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1 EDST - UL Ecole Doctorale des Sciences et de Technologie Université Libanaise “Viscoelastic Shear Properties of In Vivo Thigh Muscles Measured by MR Elastography” Submitted to Dr. Mashhour Chakouch February 18 th , 2016 Sarah Hussein Master TIS | TIS03 Course Summary of the Article: M. Chakouch, P. Pouletaut, F. Charleux, S. Bensamoun

Magnetic Resonance Elastography

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EDST - UL Ecole Doctorale des Sciences

et de Technologie Université Libanaise

“Viscoelastic Shear Properties of In Vivo Thigh

Muscles Measured by MR Elastography”

Submitted to Dr. Mashhour Chakouch February 18th, 2016

Sarah Hussein Master TIS | TIS03 Course

Summary of the Article:

M. Chakouch, P. Pouletaut, F. Charleux, S. Bensamoun

O U T L I N E S

INTRODUCTION MATERIALS & METHODS RESULTS CONCLUSIONS

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INTRODUCTION

¨  State of The Art ¨  Purpose 1�

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I N T R O D U C T I O NState of The Art

q  Noninvasive evaluation of the functional properties of soft tissues is important

q  Magnetic Resonance Elastography (MRE) is a noninvasive medical imaging

technique developed from Magnetic Resonance Imaging (MRI)

q  MRE can assess the shear elasticity of tissues by applying mechanical excitation

q  Motion-sensitive MR sequences analyze shear waves propagation in soft tissues

q  It was applied to healthy and pathological soft tissues to provide quantitative data

q  The main mechanical property provided by the MRE is the shear modulus (G)

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I N T R O D U C T I O NState of The Art

q  MRE is improved and provides reliable information on viscoelastic properties

q  Viscoelastic properties of the brain, muscle, and liver have been determined

using multi-frequency MRE (MMRE) tests

q  MMRE tests were associated with rheological models (Voigt, Zener & Springpot)

q  Voight model is the simplest to characterize viscoelastic behavior in soft tissues

q  Resulting wave images are analyzed by solving the inverse problem of

elastography to obtain the complex shear modulus (G)

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I N T R O D U C T I O NState of The Art

q  G contains a real part (G’) and an imaginary part (G’’)

q  G’ is the storage modulus and determined by restoration of mechanical energy

q  G’’ is the loss modulus associated with its viscous properties according to the

tissue’s inherent mechanical friction appearing between muscle fibers

q  Phantoms developed to realistically simulate mechanical properties of tissues

q  MMRE tests provide viscoelastic properties of phantoms, then validate it using

other mechanical techniques, such as spectroscopy tests

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I N T R O D U C T I O NPurpose

To measure the viscoelastic properties of passive thigh muscles using multi-frequency magnetic resonance elastography (MMRE)

and rheological models &

To validate the in vivo data-processing using plastic phantoms that mimicked the muscles’

viscoelastic properties under passive conditions

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MATERIALS & METHODS

¨  Participants ¨  Phantom Preparation ¨  HF Viscoelastic

Spectroscopy Tests ¨  MRE Tests ¨  Data Processing

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M A T E R I A L S & M E T H O D SParticipants

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q  Thigh muscles were studied in five healthy volunteers : 3 males & 2 females

q  Age range: 21 – 38 years à mean age = 25 ± 5.32 years q  BMI (body mass index) range: 19.4 – 28.4 kg/m2 à mean BMI = 22.6 ± 3.1 kg/m2

q  No muscle abnormality or histories of muscle disease q  This study was approved by the Institutional Review Board of Amiens Hospital q  All subjects had the experimental protocol explained and then gave their

informed written consent prior to admission into the study

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M A T E R I A L S & M E T H O D SPhantom Preparation

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Mixing of the plastic (%) and softener (%) liquid Heating (177°C)

Big Phantom Small Phantom

9.9 mm

76 m

m

50% Plastic 50% Plastic

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M A T E R I A L S & M E T H O D SHyper-Frequency Viscoelastic Spectroscopy Tests

q  HF viscoelastic spectroscopy were performed with RheoSpectris C500 instrument

q  It measures storage (G’) and loss (G’’) moduli of materials across a wide range of frequencies between 10 & 1500 Hz

q  Only 60, 80 and 100 Hz were selected to

compare with the MRE tests

q  Bland-Altman analysis used to compare viscoelastic parameters between 2 tests

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Generation of transient mechanical shear waves

inside the sample

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MRE Tests | Muscle Configurations

MRE tests were conducted on the large phantom and on thigh muscles using a 1.5T Signa HDx MRI machine (General Electric, Milwaukee, WI).

