Patient Population and Study Design

Thirty patients in sinus rhythm with a wide range of RV size and function were prospectively studied (42% women; mean age, 67 ± 16 years; mean body surface area, 2.0 ± 0.2 m ² ). These patients were referred for CMR for clinical indications and agreed to undergo transthoracic 3D echocardiographic imaging in addition. Patients were selected to include a similar number with good and with suboptimal visualization of the RV endocardial border in the 3D echocardiographic images. Of the 30 patients, 22 (73%) had dilated cardiomyopathy, 11 (37%) had systemic hypertension, seven (23%) had pulmonary arterial hypertension, six (20%) had coronary artery disease, three (10%) had simple congenital heart disease, and one (3%) had end-stage renal disease.

Three-dimensional echocardiographic imaging with and without contrast-enhancing agents was performed immediately after CMR image acquisition to minimize the impact of changing loading conditions. RV end-diastolic volume (EDV) and end-systolic volume (ESV) and RVEF were measured from 3D echocardiographic images, both with and without contrast-enhancing agents, using the same analysis technique and compared with CMR reference values obtained using the standard disk-summation technique. The study was approved by the institutional review board of the University of Chicago Medical Center, and informed consent was obtained from each patient.

CMR Imaging and Analysis

CMR was performed on a 1.5-T scanner (Philips, Best, the Netherlands) with a five-channel cardiac coil. A steady-state free-precession dynamic gradient-echo sequence was used to obtain cine loops, during approximately 5-sec breath holds (repetition time, 3.0 msec; echo time, 1.6 msec; flip angle, 60°; temporal resolution, ∼30–40 msec). In all patients, six to 10 short-axis slices were obtained from the ventricular base to the apex (6-mm slice thickness, 4-mm gaps). These images were analyzed offline using commercial software (Medis Medical Imaging, Leiden, the Netherlands). In each slice, endocardial contours were manually traced at end-diastole and end-systole by an investigator experienced with CMR-based chamber quantification (Society for Cardiovascular Magnetic Resonance level III training), who was blinded to echocardiographic data. On the most basal slices, the right ventricle was differentiated from the right atrium by advancing the cine loop frame by frame throughout systole. If the cavity became smaller and the myocardium thicker, the slice was included in the RV volume, whereas portions of the cavity that became larger and did not show wall thickening were considered part of the right atrium. Endocardial trabeculae were included in the RV cavity. Disk summation was used to calculate EDV and ESV, and RVEF was calculated using the standard formula.

Transthoracic 3D Echocardiographic Imaging

RV-focused 3D echocardiographic data sets that included the entire right ventricle in the pyramidal scan volume were acquired by an experienced sonographer using the iE33 or EPIC imaging systems equipped with an S5 transducer (Philips Healthcare, Andover, MA). Simultaneous real-time short-axis multiplanar reconstruction was used at the time of image acquisition to ensure optimal visualization of the RV free wall ( Figure 1 ). Imaging settings were optimized to obtain RV full-volume images with clear endocardial border and high frame rate (24 ± 5 Hz) by minimizing the depth and the width of the imaging sector. The same imaging settings were used with contrast enhancement, resulting in similar frame rates (22 ± 5 Hz; P > .05). Three-dimensional echocardiographic data sets were stored digitally and used for offline analysis, with the reader blinded to CMR data. The quality of the nonenhanced 3D echocardiographic images was rated as optimal or suboptimal by an expert reader on the basis of the visualization of the RV free wall.

Example of acquisition of “good”-quality 3D echocardiographic imaging of the right ventricle without contrast ( left ), which is even better visualized with contrast enhancement ( right ). (A–C) Simultaneous multiplanar reconstructed 2D views: (A) RV focused, (B) orthogonal to (A) , and (C) short axis. (D) Three-dimensional RV-focused view data set.

Contrast enhancement was achieved using injection of Lumason (Bracco, Monroe Township, NJ; 1.5- to 2-mL intravenous bolus for each acquisition). To overcome the fast contrast washout from the right ventricle, imaging settings were optimized before the injection, and acquisition was performed as soon as the right ventricle was fully opacified. In addition to the default contrast settings (mechanical index, 0.28 ± 0.07), 3D echocardiographic simultaneous real-time short-axis multiplanar reconstruction planes were used to ensure optimal visualization of the RV free wall, as well as the anterior segments and RVOT, which are frequently not well visualized without contrast enhancement. Figure 1 shows an example of a good-quality 3D RV data set without contrast ( left ), in which endocardial border definition further improved with contrast enhancement ( right ). Figure 2 shows an example of a suboptimal-quality 3D RV data set, in which the endocardial border was poorly visualized without contrast ( left ) but was considerably improved by contrast enhancement ( right ), specially for the RV free-wall anterior and lateral segments.

