Noninvasive Subharmonic Aided Pressure Estimation 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。 脑病肝硬化患者静脉曲张形成的年发生率为5-10%， 出血的发生率。每次出血事件都有高达20%的死亡风险。因此，发展 准确和无创的测量门静脉压力的技术将是一个主要的 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 通过肝静脉压梯度（HVPG）确定的高血压侵入性， 通过经颈静脉入路测量楔入和游离肝静脉导管位置之间的压力读数。我们 小组开发了对比度增强次谐波辅助压力估计的基本概念 （形状）。我们进行了一项首次在人体试验研究，该技术的能力，估计门静脉压力， 45例接受HVPG测量的成人患者得到NIDDK挑战资助（RC 1 DK 087365）的支持， 显示在临床上具有以下特征的受试者中，门静脉和肝静脉之间的SHAPE梯度显著更高： 显著门静脉高压（CSPH; HVPG>10 mmHg）的患者比HVPG较低的患者（1.37±0.59 dB vs. 1.68±0.27 dB，p<0.001）。最近，我们扩展了使用SHAPE估计门静脉压力的概念 在更大的多中心试验中（由该基金支持，R01 DK098526）。来自两个国家的178名受试者的结果 使用改进的GE Logic 9系统的研究中心非常令人鼓舞，诊断CSPH的准确率为95% (with 95%置信区间（CI）：89%-99%，p<0.001），并达到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 用于测量门静脉压代表了诊断和治疗的重大进展 门静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， 宾夕法尼亚大学医院（HUP）和伯尔尼大学（UB）， 超声扫描仪制造商（GE），以扩大SHAPE的临床实用性， 门静脉高压症我们将在代偿期肝硬化患者中开展SHAPE的大规模临床试验 接受常规肝细胞癌监测的患者（N=210）以及接受治疗的患者（N=276） 门静脉高压（特别是使用非选择性β受体阻滞剂）和（作为次要目的）患者（N=96） 可能需要使用最先进的超声扫描仪（Logiq E10，GE）进行静脉曲张筛查 Healthcare，沃基沙，WI）。最后，我们将研究78例CSPH患者， 在同一受试者中使用两种不同的超声造影剂进行HVPG测量，以确定 形状的再现性。因此，本更新研究旨在进一步开发一种新颖的，可共享的， 创新的基于超声的技术（即，SHAPE）用于门静脉高压症的无创性评价， 探讨SHAPE在门静脉高压症治疗中的临床应用价值。

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.