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Echocardiographic quantification of myocardial function using tissue deformation imaging, a guide to image acquisition and analysis using tissue Doppler and speckle tracking
© Teske et al; licensee BioMed Central Ltd. 2007
Received: 23 July 2007
Accepted: 30 August 2007
Published: 30 August 2007
Recent developments in the field of echocardiography have allowed the cardiologist to objectively quantify regional and global myocardial function. Regional deformation (strain) and deformation rate (strain-rate) can be calculated non-invasively in both the left and right ventricle, providing information on regional (dys-)function in a variety of clinical settings. Although this promising novel technique is increasingly applied in clinical and preclinical research, knowledge about the principles, limitations and technical issues of this technique is mandatory for reliable results and for implementation both in the clinical as well as the scientific field.
In this article, we aim to explain the fundamental concepts and potential clinical applicability of strain and strain-rate for both tissue Doppler imaging (TDI) derived and speckle tracking (2D-strain) derived deformation imaging. In addition, a step-by-step approach to image acquisition and post processing is proposed. Finally, clinical examples of deformation imaging in hypertrophic cardiomyopathy (HCM), cardiac resynchronization therapy (CRT) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are presented.
There is an increasing need for diagnostic modalities able to objectively quantify myocardial function. Quantification of regional myocardial function with ultrasound is challenging on its own. Visual assessment of wall motion and thickening requires extensive training and remains highly subjective. In addition to this visual assessment on 2-dimensional B-mode images and new 3-dimensional recordings, "classic" M-mode echocardiography can be used to evaluate myocardial thickening. Unfortunately, M-mode can only be used in a limited number of segments since it has to be perpendicular to the investigated myocardial segment. New techniques such as anatomical M-mode have partly overcome the problems with insonation angle, at the expense of a reduced temporal resolution. Moreover, this method only provides uni-dimensional semi-quantitative assessment of myocardial thickening/thinning without information on longitudinal or circumferential function. Tissue velocity imaging along the long axis of the ventricle is a commonly used and well validated technique to quantify longitudinal ventricular function. Tissue velocities at the ventricular base represent the integral of myocardial shortening velocity from base to apex and therefore provide information on global, rather than on regional ventricular function.
The additional value of tissue deformation imaging in the field of echocardiography
Unmasking subtle pathology
Early diagnosis coronary artery disease  and cardiomyopathy 
Quantifying myocardial function
Objective assessment of regional function 
Visualizing timing issues
Quantification of timing within a heart cycle 
Detecting subtle changes over time
Therapy evaluation in patient follow-up 
Improving inter/intra observer variability
Increasing accuracy of stress echocardiography 
Following electro-mechanical activation, the myocardium deforms during systole due to sarcomere shortening. This active deformation causes a reduction in intracavitary size, resulting in the ejection of blood from the ventricle. In diastole the original ventricular geometry is restored due to active relaxation and passive filling following atrial contraction. Since myocardial tissue is virtually incompressible, the volume of the ventricular wall remains the same during the cardiac cycle and, thus, deforms in three dimensions. During systole there is three-dimensional deformation which can be expressed in three ventricular coordinates: a longitudinal shortening and a circumferential shortening and a radial thickening.
To optimally assess regional myocardial function, both strain and SR need to be calculated since they provide complementary information: end systolic strain estimates ejection fraction and peak systolic SR is a measure of contractility. By analogy, when driving a car both the total distance of the journey as well as the speed of the car during the journey provide valuable information.
Tissue deformation imaging
Currently there are two different methods to calculate myocardial deformation using ultrasound: tissue Doppler derived strain and two-dimensional strain derived from B-mode images (speckle tracking). These two techniques will be briefly explained in the following section. Notably, differences in software packages may exist between manufacturers . The examples in this review are based on the commercially available software packages from GE Vingmed (GE Vingmed ultrasound, Horten, Norway).
Tissue Doppler strain
From this formula it is also clear that if a myocardial segment is not deforming during systole, for example due to an infarction, there is no difference in velocities and thus a SR of zero, although the segment could show a displacement and velocity due to tethering of a functional neighboring segment. This translated velocity on the non-deforming segment could give the impression of normal function when assessing it by velocity imaging only, but this is unmasked when calculating the regional SR and ε.
