Quantification of myocardial strain assessed by cardiovascular magnetic resonance feature tracking in healthy subjects—influence of segmentation and analysis software

We retrospectively screened 243 truly healthy subjects, who were prospectively examined in former studies [24‐28]. Exclusion criteria were known cardiovascular risk factors, any pre-existing diseases or medications, impaired LV ejection fraction (LVEF) (< 55%), or pathological findings in 12 lead ECG or CMR. Incomplete CMR data for feature tracking analysis led to exclusion. That included lack of long-axis (LAX) or short-axis (SAX) slices (n = 137) or variable number of cardiac phases (n = 41). The ethics committee approved all studies. Informed written consent was obtained in concordance with the Helsinki Declaration.

CMR was performed at 1.5-T and 3-T scanners. At 1.5 T (Magnetom Avanto), a 12-channel radio frequency coil was used and at 3 T (Magnetom Verio, both Siemens Healthineers) a 32-channel radio frequency coil. SSFP cine images were acquired during repeated breath-holds for LV in 4-chamber-view (4CV), 3-chamber-view (3CV), 2-chamber-view (2CV), and at least three SAX slices (SAX full coverage and/or three SAX slices in basal, midventricular, and apical plane). Recently, detailed sequence parameters were published [24‐29]: at 1.5 T: repetition time 2.8 ms, slice thickness 6 mm, flip angle 80 degrees, echo time 1.2 ms, field of view 276 × 340 mm², matrix 156 × 192, voxel size 1.4 × 1.4 × 7 mm, 30 cardiac phases; and at 3 T: repetition time 3.1 ms, slice thickness 6 mm, flip angle 45 degrees, echo time 1.3 ms, field of view 276 × 340 mm², matrix 156 × 192, voxel size 1.4 × 1.4 × 7 mm, 30 cardiac phases.

Two independent experienced readers (SCMR level III) performed the visual evaluation of the cine images.

LV function and volumes were quantified in a whole SAX stack according to the recommendation of the SCMR [30] applying CVI⁴² software (Version 4.1.2, Circle Cardiovascular Imaging Inc.). Endo- and epicardial contours were manually drawn in end-diastolic and end-systolic phase. Papillary muscles were excluded from the LV volume.

Feature tracking analysis was performed retrospectively using CVI⁴² software (prototype version 5.3.0, Circle Cardiovascular Imaging Inc.). Longitudinal strain and radial_LAX strain (RS) were assessed in three LAX views: 4CV, 3CV, and 2CV (Fig. 1). Circumferential strain (CS) and RS_SAX were analyzed using three SAX slices (basal, midventricular, and apical) in all subjects (Fig. 1). If available, strain was additionally assessed using a SAX full coverage (Fig. 2). Endo- and epicardial contours were manually drawn in end-diastolic phase, defined as the phase with the largest LV volume. End-diastolic phase had to be identical in all SAX and LAX slices of one subject. Trabeculae, papillary muscles, pericardium, and epicardial fat were consequently excluded from contouring. Left ventricular outflow tract (LVOT) was completely excluded in all SAX slices if seen in diastolic and/or systolic phases (Fig. 2). 2D strain analysis was assessed globally and segmentally for longitudinal, RS_LAX, CS, and RS_SAX strain. Segmentation included both possibilities of slice selection (three slices versus the whole stack) and the segmentation of the left ventricle according to the AHA 17-segment model [31]. We excluded the apex (segment 17) from feature tracking analysis; so far, the 16 segment model was used. Tracking quality and segmentation were evaluated using software tools like mesh, boundaries, or myocardial points. If contours did not follow the epi- or endocardial borders correctly, delineation was retraced and adjusted. In case of remaining tracking issues, all corresponding segments were excluded. Also, incorrect segmentation (see Fig. 3) led to exclusion. Excluded segments were not considered for global strain assessment.

Strain results were compared between field strengths (1.5 T and 3 T) and between different numbers of SAX slices (three SAX slices versus full coverage) in CS and RS_SAX, as well as RS between LAX and SAX analysis.

Bulls-eye plots visualizing segmental strain values were created using the Python package Matplotlib.

