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Published online before print December 29, 2003, 10.1148/radiol.2302021309
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(Radiology 2004;230:383-388.)
© RSNA, 2003

Experimental Studies

Accurate Quantification of Right Ventricular Mass at MR Imaging by Using Cine True Fast Imaging with Steady-State Precession: Study in Dogs1

Stephanie M. Shors, MD, Carina W. Fung, BS, Christopher J. François, MD, J. Paul Finn, MD and David S. Fieno, PhD

1 From the Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Ill. Received October 10, 2002; revision requested December 19; final revision received June 5, 2003; accepted June 13. Address correspondence to D.S.F., Cedars-Sinai Medical Center, S. Mark Taper Imaging Center, Room 1258, 8700 Beverly Blvd, Los Angeles, CA 90048 (e-mail: david.fieno@cshs.org).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To assess the accuracy of cine magnetic resonance (MR) imaging with a segmented true fast imaging with steady-state precession (FISP) technique for right ventricular (RV) mass quantification.

MATERIALS AND METHODS: Fourteen dogs were imaged with a 1.5-T clinical MR imaging unit by using an electrocardiographically gated true FISP sequence. Contiguous segmented k-space cine images were acquired from the base of the RV to the apex during suspended respiration (repetition time msec/echo time msec, 3.2/1.6; section thickness, 5 mm; in-plane resolution, 1.0 x 1.3 mm2). After imaging, each dog was sacrificed, and the RV free wall was isolated and weighed. Each MR imaging data set was analyzed twice by each of two independent observers who were blinded to the results of RV mass measurement at autopsy, and the mass measurements at MR imaging were compared with the autopsy results by using linear regression and Bland-Altman analysis.

RESULTS: RV mass measurements calculated by using the true FISP cine MR images were nearly identical to those at autopsy (R = 0.82, standard error of the estimate = 1.7 g, P > .05), with a mean difference between the autopsy and MR imaging measurements of 0.3 g ± 1.7 (1.9% ± 8.2) (P > .05). Inter- and intraobserver variations were small, with a mean interobserver variability of -0.1 g ± 2.3 and a mean intraobserver variability of 0.2 g ± 1.6 at every-section analysis.

CONCLUSION: In this animal model, true FISP cine MR imaging enabled accurate quantification of RV mass.

© RSNA, 2003

Index terms: Animals • Heart, MR, 523.121416 • Heart, ventricles, 523.121416 • Magnetic resonance (MR), experimental studies • Magnetic resonance (MR), pulse sequences


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Right ventricular (RV) hypertrophy may be seen in a number of congenital and acquired conditions, including valvular disease, lung disease, and chronic left-sided heart failure (1–3). When RV hypertrophy results from chronic pressure overload, it can lead to failure of the RV (4), as well as alterations in the mass, geometry, and functional status of the left ventricle (5–7). Because of the complex shape and substernal location of the RV, it is difficult to estimate RV mass with most imaging techniques (8). Thus, sparse in vivo imaging data exist regarding the pathophysiologic importance of RV hypertrophy, and RV mass is not routinely evaluated in clinical practice. If an accurate and reliable means of determining RV mass were available, it would be a valuable tool for both research and clinical studies.

Several imaging modalities, including echocardiography, computed tomography, and radionuclide imaging (9–17), have been used to provide indexes of RV hypertrophy, but the success of these techniques has been limited. More recently, attention has been focused on magnetic resonance (MR) imaging, which has been used to evaluate RV massin several studies (15,18–25). Relatively few of these investigations, however, have involved validating MR imaging–determined mass measurements by comparing them with mass measurements at autopsy (15,20–23), and even fewer have involved validation studies with in vivo MR images (22,23). The lack of in vivo data is likely due to the challenging anatomic features of the RV, such as its thin wall, crescentic shape, and extensive trabeculation. These anatomic features may be suboptimally depicted with the low-spatial-resolution, limited-contrast imaging techniques that have previously been available.

Recently, segmented true fast imaging with steady-state precession (FISP) has been introduced for cine MR imaging of the heart (26,27). Although the phenomenon of steady-state free precession has been described in the literature since the 1950s (28,29), only recently has the hardware been developed to the point where these techniques are of practical value. Modern steady-state techniques, such as true FISP, yield high-quality images of the beating heart with improved contrast between blood and myocardium and increased spatial resolution (26,27) and are now commercially available with MR imaging platforms from multiple vendors. The high contrast between blood and myocardium inherent with steady-state free precession suggests that it may enable better visualization of the RV wall and could be used in the quantification of RV mass.