TDI is one-dimensional, thus only deformation along the ultrasound beam can be derived from velocity. Therefore, only the longitudinal SR/ε in the apical views and radial SR/ε in the parasternal views can be calculated.
Several studies have established the robustness and potential useful role of this novel echocardiographic technique.
The accuracy of the measurement of velocities has recently been investigated using tissue mimicking gelatin blocks in two commercially available ultrasound systems . This in-vitro study reported a very high degree of accuracy for velocity measurements, although there was a small overestimation of ε and SR. In-vivo invasive studies, using sonomicrometry as a reference method, have confirmed the validity to calculate strain and strain-rate from tissue velocity over a wide range of strains in animal models [6, 7]. Nowadays, the reference method for non-invasive validation in humans is three-dimensional tagged magnetic resonance imaging, which relies on deformation of tag lines to assess strain in 3 dimensions. Doppler derived strain measurements in humans, both healthy controls and patients with acute myocardial infarction, under different conditions (at rest and during Dobutamine infusion) have proven to be accurate when comparing ultrasound with MRI .
Thus, tissue Doppler imaging is a well validated technique to calculate strain and SR over a wide range of conditions, indicating the feasibility for the usefulness of this technique in the clinical setting.
When evaluating regional myocardial function with tissue Doppler derived SR/ε, knowledge of the limitations of this technique is essential to ensure appropriate acquisition as well as correct post-processing since artifacts often mimic pathology. The most important and common artifacts will be briefly discussed in this section.
Deviation of the insonation angle is another important limitation of the technique. If the ultrasound beam deviates from the direction the investigated myocardial segment moves, the measured velocity (vm) is lower than the actual myocardial velocity. This underestimation is dependent on the angle between the myocardial wall and the ultrasound beam, this implies that vm reduces if the angle increases. Angle correction however, is not an option. As explained earlier, the myocardium deforms in three dimensions, meaning that when measuring longitudinal deformation, one has to keep in mind the simultaneous radial deformation. When the ultrasound beam is parallel to the myocardial wall, the vm is the actual velocity and the vm of the transverse deformation is zero, since the movement is perpendicular to the ultrasound beam. When the angle changes, the contribution of the transverse velocity increases in the vm. For the resulting SR/ε this results in a combination of both a negative (longitudinal) and a positive (transverse) strain, severely disturbing the derived SR/ε patterns. For acceptable calculations, an angle deviation below the 20 to 15 degrees is mandatory.
Image acquisition and post-processing
As pointed out, TDI is a technique which has some limitations inherent to the technique, which could potentially disturb the derived parameters. Optimal image acquisition and knowledge of post-processing techniques are essential to minimize artifacts and, respectively, deal with them in post processing.
The ultrasound investigation starts with an optimal ECG signal with a clear definition of the QRS-complex and P-wave ensuring a consistent ECG-triggering. Pulsed or continuous wave measurements of the valves are needed to incorporate event timing in the off-line measurements. An optimal quality in the 2D gray scale image is mandatory for a high quality tissue Doppler recording. In the following section we present a step-by-step approach for image acquisition.
1) The myocardial wall needs to be optimally visualized with a clear delineation of myocardial tissue and extracardiac structures (e.g. suppression of the blood pool), a minimum of extracardial artifacts should be achieved and the angle of interrogation limited (deviation below 15–20 degrees). The latter is achieved by orienting the transducer parallel or perpendicular to the investigated wall.
2) TDI settings need to be adjusted for optimal post-processing. The velocity scale needs to be adjusted to avoid aliasing. Although a reduction in the velocity scale will result in lower frame rates, the lowest possible velocity scale will result in the highest spatial and temporal resolution combination. Further optimization of the temporal and spatial resolution is achieved by narrowing of the image sector until it is slightly wider than the investigated wall or wall segment. Wall by wall acquisition is essential to achieve adequate frame rates, for reliable SR calculations the optimal sampling rate is >180 frames/sec.
3) Three complete cardiac cycles are recorded digitally during breath hold (to minimize image translation) in the presence of a regular rhythm. This will allow filtering of average noise during post processing without losing resolution.
Longitudinal ε/SR can be derived from the apical three (posterior and anteroseptal wall), two (inferior and anterior wall) and four chamber views (lateral, septal and RV free wall). Radial strain can be derived from the parasternal recordings of the posterior wall. The measurement of septal wall radial strain often produces artifacts due to the morphological and functionally bilayered architecture (LV and RV fibers) of the interventricular septal wall . Circumferential strain can be calculated from the short axis recording (lateral and inferoseptal wall).
