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Eur Radiol (2008) 18: 1784–1790 DOI 10.1007/s00330-008-0949-2 Gorka Bastarrika Maria Arraiza Carlo N. De Cecco Stefano Mastrobuoni Matias Ubilla Gregorio Rábago Received: 4 November 2007 Accepted: 22 February 2008 Published online: 20 May 2008 # European Society of Radiology 2008 G. Bastarrika (*) . M. Arraiza . C. N. De Cecco . S. Mastrobuoni . M. Ubilla . G. Rábago Department of Radiology, Clínica Universitaria, Universidad de Navarra, Avenida Pío XII, 36, 31008 Pamplona, Spain e-mail: [email protected] Tel.: +34-948-255400 Fax: +34-948-296500 G. Bastarrika . M. Arraiza . C. N. De Cecco . S. Mastrobuoni . M. Ubilla . G. Rábago Department of Radiology, Universita’ di Roma “Sapienza”–Ospedale Sant’ Andrea, Rome, Italy CARD IAC Quantification of left ventricular function and mass in heart transplant recipients using dual-source CT and MRI: initial clinical experience G. Bastarrika . M. Arraiza . C. N. De Cecco . S. Mastrobuoni . M. Ubilla . G. Rábago Department of Cardiovascular Surgery, Clínica Universitaria, Universidad de Navarra, Pamplona, Spain Abstract The purpose of this study was to compare LV function and mass quantification derived from cardiac dual-source CT (DSCT) exams with those obtained by MRI in heart transplant recipients. Twelve heart transplant recipients who underwent cardiac DSCT and MRI examination were included. Double-oblique short-axis 8-mm slice thickness images were evaluated. Left ventricular ejection fraction, end-diastolic volume, endsystolic volume, stroke volume, cardiac output and myocardial mass were manually assessed for each patient by two blinded readers. A systematic overestimation of all left ventricular Introduction Allograft rejection and arterial hypertension after orthotopic cardiac transplantation are well known factors that may provoke changes in the function and mass of the transplanted heart [1]. Accurate quantification of left ventricular volumes, ejection fraction and myocardial mass is essential for patient management. So far, in routine clinical practice assessment of these parameters is performed with echocardiography. Magnetic resonance volumes by DSCT when compared with MRI was observed. Mean difference was 16.58±18.61 ml for EDV, 4.9 4± 6.84 ml for ESV, 11.64±13.58 ml for SV and 5.73±1.14 l/min for CO. Slightly lower values for left ventricular ejection fraction with DSCT compared with MRI were observed (mean difference 0.34±3.18%, p=0.754). Correlation between DSCT and MRI for left ventricular mass was excellent (rho = 0.972). Bland and Altman plots and CCC indicated good agreement between DSCT and MRI left ventricular function and mass measurements. The interobserver correlation was good. In conclusion, DSCT accurately estimates left ventricular ejection fraction, volumes and mass in heart transplant recipients. Keywords Dual-source computed tomography (DSCT) . Heart function . Cardiac mass . Heart transplantation imaging (MRI) is considered the standard of reference for the functional evaluation of the left ventricle [2–5]. Retrospectively ECG-gated multidetector CT (MDCT) is increasingly being used for cardiac imaging. MDCT allows accurate non-invasive evaluation of coronary arteries and depiction of significant coronary artery stenoses in patients with suspicion of coronary artery disease [6–8]. Feasibility of MDCT to assess global ventricular function using coronary MDCT datasets in this group of subjects has been proved [9–11]. In heart transplant recipients 1785 MDCT has also shown its ability to detect significant coronary artery stenoses compared with invasive coronary angiography [12, 13]. A recent study demonstrates that 64row MDCT may permit detection of coronary allograft vasculopathy [14]. However, due to several factors, including high heart rates, obesity and post-surgical changes, heart transplant recipients represent a challenge for MDCT cardiac imaging [15]. MDCT scanners have a limited temporal resolution, often requiring beta-blocker premedication to obtain high quality cardiac exams [11, 16]. These limitations may cause inaccuracies when determining cardiac volumes with MDCT. Dual-source computed tomography (DSCT) provides a high constant temporal resolution of 83 ms independent of the heart rate [17]. Hence, this technology might possibly improve accuracy and reliability of LV function and mass assessment [17]. Recently quantitative assessment of LV function with DSCT has been evaluated [18]. The role of this technique in heart transplant recipients has not been evaluated yet. In this study we compared LV function and mass quantification derived from cardiac DSCT exams with those obtained by MRI as the reference standard in patients who underwent orthotopic cardiac transplantation. Materials and methods Patient population Twelve consecutive heart transplant recipients referred for exclusion of coronary allograft vasculopathy underwent retrospectively ECG-gated contrast-enhanced DSCT. In all subjects additional cardiac MR