The role of tissue harmonic imaging in fetal echocardiography

Transcription

1 Ultrasound Obstet Gynecol 2004; 23: Published online in Wiley InterScience ( DOI: /uog.962 The role of tissue harmonic imaging in fetal echocardiography D. PALADINI, M. VASSALLO, A. TARTAGLIONE, C. LAPADULA and P. MARTINELLI Fetal Cardiology Unit, Department of Gynecology and Obstetrics, University Federico II of Naples, Naples, Italy KEYWORDS: congenital heart disease; fetal echocardiography; fundamental frequency ultrasound; harmonic imaging; prenatal diagnosis; ultrasound ABSTRACT Objective To define the role of tissue harmonic imaging (THI) in fetal echocardiography. Method Three trials were conducted in a tertiary referral center: Study A was a prospective randomized trial including 50 women referred for fetal echocardiography. Those allocated to Arm 1 underwent conventional fundamental frequency ultrasound (FFU) and those allocated to Arm 2 underwent THI. Study B was conducted in 21 patients who were obese or overweight with significant weight gain in pregnancy. In these patients, both THI and FFU echocardiography were performed and compared. In Study C, THI was employed as a second-line rescue technique in cases of inadequate or incomplete examination by FFU. A subjective scoring system was used by a reviewer who had not performed the examinations to assess the comprehensiveness of the examination and the image resolution. The reviewer was blinded to the image modality. Results In Study A, no difference was found in the diagnostic accuracy between THI and FFU echocardiography but the resolution was significantly poorer in the THI arm. In studies B and C, THI performed significantly better than FFU (P < 0.001). Conclusions THI echocardiography seems to be the best technique to employ in obese women and in those in whom FFU fails to provide diagnostic information. However, due its poorer resolution in women of average weight, FFU echocardiography should remain the technique of choice. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. INTRODUCTION Tissue harmonic imaging (THI) has recently been introduced into commercially available ultrasound systems to enhance diagnostic performance in individuals with limited acoustic window mainly due to obesity or abdominal scarring. Harmonics are generated by tissue itself due to propagation of the fundamental transmitted band. When a transducer transmits a band of frequencies of, say, 2 MHz, the return energy will be in multiple frequency bands, the first of which corresponds to the transmitted fundamental band and is due to tissue interfaces and heterogeneities, whereas the second harmonic (in this case at 4 MHz) is produced by the tissue itself 1,2. Tissue harmonics increase with depth, being virtually absent at the skin level and increase up to the point where tissue attenuation makes them decrease. Therefore, their behavior is completely different from the fundamental frequency harmonic, the energy of which decreases linearly with depth. This behavior is the reason why the use of THI has been shown to improve image quality in obese individuals 3,4. As far as fetal echocardiography is concerned, there is only one report addressing the advantages of THI in fetal echocardiography 5. To assess whether this modality should be considered among the tools needed in a tertiary referral center for the diagnosis of fetal congenital heart disease (CHD), we designed a prospective study to assess the diagnostic performance of THI in comparison with fundamental frequency ultrasound (FFU). The objective of the study was to define the role of THI in fetal echocardiography in three settings: (1) as a standard technique in all patients to replace conventional FFU, (2) as a standard technique in diagnostically difficult patients only and (3) as a rescue technique in cases of diagnostic failure of conventional FFU. METHODS Study design and population The study was conducted over an 8-month period from June 2001 to January The investigation was prospective and included three components. Study A Correspondence to: Dr D. Paladini, Via Petrarca 72, Naples, Italy ( paladini@unina.it) Accepted: 30 September 2003 Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER

2 160 Paladini et al. was a randomized trial including 25 women in each of two arms: women referred to our unit for fetal echocardiography due to the presence of risk factors for fetal CHD were randomly allocated, at the time of telephone booking, to Arm 1 or Arm 2. Women allocated to Arm 1 underwent conventional FFU, whereas those allocated to Arm 2 underwent THI. This study lasted 7 weeks (June July 2001) and all cases were available for analysis. Study B was an observational study conducted in 21 patients with limited acoustic window, being overtly obese (body mass index > 30) or overweight with significant weight gain in pregnancy (> 10 kg by 22 weeks, > 15 kg by 30 weeks). In this group of patients, who were recruited after the completion of Study A, both THI and FFU echocardiography were performed, with THI examination carried out before FFU in 10 cases and after it in the other 11. Allocation to THI first or FFU first was chosen on an alternate basis. All examinations were conducted with the fetus