Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

描述（由申请人提供）：门脉高压的常见并发症包括胃食管静脉曲张、腹水和门脉系统性脑病。肝硬化患者静脉曲张形成的年发生率为5-10%，出血的年发生率为4-15%。每次出血有高达20%的死亡风险。因此，开发一种准确且无创的门静脉压测量技术将是门静脉高压诊断和治疗的重大进展。目前，临床医生通过肝静脉压力梯度（HVPG）来评估门静脉高压，HVPG由经颈静脉入路楔形和自由肝静脉导管位置之间的压力读数梯度决定。我们的团队提出了一种创新的超声技术，称为亚谐波辅助压力估计（SHAPE），用于无创压力测量，并首次在体内（在犬类中）进行了SHAPE估计。最近，我们在NIDDK挑战基金（RC1 DK087365）的支持下，对45名接受经颈静脉肝活检的患者进行了首次人体试验，研究了该技术评估门静脉压力的能力。门静脉和肝静脉之间的SHAPE梯度与相应的HVPG吻合较好（R = 0.82）。更重要的是，门脉高压（HVPG bbb10 mmHg）受试者的次谐波梯度显著高于HVPG较低的受试者（p < 0.001）。鉴于这些令人鼓舞的结果，该应用程序将托马斯杰斐逊大学（TJU）以及宾夕法尼亚大学医院（HUP）的研究人员和临床医生与超声波扫描仪的主要制造商（GE Healthcare）聚集在一起，以生产一种无创准确评估门静脉高压的设备。SHAPE算法将通过脉冲整形进行优化，并在最先进的超声扫描仪（Logiq 9, GE Healthcare, Milwaukee， WI）上实现实时压力测量。在对3只犬的肝静脉和门静脉进行校准研究之后，我们将在300名在TJU或HUP接受经颈静脉肝活检的患者（以HVPG为参考）中进行大规模的SHAPE实施临床试验。我们还将通过比较SHAPE结果与重复活检和/或临床结果来监测门脉高压患者的疾病进展或治疗反应。因此，本研究旨在进一步发展一种新型的、创新的超声技术（即SHAPE）用于门静脉高压症的无创评估，并进行大规模的人体临床试验，最终确定SHAPE用于门静脉高压症评估的准确性。

DESCRIPTION (provided by applicant): 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 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 has proposed an innovative ultrasound technique called subharmonic-aided pressure estimation (SHAPE) for noninvasive pressure measurements and produced the first ever in vivo SHAPE estimates (in canines). Recently, we conducted a first-in-humans, pilot study of this technique's ability to estimate portal pressures i 45 patients undergoing transjugular liver biopsy supported by an NIDDK Challenge Grant (RC1 DK087365). The SHAPE gradient between the portal and hepatic veins was in good agreement with the corresponding HVPG (R = 0.82). More importantly, subjects with portal hypertension (HVPG > 10 mmHg) showed significantly higher subharmonic gradients than those with lower HVPGs (p < 0.001). Given these encouraging results, this application brings together researchers and clinicians from Thomas Jefferson University (TJU) as well as the Hospital of the University of Pennsylvania (HUP) with a premier manufacturer of ultrasound scanners (GE Healthcare) in order to produce a device for noninvasive and accurate assessment of portal hypertension. The SHAPE algorithm will be optimized by pulse shaping and implemented on a state-of- the-art ultrasound scanner (Logiq 9, GE Healthcare, Milwaukee, WI) for real time pressure measurements. Following calibration studies in the hepatic and portal veins of 3 canines, we will conduct a large scale clinical trial of the novel implementation of SHAPE in 300 patients undergoing a transjugular liver biopsy at TJU or HUP (using HVPG as the reference). We will also monitor disease progression or treatment response in patients identified with portal hypertension by comparing SHAPE results to repeat biopsies and/or clinical outcomes. Hence, this study aims to further develop a novel and innovative ultrasound based technology (i.e., SHAPE) for the noninvasive evaluation of portal hypertension and to conduct a large scale human clinical trial to conclusively establish the accuracy of SHAPE for the assessment of portal hypertension.