All images were also analyzed with TomTec Image Arena (version 1.3.0.91, TomTec Imaging Systems GmbH) (Fig. 4). 4CV, 3CV, and 2CV were used for longitudinal and transversal (radial_LAX) strain. CS and RS_SAX were assessed using three SAX slices (basal, midventricular, and apical). Endo- and epicardial contours were manually drawn in end-diastolic and end-systolic phases. Trabeculae and papillary muscles were excluded from analysis, as well as LVOT. Tracking quality was checked manually, specifically whether contours followed endo- and epicardial borders correctly and were adjusted if necessary. Myocardial strain was analyzed on a global and segmental level. Three LAX (4CV, 3CV, 2CV) and three SAX slices using the exact same slice number were considered for software comparison.

Statistical analyses were performed using IBM SPSS Statistic version 23. We calculated mean values and standard deviation (SD) as well as median and interquartile ranges (IQR) for demographic parameters, LV function, and strain measurements. Volumes were indexed to body surface area (BSA) and height. The non-parametric Mann-Whitney U test for unpaired samples was used for comparisons of strain parameters between gender, analysis software, and field strength. Differences were considered to be statistically significant at p < 0.05. Intra- and inter-observer reproducibility were analyzed using intra-class correlation coefficient (ICC) and 95% confidence interval (CI). ICC was classified as poor (ICC < 0.4), good (ICC = 0.4–0.75), or excellent (ICC > 0.75) [1].

Sixty-seven healthy subjects (n = 36 at 1.5 T and n = 31 at 3 T) were included and analyzed (mean age 44.3 ± 16.3 years, n = 31 females). The proportion of men and age between the field strength groups was equalized. The 1.5 T group had 19 (52.8%), while the 3 T group accounted for 17 (54.8%) male subjects. Mean age was 45.0 ± 16.39 years at 1.5 T versus 43.48 ± 16.33 years at 3 T (p = 0.739).

All volunteers had normal LV function (LVEF 64.1 ± 4.2%) without wall motion abnormalities. Demographic parameters as well as LV function and volumes are summarized in Table 1. Seven subjects had to be excluded from 3D LV function analysis due to incomplete SAX package (n = 6) or artifacts (n = 1).

In all 67 subjects, strain was analyzed in 4CV, 3CV, 2CV, and three SAX slices. Sixty-one subjects were additionally analyzed by CVI⁴² using a full coverage. Using CVI⁴², we could include 1020 segments (95.1%) for longitudinal strain and 1033 segments (96.4%) for RS_LAX. In total, 1064 segments (99.3%) for RS_SAX and 1064 segments (99.3%) for CS were analyzed. In the SAX, strain analysis using SAX full coverage 966 segments (99.0%) from each of RS_SAX and CS could be included.

For analysis with TomTec, 1059 segments (98.8%) could be included for longitudinal strain, 1056 segments (98.5%) for RS_LAX, 1071 segments (99.9%) for RS_SAX, and 1070 segments (99.8%) for CS.

Reasons for exclusion were inaccurate tracking or incorrect segmentation.

CS and RS_SAX measurements assessed by a stack of short axes covering the whole LV differ significantly from those assessed using three short axes: global CS − 19.2 ± 2.3% (median − 19.0%, IQR − 20.6 to − 17.9%) in 3 SAX vs. − 17.6 ± 1.8% (median − 17.7%, IQR − 18.6 to − 16.7%) in full coverage (p < 0.001) and global RS_SAX 34.6 ± 7.1% (median 33.4%, IQR 29.9–38.8%) in 3 SAX vs. 29.1 ± 4.8% (median 29.1%, IQR 26.2–31.9%) in full coverage (p < 0.001) (for details, see Table 2).

Using three SAX slices, no differences were found for global strain measurements between 1.5 T and 3 T: global CS − 19.6 ± 2.3% (median − 18.9%, IQR − 21.3 to − 18.0%) at 1.5 T vs. − 18.8 ± 2.2% (median − 19.0%, IQR − 20.5 to − 17.6%) at 3 T (p = 0.263) and for global RS_SAX 36.0 ± 7.5% (median 33.4%, IQR 29.9–38.8%) at 1.5 T vs. 33.0 ± 6.2% (median 32.6%, IQR 28.9–37.3%) at 3 T (p = 0.128). However, some segmental strain values differed significantly between field strengths for both CS and RS_SAX (for details, see supplemental material online additional file 1).