M A T E R I A L S & M E T H O D S

Subjects placed in prone position

Custom-made Helmholtz surface coil around thigh

Pneumatic passive driver wrapped around thigh

The tube placed in the middle part of thigh

Periodic Air Pressure variations at 70, 90 & 110Hz

Compression mode excitation

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MRE | Muscle Configurations (Cont.)

Axial image of the thigh with placement of the imaging planes through ST, SM and BC muscles

AXIAL IMAGE 1

MMRE tests on the coronal oblique image leading to acquisition of the phase image

PHASE IMAGE 1

Axial image of the thigh with placement of the imaging planes through Gr muscle

I t r e p r e s e n t s t h e displacement of the shear waves within the muscles

PHASE IMAGE 2

M A T E R I A L S & M E T H O D S

AXIAL IMAGE 2

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MRE Tests | Phantom Configurations

MRE tests were conducted on the large phantom and on thigh muscles using a 1.5T Signa HDx MRI machine (General Electric, Milwaukee, WI).

M A T E R I A L S & M E T H O D S

Phantoms perpendicular to static scanner field

Round pneumatic driver placed under the phantom

Round pneumatic driver generates shear waves

Image slices acquired in the coronal oblique plane

Vibrations propagated parallel to axis of phantom

Harmonic frequencies of driver at 60, 80, and 100 Hz

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M A T E R I A L S & M E T H O D SData Processing | Theory

q  Experimental (G(x)) and numerical (GModel(x)) viscoelastic parameters can be determined using basic equations

q  A red profile is prescribed in the direction (x) of the wave propagation à The wave behavior along this profile was extracted

q  The amplitude of the wave along the profile is a scalar wave field u(x, t) whose temporal Fourier-transformation is U(x, w)

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M A T E R I A L S & M E T H O D SData Processing | Theory (Cont.)

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q  Assuming that the medium of propagation is linear, locally homogeneous, isotropic, incompressible, and under pure shear stress, the motion equation (Helmholtz) in the frequency domain is:

Where , f is the angular driving frequency, G is the complex shear modulus and ρ is the muscle density q  Assuming the displacement of wave following a harmonic plane is :

Where is the initial amplitude and is the complex wave number and is the attenuation coefficient

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M A T E R I A L S & M E T H O D SData Processing | Theory (Cont.)

q  The wavelength (λ) was measured with the different extrema q  The corresponding (xi) was extracted from the wave

q  A logarithmic ln(|Ui|) representation of the ith extrema was fitted with a linear least square line

q  Measurement of the attenuation parameter from the slope of the line corresponding to –

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M A T E R I A L S & M E T H O D SData Processing | Theory (Cont.)

q  Solving the G and U equations yields to the experimental viscoelastic parameters:

q  However, the viscoelastic model parameters are the following:

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M A T E R I A L S & M E T H O D SData Processing | Theory (Cont.)

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q  Voigt and Maxwell models require 2 parameters : : shear modulus : shear viscosity q  Zener and Springpot models requires 3 parameters: : parallel elastic component : series elastic component : weighting factor between purely elastic behavior ( = 0) and a purely viscous behavior ( = 1) q  Viscoelastic parameters were calculated by minimizing the cost function ( ):

Where N is the number of experimental driving frequencies (N = 3)

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M A T E R I A L S & M E T H O D SData Processing | Image Processing

q  MMRE technique provides phase images à It show the shear wave propagation within different muscles at 3 frequencies

q  Phase images are unwrapped & filtered by directional band-pass Butterworth filter

q  Then a reference profile, within an accuracy of 5° is drawn, in the direction of the wave propagation within the four thigh muscles

à calculated !

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M A T E R I A L S & M E T H O D SData Processing | Image Processing (Cont.)

q  Then, G(x) is calculated from G’ & G’’ equations assuming a density of 1000 kg/m3 q  Rheological models are estimated by minimizing the cost function

q  3 relative errors also computed to compare the quality of fit across frequencies:

q  Analyses of variance and Student’s paired t-test were performed using Statgraphics 5.0 software to compare the viscoelastic parameter between muscles

q  The level of significance was set at P < 0.1 due to the low number of subjects

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RESULTS

¨  Phantom Measurements ¨  In Vivo Measurements

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R E S U L T SPhantom Measurements

q  The dynamic viscoelastic parameters measured experimentally with the

Rheospectris and MRE are:

q  MRE technique underestimated the storage modulus (G’) and the loss modulus

overestimated the three frequencies

q  Bland-Altman test showed that the differences of the viscoelastic parameters are