in a favorable position, due to the limited acoustic window. Two cases were excluded from the analysis due to fetal position changing between the first and second evaluations, leaving 19 cases for evaluation. Study B recruitment was completed in 10 weeks (August October 2001). Studies A and B were conducted on normal fetuses only. Study C was conducted between November 2001 and January 2002 and involved THI being employed as a second-line rescue technique in cases of inadequate or incomplete examination with conventional FFU echocardiography. Of 142 cases (24 with CHD and 118 without) seen during the study period, 19 cases (15 normal fetuses and four with CHD) required THI echocardiography. Technique An Aloka 5000 Pro-Sound scanner system (Aloka, Tokyo, Japan) was used for the study. The system was equipped with two digital transducers: a multifrequency MHz convex probe and a multifrequency MHz probe with THI. The transmission frequency for THI was 2.14 MHz with four bandwidth options for harmonic reception (harmonic, resolution, standard, penetration): of these, the best suited for the single patient was used, corresponding in most instances with the highest resolution bandwidth ( MHz). Twodimensional settings were those commonly used for fetal echocardiography (very contrasted image, highest frame rate). The transmission frequency was kept as high as possible: 6.0 MHz in lean patients, MHz in women with normal adiposity and 3.5 MHz with/without THI according to the study protocols in overweight and obese women. According to the technical data provided by the manufacturer, lateral resolution was 0.6 mm at a depth of 8 10 cm for the MHz transducer in THI-resolution mode and 0.3 mm at a depth of 8 cm for the MHz transducer at 6.0 MHz. For the purposes of the study it was decided to select, out of all echocardiographic views, those aiming at the sequential analysis of intrathoracic cardiovascular anatomy, excluding extrathoracic views, such as the abdominal situs. Therefore, the echocardiographic views assessed in the present investigation were: four-chamber view, right and left outflow tracts, transverse view of the ductus arteriosus and longitudinal view of the venae cavae drainage in the right atrium. Optional views included the longitudinal view of the aortic arch with the neck vessels and the three-vessel view. Variables assessed Two variables were assessed: the comprehensiveness of the examination (diagnostic information) and the image resolution (degree of anatomic characterization). Two different scoring systems were developed to grade the quality of the examination. As to the former variable, the echocardiography was arbitrarily rated as complete, sufficient or incomplete. An examination was considered complete when all views could be obtained and all were clearly interpretable. The examination was rated sufficient when not all views could be obtained/interpretable but sequential atrioventricular and ventriculo-arterial anatomy could be confirmed. The echocardiography was judged incomplete when atrioventricular and/or ventriculo-arterial connections could not be clearly defined. Assigning a binary code to the main above reported five views (0 = not visualized/not interpretable, 1 = visualized) and an extra two points for the longitudinal view of the aortic arch, as a marker of excellent visualization, a complete echocardiography scored 5, a sufficient examination scored 3 4, while an incomplete examination scored < 3. As to image resolution, each of the six views was subjectively rated according to a four-point scale (from 1 = insufficient to 4 = optimal). The rationale for the double scoring system was to separately assess the adequacy of the standard diagnostic quality from the definition/resolution of the image. The ratings were done by a reviewer blinded to the image modality: since the type of image modality and the transducer emission frequency are shown in the upper right hand corner of the image, a paper sticker was placed on the corresponding area of the display while the reviewer rated the single frames. Follow-up All cases enrolled in Studies A and B and the 15 Study C cases with normal anatomy undergoing THI echocardiography were followed up by phone (normal cases). As to the four Study C cases with heart defects, three of them were directly followed up until 3 months of age (surgical files and echocardiography), while the autopsy confirmed the anomaly detected in the single case that underwent termination of pregnancy. Statistics The SPSS 8.0 software package (SPSS, Chicago, IL, USA) was used for statistical analysis. The ANOVA test for paired observations was used to compare intergroup mean differences. P-values < 0.05 were considered statistically

