Background
Left ventricle (LV) torsion, the counter-rotation of basal versus apical regions, is known to play a crucial role in cardiac contraction and relaxation [
1,
2]. The kinematics of the microfibers having different orientation in the myocardial wall enables rapid blood ejection and refilling during the cardiac cycle. Studies have shown that changes in the rotation patterns of the heart muscle and specifically LV torsion are connected to various cardiac diseases [
3] such as aortic valve stenosis [
4], ischemia [
5,
6], or dilated and hypertrophic cardiomyopathy [
7].
Previous studies have attempted to quantify myocardial torsion using tissue Doppler imaging [
8], or speckle tracing echocardiography [
9]. However, Doppler imaging cannot measure velocity in three dimensions and for all cardiac segments. Speckle tracking, while overcoming the previous limitations, is highly dependent on the acoustic window. Cardiovascular magnetic resonance (CMR) is a powerful alternative for analyzing local myocardial deformation. Based on MR-Tagging [
10,
11], the rapid and complex rotational motion pattern and the endo- versus epicardial differences of the heart muscle are difficult to quantify due to the low spatial resolution. Displacement-encoded image using stimulated echoes (DENSE) [
12] and Tissue Phase Mapping (TPM) [
13] can measure local motion with higher temporal (DENSE) and spatial (TPM) resolution respectively. Moreover, TPM directly measures myocardial velocities and allows for their quantitative assessment along all three principal motion directions of the heart (radial, long-axis, circumferential). Acceleration plays an important role to make high resolution TPM acquisition possible during breath hold. Existing methods employ spatio-temporal imaging acceleration k-t GRAPPA [
14] (required breath hold: 25 heartbeats) and non-Cartesian SENSE implemented on the GPU [
15] (required breath hold: 13–17 heartbeats).
Previous studies have shown the potential of TPM to detect disturbed regional myocardial motion in patients with hypertrophy [
16], cardiomyopathy [
17], after heart transplantation [
18], and other cardiac diseases [
3‐
7]. Moreover, it has been demonstrated that TPM can be employed to assess the temporal dynamics of rotational velocities during the cardiac cycle. By comparing basal versus apical LV rotation velocity, the twisting and untwisting pattern of the heart could be evaluated [
19]. Previous TPM studies [
16‐
18] have measured myocardial torsion, but a systematic quantification of endocardial and epicardial torsion and analysis of the variability of torsion-related parameters across patient cohorts has not been performed to date.
Myocardial twist has also been previously studied using local shear, mainly based on tagged CMR [
20]. The local measures for myocardial twist are circumferential-radial and circumferential-longitudinal shear which are derived based on the relative displacement and reported using the American Heart Association (AHA) model. Even though local twist measures exist, it is possible that when the rotational velocity is only locally affected, this may also have a significant impact on the global LV twist due to the complex fiber structure. The goal of this work is to investigate a global parameter that can measure the total LV torsion during the cardiac cycle. Using a single, global measure, we ultimately aim to detect changes in the LV mechanics before they impact the ejection fraction or even manifest as visible wall motion abnormalities in cine CMR. Based on a simplified mechanical model, the proposed global torsion takes into account the LV radius and length, measuring the total relative rotation of the basal myocardium with respect to the apex.
We present a method to quantify the myocardial and transmural (epicardial and endocardial) torsion using TPM imaging followed by a semi-automatic processing pipeline in a study cohort of 27 patients with non-ischemic cardiomyopathy and 14 normal controls. Our goal was to test the hypothesis that TPM can by employed to detect significant differences in LV torsion in patients with reduced ejection fraction (EF) and wall motion abnormalities (WM) compared to patients with preserved EF and control subjects.
Discussion
The findings of this study indicated that TPM is a promising tool to quantify LV torsion as a functional marker of cardiac disease. In this work, we investigated the maximum torsion as a potential biomarker for global myocardial twist motion in a cohort of patients with non-ischemic cardiomyopathy and healthy volunteers. The proposed torsion parameter is different from local shear measures, as it tries to globally characterize the twisting motion of the myocardium.
