This is explained in more detail
here. The velocity gradient and SR are
equal to the Eulerian strain rate, which normalises the velocity
difference to the instantaneous length, while it is customary to use
the Lagrangian strain, which normalises the change of length to the
initial length,which is explained in more detail
here.
The difference in shape between strain
rate and velocity curves
It is obvious that strain rate and velocity curves are different. Apart
from being inverted, which is due to the
subtraction
algorithm, the systolic strain rate curves are much more rounded,
while velocity curves show a sharper peak. If strain rate is equal to
normalised velocity, why is the shape different as illustrated below?
Above left velocity curves. It
can be
seen that the two velocity curves have an early maximum, showing that
the myocardial acceleration occurs early, and is an early event. Above
right,
the strain rate curve from the segment between the two ROI's in the
left picture. It can be seen that peak strain rate is a much later
event. This is due to the fact that the velocity difference is
normalised for the instantaneous distance (although indirectly, see below), i.e. Eulerian strain rate.
This can be demonstrated by the simulation in the lower row. Left: two
systolic velocity curves with velocities somewhat arbitrarily chosen,
but within normal range, and with a fairly normal shape. The
values on the cyan curve is two thirds of the red one, and both have
peak velocity at 0.05 sec. Left: strain rate curves calculated
from the velocity curves on the right side. Assuming an initial
distance between the points of the two velocity curves of 2.5 cm, again
a realistic distance for the velocity difference. Lagrangian
strain (yellow) is derived by dividing the velocity difference at each
time point by the initial distance. This results in a simple
inversion of the velocity difference, in a different scale, and with
minimum value (maximum absolute) at 0.05 sec. Eulerian strain (green
curve) is obtained by dividing with a strain length that decreases by
the time interval times the velocity difference. In this case the
differences between the curves is evident, and the minimum value (maximum absolute) is reached at 0.25
seconds.
This is due to the difference between Lagrangian and Eulerian strain
rate, which is explained
here.
As we use Lagrangian strain, this is displacement normalised for end
diastolic length. However, it has become customary to use Eulerian
strain, which is a normalization for instantaneous length. This means
that as velocities increase, the length decreases, (or, in
reality, the absolute velocity difference increases relatively), thus
blunting the absolute increase in the velocity difference (i.e. the
decrease in the negative difference) in the first incremental phase,
while the phase where velocities are relatively constant, strain rate
will continue to increase as the strain length decreases. Thus, peak
strain rate is a later
event than peak velocity, which means that it
may be more load
dependent than peak systolic velocity. In addition to giving a higher
and later value for peak strain, it will have consequences in resulting
in a higher peak strain value as shown below.
Strain measured by integration
of the strain rate curves in the figure above. It is evident
that the total systolic strain is about 6% higher (absolute values) by
Eulerian strain rate.
Strain rate by linear regression
Instead of measuring just the velocities at the ends of the offset
distance;

or

respectively, the velocity gradient /
strain rate can be calculated as the slope of the regression line of
all velocities along the offset distance as described originally (
14). With perfect data, the values will
be identical, both formulas defining the slope. With imperfect data,
this method will tend to make the method less sensitive to errors in
velocity measurements, as the value is an average of more measurements.

Fig.
15. Strain rate calculated over an
offset (strain length) of 12 mm (L). "True" strain rate at
the
end points are v1 = 0 and v2 = 1.2 cm s-1 giving a strain
rate of -1.0 s-1 (blue squares), the strain rate is actually
the slope of the line between the points, being equal to (v2 - v1)/L.
Due to random variability of the measurements, the measured values
deviate from the slope. Here velocities are sampled for each 0.5 mm
along the strain length (red points), and are seen to be dispersed
around the true strain rate line. The regression line through the
points (red line) is fairly close to the true strain line, and results
in a strain rate measurement of -1.14 s-1.
This makes the measurement far less vulnerable to measurement
variability than simply measuring the two velocities at the end of the
strain length (points in the green open squares), and compute SR = (v2
- v1)/L shown by the green line, yielding a strain rate of -1.63 s-1.

