Background
Three-dimensional (3D) speckle-tracking echocardiography (STE) is an emerging technology used to quantify left ventricular (LV) function. However, the accuracy and normal values of LV strain and twist using 3D STE have not been established in a large group of normal subjects. The aims of this study were to (1) to evaluate the accuracy of 3D STE analysis of LV strain against a cardiac magnetic resonance (CMR) reference and (2) to establish age-related normal values of LV strain and torsion using real-time 3D echocardiographic (RT3DE) images.
Methods
In protocol 1, RT3DE data sets and CMR images were acquired on the same day in 19 patients referred for clinically indicated CMR. Global LV longitudinal, circumferential, and radial strain was compared between the two modalities. In protocol 2, global and regional strain and twist and torsion were measured in 313 healthy subjects using 3D STE.
Results
In protocol 1, good correlations for each LV strain component were noted between RT3DE imaging and CMR ( r = 0.61–0.86, P < .001). In protocol 2, normal global longitudinal, circumferential, radial, and 3D strain were −20.3 ± 3.2%, −28.9 ± 4.6%, 88.0 ± 21.8%, and −37.6 ± 4.8%, respectively. A significant age dependency was observed for global longitudinal and 3D strain. Aging also affected LV torsion: the lowest values were found in children and adolescents, and values subsequently increased with age, while further aging was associated with a gradual reduction in basal rotation accompanied by an increase in apical rotation.
Conclusions
This study provides initial validation of 3D strain analysis from RT3DE images and reference values of normal 3D LV strain and torsion. The age-related differences in LV strain and torsion may reflect myocardial maturation and aging.
Speckle-tracking echocardiography (STE) allows the quantification of left ventricular (LV) global and regional function, which provides clinically useful information in different clinical scenarios. Because of inherent limitations of two-dimensional (2D) speckle-tracking for the analysis of LV mechanics, recent investigational efforts have shifted to speckle-tracking analysis using real-time three-dimensional (3D) echocardiographic (RT3DE) data sets. Validation of 3D STE has been performed in animal studies using sonomicrometry as the reference standard and in simulated models and in vitro as well. However, the validity of 3D STE in human subjects has yet to be determined because of the lack of a noninvasive reference standard. Also, the establishment of normal values of 3D speckle-tracking echocardiographic parameters over a wide range of ages is important before using this new technology in clinical investigations, to be able to (1) detect subtle LV dysfunction in patients with normal LV ejection fractions, (2) investigate the effect of drug therapy on LV mechanics, and (3) evaluate LV function during serial follow-up studies. Furthermore, previous studies have reported age-dependent changes in a spectrum of LV functional parameters assessed by Doppler tissue imaging or 2D STE. Thus, the age dependency of 3D strain and torsion parameters should also be determined. Accordingly, the aims of this study were (1) to validate 3D speckle-tracking echocardiographic measurements of LV strain against a cardiac magnetic resonance (CMR) reference and (2) to establish references values of the principal components of LV strain, as well as twist and torsion, using RT3DE and 3D speckle-tracking echocardiographic analysis in different age groups of normal subjects.
Methods
Study Subjects
In protocol 1, we studied 19 patients who underwent clinically indicated CMR examinations and agreed to undergo RT3DE studies on the same day. In protocol 2, 335 normal subjects (mean age, 36 ± 22 years; range, 1–88 years; 170 male subjects) were enrolled to obtain RT3DE data sets. Eligibility criteria included (1) normal blood pressure with no history of hypertension and (2) absence of diabetes and/or cardiovascular disease. Subjects who were primarily hospital employees, their relatives, and/or volunteers were recruited from 3 hospitals in the United States and Japan (University of Chicago: n = 104, mean age, 37 ± 15 years; University of Occupational and Environmental Health: n = 190, mean age, 42 ± 23 years; and Nagano Children’s Hospital: n = 41, mean age, 6 ± 4 years). All subjects underwent physical examinations and 2D echocardiographic evaluations to exclude valvular heart disease and/or wall motion abnormalities. The ethics committee at each hospital approved the study protocol, and informed consent was obtained in all subjects.
RT3DE Imaging
A Sonos 7500 or iE33 scanner (Philips Medical Systems, Andover, MA) equipped with a fully sampled matrix-array transducer (X5-1, X4, or X3-1) was used for data acquisition. Studies were performed by experienced cardiac sonographers with subjects in the left lateral decubitus position. Full-volume data sets were acquired from the apical transducer position during held end-expiration. To ensure the inclusion of the entire LV volume within the pyramidal scan volume, data sets throughout one cardiac cycle were acquired using wide-angle mode, wherein four wedge-shaped subvolumes (93° × 21°) were acquired with electrocardiographic gating during a single 5-sec to 7-sec breath-hold. The mean frame rate of RT3DE data sets was 20.7 ± 5.6 frames/sec (range, 11–48 frames/sec).
CMR Imaging
CMR images were obtained using a 1.5-T scanner (Intera Achieva; Philips Medical Systems, Best, The Netherlands) with a phased-array cardiac coil. In each patient, retrospective electrocardiographically gated localizing spin-echo sequences were used to identify the long axis of the heart. Steady-state free precession dynamic gradient-echo cine loops were acquired using retrospective electrocardiographic gating and parallel imaging techniques during 10-sec to 15-sec breath-holds, with temporal resolution of 30 frames/cardiac cycle. In all patients, three short-axis planes (basal, midventricular, and apical) and long-axis planes (two-chamber and four-chamber views as well as the apical long-axis view) were used for subsequent analysis. Slice thickness was 10 mm.
CMR images were analyzed using commercial feature-tracking software (2D CPA MR; TomTec Imaging Systems, Unterschleissheim, Germany), which is a vector-based analysis tool based on a hierarchical algorithm. For each of the three short-axis and long-axis plane cine images, the LV endocardial border was manually drawn on a single frame by an expert reader. The software then automatically propagates the contour and follows its features throughout the cardiac cycle. Peak longitudinal, circumferential, and radial strain measurements for each LV segment were recorded, along with global strain as reported by the software.
3D STE Analysis
RT3DE data sets were analyzed using 4D LV analysis software (TomTec Imaging Systems) by an experienced observer. From the 3D full-volume data sets, the apical four-chamber, two-chamber, and long-axis view as well as one short-axis view were automatically extracted. Nonforeshortened apical views were identified by finding in the data set views with the largest LV long-axis dimensions from the apex and the mitral valve. LV boundaries were initialized by manually selecting specific anatomic landmarks (i.e., the mitral annulus and the LV apex), after which the 3D endocardial surface was automatically reconstructed. The papillary muscles were included in the LV cavity. Manual adjustments of the endocardial surface were performed as necessary. Subsequently, 3D speckle-tracking analysis was automatically performed throughout the cardiac cycle. The left ventricle was automatically divided into 16 segments using standard segmentation schemes. The software provided segmental longitudinal, circumferential, radial, and 3D strain time curves, from which peak global strain and averaged peak strain at three LV levels (basal, midventricular, and apical) were determined ( Figure 1 ). Three-dimensional strain describes the tangential deformation and is calculated as the vector sum of the longitudinal and circumferential strain components, ignoring the radial component. Anatomically, it may represent the resulting direction of the contraction of the muscle fibers that are aligned tangentially to the myocardial surface.