examination was performed within 1 month before the DSCT examination. Standard exclusion criteria for MDCT coronary angiography and MRI were applied. All patients were in sinus rhythm and had normal renal function (creatinine <1.4 mg/dl). Patients with arrhythmia (more than four premature beats per minute or atrial fibrillation), hemodynamic instability, known allergy to iodated contrast media or renal failure (creatinine <1.4 mg/dl) were excluded from the study. Patients with MR unsafe ferromagnetic objects, referring claustrophobia or pacemaker or AICD implantation were also excluded. No beta blockers were employed prior to the scan to lower the heart rate. Written informed consent was obtained from all patients. The study protocol was approved by the institutional review board. DSCT image acquisition protocol and image reconstruction Retrospectively ECG-gated coronary CT angiography exams were performed with a DSCT scanner (Somatom Definition, Siemens Medical Solutions, Forchheim, Ger- many) at end inspiration. Scanning direction was craniocaudal from above the origin of the coronary arteries to the end of the diaphragm. Mean acquisition time was 8 s. Tube voltage of 120 kV and current of 410 mAs for both tubes were employed. Detector collimation was 32×0.6 mm, slice acquisition 64×0.6 mm by means of a z-flying focal spot [19] and gantry rotation time 0.33 ms. The pitch was variable (0.3–0.45) and automatically adapted to the heart rate. Full tube current was administered between 30 and 80% of the cardiac cycle by means of automatic tube current modulation (ECG pulsing) technique. Cardiac exams were performed after continuous injection of 70 ml of contrast material (Iomeron 400, Iomeprol, Bracco s.p.a, Milan, Italy) via an antecubital vein at a flow rate of 5 ml/s followed by 50 ml chaser saline flush using a dualhead power injector (CT Stellant, Medrad Inc., Indianola, PA). Data acquisition was triggered using the bolus tracking technique with the region of interest placed into the aorta with a threshold of 100 HU. A mono-segment reconstruction algorithm that uses data from a quarter rotation of both detectors was employed for retrospective image reconstruction [17]. Double-oblique short-axis orientation images encompassing the whole heart were reconstructed with section thickness of 8 mm and no interslice gap. Medium smooth convolution kernel (B26f) and image matrix of 512×512 pixels were used. Image series were directly reconstructed from the raw data in 5% steps throughout the entire cardiac cycle (0–95% of the R-R interval) resulting in 20 phases per cardiac cycle. No manual ECG-editing was performed. All DSCT images were suitable for analysis. Reconstructed images were transferred to an external workstation (Leonardo, Siemens Medical Solutions) equipped with a dedicated cardiac post-processing software tool (Argus, Siemens Medical Solutions). MRI image acquisition protocol MRI was performed using a 1.5-T MRI system (Magnetom Symphony with quantum gradients; maximum gradient amplitude 30 mT/m; slew rate, 125 mT/m/s, Siemens Medical Solutions, Erlangen, Germany) with a fourelement phased array coil. After localizer images were obtained, dynamic 8–12 contiguous short axis cine loops covering the entire left ventricle were acquired using a steady-state free precession (SSFP) sequence. The following parameters were employed: TR: 3.09 ms, TE: 1.3 ms, flip angle: 80, matrix: 156×192, field of view: 260– 280×325–375 mm. In-plane resolution was 1.7×1.7 mm and temporal resolution varied from 25–50 ms. Slice thickness was 8 mm. No interslice spacing was used. Twenty-five phases were acquired per cardiac cycle using retrospective gating. All MRI images were suitable for analysis. Reconstructed images were transferred to the same external workstation. 1786 DSCT and MRI data analysis DSCT and MRI images were assessed, in duplicate, by two blinded readers. For quantitative evaluation of cardiac parameters, slices from the base of the heart to the apex were analyzed. The base of the left ventricle was defined as the most basal slice surrounded by at least 50% myocardium in all cardiac phases [20] and the apex as the last slice with a visible lumen along the entire cardiac cycle. In each patient end-diastolic and end-systolic phases were visually determined and manually marked by the observers as the images showing the largest and smallest LV cavity areas, respectively. Endocardial and epicardial borders of the left ventricle were manually traced on serial short axis slices at end-systolic and end-diastolic phases using Argus software (Fig. 1). Papillary muscles and trabeculations were excluded from the volumetric analysis and included in myocardial mass quantification. Left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), cardiac output (CO), and myocardial mass were calculated for all patients using the Simpson’s method. This method consists of summing the endo- and epicardial area of all end-diastolic and endsystolic images and multiplying the result by the