Portal hypertension is defined as an increase in the pressure gradient between the portal vein and hepatic veins or the inferior vena cava (IVC). 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 noninvasive technique for measurement of portal venous pressure would represent a major advance in the diagnosis and management of portal hypertension. Our group has proposed and patented a novel and innovative ultrasound technique called subharmonic-aided pressure estimation (SHAPE) for noninvasive pressure measurements and this application brings together basic scientists (who developed the fundamental concept of SHAPE) and clinicians from Thomas Jefferson University (TJU) 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 implemented on a state-of-the-art ultrasound scanner (Logiq 9, GE Healthcare, Milwaukee, WI) for real time pressure measurements. The in vivo SHAPE results will be calibrated based on manometer-tipped catheter (i.e., pressure transducer) measurements in the IVC, hepatic and portal veins of 5 canines. Finally, the novel implementation of SHAPE will be tested in 45 patients undergoing a trans-jugular liver biopsy at TJU. In all cases hepatic venous pressures will be measured and Child Pugh as well as MELD scores calculated. Corresponding SHAPE measurements will be performed and the results compared to the clinical data. In conclusion, this proposal aims to develop a novel and innovative ultrasound based method (i.e., SHAPE) for noninvasive and accurate evaluation of portal hypertension in vivo and to translate this technology from pre-clinical studies to application in patients.

Public Health Relevance

Increased pressure in the blood vessels of the liver, especially the portal vein, can lead to significant complications including internal bleeding. Each bleeding episode carries up to a 20% risk of death. An accurate marker for portal hypertension would impact literally millions of Americans with liver disease. This project will bring together basic scientists and clinicians from Thomas Jefferson University with a premier manufacturer of ultrasound scanners (GE Healthcare) in order to produce a device for noninvasive and accurate assessment of portal pressures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
NIH Challenge Grants and Partnerships Program (RC1)
Project #
5RC1DK087365-02
Application #
7942988
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (58))
Program Officer
Serrano, Jose
Project Start
2009-09-30
Project End
2011-12-30
Budget Start
2010-07-01
Budget End
2011-12-30
Support Year
2
Fiscal Year
2010
Total Cost
$441,649
Indirect Cost
Name
Thomas Jefferson University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Halldorsdottir, Valgerdur G; Dave, Jaydev K; Marshall, Andrew et al. (2017) Subharmonic-Aided Pressure Estimation for Monitoring Interstitial Fluid Pressure in Tumors: Calibration and Treatment with Paclitaxel in Breast Cancer Xenografts. Ultrasound Med Biol 43:1401-1410
Dave, Jaydev K; Kulkarni, Sushmita V; Pangaonkar, Purva P et al. (2017) Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans. Ultrasound Med Biol 43:2718-2724
Eisenbrey, John R; Sridharan, Anush; Liu, Ji-Bin et al. (2015) Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound. Biomed Res Int 2015:640397
Halldorsdottir, V G; Dave, J K; Eisenbrey, J R et al. (2014) Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept. Ultrasonics 54:1938-44
Eisenbrey, John R; Dave, Jaydev K; Halldorsdottir, Valgerdur G et al. (2013) Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient. Radiology 268:581-8
Dave, J K; Halldorsdottir, V G; Eisenbrey, J R et al. (2013) On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation. Ultrasonics 53:880-8
Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R et al. (2012) Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures. Am J Physiol Heart Circ Physiol 303:H126-32
Dave, Jaydev K; Liu, Ji-Bin; Halldorsdottir, Valgerdur G et al. (2012) Acute portal hypertension models in dogs: low- and high-flow approaches. Comp Med 62:419-26
Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R et al. (2012) Investigating the efficacy of subharmonic aided pressure estimation for portal vein pressures and portal hypertension monitoring. Ultrasound Med Biol 38:1784-98
Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R et al. (2012) Noninvasive LV pressure estimation using subharmonic emissions from microbubbles. JACC Cardiovasc Imaging 5:87-92

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