Download Novel Techniques for Characterizing Myocardial Structure and

Novel echocardiographic techniques for evaluating myocardial structure and function
Aman Mahajan, MD, PhD
Professor and Vice Chair
Chief, Cardiothoracic Anesthesiology
Co-Director, UCLA Cardiac Arrhythmia Center
David Geffen School of Medicine at UCLA
Los Angeles, CA
For decades, B-mode imaging and spectral Doppler analysis were the only methods available
for the quantification of ventricular function. Recently new technologies have become available
that allow for more accurate quantification of global and regional ventricular function: contrast
echocardiography, 3D echocardiography, tissue Doppler imaging, Doppler Strain imaging and
speckle tracking. The high degree of accuracy and reproducibility make all of these techniques
powerful diagnostic tools, but they are at present to slow to be used as intraoperative monitors.
The technology, however, evolves vary rapidly with ever increasing speed and user friendliness,
making all of them good candidates for the intraoperative monitoring of global and regional
ventricular function. The increasing temporal and spatial resolution of cardiac imaging
techniques allows us to examine the myocardial structure almost at the level of the individual
fibers, and has given us new insights in the organization and function of the ventricle.
Left ventricular structure and function
Structural organization of the myocardium: Myocardial muscle fibers are organized in two
counter directional helices with opposite orientation or handedness. From the epicardium
inward, the fibers first have a longitudinal arrangement in a left-handed helix. Fiber orientation
becomes circumferential in the mid wall. And finally, the fibers are arranged longitudinally in a
right-handed helix at the subendocardial level. In a long axis section, the fibers at the base of
the heart can be seen to run cephalad from endo- to epicardial, while the apical fibers have a
caudad orientation. The angle between these fibers and the epicardial plane varies during the
cardiac cycle. In a short axis section, the fibers fan out fan out in their radial course through the
LV wall. As a consequence of the variable orientation of the myofibers, the ultrasound waves
interact with them at different angulations, producing different backscatter intensities. The
resulting speckled pattern of the reconstructed image can be used by speckle tracking software
to analyze displacement and velocities of the myocardium.
Activation and contraction: The insulated Purkinje fibers run from the base of the septum to the
apex of the LV where they transmit the action potential to the subendocardial myocardium in the
apical septal and LV free wall regions. The electrical wave front travels from the endocardium
towards the epicardium along the orientation of the myofibers and from the apex towards the
base, where the subepicardial region of basal posterior wall is the last portion of the LV to
depolarize. Repolarization occurs in a base to apex direction without significant transmural
differences, the apical subepicardium is the last region to repolarize. Contraction of the
subendocardial right handed helix follows the rapid spread of the depolarizing front. The
shortening of the subendocardial layers produces a rapid pressure build-up in the LV and
coincides with the isovolumic contraction (IVC) phase. During this short period, the outer left
handed helix is passively stretched out. The concurrent shortening of the subendocardial
myocardium with the stretching of the subepicardial myocardium during IVC produces a typical
biphasic signal when myocardial velocities and strain rates are measured with ultrasound.
Contraction of the left handed subepicardial helix coincides with the end of IVC and the onset of
ventricular ejection. During the ejection phase, both subendocardial and subepicardial fibers
shorten from apex to base, resulting in a reduction of the size of the LV cavity in all directions.
However, strain or shortening shows transmural and apex-to-base gradients with shortening
being larger in the subendocardium than in the subepicardium and larger in the apical than in
the basal segments. Just before aortic valve closure, the apical subendocardium relaxes with a
subsequent spread for apex to base. Subepicardial relaxation, on the other hand sets of just
after aortic valve closure and spreads form base to apex. The subepicardial apex, thus, is last
to lengthen, and still shows shortening into the isovolumic relaxation (IVR) phase and early
diastolic filling. This phenomenon is likely to represent an active component of ventricular
relaxation, facilitating ventricular expansion and creating ventricular suction in early diastole.