Firstly, the positive correlation between maximum torsion and ejection fraction showed that the maximum torsion during systole could be an additional index of global cardiac function. Moreover, torsion was also significantly lower for patients having wall motion abnormalities, even when ejection fraction is preserved, compared to healthy controls, suggesting that torsion is additionally sensitive to local changes in the myocardial motion which were not captured by ejection fraction. Secondly, when analyzing torsion transmurally, we observed that endocardial torsion was significantly higher than epicardial for normal volunteers and patients with preserved ejection fraction. Thirdly, another important finding was the positive correlation of the absolute and relative difference in torsion between the endo- and epicardial regions with ejection fraction.
Reduction in ejection fraction has been previously associated with a reduction in maximum myocardial torsion in studies performed using speckle tracking [
30] and tagging CMR [
7,
8,
31,
32], which was also confirmed by our results. This shows that maximum torsion can be used as an index of global cardiac function. This is also reflected by the findings in our study, namely the correlation of maximum torsion and ejection fraction, as well as the significantly lower maximum torsion for the subgroup of patients with reduced ejection fraction compared to the patients with preserved ejection fraction and to controls.
However, the added value of torsion as a cardiac parameter could be its sensitivity to local changes in myocardial motion caused by various cardiovascular diseases (hypertrophy, diastolic dysfunction) in patients with preserved ejection fraction [
3]. For example, it has been inferred that if an increase in myocardial torsion is observed in early left ventricular dysfunction, it may serve as a compensatory mechanism for a reduction in left ventricular longitudinal shortening [
9]. The sensitivity of torsion to manifestations of cardiovascular disease as wall motion abnormalities is also supported by the finding in our study: Maximum torsion was significantly lower in the presence of wall motion abnormalities even when ejection fraction was preserved, compared to the rest of the patients and controls. These findings indicate the potential utility of torsion to detect patients with local abnormalities despite a preserved ejection fraction. However, the number of patients with impaired wall motion and preserved ejection fraction considered in our study is too low for these results to be conclusive and larger studies are needed to confirm these findings.
Myocardial torsion can be computed between any pair of short-axis slices, taking into account their variable distance and radii. The base-mid torsion has generally higher values than the base-apex and mid-apex, especially for non-ischemic cardiomyopathy patients with preserved ejection fraction. However, the base vs. apex torsion parameter has the advantage of quantitatively describing the twisting motion of the entire left ventricle over time.
Furthermore, our results showed that myocardial torsion was higher in the endocardial tissue layer compared to the epicardial tissue layer in subjects with normal heart function. This is in accordance with the observation of a more dynamic motion pattern in the sub-endocardial fibers, which have a higher velocity than the epicardial during the cardiac cycle [
13,
33]. In the literature, however, there has been some disagreement on the relative proportion of endo- and epicardial torsion depending on the imaging technique. For example, Rüssel et al. [
10] used tagging in their study and found that the endocardial twist angle is larger than the epicardial, but when normalizing to the radius of the LV to obtain the torsion, the relation was inverted. This inconsistency could be a result of different methodology and calculation methods (normalization to heart size and local radii), which are not yet standardized. In contrast, using our method the relation of higher endocardial motion was preserved after normalization to the LV radius, in agreement with the study by Buchalter et al. [
11] and other studies reviewed in [
3].
Moreover, we examined the variation of absolute and relative difference between endo- and epicardial torsion for our patient subgroups. Our correlation analysis showed that the difference in dynamics between the endocardial and epicardial fiber clusters was significantly smaller for patients with reduced cardiac function. We observed a reduction in the maximum torsion difference between the endo- and epicardial layers, both in absolute and relative values, for progressively higher LV dysfunction. More specifically, the transmural difference in torsion was reduced close to zero for patients with ejection fraction smaller than 40 %.
