TECHNOLOGY

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TECHNOLOGY - A
TISSUE DOPPLER IMAGING IN CORONARY ARTERY DISEASE

Gabriel W. Yip, MD; Steve R. Ommen, MD, FACC Division of Cardiovascular Diseases and, Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

 ABSTRACT

 1. BACKGROUND

 2. PHYSICAL BASIS AND TECHNICAL ASPECTS

 3. CLINICAL APPLICATION OF TISSUE DOPPLER TECHNIQUES

 4. FUTURE DIRECTIONS
 References

ABSTRACT

Tissue Doppler imaging (TDI) has rapidly evolved over the last decade as a sensitive clinical tool of measuring both global and regional myocardial velocities and their relationship to the cardiac cycle with high spatial and temporal resolution. 
Measurement of mitral annular velocities reflects global left ventricular LV function at rest or during stress echocardiography. 
Regional analysis of peak segmental systolic myocardial velocities during stress improves accuracy of novice readers, of interpreting basal segments, and concordance between observers. 
Moreover, it has higher sensitivity and comparable specificity to standard dobutamine stress echocardiography in detecting myocardial viability.
 Myocardial velocity gradient, being independent of cardiac translational movement, has also shown promise for detecting resting and induced ischemia and viable myocardium. Strain rate imaging (SRI), based on tissue Doppler technology, has clinical potential of quantitative assessment of regional contractility and function during stress echocardiography. Abnormal wall motion during isovolumic contraction and relaxation periods and their clinical implications of correlating myocardial viability has been discussed. Improved data acquisition and rapid postprocessing of TDI will facilitate its incorporation into standard regional myocardial assessment.

 (Heart Views. 2002;3(1):6-20) © 2002 Gulf Heart Association.

1. BACKGROUND

1.1 Detection and assessment of coronary artery disease                         1.2 Evolution of tissue imaging

1.1 Detection and assessment of coronary artery disease

Coronary artery disease (CAD) remains the leading cause of death in the USA, causing one in every 4.9 deaths and over 12 million people report a history of angina, previous heart attack or both (1).
 Accurate early identification of CAD is critical in reducing morbidity and mortality. Stress echocardiography is widely used to diagnose flow-limiting CAD. In general, exercise and pharmacologic stress echocardiography are more sensitive in detection of myocardial ischemia than electrocardiographic variables and have evolved as cost-effective alternatives to nuclear methods (2-4).
 Traditional diagnostic criteria of regional dysfunction are based on detection of: 1) regional delay in myocardial motion, 2) differences in amplitude and direction of regional wall motion and 3) regional wall thickening and thinning characteristics. Unfortunately, most stress-echo interpretations are still based on subjective visual recognition of abnormalities of wall motion or thickening with segments scored in a semi-quantitative manner.
 Furthermore, issues of reproducibility (5) and requirement for adequate training (6) are also important limitations of the technique.
 An objective and quantitative assessment of regional wall motion should enhance concordance between interpreters and improve accuracy of the novice readers.
 In this regard, tissue Doppler echocardiography (TDI) and strain rate imaging (SRI) – an evolving technology of the former, may herald an improvement in the noninvasive assessment of regional myocardial function.

1.2 Evolution of tissue imaging

Tissue Doppler imaging (TDI) is an extension of conventional Doppler flow echocardiography and has been proven to be a useful and feasible clinical tool for assessing global as well as regional ventricular function since its introduction in the early 90s. Isaaz et al (8) pioneered pulsed-wave Doppler measurements of myocardial wall velocity and mitral annular motion in the late 1980s. In 1994, Sutherland et al (9) and Yamazaki et al (10) introduced color-coded Doppler myocardial imaging which recently became a standard built-in technology in many commercially available equipment packages.
 TDI has been validated both in vitro (11-12) and in vivo (13-17). It has been clinically applied in assessing regional and global left ventricular (LV) systolic (18-19) and diastolic function (20-24); estimating the LV filling pressure in various clinical states (25-29) and detecting allograft rejection in cardiac transplant recipients (30-33). 
It helps in differentiating constrictive pericarditis from restrictive cardiomyopathy (34-35), differentiating athletic heart from hypertrophic cardiomyopathy (36), and detecting hypertrophic cardiomyopathy (HCM) gene carriers even in the absence of fulminant phenotypic expression (37). 
This review will examine the role of tissue Doppler techniques (myocardial velocity assessment and strain rate imaging) in the detection of coronary artery disease.

2. PHYSICAL BASIS AND TECHNICAL ASPECTS

2.1 Tissue Doppler Imaging                     2.2 Strain rate imaging                      2.3 Myocardial velocity gradient

2.1 Tissue Doppler Imaging

The pulsed and color Doppler echocardiography can detect motion and velocity of both moving blood and myocardial tissue. 
We have traditionally processed blood flow signals in the conventional Doppler flow imaging, so that the high velocity and low amplitude Doppler signals reflected by the moving blood are measured whereas the myocardial Doppler signals with high amplitude but low velocity are suppressed. 
To better analyze myocardial signals, the high-pass filter used to optimize blood flow signals is minimized. In addition, a signal intensity threshold filter has to be altered with lower gain amplification to eliminate the weak intensity of blood flow signals.
 These improve the ability to measure low velocity myocardial signals that are typically in the range of 0.6 – 24 cm/s. TDI analysis, with generally favorable signal to noise ratio, is relatively independent of 2-dimensional image quality. Another important aspect of the TDI is high frame rate image acquisition, which is crucial for temporal resolution. With digital parallel processing techniques, frame rate of >150 frames per second can be achieved with increased pulse-repetition frequency (PRF) and narrow sector angle of region of interest (ROI).

Figure1.Real-time pulse-wave tissue Doppler at the inferior aspect of the mitral annulus. Sm= Systolic mitral annular velocity; Em= Early diastolic mitral annular velocity; Am= Late diastolic mitral annular velocity; IVRTm= isovolumic relaxation velocity; IVCTm= isovolumic contraction velocity (biphasic in this case). Figure 2

Figure 2. Tissue Doppler velocity of various segments of the anterolateral and inferoseptal walls of the left ventricle. Mitral annular velocity of a particular LV wall is similarly obtained when the sampling volume is placed at the insertion of the annulus near the basal segment. Figure 3

As mentioned, pulse-waved TDI as opposed to color-coded TDI measures peak, rather than mean myocardial velocities. It does not require off-line analysis and provides instantaneous temporal display of Doppler spectral velocity data (Figure 1). The sampling, however, cannot be localized to the endocardial or epicardial layers. While requiring off-line analysis, color Doppler has the advantage of simultaneously acquiring multiple segments in one view and this is particularly useful within a limited acquisition window of stress echocardiography (Figure 2).

