7/15/2015
Viscoelastic Response (VisR) Ultrasound
for Noninvasively Assessing the
Viscoelastic Properties of Tissue
Caterina M. Gallippi, Ph.D.
The Joint University of North Carolina Chapel Hill,
North Carolina State University
Department of Biomedical Engineering
The Mechanical Properties of
Tissue are Diagnostically Relevant
Breast
Abdominal Organs
Musculoskeletal System
The Mechanical Properties of Tissue
May be Assessed by Ultrasound
1. Expedite detection and
differential diagnosis of
diseases
2. Improve accuracy of disease
diagnoses
3. Monitoring response to
treatment
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7/15/2015
Ultrasound May Be Implemented to
Assess Tissue Mechanical Property
www.usa.healthcare.siemens.com/ultrasound
Ultrasound May Be Implemented to
Assess Tissue Mechanical Property
www.usa.healthcare.siemens.com/ultrasound
Ultrasound May Be Implemented to
Assess Tissue Mechanical Property
www.usa.healthcare.siemens.com/ultrasound
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Methods for Tissue Mechanical
Property Assessment by Ultrasound
1. Introduce mechanical excitation
- Intrinsic or extrinsic
- Static, periodic, or impulsive
2. Monitor tissue response
- Deformation
- Shear wave velocity
Acoustic Radiation Force
“The acoustic radiation force is produced by a change in the
density of energy and momentum of the propagating waves
because of the absorption, scattering or reflection from
inclusions or from spatial variations in propagation velocity.”
Optical Tracking of ARF Excitation
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ARF in Application to 2D Imaging
ARFI for Delineating Mechanical Property
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1111
Peak displacement conveys elasticity. How to
measure viscosity?
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Voigt Model
Viscoelastic Creep
𝑠=
𝐴
.
𝜇
(7.7)
Equation (7.6) can be solved for displacement as a function of 𝜔, 𝜏, and 𝑠. Displacement versus
VisR Ultrasound
time profiles can be fit to this equation in order to generate estimates of these three parameters.
7.3
Methods
The FEM models used have been adapted from models previously developed by Palmeri at
al. for investigating the response of an elastic material to an ARF excitation.110 In Chapter 8,
Palmeri’sie m thods for s mulating the focal geometry of an ARF excitation pulse are
implemented; however, for clarity, the excitation is approximated as a concentrated force on a
single node at a given focal depth in this chapter.
FEM Mesh Generation
A three-dimensional, rectangular, solid mesh was assembled from 0.5 mm, cubic
elements using LS-PREPOST (Livermore Software Technology Corp., Livermore, CA). The
mesh extended 5 mm in elevation, 7.5 mm laterally, and 40 mm axially. A 5 elements thick,
Fit to Mass-Spring-Damper Model
Figure 7.1: (a) A schematic of the mass-spring-damper (MSD) model and (b) a graphical
illustration of the forcing function inpute1
perfectly matched layer (PML) was added to the exterior boundaries of the mesh to absorb any
waves generated during the simulation and ensure that they were not reflected back into the
region of interest (ROI). As a requirement of the PML, all nodes on outer faces were fully
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Experimental Phantom Results
CNR = 1.15
CNR = 0.84
CNR = 0.08
Corrected VisR Quantifies τ in FEM
Simulation
VisR τ Error is < 10% for Limited Range
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VisR Relative Elasticity Distinguishes
Material Elasticity
VisR Relative Viscosity Distinguishes
Material Viscosity
VisR in Application to Monitoring
Dystrophic Degeneration in Duchenne
Muscular Dystrophy
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Pre-Clinical VisR Demonstration in
GRMD Dogs
• Severe clinical phenotype,
genetically homologous to DMD
3 Months Old
• Muscle necrosis and
regeneration begin at an early
age
• Followed by extensive
connective tissue proliferation
and premature death from
cardiac and respiratory failure
6 Months Old
VisR Discriminates Fibrotic RF Muscle
Versus Control
GRMD VisR
Control VisR
VisR Discriminates Fibrotic RF Muscle
Versus Control
GRMD Histology
Control Histology
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Higher VisR τ Standard Deviation in GRMD
VL Corresponds to Fibrosis in
Cross-sectional Study
VisR τ Standard Deviation (ms)
Histology % Collagen
p=0.001
VisR τ Standard Deviation Versus MRI T2
VisR τ Standard Deviation (ms)
MRI T2
p=0.001
VisR τ Standard Deviation Versus MRI RP
VisR τ Standard Deviation (ms)
MRI RP
p=0.001
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Phenotypic Human DMD Muscle
Variation
• Sartorius: relatively
spared
Vastus Intermedius
• Gastrocnemius:
enlargement, with
predominantly
fatty deposition
• Vastus
Intermedius: cyclic
necrosis and
fibrous deposition
VisR τ Relatively Unchanged in Subject 1
Sartorius
6.2 years old
7.4 years old
VisR τ Increases in Subject 1
Gastrocnemius
6.2 years old
7.4 years old
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VisR τ Decreases in Subject 3
Vastus Intermedius
5.4 years old
6.6 years old
Next Steps: Anisotropy
Biological Tissue Exhibits Structural Anisotropy
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Asymmetric vs Symmetric ARF PSF
Lateral
0°
Elevational
90°
VisR τ is angle dependent for asymmetric, but
not symmetric, ARF focal configuration
VisR τ is Angle Dependent for Asymmetric, but
not Symmetric, ARF Focal Configuration
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Conclusions
• Ultrasound may be implemented to noninvasively assess
the mechanical properties of tissue, which are
diagnostically relevant.
• VisR ultrasound is a new acoustic radiation force-based
approach to estimating tissue viscosity, elasticity, and
degree of anisotropy.
• VisR has been applied to monitoring dystrophic muscle
degeneration in Duchenne muscular dystrophy.
• Other applications under study include kidney and
atherosclerosis.
VisR Relative Elasticity and Relative
Viscosity in Excised Pig Kidney
Thank You
Siemens Medical Solutions
USA, Inc. Ultrasound
Division
Gallippi Lab Members and
Alumni
•
•
•
•
•
•
Mallory Selzo
Tomek Czernuszewicz
Chase DuBois
Robert Hinson
Rebecca Geist
Chris Moore
Preclinical Studies
• Amanda Bettis
• Sharla Birch
• Dan Bogan
• Janet Bogan
• Jennifer Dow
• Heather Heath-Barnett
• Joe Kornegay
• Gayle McGhee
• Kathy Spaulding
• Eric Snook
• Martin Styner
• Jiahui Wang
• Janice Weaver
FEM Simulations
• Kathy Nightingale
• Mark Palmeri
Clinical Studies
• Melissa Caughey
• Manisha Chopra
• Melrose Fisher
• James Howard Jr.
• Regina Emmett
• Diane Meyer
Funding Sources
• NIH Grants R01NS074057, R01HL092944, K02-HL105659
• The NIH Integrated
Biomedical Research
Training Program
• Muscular Dystrophy
Association
• Parent Project Muscular
Dystrophy
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Ultrasound May Be Implemented to
Assess Tissue Mechanical Property
Barr R.G. Applied Radiology. December, 2012.
Ultrasound May Be Implemented to
Assess Tissue Mechanical Property
Kato K et al. Liver International. 2008;28(9):1264-1271.
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