3 Harmonic imaging in fetal echocardiography 161 significant. Confidence limits were calculated for all variables. (P < and P < 0.01, respectively; Table 3). Images of four cases enrolled in this study are shown in Figure 1. RESULTS Study A The characteristics of the patients are reported in Table 1 and the mean visualization scores are shown in Table 2. As is evident from the data, in this unselected group of patients no difference was found in the diagnostic accuracy between THI and FFU echocardiography, though there was a trend towards better performance with THI (P = 0.06); on the contrary, FFU scored better in terms of image definition (P < 0.001). The number of fetuses in favorable position was not significantly different between the two arms (21/25 and 20/25). Study B In this subset of obese or overweight women, THI performed significantly better than FFU both in terms of standard diagnostic performance and image quality Study C In the rescue trial, THI was employed as a secondline imaging technique in 19/142 (13.3%) cases in which FFU echocardiography was judged incomplete or inadequate. It allowed normal cardiac anatomy to be confirmed in 14/15 normal cases, whereas only normal atrioventricular connections could be seen in the fetus Table 1 Characteristics of patients in the two arms of Study A* Variable Arm 1 Mean (SD) Arm 2 Mean (SD) Significance Maternal age (years) 30.0 (7.3) 30.2 (7.0) NS Gestational age (weeks) 22.4 (3.4) 21.4 (2.5) NS Mean maternal weight (kg) 71.4 (7.7) 75.2 (11.2) NS *Arm 1, fundamental frequency ultrasound echocardiography; Arm 2, tissue harmonic imaging echocardiography. NS, not significant. Figure 1 Comparison of tissue harmonic imaging (THI) with fundamental frequency ultrasound (FFU) in normal fetal hearts: Study B (in each image, the left panel is obtained with THI, the right with conventional FFU). (a) Four-chamber view, 89 kg patient, 23 weeks gestation: the apical area and the left ventricular wall are ill-defined in the FFU image, making the four-chamber view inadequate to evaluate the atrioventricular junction and the ventricular volumes. (b) Four-chamber view, 93 kg patient, 26 weeks gestation: both images are adequate to assess atria and ventricles, but the THI image (left) is clearer. (c) Four-chamber view, 110 kg patient, 21 weeks gestation: heart anatomy can be assessed on the THI image, but not on the FFU one, which is completely blurred. (d) Longitudinal aortic arch view, 91 kg patient, 22 weeks gestation: the whole arch is visible in the THI image (arrowheads indicate neck vessels and isthmus), whereas in the FFU image only the ascending aorta and the transverse arch are visible. LV, left ventricle; RA, right atrium.

4 162 Paladini et al. of one woman. In the remaining four cases (all with CHD), THI allowed the type of defect to be defined in three instances (critical aortic stenosis, double-inlet single ventricle with malposition of the great arteries, Shone syndrome; Figure 2a c). The fourth case was a 33-year-old woman weighing 123 kg. In this patient, conventional FFU echocardiography was able only to raise the suspicion of an abnormality of the ventriculoarterial junction because the two outflow tracts and the crossover of the vessels could not be seen. THI allowed detection of a tetralogy of Fallot (Figure 2d) and prompted a rapid karyotype, which revealed the presence of trisomy 21. The patient opted for termination of pregnancy and the postmortem examination confirmed the presence of the heart defect. At follow-up, no case of CHD was present in the 69 neonates of Studies A and B and in the 15 Study C cases considered normal. As to the other three cases of CHD, the prenatal diagnosis was confirmed by postnatal echocardiography. Table 2 Results of Study A (randomized trial) ANOVA test* Scoring system Arm Mean SD SE 95% CI ANOVA Visuali- 1 (FFU) P = 0.06 zation 2 (THI) Resolution 1 (FFU) P < (THI) *Arm 1, fundamental frequency ultrasound (FFU) echocardiography; Arm 2, tissue harmonic imaging (THI) echocardiography. SE, standard error. Table 3 Results of Study B (obese and overweight women) ANOVA test Scoring system Method Mean SD SE 95% CI ANOVA Visuali- FFU P < zation THI Resolution FFU P < 0.01 THI FFU, fundamental frequency ultrasound; SE, standard error; THI, tissue harmonic imaging. Figure 2 Comparison of tissue harmonic imaging (THI) versus fundamental frequency ultrasound (FFU) in fetal congenital heart disease: Study C (in each image the left panel is obtained with THI, the right with conventional FFU). (a) Critical aortic stenosis at 33 weeks gestation. The inversion of the foramen ovale flap indicating reverse left-to-right shunt is readily evident only in the THI image (arrowhead). Also the right ventricle is barely visible in the THI image only (arrow). (b) Double-inlet single ventricle at 29 weeks gestation. The atrioventricular plane (arrows) and the redundant chordae tendinae of the two valves are evident in the THI but not in the FFU image. Also the ventricular wall is ill-defined in the latter image. (c) Mitral stenosis in Shone syndrome (mitral and aortic stenosis, aortic coarctation) at 28 weeks gestation. The hypertrophy of the right ventricle and the mitral stenosis can be better assessed in the THI image. (d) Tetralogy of Fallot in a fetus with trisomy 21 at 21 weeks gestation. Extreme maternal obesity made the visualization of the ventriculo-arterial connection impossible on FFU (right); on THI (left) it was possible to detect the malalignment of the ventricular septal defect (VSD) with an overriding aorta. The arrowhead indicates the bright dot at the end of the VSD, which is distinguishable only on the THI frame. Ao, aorta; LV, left ventricle; RA, right atrium; SV, single ventricle.