Fig. 16a. In short axis view,
the septum and inferior wall can be imagined in cross section. Here
displacement and velocity can be measured across the wall, meaning that
deformation imaging with tissue Doppler can be done in only those two
areas in real time.
|

Fig. 16b. Wall thickening .
The relatively constant outer contour and inward moving endocardium,
shows clearly a displacement gradient (strain) and hence, a velocity
gradient across the wall.
|
In the transmural direction, strain and strain rate can be measured
where the ultrasound beam crosses the wall at an angle. This means in
the septum and inferior wall, just as the M-mode. As the outer contour
of the left ventricle is relatively stationary, while the endocardium
moves inwardly, there is a
gradient of
displacement and velocity across the wall.
Thus, the concepts transmural
displacement and transmural velocity are in reality meaningless in a
physiological sense. The displacement and velocity in the transmural
direction is dependent on where across the wall it is measured, i.e.
the transmural depth of the ROI placement. Different data sets from
tissue Doppler in
the transmural direction is thus not comparable, and the measurements
have
little clinical value. Some applications like
2D
strain will give the segmental average value for transmural
velocity and displacement. They may have a clinical meaning, in that
they may separate normal from reduced function, but the use of clinical
measurements that are physiologically unsound, is doubtful.
The velocity gradient can be
measured by the strain rate imaging method, which is quicker than
tracing the endo- and epicardial borders. Measuring the transmural
systolic strain by integrating strain rate, however,
is a roundabout way of
arriving at the relative wall thickening, which can be measured
with
equal temporal resolution and much higher reliability with M-mode. In
addition, anatomical M-mode can imagine wall thickening in other
directions as well, although with only 2D grey scale frame rate.
Segmental strain rate.
Instead of calculating strain rate along one ultrasound beam as shown
in figs 10 a and b, it has been proposed (44) to calculate strain rate
from the velocity differences at the segmental interfaces and segment
length along the wall. (Any points will do actually), as shown in fig.
10c.
Fig.
17. Segmental strain rate, measured by tissue
Doppler, but by
segmental velocities that do not lie on one ultrasound beam, while
strain length is measured along the wall, between the velocity
points.
The advantage of this is that there may be less
insonation angle dependency. The
disadvantage is that this method will give slightly different values.
This is due to the fact that the velocities will not be parallel to the
segments,
so there is a smaller, but less variable insonation angle error.
Thus findings will not be directly comparable to existing reference
values, and it will be more sensitive to errors in velocity
measurement than a regression along the ultrasound line.
Strain rate by speckle tracking in grey scale
images.
The basic principle of speckle tracking is based on the interference of
the reflected ultrasound giving rise to an irregular - random -
speckled
pattern. The random distribution of the
speckles ensures that each
region of the myocardium has an unique pattern, a
fingerprint (fig. 18a). The speckles follow the motion of the
myocardium so when the
myocardium moves from one frame to the next, the position of this
fingerprint will shift slightly, remaining fairly constant (fig 18b).
Thus, if a region (kernel) is defined in one frame, a search algorithm
will be able to recognise the lie sized and -shaped area with the most
similar speckle pattern in the next frame, within a defined search area
(fig. 18c), and hence, to
find the new position of the kernel (
26).
This has
been shown to be feasible in flow (
94)
and strain rate imaging (
95).
The basics of speckle formation and speckle tracking is given in more
details
here.

