Our group has demonstrated that the nonlinearly generated, subharmonic signal component from microbubble-based ultrasound contrast agents is an excellent indicator of the hydrostatic pressure variation (from 20 to 200 mmHg). Based on such results, a technique called SubHarmonic-Aided Pressure Estimation (SHAPE) has been proposed. SHAPE has the potential to noninvasively measure changes in pressure. It estimates internal pressure variations by transmitting at one frequency but receiving only at its subharmonic frequency. The fundamental hypothesis of this project is that ambient blood pressure can be monitored and quantified noninvasively using SHAPE. Thus, essential information regarding the functional integrity of the cardiovascular system can be provided noninvasively. Initial experiments will be conducted in vitro to test the effects of hydrostatic pressure on the subharmonic performance of ultrasound contrast agents in order to select the best agent for SHAPE. These efforts will be supported by a computer simulation study of SHAPE. Next, the SHAPE algorithm will be implemented on a state-of-the-art ultrasound scanner (Logiq 9, GE Healthcare, Milwaukee, Wl) 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 inferior vena cava (IVC) of 5 canines. Following the calibration studies, in vivo pharmacologically induced pressure changes in the aorta (selected to investigate higher pressure variations) will be studied (in 10 dogs) using SHAPE and results compared to catheter based pressure measurements. Finally, two groups of 10 dogs with portal hypertension (induced by embolization or by a surgically created arterio-venous fistula) will be studied with SHAPE comparing results to catheter based pressure measurements. In conclusion, this study aims to develop a novel and innovative ultrasound based method (i.e., SHAPE) for noninvasive evaluation of blood pressure and portal hypertension in vivo. Currently there are no accurate, methods available to measure the pressure in blood vessels deep in the body. This grant will develop such a technique by monitoring the behavior of very small, gas bubbles within the blood using ultrasound. This will allow potentially life-threatening diseases, such as increased pressure in the liver, to be diagnosed early. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HL081892-02
Application #
7340208
Study Section
Special Emphasis Panel (ZRG1-SBIB-L (51))
Program Officer
Adhikari, Bishow B
Project Start
2007-01-15
Project End
2009-12-31
Budget Start
2008-01-01
Budget End
2009-12-31
Support Year
2
Fiscal Year
2008
Total Cost
$206,200
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
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) Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures. Ultrason Imaging 34:81-92
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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