Knowledge and experience in the post-processing techniques are important to interpret the ε and SR graphs and to distinguish pathological deformation from artifacts. All commercial software programs are equipped with numerous settings to offer the possibility to optimize the calculations to derive SR from velocity. These settings are available to reduce the 'random-noise' in the SR and ε graphs. With the reduction of noise, the SR and ε graphs are smoothed with the consequence that potentially important temporal or regional information is lost. Therefore, a maximal signal to noise ratio should be achieved with a maximal spatial resolution. Averaging more than one cardiac cycle (reduction of random noise and the beat-to-beat variation), temporal (reducing the effective sampling rate) and spatial averaging and increasing the offset length (changing the Δx in figure 1) are alternative options to reduce noise, although, with careful tracking this is often unnecessary using default settings. Another important setting is the correction for drift in the strain graphs. Assuming that the length of the myocardium returns to its original length at the end of the cycle, the strain value should return to zero. Time integrating the strain-rate can result in drifting of the strain curve. Drift compensation could introduce an error in the strain estimates and should be taken into account when interpreting the strain graphs.
All derived parameters are calculated within a specific region of interest (ROI), therefore the ROI needs to follow myocardial motion during the cardiac cycle. A brief explanation on tracking is described in the following segment.
1) The ROI should be defined; this implies adjustment of both the offset length and ROI size. These parameters can vary and depend on the investigated parameter (radial vs. longitudinal strain) or the clinical question (since small defects appear normal in a large ROI or offset length).
2) The ROI should be placed in the myocardium, typically, three ROI locations are defined in each wall (basal-, mid- and apical segment).
Additional file 1: ROI tracking in tissue Doppler imaging. The ROI is tracked (bottom left) as described in the text in the basal segment of the RV. Note the changes in the strain-graph during the tracking. After careful tracking, the ROI follows the myocardial motion. (AVI 10 MB)
4) Finally the quality of the tracking should be checked. Sub-optimal tracking of the ROI will result in drift in the strain-graphs and in a noisy SR-graph. The ROI position can be corrected after the identification of the noisy frames (to eliminate frame-to-frame artifact or blood-pool noise) which are best identified in the SR graph.
Speckle tracking/two-dimensional strain
Validation of early versions of 2DSE software in a tissue mimicking gelatin block revealed a good correlation compared to sonomicrometry, although values (both strain and strain-rate) were overestimated in the lower range of values . These findings were also found in an animal model (sonomicrometry in pigs with myocardial infarction), where 2DSE was found to slightly overestimate values compared to the reference test. A weaker correlation was found in the lower range of deformation values . Tracking is affected by dyskinetic segments (e.g. ischemia), causing the fiber orientation to change, thus affecting acoustic properties and speckle integrity. Using a new (two-stage) tracking algorithm, a better correlation was found between the 2DSE values and those obtained using sonomicrometry over the entire broad range of tested clinical relevant values . For radial and circumferential parameters, a good correlation was found using sonomicrometry in dogs .
The first study to determine the feasibility and accuracy of 2DSE in patients with myocardial infarction reported that of all segments, 98% in the control population and 80% in the patient group could be analyzed, findings which were reproduced in later studies . Importantly, 2DSE data are highly reproducible and analysis is affected by only small intraobserver (mean 4.4 (SD 1.6)%) and interobserver variability (7.3 (SD 2.5)%) . Values were significantly reduced in the infarcted segments, implying a reduction in systolic deformation. There was no significant difference between TDI and 2DSE parameters . In a direct comparison of TDI and 2DSE with MRI-tagging as a reference, comparable values were found for 2DSE and TDI in both normal and dysfunctional segments. For radial measurements, 2DSE was more reliable than TDI .
At present, the optimal frame rate for speckle tracking seems to be 50–70 frames per second (FPS), which is lower compared to TDI (>180 FPS): this could result in undersampling, especially in patients with tachycardia. Rapid events during the cardiac cycle (e.g. isovolumic phases) may disappear all together, and peak SR and velocity values may be reduced due to under sampling, especially in isovolumic phases and in early diastole. Higher frame rates could reduce the undersampling problem, although this will result in a reduction of spatial resolution and, consequently, less optimal ROI tracking . Low frame rates increase the spatial resolution, but introduce a new problem. Speckle-tracking software uses a frame-by-frame approach to follow the myocardial movement and searches each consecutive frame for a speckle pattern closely resembling and in close proximity to the reference frame. With a too low frame rate the speckle pattern could be outside the search area, again resulting in poor tracking.