|

|
|
| Fig 18 a. Typical
speckle pattern in
the myocardium. The two
enlarged areas show completely different speckle patterns, which is due
to the randomness of the interference. This creates an unique pattern
for any selected region that can identify this region and hence, the
displacement of the region in the next frame. |
b. When the speckle pattern is
followed by an M-mode in
the wall, the alternating bright and dark points are seen as
alternating bright and dark lines. The lines remaining to a large
degree unbroken, shows the pattern to be relatively stable, the
speckles moving along with the true myocardial motion, and thus
myocardial motion can be tracked by the speckles. |
Fig c. Speckle
tracking. Defining a kernel in the myocardium will
define a speckle pattern within (red). Within a defined search area (
blue), the new
position of
the kernel in the next frame (green) can be recognised by finding the
same speckle pattern
in a new position. The movement of
the kernel (thick blue arrow) can then be
measured. |
In principle,
pure speckle tracking is direction independent,
and can track crosswise. However, lateral resolution is important in
delineating the speckles in the lateral direction. If the lateral
resolution is low, the
interpolation will result in a "smeared" picture, with speckles that
are
nor so easily tracked in the lateral direction. In addition the
lateral resolution decreases in depth with sector probes.
However, the speckle
pattern will not repeat perfectly. This is due to both true out of
plane motion (rotation and torsion relative to apical planes and
longitudinal deformation relative to short axis planes) and to small
changes in the interference pattern. But the frame
to frame change is small, and the approach to recognition is
statistical, the basic algorithms are shown
here. This means, however,
that the with lower frame rate, the changes from frame to frame are
greater, resulting in poorer tracking.
 |
 |
| Fig. 19a. The resulting tracking of
the kernels shown in motion. As can
be seen, with a drop out apicolateral, this ROI tracks less than
perfect, giving too low strain both in LA and MA segments. |
b. Speckle
tracking can be applied crosswise. In this parasternal long axis view,
the myocardial motion is tracked both in axial and transverse
(longitudinal) direction. It is evident that the tracking is far poorer
in the inferior wall, due to the poor lateral resolution at greater
depth. |
Motion of one kernel can thus be measured throughout one heart cycle.
Velocity can be derived from the motion curve or calculated by the
motion divided by the frame interval (fig 20a). With two kernels, the
relative displacement per distance can be derived. This is equal to
strain (fig. 20b). Likewise the relative velocity per distance
(velocity gradient / strain rate) can be calculated or derived from the
strain curve.
Strain by speckle tracking has been validated experimentally by
ultrasonomicrometry (
124,
125).
One way of using this approach, is to place
defined ROI in the
myocardium at the segmental borders and measure
segmental
strain and strain rate directly by changes in
segment length. This is true segmental strain rate, and angle
independent measures, eliminating the
insonation angle problems
discussed elsewhere..

20a. Kernel
displacement Displacement curve obtained by tracking through a
whole heart cycle shown to the right, derived velocity curve shown
below.
|

b. From two different kernels, the
relative displacement and hence, strain as well as strain rate can be
derived.
|