Although the use of true FISP has been well validated for the quantification of left ventricular mass (30), to our knowledge true FISP has not previously been evaluated for the more challenging quantification of RV mass. Therefore, the purpose of this study was to assess the accuracy of segmented true FISP cine MR imaging for RV mass quantification.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Experimental Protocol
Fourteen 15–24-kg adult mongrel dogs were included in the study. All study activities were performed in accordance with the guidelines of the Animal Care and Use Committee at our institution. Before imaging, anesthesia was induced in each animal with intravenous administration of 11 mg of methohexital sodium (Brevital; Eli Lilly, Indianapolis, Ind) per kilogram of body weight. Intubation was then performed for each dog, and mechanical ventilation was initiated. A 14 x 28-cm flexible surface coil was secured around the thorax, and imaging was performed with a clinical 1.5-T Sonata MR imaging unit (Siemens Medical Solutions, Iselin, NJ).

After imaging, each dog was sacrificed by using an overdose of sodium pentobarbitol (Nembutal; Abbott Laboratories, North Chicago, Ill). The heart was removed, and the great vessels, atria, valves, and epicardial fat were trimmed from it. The left ventricle and interventricular septum were separated from the RV free wall, and the RV free wall, including the papillary muscles, was weighed to determine the RV mass.

MR Imaging Protocol
Contiguous short-axis images were acquired from the base of the RV to the apex by using a previously described (27,30) segmented k-space cine true FISP sequence. Image acquisition required a 14-second breath hold and a simultaneous acquisition of electrocardiographic data. Imaging parameters were similar to those used in human imaging. Typical imaging parameters included the following: repetition time msec/echo time msec, 3.2/1.6; flip angle, 60°; bandwidth, 700 Hz/pixel; field of view, 260 x 195 mm2; matrix, 256 x 150; in-plane resolution, 1.0 x 1.3 mm2; and phases, 32. Section thickness was 5 mm, and section spacing was not used. Eight to 10 contiguous short-axis sections typically encompassed the entire RV. To ensure complete coverage of the RV, short-axis images were acquired from the level of the tricuspid valve to the level of the left ventricular apex.

Image Analysis
MR images were randomly sorted and analyzed twice by each of two independent observers who were blinded to the autopsy results (S.M.S., C.W.F.), for a total of four readings.

The first and second readings were conducted independently for each observer at least 2 weeks apart, with the images arranged in a different order for the second reading. Images were analyzed at a remote workstation by using dedicated cardiac analysis software (Argus; Siemens Medical Solutions). The observers were familiar with the anatomic features of the RV and had had substantial experience with the postprocessing software.

Each data set was displayed in a cinematic format, and end diastole was identified as occurring in the first frame of the electrocardiographically triggered acquisition. For each end-diastolic image obtained from the base to the apex, contours were drawn manually around the endocardial and epicardial borders of the RV, as shown in Figure 1. The most basal section in which the tricuspid valve was seen was considered to show the base of the RV, and the most apical section containing a portion of the RV chamber was considered to show the apex. Papillary muscles were included in the contours, while the interventricular septum, epicardial fat, and the pericardium were excluded, as shown in Figure 2. During manual contour placement, the observers could review their contours and redraw or fine-tune them as necessary.



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  		Figure 1. Long-axis (left) and short-axis (middle) true FISP cine MR images (3.2/1.6, 60° flip angle) of the RV in a dog demonstrate typical positions (dashed lines) in which short-axis sections (arrows) were obtained. RV contours (gray portions of diagrams) were drawn on end-diastolic images.

 


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  		Figure 2. Typical short-axis true FISP cine MR image (3.2/1.6, 60° flip angle) before (left) and after (right) tracing of RV contour. In tracing the contour and subsequently calculating RV mass, epicardial fat (1) was excluded, papillary muscles (2) were included, and interventricular septum (3) and pericardial adhesions (4) were excluded.