2.2 Strain rate imaging

First introduced in 1973 by Mirsky and Parmley (40), strain (e) and strain rate (SR) are measures of regional myocardial thickening and thinning of the heart muscle. Myocardial strain is a dimensionless index of change in myocardial length in response to an applied force. Strain rate is the time derivative of strain with unit of change per second (sec -1) and represents the differential velocity of two points adjusted for the distance between them (Figure 3). Strain rate imaging (SRI) is therefore an extension of technology derived from the tissue Doppler imaging (TDI).

Previously, intrinsic myocardial deformation or strain was invasively measured by tracking movement of implanted radio-opaque markers (eg., metallic beads) by biplane cineangiography (41-42) or video technique (43), measuring mutual motion and angulation of three needles pierced into the myocardial wall, using an electromagnetic inductive technique (44), or by sonomicrometry in the myocardium (45).

Now both parameters (strain and strain rate) can be derived non-invasively from either magnetic resonance imaging (MRI) tagging techniques (46-48) or echocardiography using M-mode (49-50) or more commonly high frame rate (>150 frames/sec) tissue Doppler velocity data after post-processing (51-52) (Figures 4-5). These non-invasive techniques overcome the inherent 

Figure 4

2.3 Myocardial velocity gradient

The MVG is simply a measure of regional radial strain rate of a small area of myocardium. Unfortunately, based on processed color-encoded velocity data, it lacks spatial resolution and, therefore, may not detect lower strain rate. Technical development of on-line, high speed and large quantity image acquisition and storage system together with an automated myocardial edge detection technique should facilitate such application in future. Normally, the endocardium moves faster than the epicardium except during isovolumic relaxation when the reverse is seen. Thus, there is a gradient of increasing velocity from the epicardium to the endocardium as myocardial wall thickens in systole, which can be served as a marker of regional contractility. The myocardial velocity gradient (MVG) can be obtained from color M-mode recording of anteroseptal or posterior wall from parasternal position using either high frame rate M-mode data (38) or lower frame rate (up to 59 frames/sec) two-dimensional data (39).

Several other methods, including centerline methods (54), color kinesis (55), and automatic boundary detection (56) have been proposed to aid qualitative interpretation of wall motion scoring and to give some semi-quantitative measure of regional contractility. In general, these methods require reasonable endocardial border definition and /or lengthy time for post-acquisition data analysis.

3. CLINICAL APPLICATION OF TISSUE DOPPLER TECHNIQUES

3.1 Myocardial Velocity Assessment (Standard TDI)                     3.2 Myocardial strain rate imaging

3.1 Myocardial Velocity Assessment (Standard TDI)

3.1a Global assessment of LV function to detect CAD                     3.1b Regional assessment of LV function for detection of CAD                       3.1c Use of TDI velocity assessment in myocardial viability                            3.1d Limitations of TDI

3.1a Global assessment of LV function to detect CAD

The global LV systolic function can be assessed by peak mitral annular (MA) velocity in apical views.
 Although myocardial synchronous contraction and relaxation depends critically on coordination of circumferential and longitudinal fibers, the longitudinal fibers are particularly vulnerable to myocardial ischemia and activation disturbance likely related to their subendocardial position (57).
 Because the epicardial apex is relatively fixed (58), the longitudinal fiber shortening draws the atrioventricular ring towards the apex of the ventricle. Not only does this contribute to the fall in the left ventricular cavity volume with ejection, but at the same time increases the volume of the left atrium.
 Similarly, during diastole, the backward movement of the atrioventricular ring aids the LV filling. Dumesnil et al. 
showed that with a 40% decrease of LVEF (M-mode) in disease, there might be only 15-20% corresponding decrease in the circumferential fiber (short-axis) shortening (59), highlighting the significant contribution of longitudinal fibers in overall LV function.

Figure 5

3.1b Regional assessment of LV function for detection of CAD

3.1c Use of TDI velocity assessment in myocardial viability

There are many reports on clinical feasibility of TDI in the setting of induced ischemia during stress echocardiography, but fewer reports on the clinical potential of tissue Doppler imaging in detecting myocardial viability. Rambaldi et al. reported detection of hibernating myocardium in 40 patients with chronic ischemic heart disease and LV dysfunction (mean EF 33±11%) using regional peak systolic myocardial velocity during dobutamine stress echocardiography. F18-fluorodeoxyglucose single photon emission computer tomography (FDG-SPECT) served as the reference (92). The baseline regional peak systolic myocardial velocity did not differ between viable and non-viable segments. However, viable myocardium showed higher systolic velocities at low and peak-dose dobutamine than non-viable segments. An increase in regional systolic velocity low-dose of >1±0·5 cm/s predicted viability. For the prediction of viability, the sensitivity (95%CI) of pulsed-wave Doppler was significantly better than standard dobutamine stress echocardiography {87% (82–92) versus 75% (67–81)}, while the specificity {52%(44–59) versus 51% (45–59)} was comparable.

3.1d Limitations of TDI

Like many other regional quantitative myocardial indices, tissue myocardial velocity is affected by cardiac translation. Moreover, adjacent ischemic or scarred segments may affect normal segments through “tethering” of their motion, thus lowering the measured velocity, and conversely, normal segments may augment the velocity in abnormal segments. Because of a relatively fixed epicardial apex and a longitudinal velocity gradient from base to apex, apical velocities are close to zero and differentiating normal from abnormal apical segments based on their myocardial velocity is difficult.

To partially circumvent this problem, the imaging window is narrowed to a sector angle of 20-30 for imaging individual ventricular wall with tilting in an apical view so that the whole wall is parallel to sampling cursor. In this way, the frame rate is enhanced, and the proximal one-third of the apical segments can be measured for myocardial velocities within acceptable angle of insonation.

3.2 Myocardial strain rate imaging

Because strain and strain rate are derived from the motion of segments relative to each other, tethering and translation will affect both velocity vectors equally and are therefore minimized. Measurement of strain at one site reflects function at that site and therefore might be expected to have greater spatial resolution than tissue Doppler velocity data alone. Normally, the longitudinal strain rates in the anterior and septal walls are comparable but higher than those in the antero-lateral and infero-lateral walls (93).