Strain, Strain Rate, Twist and Torsion: Myocardial deformation is quantified by the
dimensionless parameter strain (ε). Strain is the ratio of the change of length to the initial length
of an object that changes size. Imagine a rubber band with length L0 being stretched out to
length L1. The strain is than defined as the ratio of L1 – L0 to L0. Since the rubber band got
stretched out, L1 is larger than L0, and ε is positive; in the event that an object shortens, ε will be
negative. The rate at which the length of the rubber band changes is the strain rate (SR =
Δε/Δt). During systole and diastole, the longitudinal and circumferential shortening or
lengthening are necessarily accompanied by thickening or thinning in the third or radial
dimension. When myocardial strain is plotted against time on a strain curve, myocardial length
and thickness are at baseline at the end of diastole. During systole, longitudinal and
circumferential shortening create negative strain that will reach their minimum negative value
(shortest myocardial length) at peak systole, around aortic valve closure. After the onset of
diastole, early ventricular filling brings the curve back up to a less negative value where it will
plateau during diastase. The atrial contraction completes ventricular filling and brings the strain
curves back to baseline. Strain rates curves contain usually much more noise. In the presence
of dyskinesia, positive longitudinal and circumferential strain values, quantify the lengthening of
the myocardium beyond its end diastolic value. Radial thickening in systole and thinning in
diastole produce similar strain and strain rate curves except for the inversion positive and
negative values. Finally, not only does the left ventricle shorten and thicken during systole, it
also twists around the longitudinal axis. Seen from the apex, the base of the heart turns
clockwise during systole while the apex turns counterclockwise. These opposite movements
create a wringing effect or torsion (like the wringing of a wash cloth), and can be quantified with
some of the new techniques in ultrasound that will be discussed. Twist and untwist are defined
as the number of angular degrees a given point in the myocardium turns during systole and
diastole respectively. Twist is also referred to as rotation. Counterclockwise twist or rotation is
by convention denoted as positive, clockwise twist as negative. Torsion is the gradient between
apex and base, and is calculated as the net difference between basal and apical twists.
Contrast enhanced echocardiography (CEE).
Opacifying the blood volume in the imaging plane, using an ultrasound contrast agent, can
improve the quality of some of the features of the image and moreover, it can generate
information that cannot be obtained from the standard 2D gray scale images. Anesthesiologists
frequently use agitated saline as a contrast agent to opacify the right atrial cavity and assess the
presence of a PFO. By intravenous injection in a vein of the left arm one can detect a persistent
left sided superior vena cava if the coronary sinus opacifies before the right atrium does. The
injection of the saline into the superior vena cava (SVC) produces an intense opacification of the
right sided cavities, but, after passage through the pulmonary vasculature, the density of these
air filled microbubbles is to low to produces the same effect in the left side. In the past few
years, synthetic microspheres have been developed that have a much higher stability; and a
significant portion of the dose will reach the LV. The shells of these microspheres are mostly
made of phospholipids or albumin and they are filled with fluorinated hydrocarbon gases. A
single intravenous injection of only a small dose of these microspheres will produce intense
opacification of the left ventricular cavity. Subsequent passage into the coronary circulation, will
opacify the entire myocardium. The opacification of the ventricular cavity leads to a highly
detailed demarcation of the endocardial border and will consistently improve the sonographer’s
ability to subjectively estimate or measure global ventricular function by visual estimation or
semi quantitative techniques based on endocardial border tracing. Filling of the myocardium will
allow for the detection of filling delays or defects in the presence of coronary artery stenosis.
Assessment of global ventricular function: Opacification of the left ventricular cavity using
contrast consistently results in a superior delineation of the endocardial border in all patients,
but is particularly useful in patients with poor acoustic windows. It can also influence the quality
of the exam by improving image alignment and avoiding off-axis scanning. Compared to
Magnetic Resonance Imaging (MRI) and cineventriculography, 2D CEE using the Simpson’s
method of discs, shows a higher degree of correlation for LV volumes and EF, with significantly
tighter limits of agreement than echo without contrast. Also, CEE is shown to be superior for the
identification of low EF and classification of patients in different EF categories, and shows less
interobserver variability compared to unenhanced echocardiography.