 
After the contours were drawn, the software calculated the RV mass by using the acquired image resolution parameters and assuming a myocardial tissue density of 1.05 g/mL. So that we could later determine the effect of section spacing, contouring was also performed on every other section of each data set, beginning with the most basal section; this resulted in an effective section spacing of 10 mm.

Statistical Analysis
The relationship between the RV mass measurements at MR imaging and those at autopsy was assessed with linear regression analysis and the Bland-Altman method (31). The linear correlation coefficient (R value) and the standard error of the estimate (SEE) were calculated by using linear regression analysis, while the estimated bias (ie, the mean difference between RV mass measurements at MR imaging and those at autopsy) was calculated by using the Bland-Altman method. In addition, two-tailed paired t tests were used to determine if there was a significant difference between the RV mass measurements at MR imaging and those at autopsy. A P value of less than .05 was considered to indicate a statistically significant difference. To determine if this study was powerful enough to reveal important differences between the MR imaging and autopsy masses, a power analysis was performed by using a two-sided significance level of .05.

The same statistical methods were used to compare the MR imaging mass measurements made by the two independent observers (ie, to determine interobserver variability) and to compare the two MR imaging mass measurements made by the same observer (ie, to determine intraobserver variability) for the every-section method. In addition, formal outlier analysis was performed for all of the data by using the Grubbs method (32). All results are expressed as means ± SDs.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
High-quality dynamic MR images of the RV were obtained in all animals. An example of the RV images is shown in Figure 1; the endocardial and epicardial surfaces of the RV are clearly visualized. Figure 2 shows an additional example.

All RV mass measurements are given in Tables 1 and 2. Formal outlier analysis did not reveal any statistically significant outliers. The mean RV mass determined by weighing the RVs at autopsy was 22.3 g ± 3.0, while the mean RV mass calculated at MR imaging was 22.6 g ± 2.9 for the every-section analysis and 22.0 g ± 3.1 for the every-other-section analysis.


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  		TABLE 1. RV Mass Measurements at Every-Section Analysis

 

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  		TABLE 2. RV Mass Measurements at Every-Other-Section Analysis

 
For the four readings in which contours were drawn on every section (Table 1), linear regression analysis revealed close correlation between the RV mass measurements at autopsy and those at MR imaging (R values for the four readings were 0.78, 0.80, 0.89, and 0.91; corresponding SEE values were 2.3, 2.1, 1.1, and 1.2 g). In addition, results of Bland-Altman analysis indicated a high level of agreement between the RV mass measurements at MR imaging and those at autopsy, with a mean difference between the two measurement methods (ie, estimated bias) of less than 1 g for all readings. Finally, two-tailed paired t testing revealed no statistically significant difference between the RV mass measurements at autopsy and those at MR imaging. Combining the data from all MR image readings yielded an average correlation coefficient of 0.82 (SEE = 1.7 g) and an average estimated bias of 0.3 g ± 1.7 (1.9% ± 8.2 of the RV mass at autopsy), as shown in Figure 3.



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  		Figure 3. Linear regression (left) and Bland-Altman (right) plots of every-section analysis data show close agreement between RV mass measurements at MR imaging and the true RV masses at autopsy. Solid black squares = observer 1, reading 1; open black squares = observer 1, reading 2; solid gray triangles = observer 2, reading 1; open gray triangles = observer 2, reading 2.

 
For the four readings in which contours were drawn on every other section (Table 2), statistical analysis revealed a slightly greater difference between the RV mass measurements at autopsy and those at MR imaging, with a mean correlation coefficient of 0.75 (SEE = 2.1 g) and a mean estimated bias of -0.3 g ± 2.1 (-1.0% ± 9.8).

Assuming a clinically relevant difference to be 10% of the mean RV mass (ie, 2.2 g), the power of this study to reveal a clinically relevant difference between the RV mass measurements at MR imaging and those at autopsy was 99% for the every-section analysis and 93% for the every-other-section analysis.

