DYNAMIC AND QUANTITATIVE ASSESSMENT OF MYOCARDIAL ... · the myocardial stiffness in Langendorff perfused rat heart. The Langendorff method [6] consists of perfusing an excised heart

DYNAMIC AND QUANTITATIVE ASSESSMENT OF MYOCARDIAL STIFFNESS USING SHEAR WAVE IMAGING

Mathieu Pernot1, Mathieu Couade1, Philippe Mateo2, Rodolphe Fischmeister2, Bertrand Crozatier2, Mickael Tanter1

1Institut Langevin, ESCPI ParisTech CNRS UMR 7587, INSERM U979, Paris France 2INSERM U769-IFR141, Univ Paris-Sud 11, Fac Pharmacy, Châtenay-Malabry, France

ABSTRACT

Shear Wave Imaging was used to assess the myocardial stiffness in Langendorff perfused rat heart. This technique was used to quantify the myocardial stiffness and its dynamics over the cardiac cycle. This method is based on the generation of a shear wave (typically in the kHz range) that propagates in soft tissues at a velocity of a few meters per second that is linked to the tissue stiffness. The acquisition of the shear wave propagation was performed in less than 10 ms, enabling the possibility to follow dynamically the variation of the myocardial stiffness during the cardiac cycle. The feasibility of imaging the myocardial elasticity was demonstrated up to 15 times per cardiac cycle. The mean shear wave velocity was found to be 3.8 ± 0.6 m/s in the systolic phase and 1.1 ± 0.15 m/s in the diastolic phase when the probe was set in the long axis orientation.

Index Terms— Myocardial stiffness, Shear wave, radiation force, elasticity imaging, cardiac imaging, elastography.

1. INTRODUCTION

The quantitative assessment of regional myocardial functionis an important goal in clinical cardiology. Using conventional echocardiography, the evaluation of regional function is mainly based on the visual, and therefore subjective, interpretation of myocardial thickening and thinning [1]. Recent imaging techniques have been introduced to quantify the myocardial deformation such as tissue doppler imaging [2] and strain rate imaging [3] in the field of ultrasonic imaging, or MR cardiac tagging [4] in the field of Magnetic Resonance Imaging. All these techniques are based on the measurement of myocardial strain, the resultant deformation of the myocardium in response to a developed stress. However, although the concept of myocardial strain is very useful for the diagnostic of cardiac pathologies, it is also limited by the fact that the stress distribution in the myocardium remains unknown. The stress/strain relationship in soft tissues or tissue stiffness is an important local parameter that characterizes the tissue

mechanical property. This parameter varies usually significantly under pathological states as it is related to cellular and higher levels of tissue structural organization.

Shear Wave Imaging is a novel ultrasound-based technique for imaging non-invasively and quantitatively the elastic modulus of soft tissues [5]. This method is based on the generation of a shear wave (typically in the kHz range) that propagates in soft tissues at a velocity of a few meters per second that is linked to the elastic modulus. The shear wave is generated via the acoustic radiation force of an ultrasonic beam focused in the myocardium by a conventional linear imaging array. The originality of this approach consists in acquiring ultrasound images of tissues at very high frame rates (up to 12,000 frames per second) just after the shear wave generation. Thanks to an ultrafast scanner, a complete movie of the transient event corresponding to the shear wave propagation through the organ can be provided.Contrary to other approaches, ultrafast imaging of heart motion can be achieved during a single cardiac cycle and does not require ECG triggering for stroboscopic reconstruction of an ultrafast movie from several tens of cardiac cycles.

We propose here to use this novel approach for measuring the myocardial stiffness in Langendorff perfused rat heart. The Langendorff method [6] consists of perfusing an excised heart with oxygen and nutrients and has become a fundamental tool in physiological research in cardiology. In this study, the use of this system offers many advantages such as offering a large acoustic window and completely stabilized experimental conditions that would be difficult to maintain in vivo. In this study, we measure the myocardial stiffness variation during a single cardiac cycle. Thanks to the fact that one complete acquisition of the shear wave propagation is performed in less than 10 ms, it is possible to follow dynamically in real time the variation of the myocardial stiffness during the cardiac cycle. First, the shear wave imaging sequences are presented. The method for filtering the myocardial motion is presented as well as the method for computing the shear wave group velocity. Finally, experimental results are shown on 3 rats.