Contrast can be used to identify other pathologies related to ventricular dysfunction, such as the
presence of a ventricular mass or thrombus, or to diagnose LV noncompaction. In TEE, the long
distance between the transducer and the LV apex can impede the clear visualization of an
apical thrombus. When contrast is used, thrombus typically shows up as a non-opacified
structure.
Assessment of regional ventricular function: After a bolus injection or a continuous infusion of
contrast agent the entire myocardium will brighten as the blood volume in the coronary
circulation gets saturated with contrast. Since the coronary vessels only contain 7% of the
cardiac blood, the myocardium will opacify less than the ventricular cavity. Using a high power
ultrasound pulse, all microbubbles will be destroyed, after which the myocardium will again fill
up with contrast-laden blood. Areas distal to a coronary stenoses will show a delay in
replenishment. Areas distal to a coronary obstruction will not opacify and show up as a defect.
The signal intensity can be quantified and displayed in destruction/refilling curves that correlate
closely with coronary blood flow. Real time myocardial CEE accurately estimates the risk area
and infarction area in acute coronary syndromes.
Real-time 3D Echocardiography.
The recent advancements in computational power and miniaturization of ultrasound equipment
have allowed for the development of real-time 3D echocardiography (RT3DE). The matrix array
ultrasound transducer has up to 3000 ultrasound elements that fire non-simultaneously to
reproduce a real time, pyramid shaped, three dimensional image of the interrogated region of
the heart. The size of the imaged volume is, at this time, still not enough to contain the whole
adult LV. Thus, currently a series of 4 or more gated cycles needs to be combined to recreate a
full volume image of the ventricle, resulting in a maximum frame rate of 25 Hz.
Assessment of Global ventricular function: When a full volume 3D image is acquired, only the
outer surface of the pyramid shape is displayed. The image can then be cropped in different
plains to expose the structures within and to evaluate wall motion of the different segments.
Several semi- automated algorithms have been developed to calculate LV volumes. After
identifying several landmarks, the endocardium is traced by an automated endocardial border
detection algorithm, which can be visually inspected and manually corrected if needed. Based
on this data an endocardial cast and its displacement throughout the cardiac cycle is generated
and displayed as the “jelly-bean image”.
Ventricular volumes are numerically and graphically displayed as time-volume curves, and enddiastolic volume (EDV), end-systolic volume (ESV) and EF can be calculated. The accuracy of
the calculated volumes and EF depends on the number of elements in the transducer, the
spatial and temporal resolution of the image, and the accuracy of the endocardial border
delineation. The accuracy and reproducibility of real time 3D echocardiography has been
established in several studies. Global LV volume and EF measurements using RT3DE correlate
highly with cardiac MRI (r = 0.98) with minimal bias (1.4 ml) and narrow limits of agreement (±
20 ml). In fact, the correlation with cardiac MRI is better for RT3DE than for Single Photon
Emission Computed Tomography (SPECT) and cardiac Computed Tomography (CCT), albeit
with higher variability. The limited temporal and spatial resolution of the technology accounts for
some of the reported underestimation and variability of LV volumes by RT3DE.
Never the less, the inter- and intra-observer variability is significantly lower for RT3DE than for
2D echocardiography. Its superiority to 2D echocardiographic imaging is largely due to the fact
that no geometrical assumptions and no extrapolation of the endocardial border for the regions
in between scanning planes are necessary.
Assessment of regional ventricular function: The volume enclosed in the ventricular cavity is
divided in 16 pyramidal segments according to the 16 segment nomenclature. The base of
every pyramid is defined by the endocardial border of the segment and the tip is a point on the
longitudinal axis of the ventricle. The difference between the EDV and the ESV of this pyramid
is defined as the regional EF for the segment. On the computer generated endocardial cast the
16 segments can be displayed in different colors and for every segment a time-volume curve
can be displayed. Automated quantification of regional EF using RT3DE, correlates well with
cardiac MRI derived measurements with r > 0.8 for regional volumes, r = 0.71 for regional EF,
with minimal bias (0.2 ml) and tight limits of agreement (7 ml). Compared to visual assessment
of regional ventricular function, where segmental function was graded as normal or abnormal by
an experienced echocardiographer, RT3DE has a sensitivity of 0.84, a specificity of 0.78, a
positive predictive value of 0.95, a negative predictive value of 0.47 and an accuracy of 0.84.