slice thickness. Left ventricular mass was calculated as the Fig. 1 DSCT (upper row) and MRI (lower row) images of a 51-year-old heart transplant recipient. End-diastolic (a, c) and end-systolic images with manually traced endo-and epicardial borders are shown difference between endo- and epicardial volumes at enddiastole multiplied by myocardial density (1.05 g/ml). Statistical analysis All data are summarized as mean ± standard deviation. A Wilcoxon test for paired samples was employed to calculate differences in left ventricular parameters for respective DSCT and MRI values. For linear correlation analysis the Spearman rank correlation coefficient (rho) was determined. Correlation was defined as poor (rho=0); minimal (rho=0.1–0.40), moderate (rho=0.41–0.60), good (rho=0.61–0.80) and excellent (rho=0.81–1.0). To assess the degree of agreement between the results of DSCT and MRI for each pair of left ventricular values Bland and Altman plots including mean differences and limits of agreement [21] were generated. Concordance-correlation coefficient (CCC) was also calculated for each measured variable and to assess interobserver variability [22]. The CCC can range from 0 to 1, with a CCC of zero representing no agreement and a CCC of 1 meaning perfect reliability. A p-value of 0.05 or less was considered statistically significant. Data analysis was performed using commercially available statistical softwares (MedCalc, 1787 Version 9.3.0.0. MedCalc Software; Mariakerke, Belgium, and SPSS for Windows, version 13.0/SPSS Inc., Chicago, IL). Results Patient population Twelve consecutive patients underwent cardiac DSCT and MRI. The study population was predominantly male (11 men, 1 woman) with a mean age of 63.92±11.81 years (age range 36–77). The mean time from transplantation to study enrolment was 10.42±5.06 years (range: 4.5–19.8 years). The mean heart rate was 88.42±11.86 bpm during DSCT (range: 71–109 bpm) and 87.5±12.19 bpm during MRI (range: 64–114 bpm) (p=0.97, NS). Left ventricular function and mass In all patients cardiac DSCT and MRI exams were successfully performed without complications. All studies were of adequate quality for function and mass assessment allowing optimal manual segmentation of the left ventricle. The mean left ventricular ejection fraction, left ventricular volumes and left ventricular mass are summarized in Table 1. Overall values were within normal limits. The mean EF assessed on DSCT was 68.19±4.52%, wheareas the mean EF estimated from MRI was 68.53±2.853%. Left ventricular volumetric measurements as determined with DSCT showed a mean EDV of 113.47±24.37 and a mean ESV of 35.43±6.42 ml, whereas MRI revealed a mean EDV of 96.88±20.71 ml and a mean ESV of 30.49± 6.82 ml. The mean SV calculated from DSCT was 78.02± 20.35 ml and the mean SV estimated from MRI was 66.37±14.79 ml. The mean CO derived from DSCT was 6.83±1.99 l/min, wheareas the mean CO estimated from MRI was 5.73±1.14 l/min. There was good correlation between DSCT and MRI measurements of left ventricular function parameters except for the end-systolic volume for which correlation was minimal (rho=0.392). A systematic overestimation of all left ventricular volumes by DSCT when compared with MRI was observed (Table 1). BlandAltman analysis demonstrated a trend toward DSCT resulting in slightly lower values for left ventricular ejection fraction compared with MRI (mean difference 0.34±3.18%). Mean left ventricular mass as determined with DSCT was 120.29±34.45, whereas the mean left ventricular mass estimated from MRI was 116.08±27.35 g. This difference was not statistically significant (p>0.05). Spearman rank correlation between DSCT and MRI for left ventricular mass was excellent (rho=0.972). Bland and Altman plots and CCC indicated good agreement between DSCT and MRI left ventricular function and mass measurements (Fig. 2). Results are shown in Table 1. The interobserver agreement for left ventricular parameters by means of DSCT was 0.74 (0.33 to 0.92) for EF, 0.90 (0.73 to 0.97) for EDV, 0.87 (0.66 to 0.95) for ESV, 0.88 (0.69 to 0.96) for SV, 0.83 (0.56 to 0.94) for CO, and 0.92 (0.79 to 0.97) for left ventricular mass. The interobserver agreement was 0.50 (0.15 to 0.73) for EF, 0.91 (0.74 to 0.97) for EDV, 0.84 (0.66 to 0.93) for ESV, 0.79 (0.51 to 0.91) for SV, 0.78 (0.43 to 0.93) for CO, and 0.68 (0.30 to 0.87) for left ventricular mass using MRI. Discussion The main finding of this study is that DSCT provides accurate measurements of left ventricular ejection fraction, volumes and mass in orthotopic heart transplant recipients. Recent reports have emphasized the potential of MDCT to evaluate coronary arteries and measure cardiac function within a single exam [9–11]. However, as heart transplant recipients represent a challenge for cardiac MDCT imaging, only few papers focus on the role of 64-row MDCT scanners in determining coronary allograft vasculopathy and assessing cardiac function [12, 13, 15]. High resting heart rates and the absence of response to oral