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2. MATERIALS AND METHODS

2.1 Imaging sequence Shear wave imaging is based on the remote generation of shear waves in soft tissue by the acoustic radiation force at the focus of the ultrasound field. A short duration burst (200μs) of focused ultrasound is transmitted by a diagnostic ultrasonic probe (12MHz central frequency) to induce tissue displacements in a small focal zone of the myocardium thanks to the acoustic radiation force. In response to that transient mechanical excitation, a shear wave is generated in the low kHz frequency range and propagate in the myocardium at relatively low velocities (between 1 and 10 m/s), depending on tissue elasticity. The shear wave propagation is imaged at ultra-high frame rate (up to 12,000 images/s) using the same diagnostic probe. From the spatio-temporal data of the shear wave propagation, the shear velocity was computed and the shear modulus μ was derived from:

2cρμ = Eq. 1

where c is the shear velocity, the volumic mass.

The stiffness measurement was repeated several times over the cardiac cycle in order to dynamically investigate the stiffness variations. 15 measurements were performed over one single cardiac cycle. Each elasticity measurement was achieved in less than 10 ms and was repeated 15 times every 18 ms allowing to measure variation of elasticity within one cardiac cycle.

2.2 In vivo experimental procedure Shear wave imaging was performed in Langendorff perfused isovolumically contracting rat hearts. Experiments were conducted in rats (N=3, Heart weight/body weight ratio: 3.79±0.21 mg/g).

Fig. 1: Langendorff experimental setup

The heart was attached to a cannula inserted in the aorta and was immersed into a saline bath. A latex balloon was inserted in the left ventricle and inflated to control the left ventricle volume and measure the ventricular pressure. The linear ultrasonic array was positioned through an acoustic window performed on the water tank. The ultrasonic array could be rotated in order to select the plane of view: short axis or long axis. An electrode was placed in the right atrium in order to electrically pace the heart.

2.3 Data processing The elasticity estimations are obtained off line by processing the raw data (per channel signal of backscattered echos of the transmitted plane waves):

1. Raw data are beamformed to obtain a stack of IQ images (phase and amplitude decomposition). This stack of images is processed using conventional IQ cross-correlation method to obtain images of tissue axial displacements.

2. The myocardium wall motion is removed. Myocardial wall motion has low frequency components below 100 Hz which is removed by applying to the velocity movie a high pass filter (2nd order high pass butterworth filter with cut-off frequency = 100 Hz)

3. The depth of interest is chosen on the conventional B-mode anatomical image. The average elasticity at this depth displacements are first averaged around the depth of interest which results in a two dimensional matrix of tissues displacement function of the time and the lateral position. This matrix M(x,t) is compared to theoretical propagation matrixes Mt(x,t,v) with different propagation speeds v in order to find the actual propagation speed:

Eq. 2

Mt is a theoretical matrix representing a plane wave propagation in one direction with a phase velocity v and a frequency f. f is fixed by computing the central frequency of the experimental signal. W is an apodization window. The introduction of this spatio-temporal matrix modelling the shear wave propagation along a chosen direction enables a more accurate estimation of the local experimental shear wave speed as the comparison between experimental and simulated results is achieved over a large space and time area.

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a)

Fig. 2: a) Theoretical matrix for thE is reach when v is equal to the pr

3. RESULTS

After removing the wall motion, the shewas imaged with good accuracy as showshear wave velocity was determined in of the myocardium within a window strong variation of the myocardial s

Fig. 3: Shear wave propagation in the myofiltering the low frequency wall motion.

2

4

6

8

10

12

14

16 b) c)

e estimated velocity ; b) Experimental matrix; c) Energy furopagation speed of the shear wave.

ear wave propagation wn in Figure 3. The the mid-wall region of 2mm x 2mm. A

stiffness was found

during a cardiac cycle (betstiffness was found to increthe systolic phase. After restiffness progressively decreand returns to its initial valuemodulus dynamics averaged

ocardium. The tissue velocity in color is superimposed onto tThe four frames show the shear wave a) 1 ms b) 2 ms c) 3 m

generation.