c. With kernels
at
all segmental borders, segmental motion and deformation can be tracked,
as shown in b.
|
The application also uses automatic segmentation, reducing the
variability compared to manual placement of the ROI.
The advantage of this method is that it tracks in two
dimensions, along
the direction of the wall, not
along the ultrasound beam, and thus is angle independent. This means
true longitudinal strain. The disadvantage is that
if the algorithm does not track one kernel correctly, the strain values
will be wrong for the segments on both sides of the kernel. This is
evident in areas of drop outs or reverberations as shown
here. This can be
overcome by increasing the number of kernels, or manually avoiding
placing a kernel in an area of drop out or reverberation.
It is important to be aware that strain measured by speckle
tracking is
Lagrangian
strain directly. Derivation yields Lagrangian strain rate, while
tissue Doppler yields Eulerian strain rate. Commercially, it has been
customary to display the Eulerian or natural strain rate (
velocity gradient) derived directly from tissue
velocity data, but to apply a
correction
when integrating to strain rate and display Lagrangian strain. For
Strain rate from speckle tracking, a reverse correction has to be
applied, either calculating velocity from displacement and then strain
rate from velocity, or calculate strain rate from strain and then apply
a conversion. If not, the values are not comparable. Even so, the
values are not absolutely identical, speckle tracking measuring along
the wall, tissue Doppler along the ultrasound beam, and that may affect
the relation to previously published normal values. The method
described above, is robust, due to the large kernel size.
This
method is also relatively angle independent, giving true longitudinal
strain. In
addition, it gives very much improved lateral resolution, using the
line density of grey scale rather than tissue Doppler imaging. Finally,
the lateral resolution is better, as the grey scale images has much
higher number of scan lines (typically 64) as compared to tissue
Doppler
(typically 16).
However,
as the lateral resolution is far less than
tha axial, the two directions are not equal. This means that tracking
in the longitudinal direction is better than tha lateral, so the method
is angle depentden to some degree. And increasing the frame rate (for
instance to compensate for high heart rate) reduces the lateral
resolution even more, reducing the angle independency of the speckle
tracking method even further. The clinical value of the angle
independency remains to be demonstrated.
The method is dependent on
frame
rate. Too low frame rate will result in too great changes from
frame to
frame, resulting in poor tracking. This may also limit the use in high
heart rates, as the motion and thus frame to frame change increases
relative to the frame rate. On the other hand, too high frame rate is
obtained by reducing lateral resolution,
and thus resulting in poorer tracking at least in the transverse
direction. At present, the optimal frame rate for speckle tracking
seems to be 50-70 FPS. Thus, speckle tracking has limitations in
sampling rate. Shorter events
like the isovolumic phases may disappear
all together, and peak values may be reduced due to under sampling,
especially isovolumic and diastolic velocities and strain rate. This is
most
important for measuring peak values in diastole and isovolumic phases,
not so much in systolic strain rate, and systolic strain has least
frame rate sensitivity of all.
2D Strain by speckle tracking.
With a greater number of kernels, distributed
both along and across the
wall, each can be tracked individually,
and displacement and velocity can be measured in two dimensions, both
longitudinally and transversally for
each
(
73). From this, differential motion
- i.e. deformation - can in principle be measured, both in the
longitudinal and transverse direction. The smaller the kernel, the less
certain will the tracking be, but this can be compensated by selection
of kernels on the basis of a stable pattern from one frame to
next. One method of insuring stable tracking is to discard
kernels that are
not present in a sufficient number of frames. In the same way, kernels
that does not move can be discarded, reducing the influence of
reverberations.However, the dependence on recognising stable kernels
from
one frame to next, makes the method even more frame rate sensitive.
Averaging a large number of kernels may make tracking more
robust, although this reduces the number of useful speckles in each
kernel. This can be done in various ways and combinations. With more
than one layer of kernels across the wall, the longitudinal
measurements can be averaged from all layers, giving a transmural
average. Longitudinal averaging can be done along one segment, giving
the segmental average. This can also be done in a more sophisticated
way, by spatial interpolation along the wall. This will result in a
gradual effect of spatial smoothing, although the extent of the
smoothing is less easily discerned. It will reduce the effect of
artefacts such as drop outs and
reverberations. But it
may also mask abrupt changes
in deformation pattern, e.g. at infarct borders. In addition, this kind
of interpolation will reduce temporal resolution as well, in the case
of regional timing differences.
The 2D strain method uses stable speckles, and measures the
displacement
On top of this, smoothing in post processing may be applied in the same
way as for tissue Doppler based methods.

Fig. 21 a. 2-dimensional
strain by speckle tracking. Each red point represents a kernel
for speckle tracking. Velocity and displacement decreases from base to
apex, and the differential motion along the segment gives longitudinal
strain and strain rate. As the true direction of the motion is tracked
in this instance, the transverse component can also be tracked, and the
differential motion from epi- to endocardium can also be tracked.,
giving transmural strain and strain rate.
|

b. 2D strain in practice. The
midwall line is used for the longitudinal strain, being an average of
all points in the wall. The ROI follows the wall, the limits can be
seen diverging in systole, converging i n diastole, giving the
transmural strain and strain rate at the same time. The colours show
longitudinal strain rate, green is shortening and red is lengthening.
|