Myocardial strain derived from color tissue Doppler data promises to improve the quantitation of regional myocardial contractile function in the future.

The regional strain values have been validated to correlate with those obtained from sonomicrometry in an acute ischemic canine model (53). The real-time color SRI was shown to have moderately good correlation (weighted k of 0.55) with the wall motion score of standard echocardiography in 15 patients with acute myocardial infarction (94) and also in identifying infarct related artery of 20 similar patients (weighted k of 0.64) undergoing coronary angiography (95).

Voigt et al. compared 12 patients with history of transmural myocardial infarction with 10 normal controls and found that longitudinal peak segmental systolic strain and strain rate decreased with increasing wall motion score (96). Edvardsen et al showed that longitudinal segmental systolic strain and strain rate are more sensitive in detecting regional myocardial ischemia than tissue Doppler velocity measurements in patients undergoing percutaneous coronary intervention (97).

In the canine model, reduced systolic strain appears earlier than tissue Doppler velocity abnormality and semi-quantitative visual wall motion abnormalities in acute ischemia (98). Using closed chest animals, the strain rate has been shown to correlate linearly with maximal value of the first LV pressure time derivative (dP/dtmax) and peak elastance(Emax), both global measures of LV systolic function or contractility (99,100). In both normal human and stunned porcine myocardium, the dobutamine-induced increase in systolic strain rate (SR) preceded the increase in strain itself (e) and the increase in LV systolic wall thickening (76,99).

An increase of peak systolic strain rate of more than –0.23 per sec from rest during low-dose dobutamine discriminates viable from non-viable myocardium, as determined by 18F-fluorodeoxyglucose positron emission tomography (FDG PET). The regional SRI compares favorably with TDI with better sensitivity (83% vs 69%) and specificity (84% vs 64%) in the detection of myocardial viability (101).

All these indicate that segmental strain rate analysis has a promising and potentially superior role than tissue Doppler imaging in quantitative assessment of regional contractility and function during stress echocardiography.

3.2a Myocardial velocity gradient in detection of induced ischemia and viability                     3.2b Abnormal left ventricular wall movement during isovolumic periods                       3.2c Post-ejection wall motion                           3.2d Pre-ejection velocities

3.2a Myocardial velocity gradient in detection of induced ischemia and viability

The MVG has an advantage of being independent of translational movement of the heart (102). Secondly, it is more sensitive in differentiating ischemic from non-ischemic segments in submaximal dobutamine challenge than either endocardial velocity measurements or wall motion abnormality (103).
 It detects resting regional myocardial dysfunction in post-MI patients with single vessel coronary disease (11, 103) and induced ischemia during submaximal dobutamine stress echocardiography in patients with single vessel coronary disease, prior MI and preserved LV function (104). It has been used in distinguishing viable from non-viable segments during low-dose dobutamine in patients with significant chronic triple coronary disease (>70% diameter narrowing) and LV dysfunction (LV ejection fraction <50%) (105).

Figure 6

3.2b Abnormal left ventricular wall movement during isovolumic periods

Recently, there has been a renewed research interest in clinical significance of inward wall movement during the isovolumic contraction (IVCT) and relaxation (IVRT) period detected either by TDI or SRI in ischemic and post-ischemic myocardium. During coronary occlusion in dogs, most of the systolic lengthening occurs during IVCT and most of the subsequent shortening during the IVRT with more rapid change of LV pressure during these phases than during ejection (106). Thus, the abnormal wall motion during these periods may serve as better measures of regional LV function than peak wall motion during systole.

3.2c Post-ejection wall motion

Figure 7

Based on centerline method of analyzing endocardial wall motion in 35 patients with acute myocardial infarction undergoing ventriculography before and after angioplasty, PSS in the infarct region predicts recovery after reperfusion (115). In 23 patients with angiographically proven significant coronary artery disease, 98% of all hypo- and akinetic regions with PST and only 6% of those without PST improved at low dose dobutamine stress-echo. Furthermore, 92% of segments with PST and 38% without PST improved after revascularization (116). All these indicate that PSS (PST) is related to myocardial viability. Larger clinical trials are needed for defining its role in myocardial viability.

One of the potential clinical applications using SRI in detecting PST is differentiation of ischemic from reperfused yet stunned myocardium during dobutamine stress echocardiography. In closed chest porcine model, total and graded ischemia results in delayed onset and decrease in regional systolic strain and strain rate but increased post-systolic thickening (117-118). Dobutamine infusion causes a further decrease in maximal regional strain and concomitant increase in postsystolic thickening in persistent ischemic segments, whereas it normalizes regional PST gradually with further increase in systolic strain and strain rate at higher stimulation in the stunned myocardium (99).

SRI can also depict segmental PSS as a prolonged transition from myocardial compression to expansion i.e., prolonged time from peak R wave on ECG to compression/expansion crossover (TCEC) (Figure 7). Using this new parameter, prolonged TCEC correlates with and spatially quantifies ischemic myocardium measured from both stained porcine myocardium (119) and perfusion defects from myocardial contrast echocardiography (120). An initial study of 40 patients suggests that this new parameter is feasible with additional 5 minutes of SRI to standard dobutamine stress-echo time. In normal myocardial segments, TCEC at peak stress decreases significantly from baseline but this response is attenuated in ischemic segments. Using a 20% reduction of TCEC as cut-off based on receiver operator characteristic curves, sensitivity and specificity for detection of ischemic segments were 77% and 55% respectively with corresponding values of 62% and 88% for standard dobutamine stress-echo (121).

Figure 8

3.2d Pre-ejection velocities

ntraction represent asynchronous and rapid myocardial contraction after ventricular activation but before aortic valve opening, resulting in minor changes in the LV volume and wall thickness. Similar to postsystolic thickening in the IVRT period, they are also sensitive to acute myocardial ischemia and correlates with transmural myocardial infarct (Figure 8). It has been shown in acute ischemic animal models that segmental IVCT velocities decreased to zero when >20% transmural necrosis was involved in the corresponding segment after staining. The IVCT velocities also correlated better with extent of transmural infarct after reperfusion than segmental peak systolic and early diastolic velocities (122). Thus, the resting segmental IVCT velocity potentially provides a rapid clinical, non-invasive bedside technique of quantifying transmural extent of viable myocardium after reperfusion in acute myocardial infarction.