Finally, regional volumetric RT3DE has been compared to Gated Myocardial Perfusion SPECT
to evaluate intraventricular dyssynchrony of the LV and showed good correlation (r = 0.80) with
excellent interobserver agreement (mean difference of 0.1% for dyssynchrony index and of
0.4% for EF). Real time 3D assessment of ventricular function is still to slow to be of value as
an intraoperative monitor of LV volumes and function. Multiple steps with manual correction of
the tracing of the endocardial borders and adjustments of the orientation of the axes make the
acquisition of the data take to much time for use in the surgical setting. Furthermore the
acquisition of multiple gated images makes the technique prone to artifacts due to movement
and ventilation of the patient and electrical interference. But, this technology has evolved
rapidly; we can expect the scanning angles to become large enough for the whole left ventricle
to be comprised in a single cycle, full volume, loop, and the introduction of more powerful
endocardial border detection algorithms will make this technique a valuable tool for the rapid
evaluation and quantification of global and regional ventricular function.
2D-Speckle Tracking.
The most important limitation of Doppler based techniques for evaluating myocardial
deformation and ventricular function is the angle dependency. Particularly in TEE it can be
impossible to properly align the interrogating sound beam with the region of interest. In 2004 a
new technology named speckle tracking, was introduced that has the great advantage of
measuring tissue velocities and deformation in an angle independent fashion. When an
ultrasound pulse interacts with tissue, the pulse gets distorted in a way that is highly dependent
on the ultrastructure of that tissue. After being received by the transducer, a specific tone in the
grayscale will be attributed to the pixel representing the distorted sound pulse. A group of 20 to
40 pixels, each with their distinct grayscale color, is called a speckle. Within the myocardium,
we can find ultrasound reflectors that will distort the sound wave in a relatively constant way
throughout the cardiac cycle, resulting in a consistent grayscale pattern being attributed to the
same speckle. These myocardial elements are called natural acoustic markers and have a
homogenous distribution throughout the entire myocardium. Using pattern recognition
algorithms, the position of these speckles can be tracked form image to image in a digitally
stored cineloop of a cardiac cycle. The displacement of the speckle in both dimensions of the
2D image can thus be measured throughout diastole and systole. By tracking different speckles
in the same myocardial segment, the distance between the speckles can be measured and
segmental shortening or strain can be calculated. Since the analysis is not based on the
Doppler shift of the reflected sound wave, it is not angle dependent, and it can be performed on
the regular 2D grayscale image as it is stored in digital format. Speckle tracking has, however,
some limitations of its own. Since the software tracks features in the 2D image, the quality of
speckle tracking depends highly on the spatial resolution of the image and on the frame rate of
the cineloop. Myocardial deformation occurs in the three spatial dimensions, resulting in
speckles moving out of the two dimensional scanning plane. The computer compensates for this
out of plane motion by tracking new speckles as they move in while previous ones fade out of
the scanning plane. Low frame rates will lead to undersampling and speckles will move out of
the search area to soon for the computer to compensate. High frame rates will reduce this
problem but may lead to inadequate tracking due to reduced spatial resolution. The optimal
frame rate for adequate speckle tracking seems to be somewhere between 60 and 90 frames
per second, which is considerably lower than Doppler based techniques and may lead to
inadequate detection of short lasting events, e.g. the isovolumetric phases of the cardiac cycle.
The software evaluates the tracking quality using several criteria: The position of the speckles in
the first frame of the loop should coincide with the position of the speckles in the last frame, the
velocity of adjacent speckles should be similar and drift compensation should be low. Based on
these criteria the software will grade the tracking and can accept or reject the result. Visual
control of the process remains necessary to correct misinterpretation of artifacts by the
software.