c. In order to make the
speckle tracking more robust, values are averaged over a whole segment.
|
This method can the calculate segmental longitudinal velocity and
displacement:
Fig. 22.
Longitudinal displacement and velocity, derived from speckle tracking.
Each curve represents the average of a segment. The curves are very
smooth, due to a specific smoothing by curve fitting from segment to
segment as well as temporal averaging.
We did an initial evaluation of an earlier version of
this application in February 2004, comparing the longitudinal motion
and deformation measurements by this application with those obtained by
tissue Doppler, in separate images. The study consisted of 20 patients
with a wide range of function.
Fig. 23. Strain rate and
strain, comparison of 2D strain and Tissue Doppler. There is a
considerable spread between methods, but most probable due to
variability of both methods. There 2D strain gives lower values than
DTI, and this tendency increases with increasing strain rate/strain.
The term "CEB" meaning "computerized eye balling" was an early term to
describe the application.
When measurements was sorted in quartiles, Concordance was only
between 27 and 34%. Feasibility was the same with 2D strain and TVI.
Further investigation was not undertaken at that time, as the
application was modified in later versions.
Other authors have found a much better correspondence between TDI and
2D strain (
73), with correlations of
0.94 and 0.96 for strain rate and strain, respectively. However, as
seen by the curves in the figure below, both data sets are analysed by
the 2Dstrain software, and thus subject to the same high degree of
smoothing, so the results do not reflect independent analysis.
From a validation study where
tissue Doppler and 2D strain derived strainrate (left) and strain
(right) values were compared. However, as can be seen
from these curves, both curves are very smoothed and concordant. Thus,
much of the concordance must be assumed to be due to smoothing, as both
methods were processed by the 2D strain software, and not by
independent analysis software. Adapted from Modesto 2006 (73).
Another study by Cho et al (
148)
finds only correlations of longitudinal strain by 2DS and TVI with MR
tagging of 0.51 and 0.40, respectively. This may reflect the real
precision of both methods (and of MR tagging as well?) but then the
correlation between the methods cannot be higher.
Transverse displacement an velocity can also be derived, but as this
will be the segmental average, this value has little meaning, the
velocity and displacement increased from outer to inner contour (
c fr. fig. 16b). It is the displacement and velocity
gradient that is of interest, i.e. transverse strain and strain rate.
However, this can also be calculated by this method:
|
Longitudinal |
Transverse
|
Strain
rate
|
 |
 |
Strain
|
 |

|
Fig 23.
Longitudinal and
transverse strain derived from speckle tracking. It can be seen
that in this case the differential tracking in the transverse direction
is poor in the basal segments, thus underestimating transverse
thickening in this healthy subject.
Whether this adds clinical information, remains to be seen, as
longitudinal and transverse strain are
interrelated.
As speckle tracking is angle independent, it may be applied to the
short axis as well:

|

|

|
Fig. 24a. 2D strain applied to
short axis image. Again this can be seen to track in two dimensions,
the thickness following the wall thickening, and the mid line in the
ROI Showing midwall circumferential shortening.
|
b. Transmural strain. In this image
the application only measures between 10 and 15% transmural strain,
while the true values in a normal person as this may be as high as 40
- 50%.
|
c. Midwall circumferential
shortening. In this image about 15%, which may be closer to the
actual values.
|
The transmural strain measurement needs to be validated, while the
physiological meaning of midwall circumferential shortening may be
discussed in terms of the circumferential strain tensor. However,
subject to validation, midwall circumferential shortening may be
established as a separate measurement with its own reference values.
Whether this adds information remains to be shown, as the different
strain components are
interrelated.
The application will also give transmural velocity and displacement as
an average of the whole segment. These values have no physiological
meaning, as there is a transmural gradient of both displacement and
velocity as described
before.
However, in a clinical setting, the measurements may separate normal
from reduced wall function, and thus have a meaning in a clinical
setting. It is rather doubtful, however, if this adds anything to
transmural strain and strain rate, and
the use of these values is
physiologically unsound.
The lines looking smoother, is a function of the averaging function
used in the algorithm, the application will do the same to tissue
Doppler data.
Fig. 25. Strain rate
curves from speckle tracking and tissue Doppler from the same cine -
loop. The same smoothing is applied to both, showing that
smoothing of the curves is not the result of the robustness of the
algorithm, but of specific temporal and spatial smoothing applied by
the application. The curves differ
somewhat (but not too much), as strain rate is calculated with
different
angle and lateral resolution.
There is a liberal amount of temporal smoothing. In addition there is
built in a curve fitting along the mid ROI curve, resulting in a
smoother transition from segment to segment. This may result in
diminishing the differences between normal an hypokinetic segments, and
reduced sensitivity for hypokinesia. In the case of asynchrony, this
may be reduced as well by the same spline function. Thus the diagnostic
accuracy of this application is so far not very well documented.
The same limitations apply to this application as to speckle tracking
in general, concerning
frame
rate, heart rate and under sampling. The amount of smoothing may
increase the under sampling even more.
Both methods have been compared for longitudinal strain, and compared
to tissue Doppler (
126). Both seem
to agree fairly well. In addition variability is lower by both methods
than by tissue Doppler. However, as both methods use automatic
segmentation, this may be the main cause for better repeatability, not
speckle tracking vs. tissue Doppler per se. Feasibility of both methods
is reported to be between 70 and 80% of segments.
Combined use of tissue Doppler and
Speckle tracking.
Modern ultrasound equipment has the
capability of acquiring second harmonic grey scale images with an
acceptable frame rate of 40 - 50 FPS and good lateral resolution,
simultaneously with tissue Doppler data. This opens the possibility of
tracking along the ultrasound beam by tissue Doppler, while
tracking transverse to the ultrasound beam by speckle tracking (
124) in the grey scale data.
Combined search by tissue Doppler
and speckle tracking. The kernels are shown as the small,
round, yellow circles. The longitudinal search area along the
ultrasound beam by tissue Doppler is shown in red. The lateral search
area by speckle tracking is shown in white.
This simplifies the
search algorithm, limiting the search area to a sector extending in the
radial direction and thus reducing the time for the speckle
search. In addition, if the method is used to compute
longitudinal velocities or
strain rate, the longitudinal tracking is done with the high sampling
frequency of tissue Doppler. Finally, it utilises the full
dataset inherent in the combined image.
In fact, it seems rather absurd that having
access to high quality grey scale tissue data as well as high frame
rate tissue Doppler data in the same image, the quality of measurements
will improve by discarding one of the data sets.
Thus it seems probable that in the future, some combined approach will
be the state of the art. The combined method can be used in different
ways to analyse strain rate
imaging (
127).
- Segmental strain and strain rate can be calculated directly from
segment length, in the same way as by speckle tracking alone as
described above.
- Velocity, displacement, strain rate and strain can be calculated
by tissue Doppler, placing an ROI in the middle of the segment, and
letting the ROI follow the segment as it moves longitudinally and
transversally by the combined tracking method, ensuring that the
ROI stays in the same position relative to the myocardium, instead of
in space as in the original application and in standard tissue Doppler,
we have called it dynamic TVI.
- The automated segmentation can be used to place the ROI in mid
segment in the first frame, without tracking. This results in a
stationary ROI as in traditional tissue Doppler, but the
reproducibility will improve compared to manual ROI placement.
Feasibility was reported to be between 75 and 80% of segments, compared
to 92% with manual analysis. There may, however be reasons why the
latter number may be too high.
This method (N
o 2,
dynamic TVI) has
already been shown clinically useful in stress echo (
128), giving a sensitivity of peak
systolic strain rate for ischemia of 84% and an AUC of 0.9, compared
to coronary angiography, and with a feasibility
at peak stress of 80% of segments.