Strain and strain rate measurements have their technical limitations. Similar to any Doppler techniques, they are highly dependent on angle of insonation. Every effort is made to ensure the tissue direction is less than 30o from the beam direction but this is technically challenging in the apical segments as the angle becomes wider. The narrow sector angle approach on individual wall obviates some of the above problem. But it lacks of concurrent comparison of regional wall motion with contralateral segments. Like myocardial Doppler velocities, strain is markedly load-dependent (53).

4. FUTURE DIRECTIONS

References

1.    American heart Association. 1999 Heart and Stroke Statistical Update. 
       Dallas, Tex.:  American heart Association, 1998.

2.   Quinones MA, Verani MS, Haichin RM, Mahmarian JJ, Suarez J, Zoghbi WA. 
      Exercise echocardiography versus 201Tl single-photon emission computed 
      tomography in evaluation of coronary artery disease. Analysis of 292 patients. 
      Circulation 1992;85:1026 –1031.

3.   Fleischmann KE, Hunink MG, Kuntz KM, Douglas PS. 
      Exercise echocardiography or exercise SPECT imaging?
      A meta-analysis of diagnostic test performance, JAMA 1998;280:913–920.

4.   Geleijnse ML, Fioretti PM, Roelandt JR. 
      Methodology, feasibility, safety and diagnostic accuracy of dobutamine stress 
      echocardiography. J Am Coll Cardiol 1997;30:595– 606.

5.   Hoffman R, Lethen H, Marwick T, Arnese M, Fioretti P, Pingitore A, Picano E, 
      Buck T, Erbel R, Flachskampf FA, Hanrath P. Analysis of interinstitutional 
      observer agrement in interpretation of dobutamine stress echocardiograms.
      J Am Coll Cardiol 1996;27:330 –336.

6.    Picano E, Lattanzi F, Orlandini A, Marini C, L’Abbate A. 
       Stress echocardiography and the human factor: the importance of being expert. 
       J Am Coll Cardiol 1991;17:666–669.

7.    Bach DS, Muller DW, Gros BJ, Armstrong WF.
       False positive dobutamine stress echocardiograms:
       characterization of clinical, echocardiographic and angiographic findings. 
       J Am Coll Cardiol 1994;24:928 – 933.

8.    Isaaz K, Thompson A, Ethevenot G, Cloez JL, Brembilla B, Pernot C.
       Doppler echocardiographic measurement of low velocity motion of 
       the left ventricular posterior wall. Am Cardiol 1989;64:66-75.

9.    Sutherland GR, Stewart MJ, Groundstroem WE, Moran CM, Fleming A,
       Guell-Peris FJ, Riemersma RA, Fenn LN, Fox KA, McDicken WN. 
       Color Doppler myocardial imaging: a new technique for the assessment
       of myocardial function. J Am Soc Echocardiogr 1994;7:441- 458.

10.  Yamazaki N, Mine Y, Sano A, Hirama M, Miyatake K, Yamagishi M,Tanaka N.
       Analysis of ventricular wall motion using color-coded tissue Doppler
       imaging system. 
       Jpn J Appl Phys 1994;33:3141–3146.

11.  Miyatake K, Yamagishi M, Tanaka N, Uematsu M, Yamazaki N, Mine Y,
       Sano A, Hirama M. New method of evaluating left ventricular wall motion by 
       color-coded tissue Doppler imaging: in vitro and in vivo studies. 
       J Am Coll Cardiol 1995;25:717–724.

12.  Fleming AD, McDicken WN, Sutherland GR, Hoskins PR. 
       Assessment of colour Doppler tissue imaging using test phantoms.
       Ultrasound Med Biol 1994;20:937-951.

13.  Fleming AD, Palka P, McDicken WN, Fenn LN, Sutherland GR.
       Verification of cardiac Doppler tissue images using grey-scale m-mode images.
       Ultrasound Med Biol 1996;22 5 :573-581.

14.  Palka P, Lange A, Fleming AD, Sutherland GR, Fenn LN, McDicken WN. 
       Doppler tissue imaging: myocardial wall motion velocities in normal subjects.
       J Am Soc Echocardiogr 1995;8:659-668.

15.  Donovan CL, Armstrong WF, Bach DS. 
       Quantitative Doppler tissue imaging of the left ventricular myocardium: 
       validation in normal subjects. Am Heart J 1995;130:100- 104.

16.  Garcia MJ, Rodriguez L, Ares M, Griffin BP, Klein AL, Stewart WJ, Thomas JD.
       Myocardial wall velocity assessment by pulsed Doppler tissue imaging: 
       Characteristic findings in normal subjects. Am Hear J 1996;132:648-656.

17.  Ramdas GP, Kanwaljit SG. Amplitudes, durations, and timings 
       of apically directed left ventricular myocardial velocities:
       I. Their normal pattern and coupling to ventricular filling and ejection. 
       J Am Soc Echocardiogr 1998;11:105-111.

18.  Bach DS. Quantitative Doppler tissue imaging as a correlate of left ventricular
       contractility. Int J Cardiac Imaging. 1996; 12:191–195.

19.  Pellerin D, Cohen L, Larrazet F, Pajany F, Witchitz S, Veyrat C.
       Preejectional Left Ventricular Wall Motion in Normal Subjects 
       Using Doppler Tissue Imaging and Correlation With Ejection Fraction.
       Am J Cardiol 1997;80:601–607.

20.  Rodriguez L, Garcia M, Ares M, Griffin BP, Nakatani S, Thomas JD. 
       Assessment of mitral annular dynamics during diastole by Doppler tissue imaging:
       comparison with mitral Doppler inflow in subjects without heart disease and 
       in patients with left ventricular hypertrophy. Am J Heart 1996;131:982-987.

21.  Oki T, Tabata T, Yamada H, Wakatsuki T, Shinohara H, Nishikado A, Luchi A, 
       Fukuda N, Ito S.
       Clinical application of pulsed Doppler tissue imaging for assessing abnormal left 
       ventricular relaxation.
       Am J Cardiol 1997;79:921-928.

22.  Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS,
       Seo JD, Lee YW.
       Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation 
       of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474-480.

23.  Ramdas PG, Kanwaljit SG. Amplitudes, durations, and timings of apically directed
       left ventricular myocardial velocities:
       II. Systolic and diastolic asynchrony in patients with left ventricular hypertrophy.
       J Am Soc Echocardiogr 1998; 11:112-118.

