Shear Wave Imaging of Passive Diastolic Myocardial Stiffness Stunned Versus Infarcted Myocardium

OBJECTIVES The aim of this study was to investigate the potential of shear wave imaging (SWI), a novel ultrasound-based technique, to noninvasively quantify passive diastolic myocardial stiffness in an ovine model of ischemic cardiomyopathy. BACKGROUND Evaluation of diastolic left ventricular function is critical for evaluation of heart failure and ischemic cardiomyopathy. Myocardial stiffness is known to be an important property for the evaluation of the diastolic myocardial function, but this parameter cannot be measured noninvasively by existing techniques. METHODS SWI was performed in vivo in open-chest procedures in 10 sheep. Ligation of a diagonal of the left anterior descending coronary artery was performed for 15 min (stunned group, n ¼ 5) and 2 h (infarcted group, n ¼ 5). Each pro-cedure was followed by a 40-min reperfusion period. Diastolic myocardial stiffness was measured at rest, during ischemia, and after reperfusion by using noninvasive shear wave imaging. Simultaneously, end-diastolic left ventricular pressure and segmental strain were measured with a pressure catheter and sonomicrometers during transient vena caval occlusions to obtain gold standard evaluation of myocardial stiffness using end-diastolic strain-stress relationship (EDSSR). RESULTS In both groups, the end-systolic circumferential strain was drastically reduced during ischemia (from 14.2 (cid:2) 1.2% to 1.3 (cid:2) 1.6% in the infarcted group and from 13.5 (cid:2)

A ssessment of diastolic left ventricular function is critical for the evaluation of heart failure and ischemic cardiomyopathy. Myocardial stiffness is thought to play a key role in diastolic function (1). In patients with preserved ejection fraction, abnormalities in left ventricle (LV) relaxation and LV stiffness are key pathophysiological mechanisms (2). Myocardial stiffness is also known to be a very strong prognosis parameter in hypertrophy (3) and dilated cardiomyopathy (4). In myocardial infarction, tissue Doppler and strain echocardiography are established methods for tracking myocardial deformation for the evaluation of systolic function (5)(6)(7). Few studies, however, have reported the use of these techniques to describe diastolic deformation, and none of the techniques are able to evaluate diastolic myocardial stiffness. However, diastolic myocardial stiffness changes appear very early during myocardial ischemia (8,9). Moreover, several studies demonstrated an increase in myocardial stiffness after myocardial infarction using different techniques such as finite elements analysis (10) or stress-strain measurements (11). Pislaru et al. (12) demonstrated, using strain imaging, that passive diastolic myocardial deformation was correlated to the change in myocardial stiffness during myocardial ischemia. However, they emphasized that the magnitude of passive deformation was load-dependent contrary to indexes of myocardial stiffness. Thus, currently, myocardial stiffness cannot be quantified noninvasively by echocardiographic tools such as tissue Doppler or strain echocardiography.
Recently, we developed shear wave imaging (SWI), a new ultrasound-based technique for quantitatively mapping the stiffness of soft tissues characterized by using the Young modulus defined by the slope of the stress-strain curve. This technique belongs to the field of multiwave imaging as it combines 2 waves: a shear wave providing stiffness contrast and ultrasonic waves providing millimeter-level spatial resolution (13). The clinical potential of this approach has been recently demonstrated in the field of breast lesion imaging (14), as well as in liver (15) and arteries (16). In the field of cardiac imaging, we have already shown its potential for the evaluation of myocardial contractility (17) and fiber architecture (18).
The present study investigated the potential of SWI in vivo to noninvasively quantify changes in passive diastolic stiffness in an ovine model of ischemic heart failure in order to discriminate between infarcted myocardium and stunned myocardium. This is of upmost importance because in a clinical setting it is still challenging to differentiate between these 2 types of ischemia only by using strain echocardiographic evaluation of the regional active systolic function at rest. The 10 animals were divided into 2 different groups. In group I (n ¼ 5), acute myocardial ischemia was induced by ligating 1 diagonal branch of the left anterior descending coronary artery for 15 min, followed by 40 min of reperfusion. In group II (n ¼ 5), acute myocardial ischemia was induced for 120 min, followed by 40 min of reperfusion. The objective was to achieve infarction in order to compare the stiffness of infarcted myocardium (group II) with that of stunned myocardium.

MYOCARDIAL STIFFNESS MEASURED BY SHEAR
WAVE IMAGING. SWI is based on the remote generation of shear waves in soft tissue by acoustic radiation force combined with ultrasonic ultrafast imaging of the shear wave propagation, using the same ultrasonic transducer (19). A short burst (300 ms) of focused ultrasound was transmitted by a diagnostic ultrasonographic probe (linear array, 8-MHz central frequency; SuperSonic Imagine, Aix-en-Provence, France) to induce micrometric tissue displacements in a small zone of the myocardium due to acoustic radiation force ( Figure 1A). In response to that transient mechanical excitation, a shear wave is generated in the low-kHz-frequency range and propagates in the myocardium at velocities from 1 to 10 m/s, depending upon tissue stiffness ( Figure 1B). The originality of SWI consists of imaging the shear wave propagation at an ultrahigh frame rate (10,000 images/s) by using the same diagnostic probe connected to an ultrafast ultrasonic scanner (Aixplorer, SuperSonic Imagine). Tissue velocity maps were computed offline for each frame by using in-phasequadrature frame to frame cross-correlation.
where L 0 is the end-diastolic segment length at baseline (crystals 5-6 where a and b are the internal and external radii, respectively, and P is the LV ventricular pressure. The term b was computed as the sum of a, and the thickness was measured by echocardiography.  Pernot et al. Moreover, the diastolic stiffness constant measured invasively by sonomicrometry confirmed that enddiastolic stiffness increased strongly in infarcted myocardium and was unchanged in stunned myocardium ( Figure 3). Figure 4 compares the stiffness changes measured by SWI and that by sonomicrometry for all 10 animals and shows that enddiastolic myocardial stiffness differs drastically in stunned and infarcted myocardium, using both techniques.

DISCUSSION
This is the first study to quantify diastolic stiffness during myocardial ischemia by ultrasonography imaging and without the need of invasive sensors such as pressure catheters or sonomicrometer crystals. We demonstrated that reperfused infarcted myocardium has markedly increased diastolic myocardial stiffness which persisted after reperfusion. In addition, we showed that stunned myocardium preserved tissue compliance with no significant change of diastolic myocardial stiffness. As opposed to stiffness, regional systolic myocardial function significantly decreased in both groups.
In contrast to systole, for which there is a gold standard (end-systolic elastance) that can be obtained relatively easily, there is no universally accepted

Occlusion
The variation of SWI myocardial diastolic stiffness during occlusion and reperfusion is shown on 1 animal from the stunned group (green) and 1 from the infarct group (pink). The end-diastolic strain-stress relationship is shown for 1 animal from each group. In the infarcted myocardium group (A), the exponential constant of the stress-strain relationship increased strongly after ischemia reperfusion whereas in the stunned group (B), the exponential constant did not change after ischemia reperfusion (pink) compared with baseline (green).