Using SAX full coverage, both global and segmental strain values did not show any significant difference between field strengths: CS − 17.7 ± 1.8% (median − 17.7%, IQR − 18.8 to − 16.6%) at 1.5 T vs − 17.6 ± 1.8% (median − 17.6%, IQR − 18.5 to − 16.9%) at 3 T (p = 0.85) and global RS_SAX 29.4 ± 5.1% (median 29.6%, IQR 25.9–32.3%) at 1.5 T vs 28.7 ± 4.5% (median 28.7%, IQR 26.6–31.1%) at 3 T (p = 0.665) (for details, see supplemental material online additional file 1).

In both, three selected slices and a whole SAX stack global circumferential and radial_SAX strain differed significantly between genders (for details, see Table 2). Gender-related strain values are visualized in the supplemental material additional file 2.

Global radial strain acquired in LAX (radial_LAX) versus SAX (radial_SAX) differed significantly: global radial_LAX 29.1 ± 5.3% (median 29.1%, IQR 25.1–32.8%) versus global radial_SAX 34.6 ± 7.1% (median 33.4%, IQR 29.9–38.8%) (p < 0.001).

Longitudinal strain did not show any significant difference for both global and segmental strain measurements between 1.5 T and 3 T: − 17.0 ± 2.1% (median − 17.0%, IQR − 18.4 to − 15.3%) vs. − 17.0 ± 1.7% (median − 17.1%, IQR − 18.0 to − 15.8%) (p = 0.845 accordingly). No significant differences have been found between females and males: − 17.4 ± 2.0% (median − 17.7%, IQR − 18.4 to − 15.8%) and − 16.6 ± 1.8% (median − 16.6%, IQR − 18.0 to − 15.3%) (p = 0.098). On a segmental level, only AHA segment 5 (basal inferolateral) showed a significant difference between genders: − 25.8 ± 5.9% (median − 26.7%, IQR – 30 to − 22.8%) in females versus − 23.3 ± 5.0% (median − 23.4%, IQR − 27.5 to − 18.4%) in males (p = 0.048). Segmental strain measurements for longitudinal strain are presented in Fig. 5.

Strain measurements assessed with TomTec software were significantly different to those assessed with CVI⁴² (Table 3). GLS was − 17.0 ± 1.9% (median − 17.0%, IQR − 18.4 to − 15.6%) for CVI⁴² and − 20.5 ± 2.7% (median − 20.2%, IQR − 22.6 to − 18.8%) for TomTec (p < 0.001). Significant differences were also found for most segmental strain values (for details, see supplemental material online additional files 3–6).

Gender-related global strain values using TomTec are summarized in Table 2. Unlike differences in global RS_SAX, GLS and global CS were not associated with gender.

GLS reproducibility was as follows: ICC was 0.941 (95% CI 0.759–0.985) for intra-observer and 0.829 (95% CI 0.273–0.958) for inter-observer analysis. We observed an excellent intra- and inter-observer reproducibility across all global strain measurements (for details, see supplemental material 7). Intra-observer agreement was best for CS (ICC 0.977, 95% CI 0.907–0.994) and lowest for RS_LAX (ICC 0.930, 95% CI 0.715–0.983). Inter-observer agreement was best for radial_SAX strain (ICC 0.975, 95% CI 0.889–0.994) and lowest for longitudinal strain (ICC 0.829, 95% CI 0.273–0.958).

This study is limited by a relatively small, but carefully and well-characterized healthy study cohort. As our analysis was performed retrospectively in prospectively enrolled volunteers, scan protocols were slightly different. This led to exclusion of 176 subjects due to incomplete CMR data. This may be preventable by a prospectively designed study, but our settings also reflect potential difficulties in clinical routine.

Our statistical analysis was only descriptive and exploratory. It indicates that differences among vendors or segmentation procedures may exist, but further validation remains necessary.

The CMR examinations performed at 1.5 T and 3 T did not contain the same subjects, but showed an equal distribution regarding gender and age. In accordance with our results, pre-existing studies have also shown that field strength does not influence global strain values [32].

CMR feature tracking is less validated for regional strain and radial_LAX strain, but they can presumably reveal different physiological mechanisms of the myocardium. Regional assessment is limited by inaccurate tracking or incorrect segmentation which may distort segmental strain values. We provide numbers, but long-term studies have to show the potential significance before CMR-FT may enter clinical routine.