Diastolic dysfunction is the impaired ability of the left ventricle to fill at physiologic pressures, often resulting in a compensatory increase of atrial filling pressures to maintain the stroke volume. This condition is usually associated with increased stiffness of the heart wall. Echocardiography can provide the most comprehensive information on diastolic function of the heart by integrating a variety of measurements with the clinical information. The goals of the next grant cycle are to produce ultrasound apparatus and techniques for quantitative and noninvasive high temporal and spatial resolution biopsy-like measurement of myocardial mechanical properties, specifically the anisotropic visco-elastic moduli of the heart wall in vivo. The new method, which we call vibrometry, uses radiation pressure of a focused ultrasound beam to stimulate formation and propagation of shear waves along the appropriate axes within the region of interest. The velocity and dispersion of the shear wave is measured with pulsed Doppler, B-scan correlation, or our new Kalman method. Mathematical models for the propagation of the wave in the particular geometry being studied will be used to solve analytically or with advanced inverse finite element methods for relevant mechanical properties such as the anisotropic visco-elastic moduli. Models will be validated with independent in vitro and in vivo measurements. In preliminary investigations of phantoms and excised hearts the method has been shown to be capable of performing fast, accurate and noninvasive measurements of the elastic (mu1) and viscous (mu2) terms of the shear modulus along and across the myofibers of excised myocardium and striated muscle. The goals of this program will be achieved through four Specific Aims.
Aim 1 : In a sequential development of increasingly complex theories, we will derive the analytic mathematical relationships between harmonic or impulse radiation force at a point or line in the heart wall and the resulting nearby propagating wave displacements caused by the force.
Aim 2 : We will use harmonic and impulse radiation force methods to induce motion and high precision methods to measure the resulting dynamic strain versus time and space in phantoms and tissues to validate the inverse solutions developed in Aim 1.
Aim 3 : Theory and methods from Aims 1 and 2 will be tested in isolated perfused beating and non beating hearts. A commercial scanner will be modified to make vibrometry measurements.
Aim 4 : Vibrometry will be extended to closed chest pigs in anticipation of clinical application. Successful completion of this program will result in techniques and procedures for measuring mechanical heart wall properties in humans providing a tool for evaluating cardiac abnormalities associated with alterations in heart wall stiffness. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
2R01EB002167-17
Application #
7208208
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Lopez, Hector
Project Start
1989-04-01
Project End
2010-07-31
Budget Start
2006-09-30
Budget End
2007-07-31
Support Year
17
Fiscal Year
2006
Total Cost
$571,534
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Nenadic, Ivan Z; Urban, Matthew W; Pislaru, Cristina et al. (2018) In Vivo Open- and Closed-chest Measurements of Left-Ventricular Myocardial Viscoelasticity using Lamb wave Dispersion Ultrasound Vibrometry (LDUV): A Feasibility Study. Biomed Phys Eng Express 4:
Nenadic, Ivan Z; Qiang, Bo; Urban, Matthew W et al. (2017) Attenuation measuring ultrasound shearwave elastography and in vivo application in post-transplant liver patients. Phys Med Biol 62:484-500
Urban, Matthew W; Qiang, Bo; Song, Pengfei et al. (2016) Investigation of the effects of myocardial anisotropy for shear wave elastography using impulsive force and harmonic vibration. Phys Med Biol 61:365-82
Urban, Matthew W; Nenadic, Ivan Z; Qiang, Bo et al. (2015) Characterization of material properties of soft solid thin layers with acoustic radiation force and wave propagation. J Acoust Soc Am 138:2499-507
Nabavizadeh, Alireza; Song, Pengfei; Chen, Shigao et al. (2015) Multi-source and multi-directional shear wave generation with intersecting steered ultrasound push beams. IEEE Trans Ultrason Ferroelectr Freq Control 62:647-62
Song, Pengfei; Macdonald, Michael; Behler, Russell et al. (2015) Two-dimensional shear-wave elastography on conventional ultrasound scanners with time-aligned sequential tracking (TAST) and comb-push ultrasound shear elastography (CUSE). IEEE Trans Ultrason Ferroelectr Freq Control 62:290-302
Dutta, Parikshit; Urban, Matthew W; Le MaƮtre, Olivier P et al. (2015) Simultaneous identification of elastic properties, thickness, and diameter of arteries excited with ultrasound radiation force. Phys Med Biol 60:5279-96
Warner, James E; Aquino, Wilkins; Grigoriu, Mircea D (2015) Stochastic reduced order models for inverse problems under uncertainty. Comput Methods Appl Mech Eng 285:488-514
Song, Pengfei; Urban, Matthew W; Manduca, Armando et al. (2015) Coded excitation plane wave imaging for shear wave motion detection. IEEE Trans Ultrason Ferroelectr Freq Control 62:1356-72
Warner, James E; Diaz, Manuel I; Aquino, Wilkins et al. (2014) Inverse Material Identification in Coupled Acoustic-Structure Interaction using a Modified Error in Constitutive Equation Functional. Comput Mech 54:645-659

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