24.  Nagueh, SF, Sun H, MD, Kopelen HA, Middleton KJ, Khoury DS.
       Hemodynamic determinants of the mitral annulus diastolic velocities by 
       tissue Doppler. 
       J Am Coll Cardiol

25.  Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA.
       Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular
       relaxation and estimation of filling pressures. 
       J Am Coll Cardiol 1997;30:1527-1533.

26.  Nagueh SF, Kopelen HA, Quinones MA.
       Doppler estimation of left ventricular filling pressure in atrial fibrillation.
       Circulation. 1996;94: 2138–2145.

27.  Nagueh SF, Mikati I, Kopelen HA, Middleton KJ, Quinones MA, Zoghbi WA 
       Doppler Estimation of Left Ventricular Filling Pressure in Sinus Tachycardia.
       A New Application of Tissue Doppler Imaging. Circulation 1998;98:1644-1650.

28.  Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH, Zoghbi WA, Quinones MA.
       Doppler estimation of left ventricular filling pressures in patients with hypertrophic
       cardiomyopathy. 
       Circulation. 1999;99:254 –261.

29.  Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ.
       Clinical utility of Doppler echocardiography and tissue Doppler imaging 
       in the estimation of left ventricular filling pressures:
       A comparative simultaneous Doppler-catheterization study. 
       Circulation 2000;102:1788 –1794.

30.  Puleo JA, Aranda JM, Weston MW, Cintron G, French M, Clark L, Fontanet HL.
       Noninvasive detection of allograft rejection in heart transplant recipients by use 
       of Doppler tissue imaging. J Heart Lung Transplant 1998;17:176-184.

31.  Aranda JM Jr, Weston MW, Puleo JA, Fontanet HL. 
       Effect of loading conditions on myocardial relaxation velocities determined
       by Doppler tissue imaging in heart transplant recipients.
       J Heart Lung Transplant 1998;17:693-697.

32.  Mankad S, Murali S, Kormos RL, Mandarino WA, Gorcsan J 3rd.
       Evaluation of the potential role of color- coded tissue Doppler echocardiography
       in the detection of allograft rejection in heart transplant recipients.
       Am Heart J 1999;138:721-730.

33.  Stengel SM, Allemann Y, Zimmerli M, Lipp E, Kucher N,Mohacsi P, Seiler C. 
       Doppler tissue imaging for assessing left ventricular diastolic dysfunction 
       in heart transplant rejection. Heart 2001;86:432-437.

34.  Garcia MG, Rodriguez L, Ares M, Griffin BP, Thomas JD, Klein AL.
       Differentiation of constrictive pericarditis from restrictive cardiomyopathy:
       assessment of left ventricular diastolic velocities in longitudinal axis by
       Doppler tissue imaging. J Am Coll Cardiol. 1996;27:108 –114.

35.Ragopalan N, Garcia M, Ares MA, Murray RD, Klein AL.
     Comparison of Doppler echocardiographic methods to differentiate constrictive
     pericarditis from restrictive cardiomyopathy. J Am Coll Cardiol 1998;31:164A.

36.  Palka P, Lange A, Fleming AD, Donnelly JE, Dutka DP, Starkey IR, 
       Shaw TRD, Sutherland GR, Fox KAA. Differences in myocardial velocity gradient
       measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy,
       athletes and patients with left ventricular hypertrophy due to hypertension.
       J Am Coll Cardiol 1997;30:760-768.

37.  Nagueh S, Bachinski L, Meyer D, Hill R, Zoghbi WA, Tam JW, Quinones MA, 
       Roberts R, Marian AJ. 
       Tissue Doppler imaging consistently detects myocardial abnormalities in patients
       with hypertrophic cardiomyopathy and provides a novel means for an early 
       diagnosis before and independently of hypertrophy.
       Circulation. 2001;104:128 –130.

38.  Palka P, Lange A, Fleming AD, Fenn LN, Bouki KP, Shaw TR, Fox KA, 
       McDicken WN, Sutherland GR. Age-related transmural peak mean velocities and
       peak velocity gradients by Doppler myocardial imaging in normal subjects. 
       Eur Heart J 1996;17:940 –950.

39.  Uematsu M, Miyatake K, Tanaka N, Matsuda H, Sano A, Yamazaki N, Hirama M,
       Yamagishi M. Myocardial velocity gradient as a new indicator of regional left
       ventricular contraction: detection by a twodimensional tissue Doppler imaging 
       technique.
       J Am Coll Cardiol 1995;26: 217–223.

40.  Mirsky I, Parmley WW. Assessment of passive elastic stiffness for isolated 
       heart muscle and the intact heart. Circ Res 1973;33:233-243.

41.  Fenton T, Cherry J, and Klassen G. Transmural myocardial deformation
       in the canine left ventricular wall. Am J Physiol Heart Circ 
       Physiol 1978;235:H523–H530.

42.  Waldman L, Fung Y, and Covell J. Transmural myocardial deformation
       in the canine left ventricle: normal in vivo threedimensional finite strains. 
       Circ Res 1985;57:152– 163.

43.  Prinzen TT, Arts T, Prinzen FW, Reneman RS. 
       Mapping of epicardial deformation using a video processing technique.
       J Biomech 1986;19:263-273.

44.  Prinzen FW, Arts T, van der Vusse GJ, Reneman RS. 
       Fiber shortening in the inner layers of the left ventricular wall as assessed 
       from epicardial deformation during normoxia and ischemia. 
       J Biomech 1984;17:801-811. 

45.  Freeman GL, LeWinter MM, Engler RL, and Covell JW.
       Relationship between myocardial fiber direction and segment shortening 
       in the midwall of the canine left ventricle. Circ Res 1985;56:31–39. 

46.  Zerhouni E, Parish D, Rogers W, Yang A, and Shapiro E. 
       Human heart: tagging with MR imaging–a method for noninvasive assessment of
       myocardial motion. 
       Radiology 1988;169:59–63. 

47.  Axel L and Dougherty L. MR imaging of motion with spatial modulation of
       magnetization.
       Radiology 1989;171:841–845.

48.  Axel L, Goncalves R, and Bloomgarden D. Regional heart wall motion: 
       two-dimensional analysis and functional imaging with MR imaging. 
       Radiology 1992;183: 745–750.

49.  Guth B, Savage R, White F, Hagan A, Samtoy L, Bloor C.
       Detection of ischemic wall dysfunction: Comparison between M-mode
       echocardiography and sonomicrometry. Am Heart J 1984;107:449–457.

50. Shapiro E, Marier DL, Sutton MGStJ, Gibson DG.
      Regional nonuniformity of wall dynamics in normal ventricle. 
      Br Heart J 1981; 45:264 –270.