The difference in torsion between endo- and epicardial layers was also associated with age. As the myocardial microfibers continue to grow throughout an adult’s life, the helical architecture becomes more elaborate. Evidence of an increase in fiber twist due to this remodeling has also been reported with other methods. Omar et al. [
9] reported an increase in epicardial twist with age. In contrast, Notomi et al. [
34], using Doppler imaging, reported that even though the torsion angle increases with age, when normalized by the length of the left ventricle, torsion was actually higher in younger subjects. In our study we found a significant positive association between maximum torsion and age, both globally for the entire myocardium and for each of the endocardial and epicardial bands. Also, the significant correlation detected between age and transmural torsion difference suggested that the difference between endo- and epicardial torsion is proportional to age, which could be another effect of the microfiber remodeling. However, we were not able to confirm the correlation using only the small subgroup of volunteers, to verify whether the correlation is not caused by the presence of other age-related diseases. In the future, this will be investigated this using a larger number of healthy subjects.
Limitations
Our present study only included patients with reduced ejection fraction or wall motion abnormalities, without distinguishing between the causes for the dysfunction. As a first step, our goal was to test our method for quantifying myocardial torsion based on TPM and its capability to distinguish between patients with normal and abnormal cardiac function, as well as to explore the potential of quantifying the relation between endocardial and epicardial torsion within these groups. However, the heterogeneity of the patient cohort is a significant limitation of the work. In the future, we plan to conduct more targeted studies using more specifically selected patient groups.
In our study cohort, we did not find a significant change of torsion in the presence of late gadolinium enhancement, though such findings were previously reported (using tagging on humans [
35] and animal models [
36]). However, we have not taken into account the size and position of the myocardial regions showing late gadolinium enhancement, mainly because our cohort included patients with non-ischemic cardiomyopathy where the enhancement, if present, is usually more diffuse. Moreover, since our torsion parameter is global, it is possible that high myocardial velocities in the healthy regions compensate for the reduced motion in the regions with late gadolinium enhancement for patients where the ejection fraction is not substantially reduced. In the future, we plan to extend our investigation to include ischemia patients, but this time use a local torsion measure that could be correlated with the presence of local ischemia.
One drawback of the TPM CMR acquisition method used in this study is the relatively long breath-hold time required. Some of the patients in our cohort had signs of dyspnea, which can lead to incomplete breath holding during the acquisition and thus imperfect image quality. Nevertheless, all TPM data could successfully be analyzed to determine torsion and transmural torsion difference. Also, there is tradeoff between the temporal resolution that can be acquired and the required scan and breath-holding time. Overcoming such limitations and imaging myocardial velocities with a higher temporal resolution could better characterize the complex wall motion pattern.
Another limitation is the relatively high sensitivity of our measurement to the myocardium segmentation. Especially in apical slices, the lack of contrast between blood pool and myocardium in the magnitude image combined with the low velocities in the phase images makes the myocardium segmentation very challenging, even as a manual task. As a consequence, we observed outliers in the Bland-Altman analysis, which led to a moderate overall reproducibility of our method. Furthermore, in case of the outliers, the slightly different orientations of the short-axis plane positioning between scan and rescan also accounts for the larger variations. Variability in the apex segmentation could also be a reason why the torsion parameters showed relatively high variability even among healthy subjects, but further investigation is required to establish the normal limits of these variations. Therefore we think that the myocardium segmentation used to analyze velocity images should be subjected to a higher standard of precision and results from automatic and semi-automatic segmentation method should be carefully monitored corrected for optimal results.
As the thickening of the myocardium during systole is more substantial in the endocardial region compared to the epicardial, another limitation of the segmentation approach is always considering the centerline to separate between the epicardial and endocardial regions of the myocardium. In the future we will track the myocardium centerline with a similar approach which was used to propagate the manual myocardium contours from a single time point to the entire image series.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
TC Implementation of automatic analysis pipeline, statistical analysis, manuscript preparation; SS results interpretation and drafted the manuscript; JCo, JCa data collection, clinical analysis, and revised the manuscript; VC, ARH data analysis and manuscript revision; AH contributed to analysis pipeline design and implementation, and revised the manuscript; LL contributed to analysis pipeline design and revised the manuscript; HKH results interpretation, manuscript revision; MM study design, results interpretation, and manuscript revision. All authors read and approved the manuscript.