Optimal tracking of the ROI is not only dependent on optimal image quality, but also on the implemented tracking algorithm. Software programs designed for speckle tracking are relatively new and are subjected to periodical improvements. Implementation of a new two-stage tracking algorithm (correcting initial 'rough', block matching estimates using optical flow techniques ) has indeed shown to improve tracking quality . However, different tracking algorithms potentially produce different results, therefore it should be kept in mind that a periodical update of the software package conceivably influences reference values.
Image acquisition and post-processing
The same basic principles for image acquisition as mentioned for TDI recordings apply for 2DSE: digitalized recordings of a minimum of one cardiac cycle are made during breath hold (to minimize through plane motion) with a stable ECG recording. Since the angle of interrogation does not influence strain and strain-rate calculations, the transducer can be placed off-axis to obtain the optimal gray scale image. However, misalignment in the third dimension (foreshortening in apical views and oblique transsections in parasternal views) cannot be corrected in post-processing and should be correct. We would like to state that optimal frame rates for 2DSE are still under discussion, but in our own experience: a frame rate of 50–80 FPS seems to result in the optimal tracking quality in the left ventricle long and short axis. For single wall recordings, a frame rate between 70–110 FPS will result in proper tracking .
Visualization of the myocardial wall needs to be optimal, with a clear delineation of myocardial tissue and extracardiac structures and avoidance of drop-out since this will result in unacceptable ROI tracking and drift. The optimal balance between temporal and spatial resolution is achieved when adjusting the image sector slightly wider than the interrogated wall. For small-angle acquisitions this has the advantage that frame-rate can be reduced into the 50–110 FPS range while greatly enhancing the lateral resolution and overall quality of the image. Moreover, near field clutter can be reduced with the implementation of dual-focus imaging when artifacts are prominent. For parasternal recordings (for radial and circumferential function on the short axis) small angle recordings are not possible, all myocardial segments need to be in the image field. For any recording, it should be kept in mind that all myocardial segments need to be visualized optimal, since poor tracking of any segment often affects tracking of the adjacent segments.
Comparable to TDI calculations, careful post-processing is mandatory to obtain reliable regional data, although ROI tracking is less influenced by artifacts and are easier to identify as inappropriate ROI tracking. ROI tracking in 2DSE is discussed in the following section.
1) The ROI is defined by tracing the endocardium in a still frame (default at end systole).
2) The ROI width is set to match the myocardial thickness. An automated software program calculates the frame-to-frame displacements of the speckle-pattern within the ROI throughout the cardiac cycle.
3) The resulting tracking quality is then scored as either acceptable or non-acceptable. Since the program follows any speckle pattern, tracking of a stationary artifact during the cardiac cycle is not uncommon, and often scored as appropriate tracked. Therefore, the tracking has to be visually checked and adjusted if necessary. Even the slightest failure of ROI tracking can result in drifting of the calculated strain curve.
For each myocardial segment, velocity, displacement, strain and SR are calculated in two dimensions: longitudinal and transverse parameters in the apical recordings and circumferential and radial parameters in the parasternal recordings (Figure 10). For the right ventricle, only longitudinal parameters can be reliably calculated due to the thin wall. Additionally, ventricular rotation and rotation-rate are calculated for the short axis recordings. With these parameters, left ventricular torsion can be calculated. Likewise for the TDI parameters, temporal and spatial smoothing can be adjusted.
Comparability between TDI and 2DSE
Both TDI and 2DSE derived parameters are accurate quantitative measures of local longitudinal myocardial deformation, and thus (dys)function and will general yield comparable values for local deformation and deformation rates in both the LV  and the RV . Variability in the measurements and technical factors however, make that minor differences between the calculated parameters should be anticipated when comparing values of TDI and 2DSE in a single patient.