51.  Sutherland GR, Stewart MJ, Groundstroem KW, Moran CM, Fleming A,
       Guell-Peris FJ, Riemersma RA, Fenn LN, Fox KA, McDicken WN. 
       Color Doppler myocardial imaging: 
       a new technique for the assessment of myocardial function.
       J Am Soc Echocardiogr 1994;7:441- 458.

52.  Heimdal A, Stoylen A, Torp H, Skjaerpe T. 
       Real-time strain rate imaging of the left ventricle by ultrasound. 
       J Am Soc Echocardiogr 1998;11:1013–1019.

53.  Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA.
       Myocardial strain by Doppler echocardiography.
       Validation of a new method to quantify regional myocardial function. 
       Circulation 2000;102:1158-1164.

54.  Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW. 
       Advantages and applications of the centerline method for characterizing regional
       ventricular function. 
       Circulation 1986;74:293–305.

55.  Lang RM, Vignon P, Weinert L,. 
       Echocardiographic quantification of regional left ventricular wall motion 
       with color kinesis.
       Circulation 1996;93:1877–1885. 

56. Perez JE Waggoner AD, Davila Roman VG, Cardona H, Miller JG. 
     On line quantification of ventricular function during dobutamine stress
     echocardiography.
     Eur Heart J 1992;13:1669 –1676.

57.  Greenbaum RA, Ho SY, Gibson DG, Becker AF, Anderson RH. 
       Left ventricular fibre architecture in man. Br Heart J 1981; 45:248-263.

58.  Hamilton WF, Romf JH. Movements of the base of the ventricle and 
       the relative constancy of the cardiac volume. 
       Am J Physiol 1932;102:559-565.

59.  Dumesnil JG, Shoucri RM, Laurenceau JL, Turcot J. 
       A mathematical model of the dynamic geometry of the intact left ventricle 
       and its application to clinical data. Circulation 1979;59:1024-1034.

60.  Feigenbaum H, Zaky A, Nasser WK. Use of ultrasound to measure left ventricular
       stroke volume .
       Circulation 1967;38:1092-1099.

61.  Simonson J, Schiller NB. Descent of the base of the left ventricle:
       an echocardiographic index of left ventricular function. 
       J Am Soc Echocardiogr 1989;2:25-35.

62.  Jones CJH, Raposo L, Gibson DG.
       Functional importance of the long axis dynamics of the human left ventricle.
       Br Heart J 1990;63:215-220.

63.  Pai RG, Bodenheimer MM, Pai SM, Koss JH, Adamick RD. 
       Usefulness of systolic excursion of the mitral annulus as an index 
       of left ventricular sustolic function. Am J Cardiol 1991;67:222-224.

64.  Alam M, Rosenhamer G. 
       Atrioventricular plane displacement and left ventricular function. 
       J Am Soc Echocardiogr 1992;5:427–433.

65.  Alam M, Hoglund C.
       Serial echocardiographic studies following thrombolytic treatment 
       in myocardial infarction with special reference to the atrioventricular valve
       plane displacement. Clin Cardiol 1992; 15:30-36.

66.  Gulati VK, Katz WE, Follansbee WP, Gorscan J. 
       Mitral annular descent velocity by tissue Doppler echocardiography as an index 
       of global left ventricular function.
       Am J Cardiol 1996;77:979-984.

67.  Willenheimer R, Cline C, Erhardt L, Israelsson B. 
       Left ventricular atrio-ventricular plane displacement: 
       An echocardiographic technique for rapid assessment of prognosis in heart failure.
       Heart 1997; 78:230-236.

68.  Henein MY, O’Sullivan C, Davies SW, Sigwart U, Gibson DG. 
       Effects of acute coronary occlusion and previous ischaemic injury 
       on left ventricular wall motion in humans. Heart 1997;77:338-345.

69.  Henein MY, Priestley K, Davarashvili T, Buller N, Gibson DG.
       Early changes in left ventricular subendocardial function after successful
       coronary angioplasty. 
       Br Heart J 1993;69:501-506.

70.  Henein MY, Anagnostopoulos C, Das SK, O’Sullivan C, Underwood SR, Gibson DG.
       Left ventricular long axis disturbances as predictors for thallium perfusion defects 
       in patients with known peripheral vascular disease. Heart 1998;79:295-300.

71.  Gibson DG, Prewitt TA, Brown DJ. Analysis of left ventricular wall movement
       during isovolumic relaxation and its relation to coronary artery disease. 
       Br Heart J 1976;38: 1010-1019. 

72.  Koh TW, Pepper JR, Gibson DG. Early changes in left ventricular
       anterior wall dynamics and coordination after coronary artery surgery. 
       Heart 1997;78:291-297.,

73.  O’Sullivan CA, Henein MY, Sutton R, Coats AJS, Sutton GC, Gibson DG. 
       Abnormal ventricular activation and repolarization during dobutamine
       stress echocardiography in coronary artery disease. Heart 1998;79:468-473.

74.  Fukuda K, Oki T, Tabata T, Iuchi A, Ito S. Regional left venticular 
       wall motion abnormalities in myocardial infarction and mitral annular 
       descent velocities studied with pulsed tissue Doppler imgaing. 
       J Am Soc Echocardiogr 1998;11:841-848. 11.  Miyatake K, Yamagishi M,

75.  Henein MY, O’Sullivan C, Das SK, Khir A, Anagnostopoulos C, 
       Underwood RS, Gibson DG. Assessment of cardiac risk before peripheral vascular
       surgery:
      a comparison of myocardial perfusion imaging and long axis echocardiography 
      at rest. Int J Cardiol 2001;80:125-132.

76.  Gorcsan J 3rd, Deswal A, Mankad S, Mandarino WA, Mahler CM, Yamazaki N,
       Katz WE. 
       Quantification of the myocardial response to low-dose dobutamine using tissue
       Doppler echocardiographic measures of velocity and velocity gradient. 
       Am J Cardiol 1998;81:615-623.

77.  Ehring T, Heusch G. Left ventricular asynchrony: 
       an indicator of regional myocardial dysfunction.
       Am Heart J 1990;5:1047–1057.

78.  Kvitting JPE, Wigström L, Strotmann JM, Wilkenshoff UM, Kukulski T, 
       Voigt JU, Janerot-Sjöberg B, Von Bibra H, Engvall J, Sutherland GR. 
       The accuracy of visual assessment of synchronicity in myocardial motion:
       an invitro study using computer simulated regional delay in myocardial motion.
       Clinical implication for rest studies and stress echocardiography.
       J Am Soc Echocardiogr 1999;12:698 –705.

