Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

门脉高压的常见并发症包括胃食道静脉曲张、腹水和门脉闭塞。 脑病。肝硬变患者每年静脉曲张的发生率为5-10%，每年为4-15%。 出血发生率。每一次出血发作都有高达20%的死亡风险。因此，这一发展 一种准确和非侵入性的门静脉压力测量技术将是一个重要的 门静脉高压症的诊治进展。目前，临床医生评估门户 经肝静脉压力梯度(HVPG)决定的侵袭性高血压 经颈静脉入路测量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)。我们进行了一项首次人类试点研究，以了解这项技术估计门脉压力的能力。 45名成年患者接受了NIDDK挑战基金(RC1DK087365)的HVPG测量，该基金 门静脉和肝静脉之间的形状梯度在临床上显示出显著更高的梯度 显著门脉高压(CSPH；HVPG&GT；10 mm Hg)较低的门脉高压(1.37±0.59dBvs. 1.68±0.27分贝，p&lt；0.001)。最近，我们扩展了使用SHAPE估计门脉压力的概念 在更大的多中心试验中(由本拨款支持，即R01 DK098526)。来自178名受试者的结果 使用改进的GE Logic9系统的站点非常令人鼓舞，诊断CSPH的准确率为95% (95%可信区间：89%-99%，p&lt；0.001)，灵敏度为91%(95%可信区间：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 门静脉压力的测量是诊断和治疗门静脉高压症的一大进步。 门静脉高压症。这鼓励我们将来自托马斯·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(HUP)和伯尔尼大学(UB) 超声扫描仪(GE)制造商，以扩大SHAPE的临床应用管理 门静脉高压症。我们将在代偿性肝硬变患者中进行大规模的临床试验 接受常规肝细胞癌监测(N=210)以及接受治疗的患者(N=276) 门脉高压(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扫描仪(Logiq E10，GE)进行静脉曲张筛查 医疗保健，沃基沙，威斯康星州)。最后，我们将研究78名计划经颈静脉途径治疗的CSPH患者。 用两种不同超声造影剂测定同一受试者的HVPG 形状的重现性。因此，这项更新研究旨在进一步开发一种新颖、可共享和 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估和 目的：探讨门脉高压症门脉高压症的临床应用价值。

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.