in the range ± 2 SD

Method Parameter 60 Hz 80 Hz 100 Hz

RheoSpectris G’(kPa) 1.835 ± 0.001 1.843 ± 0.001 1.853 ± 0.001

G’’(kPa) 0.1902 ± 0.0004 0.2530 ± 0.0005 0.3154 ± 0.0006

MR elastography G’(kPa) 1.358 ± 0.013 1.579 ± 0.004 1.574 ± 0.015

G’’(kPa) 0.2129 ± 0.0092 0.3319 ± 0.0016 0.4162 ± 0.0247

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R E S U L T SIn Vivo Measurements | Characterization of The Shear Wave Within The Muscle

q  Phase images shows clear and consistent displacement of waves within the ishio

and gracilis muscles

q  The same quality of propagation is obtained at all three frequencies

q  Present experimental MRE muscle protocol allowed propagation of waves along a

large piece of muscle (along 20 cm of the Gr)

q  For all muscles, the wave was attenuated along its propagation and had a

decreases wavelength in accordance with the increase in frequency

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R E S U L T SIn Vivo Measurements | Viscoelastic Properties | Experimental G

q  The experimental viscoelastic values for the three frequencies:

¨  Gr muscle has higher G’ for the 3 frequencies ¨  BC, SM & ST had close G’ at 90 Hz ¨  Both G’ and G’’ increases with frequency

G’ G’’ G’’/G’ (kPa)

¨  G’’ has less variation w.r.t. G’ at each frequency & between all muscles

¨  G’’/G’ was similar (0.3) at 70 and 90 Hz

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Model Parameter BC Gr SM ST Voigt η (Pa s) 2.51 ± 0.18 2.85 ± 0.27 2.93 ± 0.24 2.20 ± 0.17

μ (kPa) 4.38 ± 0.26 6.88 ± 0.78 3.86 ± 0.22 5.00 ± 0.40

Χ (kPa) 0.35 ± 0.11 0.46 ± 0.13 0.42 ± 0.10 0.41 ± 0.10

Maxwell η (Pa s) 25.35 ± 1.41 55.10 ± 8.71 18.60 ± 1.04 40.27 ± 9.75

μ (kPa) 4.90 ± 0.30 7.32 ± 0.79 4.62 ± 0.31 5.42 ± 0.34

Χ (kPa) 0.41 ± 0.09 0.49 ± 0.09 0.46 ± 0.09 0.42 ± 0.09

Zener η (Pa s) 3.96 ± 0.54 6.65 ± 1.47 4.19 ± 0.39 4.29 ± 0.81

μ1 (kPa) 3.42 ± 0.20 5.20 ± 0.56 2.92 ± 0.18 3.92 ± 0.44

μ2 (kPa) 6.90 ± 3.28 6.36 ± 2.63 7.38 ± 3.22 3.34 ± 0.21

Χ (kPa) 0.31 ± 0.08 0.37 ± 0.08 0.38 ± 0.09 0.35 ± 0.08

Springpot η (Pa s) 3.96 ± 0.54 6.65 ± 1.47 4.19 ± 0.39 4.29 ± 0.81

μ (kPa) 5.65 ± 0.33 8.10 ± 0.80 5.30 ± 0.29 6.10 ± 0.38

α (kPa) 0.210 ± 0.009 0.158 ± 0.012 0.266 ± 0.010 0.172 ± 0.022

Χ (kPa) 0.35 ± 0.08 0.44 ± 0.09 0.42 ± 0.09 0.38 ± 0.08

R E S U L T SIn Vivo Measurements | Viscoelastic Properties | Rheological Models G

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R E S U L T SIn Vivo Measurements | Viscoelastic Properties | Rheological Zener Model G

q  The results obtained with the Zener model are:

¨  Gr muscle are different from BC, SM and ST ¨  Gr muscle has similar greater elastic behavior than the

experimental G’ at 90 Hz ¨  The values of were higher than for BC, SM and ST

¨  A similar range of was obtained for BC, SM and ST with the Gr showing higher values

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R E S U L T SIn Vivo Measurements | Viscoelastic Properties | Rheological Springpot Model G

¨  Higher values of were observed

for the Gr w.r.t. other

¨  Similar result to the experimental elastic shear modulus at 90 Hz

¨  The SM muscle has higher value compared to other muscles

¨  The trend of values for each muscle was equivalent to that obtained for G’’/G’ at 90 Hz

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q  The results obtained with the Springpot model are:

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CONCLUSIONS

¨  Brief Summary ¨  Perspectives 4�

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C O N C L U S I O N SBrief Summary | Perspectives

q  Present MMRE tests associated with the data-processing method showed that

the complex shear modulus of passive muscle can be analyzed using two

rheological models ( Zener, Springpot )

q  The elastic and viscous data could be used as a reference for future assessment

of muscular dysfunction in addition to the parameters related to the aging

process and anthropometry

q  Perspectives: further experiments will be performed on a much larger number of

participants and on the other thigh muscles under active conditions in order to

obtain a complete muscle database of their functional properties

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THANK YOU

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