79.  Derumeaux G, Ovize M, Loufoua J, Andre-Fouet X, Minaire Y, Cribier A, Letac B.
       Doppler tissue imaging quantitates regional wall motion during myocardial ischemia
       and reperfusion. Circulation 1998;19:1970 – 1977.

80.  Pasquet A, Yamada E, Armstrong G, Beachler L, Marwick TH.
       Influence of dobutamine or exercise stress on the results of pulsed-wave Doppler
       assessment of myocardial velocity. 
       Am Heart J 1999;138:753–758.

81.  Gorcsan J, Strum DP, Mandarino WA, Gulati VK, Pinsky MR.
       Quantitative assessment of alterations in regional left ventricular contractility 
       by color-coded tissue Doppler echocardiography:
       comparison with sonomicrometry and pressure-volume relations.
       Circulation 1997;95:2423- 2433.

82.  Bach DS, Armstrong WF, Donovan CL, Muller DWM. 
       Quantitative Doppler tissue imaging for assessment of myocardial velocities
       during transient ischemia and reperfusion. Am Heart J 1996;132:721–725.

83.  Katz WE, Gulati VK, Mahler CM, Gorcsan J III. 
       Quantitative evaluation of the segmental left ventricular response to dobutamine
       stress by tissue Doppler echocardiography. Am J Cardiol 1997;79:1036 –1042.

84.  Wilkenshoff UM, Sovany A, Wigstrom L, Olstad B, Lindstrom L,
       Engvall J, Janerot-Sjoberg B, Wranne B, Hatle L, Sutherland GR.
       Regional mean systolic myocardial velocity estimation 
       by real-time color Doppler myocardial imaging: 
       a new technique for quantifying regional systolic function. 
       J Am Soc Echocardiogr 1998;11:683– 692.

85.  Yamada E, Garcia M, Thomas JD, Marwick TH. 
       Myocardial Doppler velocity imaging – a quantitative technique for interpretation 
       of dobutamine echocardiography. Am J Cardiol 1998;82:806–809. 

86.  Pasquet A, Armstrong G, Beachler L, Lauer MS, Marwick TH.
       Use of segmental tissue Doppler velocity to quantitate exercise echocardiography.
       J Am Soc Echocardiogr 1999;12:901–912.

87.  Pasquet A, Armstrong G, Rimmerman C, Marwick TH.
       Myocardial Doppler velocity response to exercise correlates with independent
       evidence of ischemia by dual isotope SPECT.
       Am J Cardiol 2000;85;536 –542.

88.  Cain P, Baglin T, Case C, Spicer D, Short L, Marwick TH.
        Application of tissue Doppler to interpretation of dobutamine echocardiography:
        comparison with quantitative coronary angiography. Am J Cardiol 2001;87:525–531.

89.  Fathi R, Cain P, Nakatani S, Yu HCM, Marwick TH. 
       Effect of tissue doppler on the accuracy of novice and expert interpreters of
       dobutamine echocardiography Am J Cardiol 2001;88:400–405.

90.  Fraser A, Payne N, Grocott-Mason R, et al.
       Could stress echocardiography with off-line tissue Doppler quantification
       of long-axis function be used to diagnose ischaemia? 
       Eur J Echocardiogr 1999;1(suppl):S48.

91.  Grocott-Mason R, Payne N, Wilkenshoff U, et al. 
       Can off-line tissue Doppler echocardiography make dobutamine stress
       echocardiography objective? Eur Heart J 1999;20(suppl):687.

92.  Rambaldi R, Poldermans D, Bax JJ, Boersma E, Elhendy A, Vletter W,
       Roelandt JR, Valkema R. Doppler tissue velocity sampling improves diagnostic
       accuracy during dobutamine stress echocardiography 
       for the assessment of viable myocardium in patients with severe left 
       ventricular dysfunction. Eur Heart J 2000;21:1091–1098.

93.  Kowalski M, Kukulski T, Jamal F, D’hooge J, Weidemann F, Rademakers F, 
       Bijnens B, Hatle L, Sutherland GR. Can natural strain and strain rate quantify 
       regional myocardial deformation? A study in healthy subjects.
       Ultrasound Med Biol 2001;27:1087-1097.

94.  Støylen A, Heimdal A, Bjornstad K, Torp HG, Skjaerpe T. 
       Strain rate imaging by ultrasound in the diagnosis of regional dysfunction
       of the left ventricle. Echocardiography 1999;16:321-329.

95.  Støylen A, Heimdal A, Bjørnstad K, Wiseth R, Vik-Mo H, Torp H, Angelsen B, 
       Skjaerpe T. 
       Strain rate imaging by ultrasonography in the diagnosis of coronary artery disease.
       J Am Soc Echocardiogr 2000;13:1053-1064.

96.  Voigt JU, Arnold MF, Karlsson M, Hubbert L, Kukulski T, Hatle L, Sutherland GR.
       Assessment of regional longitudinal myocardial strain rate derived from
      Doppler myocardial imaging indexes in normal and infarcted myocardium 
      J Am Soc Echocardiogr 2000;13:588–598.

97.  Edvardsen T, Skulstad H, Aakhus S, Urheim S, Ihlen H. 
       Regional myocardial systolic function during acute myocardial ischemia 
       assessed by strain Doppler  echocardiography. J Am Coll Cardiol 2001;37:726-730.

98.  Armstrong G, Pasquet A, Fukamachi K, Cardon L, Olstad B, Marwick T.
       Use of peak systolic strain as an index of regional left ventricular function:
       comparison with tissue Doppler velocity during dobutamine stress and myocardial
       ischemia. J Am Soc Echocardiogr 2000;13:731-737.

99.  Jamal F, Strotmann J, Weidemann F, Kukulski T, D’hooge J, Bijnens B, 
       Van de Werf F, De Scheerder I, Sutherland GR. Noninvasive quantification 
       of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain.
       Circulation 2001;104:1059-1065.

100.  Greenberg NL, Firstenberg MS, Castro PL, Main M, Travaglini A, 
         Odabashian JA, Drinko JK, Rodriguez LL, Thomas JD, Garcia MJ. 
         Doppler-derived myocardial systolic strain rate is a strong index of left ventricular
         contractility. 
         Circulation 2002;105:99-105.

