4. Discussion
Beyond a scientific context, how does speckle-tracking analysis using
fetalHQ® perform in routine clinical practice and could less experienced
operators benefit from this state-of-the-art technique? The present
study aimed to scrutinize the applicability of 2D-STE based on the
expertise of two operators.
Quantification of fetal myocardial function is challenging, and several
different techniques have been used [6,14,25,66]. Already in 2012,
Crispi et al. stated that in expert hands and with adequate ultrasound
equipment, accurate assessment of cardiac function is feasible in most
fetuses [4,8]. With the continuous development of AI algorithms and
their implementation in platforms of different ultrasound devices, two
softwares – MPI+TM (Samsung Healthcare, Gangwon-do,
South Korea) and fetalHQ® (GE Healthcare, Chicago, IL, USA) – have
recently been established to examine different cardiac functional
parameters of the fetus. So far, only the learning curve for the
acquisition of the MPI manually [67] and the benefits of its
semiautomatically measurement in clinical routine for less experienced
operators have been demonstrated [47]. The additional value of the
2D-STE for less experienced sonographers has yet to be demonstrated,
although the significance in a scientific setting is undisputed.
FetalHQ® has shown excellent reproducibility for the analysis of
morphometric as well as functional cardiac parameters [2,7,14,16].
Based on our data, we were able to demonstrate good to excellent
agreement between both operators for the applicability of 2D-STE for
comprehensive analysis of global and segmental cardiac deformation.
Although, current studies have recently questioned the initially
excellent reproducibility of segmental parameters in particular
[2,5,68,69].
Despite all the advantages that 2D-STE can offer in combination with
post-processing analysis using fetalHQ®, the technique mainly depends on
the skill and experience of the operator and the quality of acquisition
of an optimal clip of the 4-CV [14,25,70]. An experienced operator
of prenatal ultrasound will certainly undergo a short learning curve to
acquire and analyze short image-optimized cine-loop sequences of the
fetal cardiac 4-CV by 2D-STE [69,71]. For less experienced operators
with initially lack of adaptive skills in visualizing an optimal 4-CV of
the fetal heart, a marked learning curve can be assumed. Germanakis et
al. summarized that, although speckle tracking technique is
algorithm-guided, offline image analysis is not user-independent. The
operator must place or adjust the endocardial tracking lines. Therefore,
a learning curve is essential prior successful implementation in
clinical routine [5,10,15,25,71]. To take these aspects into account
and to achieve the same level of standardization as in adult cardiology,
DeVore et al. have provided a practical step-by-step approach [16].
The classification of the cardial functional parameters in the
pathophysiological context and their subsequent interpretation is highly
complex. Due to differences in ultrasound equipment, measurement
techniques with non-standardized pre-settings, non-systematic image
settings and processing, vendor-specific analysis software with
different algorithms tracking speckle patterns and myocardial
deformation as well as maternal and fetal characteristics of the study
population [2,5,12,14], a wide variability in the quoted endoGLS
reference values during pregnancy results to date. Since there is
neither a mandatory standardization of the process nor of the
semiautomatic algorithms, and there are many pitfalls to deal with, the
cardiac function parameters described in the literature vary
considerably [2,5,7,8,12,14,25]. It should also be noted that any
normal reference ranges of myocardial deformation may need to be
adjusted to the corresponding GA [14]. Patey et al. reported on
intervendor discrepancies with significant clinical and research
consequences. They demonstrated that fetal 2D-STE assessments are
reliable when performed on the same ultrasound platform, while
ultrasound machines and software from different vendors produce
significantly different fetal 2D-STE parameter estimates. This should be
considered when interpreting and comparing research data [72]. The
review by Kühle and co-workers revealed that the mean value of all cited
studies – excluding those with positive values – considered for the
right ventricular GLS is reported as -19.36 % ± 4.55 pp, that of the
left as -19.21 % ± 3.88 pp. The lowest cited value for the right
ventricular GLS was -35.88 %, the highest -12.80 % and the lowest left
ventricular GLS -26.01 %, the highest -12.30 % [25]. The mean
endoGLS values of both operators in this paper are consistent with those
referenced in the literature. It is widely recognized that fetal
circulation is right-heart-dominant with higher myocardial shortening
during contraction in the right ventricle [11,25,73,74]. The more
negative the endoGLS values, the better the contractility of both
ventricles [10,14]. It would therefore be expected that longitudinal
strain values in the right ventricle are between 1.0 and 1.5 times
higher (i.e. more negative) compared to the left ventricle due to the
difference in myofiber orientation [40,75], although contradictory
measurements can be found in literature concerning this as well
[10]. As many other studies, we were unable to confirm this
hypothesis based on our data (Table 3, Figure 2 and 3) [25].
