Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension

描述(申请人提供)：门脉高压的常见并发症包括胃食道静脉曲张、腹水和门脉性脑病。肝硬变患者每年静脉曲张的发生率为5-10%，出血的年发生率为4-15%。每一次出血发作都有高达20%的死亡风险。因此，发展一种准确和非侵入性的门静脉压力测量技术将是门静脉高压症诊断和治疗的重大进步。目前，临床医生通过经颈静脉途径通过肝静脉压力梯度(HVPG)来评估门脉高压，该压力梯度是由楔形和自由肝静脉导管位置之间的压力读数的梯度决定的。我们团队提出了一种名为次谐波辅助压力估计(SHAPE)的创新超声技术，用于非侵入性压力测量，并首次在活体(犬)中进行了SHAPE估计。最近，我们进行了一项首例人类先导性研究，研究了这项技术评估门静脉压力的能力，45名接受NIDDK挑战赠款(RC1DK087365)支持的经颈静脉肝活检的患者。门静脉和肝静脉之间的形态梯度与相应的门静脉高压声学造影有很好的一致性(R=0.82)。更重要的是，门脉高压(10毫米汞柱)的受试者比门脉高压受试者表现出明显更高的亚谐梯度(p&lt；0.001)。鉴于这些令人鼓舞的结果，这项应用将来自托马斯·杰斐逊大学(TJU)和宾夕法尼亚大学(HUP)的研究人员和临床医生与一家领先的超声扫描仪制造商(GE Healthcare)结合在一起，以生产一种用于无创和准确评估门静脉高压症的设备。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，密尔沃基，威斯康星州)上实施，用于实时压力测量。在对3只犬的肝静脉和门静脉进行校准研究后，我们将对300名在TJU或HUP(以HVPG为参照物)接受经颈静脉肝活检的患者进行一项新的SHAPE实施的大规模临床试验。我们还将通过将SHAPE结果与重复活检和/或临床结果进行比较，来监测门脉高压症患者的病情进展或治疗反应。因此，本研究旨在进一步发展一种新的基于超声的无创性门静脉高压症评估技术(即SHAPE)，并进行大规模的人体临床试验，以最终确定SHAPE评估门脉高压症的准确性。

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.