101.  Hoffmann R, Altiok E, Nowak B, Heussen N, Kühl H, Kaiser H-J, Büll U,
         Hanrath P. 
         Strain rate measurement by doppler echocardiography allows improved 
         assessment of myocardial viability inpatients with depressed left ventricular function.
         J Am Coll Cardiol 2002;39:443–449.

102.  Uematsu M, Nakatani S, Yamagishi M, Matsuda H, Miyatake K. 
         Usefulness of myocardial velocity gradient derived from two-dimensional
         tissue Doppler imaging as an indicator of regional myocardial contraction 
         independent of translational motion assessed in atrial septal defect. 
         Am J Cardiol 1997;79:237–241.

103.  Garot J, Derumeaux GA, Monin JL, Duval-Moulin AM, Simon M, Pascal D,
         Castaigne A, Dubois-Rande JL, Diebold B, Gueret P. 
         Quantitative systolic and diastolic transmyocardial velocity gradients assessed
         by M-mode colour Doppler tissue imaging as reliable indicators of regional left
         ventricular function after acute myocardial infarction.
         Eur Heart J 1999;20:593– 603.

104.  Tsutsui H, Uematsu M, Shimizu H, Yamagishi M, Tanaka N, Matsuda 
         H, Miyatake K. Comparative usefulness of myocardial velocity gradient 
         in detecting ischemic myocardium by a dobutamine challenge. 
        J Am Coll Cardiol 1998;31:89–93.

105.  Larrazet F, Pellerin D, Prigent A, Daou D, Cohen L, Veyrat C.
         Quantitative analysis of hibernating myocardium by dobutamine tissue 
         Doppler echocardiography. Am J Cardiol 2001;88:418-422.

106.  Edvardsen T, Urheim S, Skulstad H, Ihlen H, Smiseth OA.
         Identification of dyskinetic myocardium by Doppler tissue 
         imaging - The importance of isvolumic phase analysis. 
         Circulation 2001;104 (Suppl II):2697.

107.  Gibson DG, Prewitt TA, Brown DJ. Analysis of left ventricular wall movement 
         during isovolumic relaxation and its relation to coronary artery disease. 
         Br Heart J 1976;38: 1010-1019.

108.  Grines CL, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF.
         Functional abnormalities in isolated left bundle branch block: the effect 
         of interventricular asynchrony. Circulation 1989;79:845–853

109.  Henein MY, Rosano GMC, Underwood R, Poole-Wilson PA, Gibson DG.
         Relations between resting ventricular long axis function, the electrocardiogram, 
         and myocardial perfusion imaging in syndrome X. Br Heart J 1994;71:541–547.

110.  Bonow RO, Vitale DF, Maron BJ, Bacharach SL, Frederick TM, Green MV.
         Regional left ventricular asynchrony and impaired global left ventricular filling 
         in hypertrophic cardiomyopathy: effect of verapamil.
         J Am Coll Cardiol 1987;9:1108– 1116.

111.  Villari B, Vassalli G, Betocchi S, Briguori C, Chiariello M, Hess OM. 
         Normalization of left ventricular nonuniformity late after valve replacement
         for aortic stenosis.
         Am J Cardiol 1996;78:66 –71.

112.  Gibson D, Mehmel H, Schwarz F, Li K, Kubler W. 
         Changes in left ventricular regional asynchrony after intracoronary thrombolysis
         in patients with impending myocardial infarction. Br Heart J 1986;56:121-130.

113.  Brown MA, Norris RM, Takayama M, White HD. 
         Post- systolic shortening: a marker of potential for early recovery 
         of acutely ischaemic myocardium in the dog. Cardiovasc Res 1987;21:703–716.

114. akayama M, Norris RM, Brown MA, Armiger LC, Rivers JT, White HD.
        Postsystolic shortening of acutely ischemic canine myocardium predicts early
        and late recovery of function after coronary artery reperfusion.
        Circulation 1988;78:994-1007.

115. Hosokawa H, Sheehan FH, Suzuki T. 
        Measurement of post-systolic shortening to assess viability and predict recovery 
        of left ventricular function after acute myocardial infarction.
        J Am Coll Cardiol 2000; 35:1842–1849.

116. Barletta G, Del Bene R, La Sapio P, Gallini C, Fantini F.
        Postejection thickening as a marker of viable myocardium: 
        an echocardiographic study in patients with chronic coronary artery disease. 
        Basic Res Cardiol 1998;93:313–324.

117. Jamal F, Szilard M, Kukulski T, Liu XS, D’hooge J, Bijnens B, Rademakers F,
        Hatle L, Descheerder I, Sutherland GR. Changes in systolic and postsystolic 
        wall thickening during acute coronary occlusion and reperfusion in closed-chest
        pigs: Implications for the assessment of regional myocardial function. 
        J Am Soc Echocardiogr 2001;14:691-697.

 118. Jamal F,Kukulski T, Strotmann J, Szilard M, D’hooge J, Bijnens B, Rademakers F,
         Hatle L, De Scheerder I, Sutherland GR. Quantification of the spectrum of 
         changes in regional myocardial function during acute ischemia in closed 
         chest pigs: An ultrasonic strain rate and strain study. 
         J Am Soc Echocardiogr 2001;14:874-884.

 119. Pislaru C, Belohlavek M, Bae R, Abraham TP, Greenleaf JF, Seward JB. 
         Regional asynchrony during acute myocardial ischemia quantified by 
         ultrasound strain rate imaging. J Am Coll Cardiol 2001;37:1141–1148.

 120. Belohlavek M, Pislaru C, Bae RY, Greenleaf JF, Seward JB.
         Real-time strain rate echocardiographic imaging: 
         temporal and spatial analysis of postsystolic compression in acutely 
         ischemic myocardium. J Am Soc Echocardiogr 2001;14:360-369.

121. Abraham TP, Belohlavek M, Seward JB, Pellikka P.
        Abnormal regional contraction-relaxation patterns during dobutamine infusion
        predict angiographic coronary artery disease. Circulation 2001;104 (Suppl II):2965.

122. Pislaru C, Bruce CJ, Belohlavek M, Seward JB, Greenleaf JF.
        Intracardiac measurement of pre-ejection myocardial velocities estimates
        the  transmural extent of viable myocardium early after reperfusion in 
        acute myocardial infarction. J Am Coll Cardiol 2001;38:1748 –1756.

Correspondence to: Steve R. Ommen, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Email: ommen.steve@mayo.edu