Noninvasive Portal Pressure Measurements in Children

小儿门静脉高压症的常见并发症是胃食道静脉曲张和静脉曲张出血 相关死亡率为1-3%，而据报道，高达20%的人出现了危及生命的并发症 患有肝硬变的儿童。目前，儿科医生通过间接方法评估门静脉高压症，因为 成人临床标准(肝静脉压力梯度-HVPG)在儿童中不是常规使用。那里 儿童肝病的病因很多(胆道闭锁、先天性肝纤维化、α-1-抗胰蛋白酶 缺乏症、自身免疫性肝病等)，每种疾病都有独特的病程，这也使成年人 指导方针很难适用于儿童。因此，开发一种准确的、非侵入性的 门静脉压力测量技术将是诊断和治疗门静脉高压症的一大进步。 儿童门脉高压症的处理。我们小组提出了形状和形状的基本概念 制作了有史以来第一个活体形状估计(在犬类中)。我们还进行了一项首次在人类中进行的初步研究 这项技术评估NIDDK挑战赛支持的45名成年患者门静脉压力的能力 Grant(RC1DK087365)，它显示门静脉和肝脏之间的形状梯度明显更高 门脉高压(HVPG&GT；10 mm Hg)受试者的静脉压力高于低门脉压受试者(1.37±0.59 vs. -1.68±0.27p&lt；0.001)。最近，我们扩展了使用SHAPE估计门脉压力的概念 正在进行的更大规模的多中心临床试验(由R01 DK398526支持)。120名受试者的初步结果 用造影剂索纳佐德(GE Healthcare，挪威奥斯陆)获得的结果非常令人鼓舞 诊断门脉高压的准确率为94.2%，并结合FDA最近批准的 用于儿科应用的超声造影剂(Lumason；布拉科，米兰，意大利)鼓励我们将 来自托马斯·杰斐逊大学(TJU)和费城儿童医院的研究人员一起 (CHOP)与一家主要的超声波扫描仪制造商(GE Healthcare)合作，以生产一种用于 无创性、准确评估儿童门脉高压症。首先，Shape算法将是 在最先进的超声扫描仪(带有C2-9儿科探头的Logiq E9；GE Healthcare， 密尔沃基，威斯康星州)，用于儿童的实时压力测量。接下来的体外研究比较了索那唑 直接到Lumason，我们将在CHOP进行体内形状的初步临床试验 门脉高压的诊断与匹配的慢性肝病但无肝病儿童组的比较 门静脉高压症。我们还将监测符合以下条件的儿童的疾病进展或治疗反应 通过比较SHAPE结果和临床结果来评估门脉高压症。因此，本研究旨在进一步发展 一种新颖的基于超声的门静脉无创评价技术(SHAPE) 并进行儿童高血压的初步临床试验，以确定其可行性和初步准确性 评估门静脉高压症的儿科形态。

A common complication of pediatric portal hypertension is gastroesophageal varices and variceal bleeds are associated mortality rates of 1-3 %, while life-threatening complications have been reported in up to 20 % of children with cirrhosis. Currently, pediatricians evaluate portal hypertension through indirect means, since the clinical standard in adults (the hepatic venous pressure gradient – HVPG) is not used routinely in children. There are many causes of liver disease in children (biliary atresia, congenital hepatic fibrosis, alpha-1-antitrypsin deficiency, autoimmune liver disease, etc.), each with a unique disease course, which also makes adult guidelines difficult to apply to children. 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 in children. Our group developed the fundamental concept of SHAPE and produced the first ever in vivo SHAPE estimates (in canines). We also conducted a first-in-humans, pilot study of this technique's ability to estimate portal pressures in 45 adult patients supported by an NIDDK Challenge Grant (RC1 DK087365), which showed significantly higher SHAPE gradients between the portal and hepatic veins in subjects with portal hypertension (HVPG > 10 mmHg) than in those with lower HVPGs (1.37 ± 0.59 vs. -1.68 ± 0.27, p < 0.001). Recently, we have expanded the concept of using SHAPE for portal pressure estimation in an ongoing larger multi-center clinical trial (supported by R01 DK398526). Preliminary results in 120 subjects obtained with the contrast agent Sonazoid (GE Healthcare, Oslo, Norway) have been very encouraging with an accuracy for diagnosing portal hypertension of 94.2% and combined with the recent FDA approval of an ultrasound contrast agent (Lumason; Bracco, Milan, Italy) for pediatric applications have encouraged us to bring together researchers from Thomas Jefferson University (TJU) as well as the Children's Hospital of Philadelphia (CHOP) with a premier manufacturer of ultrasound scanners (GE Healthcare) in order to produce a device for noninvasive and accurate assessment of portal hypertension in children. First the SHAPE algorithm will be implemented on a state-of-the-art ultrasound scanner (Logiq E9 with a C2-9 pediatric probe; GE Healthcare, Milwaukee, WI) for real time pressure measurements in children. Following in vitro studies comparing Sonazoid directly to Lumason, we will conduct an initial clinical trial at CHOP of in vivo SHAPE in children with a clinical diagnosis of portal hypertension compared to a matched group of children with chronic liver disease but without portal hypertension. We will also monitor disease progression or treatment response in children identified with portal hypertension by comparing SHAPE results to 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 an initial clinical trial in children to establish the feasibility and preliminary accuracy of pediatric SHAPE for the assessment of portal hypertension.