0 1 2-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

inte

nsity

(a.

u)

unction E(v) : the maximal value of

tween 1 m/s and 6 m/s). The ase rapidly at the beginning of eaching a peak in systole, the eases during the diastolic phase e. The Figure 4 shows the shear over 5 different heart cycles.

the grayscale Bmode image after ms d) 4ms after the shear wave

3 4 5 6 7 8

E(v)

velocity (m/s)

978

Fig. 4: Variation of the shear modulus durincurve). The trace of the ventricular pressure i

Myocardial shear modulus was found 30kPa depending on the period of the cexperimental conditions (heart rate, CalcThe passive shear modulus is in good values previously reported in the literatof the shear wave velocity is also foundorientation of the probe (see Table 1). Tdue to the anisotropy of the propagating the myocardial fibers orientation. The anshear wave velocity in agreement with ththe literature on passive myocardium [7]

Table 1: Shear wave velocity in the mid-wala function of the probe orientation (N=3). Taxis and short axis view were used.

4. DISCUSSION

In this study, the feasibility of measurindynamically the myocardial stiffness imaging was demonstrated in Langenheart. The shear wave propagation was accuracy and reproducibility in spite of twall motion during the contraction andThe stiffness dynamics was measured wresolution up to 15 times per cardiac cywas shown to increase strongly betwsystolic phase (up to 10 times). Althoumodel is not physiologic, this techpossibilities for the investigation of thestiffness in cardiac applications.measurement of the myocardial stiffnes

ng a cardiac cycle (red is shown in blue.

between 1kPa and cardiac cycle and the cium concentration). agreement with the

ture [7]. A variation d as a function of the This variation may be

medium induced by nisotropy ratio of the he values reported in ].

ll myocardial region as The conventional long

ng quantitatively and using shear wave

ndorff perfused rat imaged with a good the large myocardial d relaxation phases.

with a good temporal ycle and the stiffness ween diastolic and ugh the Langendorff hnique offers new e role of myocardial

The quantitative s may be potentially

important for the diagnosis oquantification tool of myocand systolic (contractility) eff

Shear wave velocity was alsothe probe orientation. A goothe acquisition of shear waoriented in both long axis antable 1. The study shows carefully the depth of the slivariation in fiber orientationhas to be considered. The mthe mid wall was shown to beffect of the shear wave prwith more details in furtherthis ultrafast imaging methmyocardium tissue charactequantitative and dynamic eproperties.

5. REFE

[1] Heger JJ, Weyman AE, WaCross-sectional echocardiographdetection and localization of rCirculation 1979; 60: 531–538.

[2] Sutherland GR, StewartMJFleming A, Guell-Peris FJ, RieMcDicken WN. Color doppltechnique for the assessment oEchocardio 1994; 7: 441–458.

[3] D'hooge J, Heimdal A, JRademakers F, Hatle L, Suetensand strain rate measurementsimplementation and limitations.164.170, 2000 [4] Beyar R, Shapiro EP, GraCarey RL, Soulen EA, ZerhouQuantification and validation ofa three-dimensional volume eleapproach. Circulation 1990; 81:

[5] Bercoff J, Tanter M, Fink Mtechnique for soft tissue elasticFerr. Freq. Contr. 2004; 51: 396

[6] Langendorff O. UnteSäugethierherzen. Pflügers Arch

[7] Guccione, J.M., McCullochmaterial properties of intact vefrom a cylindrical model. J Biom

of cardiac pathologies as a new cardium diastolic (compliance) ficiency.

o found to vary as a function of od reproducibility was found on ave speed when the probe is nd short axis view, as shown in

the importance of choosing ice used to derive stiffness: the n in the myocardium thickness

measure of the group velocity in e reproducible. This anisotropic ropagation will be investigated r studies. A strong potential of hod is envisioned for clinical erization as it provides local, estimation of heart mechanical

ERENCES

ann LS, Dillon JC, Feigenbaum H hy in acute myocardial infarction: regional left ventricular asynergy.

, Groundstroem WE, Moran CM, emersma RA, Fenn LN, Fox KAA, ler myocardial imaging: a new of myocardial function. J Am Soc

amal F, Kukulski T, Bijnens B, s P, Sutherland GR. Regional strain by cardiac ultrasound: principles, . Eur J Echocardiogr 2000; 1:154-

aves WL, Rogers WJ, Guier WH, uni ML, Weisfeldt ML, Weiss JL. f left ventricular wall thickening by ement magnetic resonance imaging

297– 307.

M. Supersonic shear imaging: a new city mapping. IEEE trans. Ultras. 6-409.

ersuchungen am überlebenden h 1895; 61: 291–332.

h, A.D. and Waldam, L.K. Passive entricular myocardium determined mech Eng 1991; 113 1, pp. 42–55.

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