Example of acquisition of a “suboptimal” quality 3D echocardiographic imaging of the right ventricle in the same format as in Figure 1 . See text for details.

Three-Dimensional Echocardiographic Analysis

Both contrast-enhanced and nonenhanced 3D echocardiographic data sets were analyzed (4D RV-Function 2.0, a module of TomTec-Arena; TomTec Imaging Systems, Unterschleissheim, Germany) to measure RV volumes and RVEF using a semiautomated algorithm that was recently validated against CMR reference. The first steps of analysis involved manual definition of the LV and RV long axes at end-diastole in both apical two- and four-chamber views ( Figures 3 A and 3B), LV outflow tract diameter in the apical three-chamber view ( Figure 3 C, top ), anterior and posterior junction points of the RV free wall with the interventricular septum, and the longest dimension of the RV cavity between the septum and the free wall, both in a single short-axis view ( Figure 3 C, bottom ).

Volumetric analysis of the right ventricle from a contrast-enhanced 3D echocardiographic data set: orientation and anatomic landmarks. To define a basic coordinate system, the user sets the left ( top ) and right ( bottom ) ventricular long axes in the apical four-chamber (A) and two-chamber (B) views at end-diastole. Then, LV outflow tract diameter is marked in the apical three-chamber view ( C , top ), and anterior and posterior junctions of the RV free wall with the interventricular septum, as well as the longest dimension of the RV cavity between the septum and the free wall, are set both in a single short-axis view ( C , bottom ). A2C , Apical two-chamber; A3C , apical three-chamber; A4C , apical four-chamber; AJL , anterior junction landmarks; AV1 , aortic valve annular point 1; AV2 , aortic valve annular point 2; MV , mitral valve; PJL , posterior junction landmarks; SAX , short-axis; TV , tricuspid valve.

These anatomic landmarks were used to automatically extract from the 3D echocardiographic data set the RV-focused four-chamber view, a series of short-axis views from base to apex, and an RVOT view for both end-systole and end-diastole ( Figures 4 A–4C, top and bottom , respectively), and to generate a 3D model of the right ventricle ( Figure 4 D). This RV 3D endocardial surface was then tracked throughout the cardiac cycle using speckle-tracking technology ( Figure 4 E), while manual fine-tuning was performed interactively to optimize the boundary position as necessary. Three-dimensional volumes over time were then numerically computed from the dynamic surface model and used to determine EDV, ESV, and RVEF.

Volumetric analysis of the right ventricle from a contrast-enhanced 3D echocardiography data set: extraction of the endocardial surface. After anatomic landmarks are set, an RV-focused four-chamber view (A) , short-axis view (B) , and RVOT view (C) are extracted from the 3D echocardiographic data set for both end-systole ( top ) and end-diastole ( bottom ). After endocardial borders are adjusted in these views, the 3D endocardial surface is calculated and rendered (D) . Then, the endocardium is tracked over the entire cardiac cycle using speckle-tracking, resulting in a dynamic surface that can be displayed as a fixed end-diastolic mesh with a beating RV cavity inside (E) .

Intertechnique Comparisons

EDV, ESV, and EF measurements from 3D echocardiographic images both with and without contrast enhancement were compared with the CMR reference values. These intertechnique comparisons included linear regression with Pearson’s correlation and Bland-Altman analyses to assess the mean intertechnique differences (biases) and limits of agreement (±2 SDs of the mean difference) with the CMR reference. These analyses were repeated in the subgroup of patients with suboptimal image quality.

Reproducibility Analysis

Measurements with and without contrast-enhancing agents were repeated by two readers for purposes of reproducibility analysis for the entire study group. This included repeated measurements by the same observer, at least 1 month later, as well as measurements by a second independent observer, both blinded to all prior measurements. Interobserver and intraobserver variability were calculated as an absolute difference between the corresponding pair of repeated measurements as a percentage of their mean in each patient and then averaged over the entire study group.

Statistical Analysis

Data are expressed as mean ± SD. P values < .05 were considered to indicate statistical significance. Intertechnique differences were tested for significance using paired two-tailed t tests. In addition, the biases relative to CMR were compared to better appreciate the level of intertechnique agreement.