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.,...