beta-blocker Table 1 Differences in left ventricular function and mass quantification as determined by DSCT and MRI EF (%) EDV (ml) ESV (ml) SV (ml) CO (l/min) Mass (g) DSCT MRI P value rho value Bland- Altman CCC 68.19±4.52 113.47±24.37 35.43±6.42 78.02±20.35 6.83±1.99 120.29±34.45 68.53±2.853 96.88±20.71 30.49±6.82 66.37±14.79 5.73±1.14 116.08±27.35 0.754 0.015 0.034 0.019 0.015 0.308 0.641* 0.701* 0.392 0.769* 0.776* 0.972* -0.34 (-2.37 /1.68) 16.58 (4.76 /28.40) 4.94 (0.59 /9.29) 11.64 (3.01 /20.27) 1.10 (0.31 /1.89) 4.21 (-3.68 /12.10) 0.64 0.51 0.36 0.57 0.56 0.91 (0.25–0.85) (0.09–0.78) (-0.11–0.69) (0.18–0.81) (0.24–0.77) (0.77–0.97) Data are presented as mean ± SD. EF: ejection fraction; EDV: end-diastolic volume; ESV: end-systolic volume; SV: stroke volume; CO: cardiac output; mass: myocardial mass. CCC: concordance correlation coefficient. *p<0.05 1788 Fig. 2 Bland-Altman plots show the agreement between DSCT and MRI. Plots for left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), cardiac output (CO) and LV mass (MASS) are presented premedication by heart transplant recipients have limited the widespread employment of MDCT for coronary imaging in this population [15]. On the other hand, when comparing cardiac function parameters obtained with MDCT with respect to MRI, results are inconsistent [11, 23, 24]. This inconsistency might be due to the common practice of giving beta blockers when performing cardiac MDCT exams [25–27], which may artificially reduce the heart rate and thus affect estimation of cardiac parameters [11, 28]. Dual-source CT allowed for robust cardiac image quality in our heart transplant recipient series, which was not influenced by their high resting heart rates (mean 88.42± 11.86 bpm, range: 71–109 bpm). Optimal image quality permitted accurate evaluation of left ventricular volumes and mass in all subjects, with good agreement with respect to data obtained from MRI. Even if the difference was not statistically significant, a tendency to underestimate the ejection fraction was found in this series. Results presented herein support findings of similar studies performed with MDCT [11, 29–31], but interestingly, differ from recently reported data using a DSCT scanner [18]. In their study Busch at al. [18] found non-significant differences between functional parameters acquired with DSCT and MRI. According to the authors, this might be due to the Bainbridge reflex produced by rapid contrast material injection causing increased sympathetic input in a study population that did not receive pre-scan beta-blocker therapy. As our study population consisted of subjects in whom the sympathetic reflex is inhibited, the cited positive 1789 chronotropic effect presumably may not be so intense. We also found overestimation of the end-systolic volume probably due to the fact that temporal resolution of DSCT (83 ms) still remains lower than that of MRI (40 ms). According to our results, correlation between DSCT and MRI data was good for all cardiac function parameters except for the end-systolic volume (rho =0.392). The Bland-Altman analysis showed acceptable limits of agreement and minimal bias, suggesting that data derived from DSCT may be used as an estimate of left ventricular parameters. As already demonstrated by previous studies [32, 33], we also observed equivalent quantification of left ventricular mass with DSCT and MRI (mean difference 4.21±12.42 g, p=0.308], supporting the fact that threedimensional techniques do not depend on limitations imposed by geometric assumptions [34, 35]. This issue is of particular interest in heart transplant recipients, in whom post-surgical changes, the different orientation of the transplanted heart, the inadequate acoustic window, the remodeling process, and the potential foreshortening of the left ventricular apex [34, 35] may limit accurate quantification of cardiac parameters by routinely employed diagnostic tools, such as echocardiography [36]. Our study has several limitations. First, a small cohort of heart transplant recipients was included. Second, patients did not undergo cardiac DSCT and MRI on the same day, but were clinically stable, no allograft rejection was demonstrated at the time of study, and their therapy remained unchanged. Third, the number of acquired phases in DSCT and MRI differed. This might cause differences in the identification of end-systolic and end-diastolic phases. Nevertheless, limits of agreement between DSCT and MRI were acceptable. In conclusion, our findings reveal that DSCT accurately estimates left ventricular ejection fraction, volumes and mass in heart transplant recipients. We observed that DSCT tends to overestimate left ventricular volumes when compared with MRI. One advantage of DSCT is the fact that clinicians may use this technique for a one-stop-shop evaluation of the heart in heart transplant recipients without the need of additional radiation exposure or contrast administration. References 1. 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