Echocardiographic evaluation of ventricular function is challenging,
especially assessment of the right ventricle function due to its complex
anatomy [76]. On the one hand, anatomical structures like the
moderator band can complicate the correct placement of the apical
caliper for the operator, on the other hand prominent trabeculation can
impair the automatic delineation of the endocardial border during a
cardiac cycle by the software [5,25,75]. Such inaccuracies in the
acquisition of right ventricular deformation parameters with suboptimal
contrast between the endocardium and the respective ventricular chamber
without precise wall tracking might result in underestimated endoGLS
values [10,25]. Furthermore, 2D-STE is only based on 2D 4-CV, which
neglects spatial aspects of cardiac anatomy of the right ventricle. This
might apply to our data, with lower mean endoGLS value of the left
compared to the right ventricle (Table 3, Figure 2 and 3). In addition,
the agreement of the right ventricular endoGLS measurements between the
two operators in our study is lower compared to left ventricular (Table
4, Figure 4). This assumption of lower agreement for right ventricular
parameters was also reported by Huntley et al. [5]. Altogether, all
measured functional parameters in our study – global as well as
segmental – showed good to excellent agreement between both operators
(Table 4, Figure 4 and S7 to S9). The lowest agreement, but still
considered as good, was found for the FS. These results are in
accordance with recent publications questioning the reproducibility of
FS, which was previously reported as excellent [2,5,68]. It was also
noticeable in our study that the absolute values of the FS of the
individual segments frequently deviated from the percentages defined in
the software fetalHQ®. The focus of this study was not the determination
of further reference values or the verification of reproducibility of
fetalHQ®, but rather the proof of agreement between two operators of
different expertise. Nevertheless, this aspect should be mentioned.
2D-STE can be used throughout pregnancy, even as part of first trimester
screening [25,77]. However, in clinical routine, we emphasize its
best application mid-gestational and advanced GA, as other authors have
also elaborated [5,10,14,25,28,29]. Our endoGLS values of both
ventricles assigned to gestational age are consistent with the
contradictory data in the literature, with slight decrease of right
ventricular and almost constant left ventricular endoGLS values with
increasing GA (Figure 2). Ohira et al. recently reported on similar
findings with their underlying pathophysiological mechanisms [28].
In fact, 2D-STE should have better intra- and interobserver variability
than other techniques used to evaluate cardiac function [16]. Apart
from routinely acquired 2D B-mode images of the 4-CV, no further imaging
is required. In contrast to Doppler-based methods, 2D-STE is supposed to
be angle-independent due to the simple acquisition of the 2D image,
regardless of the orientation of the heart to the ultrasound beam, and
could therefore be performed in any fetal position [15,16,27]. It is
controversially discussed that speckle tracking is less angle-dependent
or even angle-independent [2,5,10,12,14,16,17,36,40,78]. Most likely
– and we agree with this opinion – 2D-STE can be considered as less
angle-dependent but cannot be performed in every fetal position with
limited clip acquisition of the 4-CV. At least the position of the IVS
should be considered when a cine-loop of a 4-CV is recorded. In clinical
routine, it is almost impossible to record every fetal heart with the
IVS in a perpendicular position, as recommended by deVore et al.
[16]. In our study, the most common apex orientation for both
beginner and expert was ‘apex oblique up’ (Table 2). Furthermore, due to
the combination of small size of the fetal heart with high heart rate,
an adequate frame rate to achieve a high temporal and spatial resolution
with tracking of the speckles is intensively discussed
[2,5,6,8,9,14,16,25]. 2D-STE requires a high resolution 4-CV,
suitable for post-processing analysis, with high image acquisition frame
rate, depending on fetal heart rate [2,6,15,16,25,78]. Specialized
software with an automated sensitive and accurate border recognition can
contribute to simplify and standardize the procedure of speckle tracking
[6,11]. However, the quality of subsequent speckle tracking analysis
is affected by the proper visualization of the 4-CV within the cine-loop
with clear delineation of the endocardium [5,24,25]. Precise image
acquisition and quality of the 4-CV can be impaired by maternal BMI,
anterior placenta, oligohydramnios, fetal anatomy and position,
resulting artifacts caused by maternal as well as fetal movements and,
not least, from skills of the operator. Since the number of ultrasound
frames per second is assumed to have a great impact on the reliability
of 2D-STE, DeVore et al. recommend an optimal frame rate of
>80 Hz. But there is currently no consensus about the
optimal frame rate for strain imaging with recommendations for
significantly higher frame rates [25,28,79,80]. On average, we
achieved a frame rate of 76 Hz (beginner) and 73 Hz (expert) in our
study collective, which represents the clinical routine (Table 2).
Gireadă et al. exceeded the 80 Hz frame rate threshold in only 9%, we
in 43% (beginner) and 7% (expert) [36]. When interpreting the
results of a speckle tracking analysis and assessing the agreement of
measurements between operators, angel of insonation (apex orientation)
and frame rate must be kept in mind.