Assessment of global ventricular function: After manually delineating the endocardial border, the
software automatically divides the LV myocardium into six segments that are color coded and
displays velocity, displacement, strain and strain rate curves for the entire ventricle or for the
individual segments. (Figure 9) The global ventricular strain values, in the longitudinal, radial, or
circumferential dimension, are calculated as an average of all the strains measured over the
entire myocardium in the respective directions. Compared to techniques calculating derived
parameters representing global ventricular function, such as mitral annular velocity, this
technique has the advantage of evaluating the entire visible myocardium in its calculation of
global function. EF calculated using speckle tracking techniques has been shown to correlate
closely with visual estimation and Simpson’s method (r = 0.82) for TTE. And several studies
reported the technique to have low Interobserver and intraobserver variability (8.6 - 11.8% and
5.2 - 8.8% respectively). Global longitudinal strain has been proposed as a new index for left
ventricular systolic function with a high specificity and sensitivity for the diagnosis of myocardial
infarction. Reductions in global longitudinal strain closely correlate to infarct size in chronic
ischemic heart disease. And speckle tracking has been shown to demonstrate early decreases
in global longitudinal, radial and circumferential strain in patients with subclinical hypertrophic
cardiomyopathy.
By tracking angular displacement in the short axis views, speckle tracking allows for the
quantification of ventricular twist and torsion. This unique feature has been used to study
changes in ventricular rotation and rotation rate in the elderly, in patients with essential
hypertension, myocardial ischemia, ventricular hypertrophy, dilated cardiomyopathy, and
chronic mitral regurgitation. In one study, the rate of early diastolic untwist has been shown to
correlate to the degree of diastolic dysfunction as defined by classic echocardiographic
measures.
Assessment of regional ventricular function: Probably the most attractive feature of speckle
tracking is the possibility to assess regional myocardial deformation in an angle independent
manner. This allows for simultaneous qualification and quantification of regional wall motion
abnormalities in all the myocardial segments of the 2D image. Moreover, the timing and duration
of systolic and diastolic events of the different segments can be measured and compared to
assess contraction sequence and intraventricular dyssynchrony. The calculation of regional
myocardial strain and strain rate by speckle tracking has been validated in vitro using ultrasound
phantoms, and in vivo against Doppler tissue imaging, and tagged cardiac MRI. All studies
showed good correlations with low variability.
Speckle tracking correctly identifies infracted segments after induced regional myocardial
ischemia in animal models. In humans, regional reductions in strain correlate well to
angiographic findings of coronay artery disease and speckle tracking can distinguish different
states of transmurality of myocardial infarctions.
Cardiac resynchronization therapy (CRT) has been shown to improve heart failure functional
class, exercise capacity, quality of life and survival in patients with heart failure and
dyssynchrony. Yet, about 25% to 35% percentage of patients do not respond to therapy. Proper
diagnosis and quantification of dyssynchrony by echocardiographic techniques is likely to
improve patient selection for CRT. Speckle tracking offers the possibility to time myocardial
deformation in six segments simultaneously and is used in numerous trials as a tool to diagnose
dyssynchrony and guide CRT. Never the less, because of the much lower temporal resolution
compared to tissue Doppler measurements, speckle tracking may be less adapted to distinguish
events separated by only a few milliseconds. Another limitation is that the regional strain and
strain rates are the mean of all the speckles tracked in one segment. Sub-segmental pathology
will thus not be detected by speckle tracking.
Summary: It is important for the echocardiographer to be familiar with the geometry and
structure of the heart as well as the mechanical sequence of contraction in order to interpret the
data provided by new imaging modalities. This lecture will provide an overview of today’s
concepts of the structure-function relationship of the left ventricle and will introduce new
methodologies of assessing dynamic cardiac function. Further we will discuss the principles,
limitations and validity of these new technologies for the evaluation of global and regional left
ventricular function.
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