临床医生评估门户网站 通过肝静脉压力梯度（HVPG）进行侵入性高血压，该梯度由肝静脉压力梯度确定 通过经颈静脉途径读取楔形和游离肝静脉导管位置之间的压力读数。我们的 小组提出了对比度增强次谐波辅助压力估计的基本概念 （形状）。我们对这项技术评估门静脉压力的能力进行了首次人体试点研究 NIDDK 挑战补助金 (RC1 DK087365) 支持 45 名成年患者进行 HVPG 测量，其中 在临床上表现出门静脉和肝静脉之间显着更高的 SHAPE 梯度 门静脉高压症（CSPH；HVPG>10 mmHg）明显高于 HVPG 较低的患者（1.37±0.59 dB vs. - 1.68±0.27 分贝，p<0.001）。最近，我们扩展了使用 SHAPE 进行门静脉压力估计的概念 在一项更大规模的多中心试验中（由这笔拨款支持，即 R01 DK098526）。来自两个领域 178 名受试者的结果 使用改进的 GE Logic 9 系统的站点非常令人鼓舞，诊断 CSPH 的准确率达到 95% （95% 置信区间 (CI)：89%-99%，p<0.001）并实现 91% 的灵敏度（95% CI：88%-93%） 特异性为 82%（95% CI：75%-85%）。 SHAPE 作为一种精确的无创技术的发展 门静脉压的测量代表了诊断和管理方面的重大进步 门脉高压。这鼓励我们将托马斯·杰斐逊的研究人员和临床医生聚集在一起 大学 (TJU)、宾夕法尼亚大学医院 (HUP) 和伯尔尼大学 (UB) 超声波扫描仪 (GE) 制造商，以扩展 SHAPE 在管理方面的临床应用 门静脉高压症。我们将在代偿性肝硬化患者中进行SHAPE的大规模临床试验 接受常规肝细胞癌监测 (N=210) 以及接受以下治疗的患者 (N=276) 门静脉高压（​​特别是使用非选择性β受体阻滞剂）和（作为次要目标）患者 (N=96) 可能需要使用最先进的超声波扫描仪（Logiq E10、GE 医疗保健，沃科夏，威斯康星州）。最后，我们将研究 78 名计划进行经颈静脉置管术的 CSPH 受试者 HVPG 测量在同一受试者中使用两种不同的超声造影剂来确定 SHAPE 的再现性。因此，这项更新研究旨在进一步开发一种新颖的、可共享的和 基于创新超声的技术（即 SHAPE），用于门脉高压的无创评估和 确定 SHAPE 在门静脉高压治疗中的临床效用。

项目成果

Effect of Pulse Shaping on Subharmonic Aided Pressure Estimation In Vitro and In Vivo.

• DOI: 10.7863/ultra.15.11106
• 发表时间: 2017-01
• 期刊: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
• 作者: Gupta I;Eisenbrey J;Stanczak M;Sridharan A;Dave JK;Liu JB;Hazard C;Wang X;Wang P;Li H;Wallace K;Forsberg F
• 通讯作者: Forsberg F