Most of the observed differences between the two techniques are those inherent to the limitations described earlier. For example, TDI is not possible when the investigated wall is not optimally aligned, or in the presence of a stationary artifact, whereas 2DSE is less influence by these interferences. On the other hand, 2DSE has a relative low temporal resolution hindering tracking in the presence of high heart rates where also undersampling becomes an issue , this is not a problem with TDI, where frame-rates are higher (up to 250 FPS).
Feasibility and reproducibility. Feasibility is expressed as a percentage of analyzable segments in the LV [20,29] and RV . Reproducibility is expressed as 95% limits of agreement in the LV  and RV 
-17.1 ; 28.5
-9.2 ; 9.8
-7.5 ; 9.7
-8.6 ; 11.8
-0.76 ; 0.96
-0.91 ; 0.81
-0.77 ; 0.83
-0.79 ; 0.81
-9.4 ; 9.6
-9.3 ; 9.9
-0.16 ; 2.28
-13.1 ; 15.3
-0.42 ; 0.54
-0.85 ; 0.91
-0.54 ; 0.54
-0.73 ; 0.75
Clinical and experimental research on the potential role of deformation imaging in various clinical settings is currently an on going topic. The additional value of deformation imaging in echocardiography has been proposed in various pathological conditions although more research is needed  In addition, tissue deformation imaging has given us recent new insights into ventricular function, adaptation and mal-adaptation in response to pathology. In the following section we present some clinical examples (case reports) of tissue deformation imaging (either TDI or 2DSE) in various cardiac pathology, underlining the additional advantage in the field of echocardiography.
Hypertrophic (obstructive) cardiomyopathy (HCM) is a genetic disorder characterized by hypertrophy of the myocardium. The differentiation of HCM from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is cumbersome. Myocardial disarray is a typical histopathological finding in HCM and provides a substrate for potential lethal ventricular arrhythmias. This disarray also induces functional abnormalities, which could be detected using tissue deformation imaging. A recent article found that this technique reliably distinguishes HCM from H-LVH with a cut-off value for peak systolic strain of -10.6% 
Right ventricular function
Although clinical and preclinical research of left ventricular function is broadly being explored, little is known about normal and pathologic right ventricular (RV) function and there is an urgent need for more insight in RV function by quantitative techniques  In our own experience, the quantification of regional RV function using either 2DSE or TDI is feasible and reproducible  This technique has a potential place in the assessment and follow up of patients with primary (see below) or secondary RV disease such as pulmonary artery disease .
Several new developments are to be expected, not only to improve tracking quality, reduction noise and improve post processing time , but also to make this promising technique more clinically appealing. New automated programs for 2DSE ("automated function imaging"), for instance, allow rapid evaluation of left ventricular deformation in a 17 segment model and visualization of peak systolic strain and post systolic strain index in a bulls-eye figure.
Angle dependency and the impact of artifacts in TDI derived parameters and the low temporal resolution in 2DSE are important limiting factors in the technology. A combination of the two techniques (high quality, angle independent gray scale data and Doppler data with high temporal resolution) could enhance the robustness of the technique and reduce the post-processing time.
MRI-tagging is a technique to calculate deformation in three dimensions. As explained earlier, new echocardiographic techniques have "upgraded" the one-dimensional tissue Doppler to 2DSE. A next step in development is the calculation of strain in three dimensions. With the recent advances in three-dimension echocardiography, this could be possible in the near future. Currently, the low temporal resolution is a severe limitation which has to be overcome before accurate calculations of deformation parameters are feasible.
Tissue deformation imaging is a rapidly evolving technique able to objectively evaluate regional myocardial function. In this review we aimed to give insight into the basic concepts, image acquisition, data analysis and potential clinical applications. Although this quantification provides both the clinician as well as the researcher with detailed information on the myocardial function during the cardiac cycle, it should be kept in mind that, like all ultrasound techniques, image acquisition and quality remain a limiting factor. Although tissue deformation imaging is a promising technique, knowledge of image acquisition, post processing techniques and interpretation of strain and strain-rate graphs are essential to reliably differentiate myocardial pathology from artifacts both in the clinical setting, and for reliable and reproducible research. Its limitations notwithstanding, tissue deformation imaging is an accurate and robust techniques that may successfully fulfill the need for quantitative assessment of myocardial function. The application of this technique in the clinical setting is currently not routine, but the potential of tissue deformation imaging and the need for quantitative measurements of ventricular function should promote its introduction in various clinical settings in the near future.
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