In our opinion, there are three pitfalls with significant impact on the
accuracy, reliability and validity of the method as well as the
agreement between the operators that must be considered when performing
2D-STE: Firstly, the artifact-free image acquisition of a clip of the
4-CV, secondly, the orientation on the heart with recognition of the
left and right side, as well as subsequent identification of an optimal
cardiac cycle, thirdly, the manual placement of the three calipers with
any required adjustment of the endocardial tracking lines. Considering
these aspects, a short learning curve is also evident for less
experienced operators. We emphasize that 2D-STE cannot be applied in all
patients. In contrast to RV-Mod-MPI, it requires a good pre-selection
for success. Compared to other methods for the determination of fetal
cardiac function, such as the RV-Mod-MPI, the time factor has a
significant negative impact on the 2D-STE analysis. The evaluation of
the complex measurements is more time-consuming and requires further
expertise. The longer the cine-loop, the longer the import into the
software for further analysis. Therefore, 2D-STE analysis is less
suitable for performing ‘on-the-fly’ in the busy, tightly scheduled
clinical routine, especially for less experienced operators. Despite
today’s semiautomatic 2D-STE measurement using fetalHQ® and after more
than ten years since Van Mieghem et al. concluded that speckle tracking
can be performed by a sonographer with limited experience in fetal
cardiology on any prenatal ultrasound exam, we still doubt this
statement even in 2023 [40]. We agree with the opinion of Germanakis
et al. who underline the importance of understanding the basic
principles of strain and the resulting limitations of 2D-STE before
adopting it into routine clinical practice [15].
An approach to optimize the performance of the 2D-STE method more
efficient with shorter time for acquisition was recently published. The
quiver technique enables the operator to identify the endocardial
borders more precisely and efficiently. It facilitates the
identification of the septal and lateral atrioventricular valve annulus
by cine-looping two frames before and after the selected end-systolic
and -diastolic frame [24]. In our opinion, it will be of great
importance in the future to eliminate human manual adjustment for
improving reproducibility and increasing efficiency in daily clinical
routine by automatically identifying the most optimal cardiac cycle
including the accurate selection of endocardial borders by AI
algorithms. This was already demanded by Huntley et al. [5].
Although speckles move in three dimensions, most methods of speckle
tracking are based on post-processing analysis of only one acquired
plane of a 2D-clip of the fetal heart [9,14]. Speckles beyond the
insonated plane will not be analyzed [6]. Cardiac mechanics is
complex due to special geometry with myocardial three-directional motion
including longitudinal, radial, and circumferential contraction
[4,8,25,73]. The helical structure of the ventricular myocardium
with its three-dimensional (3D) deformation requires to detect speckles
in all dimensions [81]. In addition, 2D-STE excludes the right
ventricular outflow tract [11]. Theoretically, holistic, spatial
concepts might offer an important contribution in measuring more
realistic volumetric parameters. It therefore seems natural to combine
STE technique with spatial methods such as 3D- or four-dimensional
(4D)-spatio temporal image correlation (STIC) for a more precise and
realistic measurement and to overcome B-mode imaging limitations of
2D-STE [2,9,70,82].
Once a suitable 2D-clip of the 4-CV was acquired with knowledge of the
pitfalls discussed above, there was in many cases nothing to prevent
subsequent offline analysis using fetalHQ® and resulted in high
agreement between beginner and expert. Nevertheless, some limitations of
the present study must be mentioned. Only 136 unselected, normal,
singleton, second- and third-trimester fetuses without CHD in healthy
women, focusing on the 23th week of gestation on
average, were examined. The period in which these clips for 2D-STE
analysis were recorded appears to be quite long. The recording of the
clips with subsequent 2D-STE analysis was performed by only two
operators. However, these two (beginner and expert) were representative
as holders of DEGUM level 1 (German Society for Ultrasound in Medicine),
the minimum standard for a sonographer, and DEGUM level 3 for gynecology
and obstetrics. The former certifies familiarity with the basics of
ultrasound diagnostics, the latter characterizes a proven expert far
beyond basic knowledge. Representative for the base (1-8), the middle
(9-16) and the apex (17-24) of both ventricles, in this study, according
to Nogué et al., segments 1, 9 and 17 were selected for comparison of
measurements of both operators [2]. It would be possible to select
other segments, for example 1, 12 and 24, as in the study of Zhu et al.
[11]. Differences in the agreement of both operators in the
measurement of segments not examined are feasible, which applies to
segmental, but not to global parameters. In this study, we allowed
orientations of the IVS that were considered suboptimal for 2D-STE
analysis to reflect daily clinical routine. According to our results,
this did almost not impair the good to excellent agreement between the
two operators.