Analysis of interobserver and intraobserver variability at the every-section analysis revealed close correlation and a high level of agreement between the MR imaging mass measurements obtained by the two independent observers and the two sets of mass measurements obtained by each observer. Comparison of the measurements made by observer 1 and those made by observer 2 revealed a mean correlation coefficient of 0.72 (SEE = 2.3 g) and a mean difference in mass measurements of -0.1 g ± 2.3. When RV mass measurements at the first reading were compared with those at the second reading for each observer, the mean correlation coefficient was found to be 0.85 (SEE = 1.6 g), and the mean difference in mass measurements was found to be 0.2 g ± 1.6. There were no significant differences in mean RV mass measurements between any of the MR image readings.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
The results of this study demonstrate that, in an animal model, RV mass can be accurately quantified by using segmented cine true FISP MR imaging. Because of the technical challenges inherent in imaging the RV, it has been relatively neglected in the study of cardiac dysfunction. It is known that RV hypertrophy occurs in numerous conditions, however, and this complication may have prognostic significance (33). Clear visualization of the RV in a beating heart also may be helpful for evaluating RV function. The ability to accurately segment the RV wall for computation of RV mass could mean, in principle, that one could determine the percentage of wall thickening from end diastole to end systole.

Prior to our study, several other investigators had evaluated MR imaging for the quantification of RV mass (15,20–23). In the studies in which hearts were imaged ex vivo (15,20,21), MR imaging–determined values for RV mass were within 1%—12% of autopsy-determined values. Ex vivo imaging, however, eliminates potential errors caused by cardiac and respiratory motion and is of no clinical value. In two validation studies in which MR images of the RV were acquired in vivo (22,23), the reported accuracies varied. McDonald et al (22) used snapshot gradient-echo MR imaging to quantify RV mass in 10 dogs and found the error of measurement for the MR imaging–determined RV masses to be 5% when they were compared with the autopsy-determined masses. However, when cine MR imaging was used by Lorenz et al (23) to quantify RV mass in 10 dogs, MR imaging–based estimates were found to be within 13% of the true values. In a related study (24), the reproducibility of RV mass measurements at spin-echo and cine MR imaging was evaluated, and these investigators suggested that these techniques were adequate for the diagnosis of RV hypertrophy but potentially inadequate for the detection of changes at serial examinations. In the present study, our results suggest that, in an animal model, RV mass measurements calculated at cine true FISP MR imaging are within 1.9% ± 8.2 of the true values.

The close agreement between RV mass measurements at MR imaging and those at autopsy observed in the present study is at least in part due to the high signal and contrast of true FISP MR imaging. The true FISP technique has been found to yield images that are superior in quality to fast low-angle shot images and have twice the blood-myocardial contrast-to-noise ratio (27). Theoretically, this feature of true FISP should enhance the ease of image segmentation and improve the accuracy of RV mass measurements.

It should be noted that the present study had several limitations. For example, the animals used in this study underwent intubation and received mechanical ventilation, which allowed for near-perfect breath holds and eliminated respiratory motion as a potential source of error. In patients with cardiac disease, repeated consistent breath holds may be more difficult to achieve. We also did not attempt to address the potential differences between dog hearts and human hearts in this study. In addition, end diastole was selected as a starting point for our RV mass measurements at MR imaging. However, the increased myocardial thickness at end systole may facilitate manual segmentation of the RV and improve the accuracy of RV mass measurements. Finally, the results of this study establish only the accuracy of RV mass measurement with segmented k-space true FISP MR imaging. The accuracies of other conventional MR imaging sequences, such as spin-echo and non–steady-state gradient-recalled echo-sequences, were not evaluated in this study.

Practical application: We conclude that, in well-controlled conditions, cine MR imaging performed by using a segmented true FISP technique can be used for accurate in vivo quantification of RV mass. This may have important implications for future investigations of the pathophysiologic consequences of RV hypertrophy, as well as for the clinical evaluation of patients with this condition.


   FOOTNOTES
 
Abbreviations: FISP = fast imaging with steady-state precession, RV = right ventricle, SEE = standard error of the estimate

Author contributions: Guarantor of integrity of entire study, D.S.F.; study concepts, S.M.S., C.J.F., J.P.F., D.S.F.; study design, S.M.S., J.P.F., D.S.F.; literature research, S.M.S., D.S.F.; experimental studies, D.S.F.; data acquisition, D.S.F.; data analysis/interpretation, all authors; statistical analysis, S.M.S., D.S.F.; manuscript preparation, S.M.S.; manuscript definition of intellectual content, revision/review, and final version approval, all authors; manuscript editing, S.M.S., D.S.F., J.P.F.


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RESULTS
 DISCUSSION
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