5 Harmonic imaging in fetal echocardiography 163 DISCUSSION In the last few decades, obesity and overweight have become an alarming social problem 6,7. Excessive weight gain in pregnancy affects % of overweight pregnant women 8,9, and between 1 in 10 and 1 in 5 obstetric scans are performed on overtly obese or significantly overweight women, making this the most important factor responsible for poor ultrasound accuracy in pregnancy. Since incomplete or inadequate visualization of the four-chamber view represents an indication for Level II ultrasound, the proportion of obese pregnant women being seen at tertiary referral centers is high. The diagnosis of a heart defect in the fetus of overweight patients is made more challenging if we consider that maternal obesity may be associated with potential risk factors for fetal CHD such as diabetes or advanced maternal age (for the increased risk of chromosomal anomalies). Thus, having a tool to enhance visualization of the fetal heart in such poor acoustic window conditions must be considered of greater importance in tertiary referral centers. In this study, THI has been demonstrated to significantly enhance the visualization of fetal heart anatomy in obese and overweight patients both in normal and diseased cases, in agreement with the data reported by the only other study investigating the use of THI in fetal echocardiography 5. Furthermore, we have shown that in this subset of patients THI was able to define the heart anatomy in 13.3% of cases (15 normal fetuses and four diseased fetuses) in which FFU echocardiography was inconclusive or incomplete (Study C: rescue study). In patients of normal weight, THI has a comparable diagnostic power but, apparently, lower resolution than FFU, confirming also in this case the results of Kovalchin et al. 5. This apparent difference was the result of the application of the subjectively developed scoring system, but is substantiated by the technical figures provided by the manufacturer: the lateral resolution is reported to be 0.6 mm at a depth of 8 10 cm for the MHz transducer in THIresolution mode and 0.3 mm at a depth of 8 cm for the MHz transducer at 6.0 MHz. THI rendering of fetal cardiac structures shows some peculiarities worth underlining. First, THI seems to increase the brightness of anatomical structures; this enhances the identification of the apical part of the interventricular septum reducing, to a certain extent, also the echo dropout below the atrioventricular plane, which, on the contrary, is a common occurrence with FFU (Figures 1b, 1c and 2d). In addition, it should be noted that the high-contrast image that is typical of THI, together with its relative lack of lateral resolution, if compared with FFU, may erroneously lead to a falsepositive diagnosis of valvar dysplasia if the operator is not aware of the physics behind this image modality, due to the accentuated reverberation and the apparent rougher contour of valve leaflets (Figure 1b). Furthermore, the lack of lateral resolution makes THI unsuitable for ultrasound examination in early pregnancy. It must be acknowledged that the subjective evaluation score used to grade the ultrasound performance, even though the reviewer was blinded, leaves room for personal variations in perception of image clarity and informational content. The reader may easily think when studying the paired images in the two figures that they differ only in terms of receive gain setting (a few tags) or the scanning view (a few degrees), but we know that this was not the case and that those images did indeed provide profoundly different diagnostic information. In addition, it could be argued that an expert eye could easily detect the brighter and rougher texture of THI in comparison with the smoother aspect of FFU, regardless of the blinding. This might be true for an examination performed on lean patients, but scanning obese women often makes the adjustment of receive gain threshold, to differentiate between signal and background noise or dropout, very difficult with FFU and this leads in turn to a more subtle difference between THI and FFU imaging (Figure 1a and 1c). All in all, taking into proper consideration the above limitations, the subjective impression was that in difficult patients the use of THI not only makes the difference in diagnostic terms, but also reduces the duration of the scan compared with FFU, although an estimation of the length of examination was not among the endpoints of the present investigation. In conclusion, considering the objective set for the present study and the results of the three trials, we may affirm that: (1) in average weight women, FFU echocardiography remains the technique of choice, having similar diagnostic capacity but higher resolution than THI (Study A: randomized trial); (2) in obese women and in overweight women with excessive weight gain in pregnancy, THI echocardiography should become the standard technique, scoring significantly higher than FFU echocardiography both in diagnostic performance and in resolution capacity (Study B: observational trial) and (3) THI should be used whenever FFU fails to achieve diagnostic information (Study C: rescue trial). These findings suggest that ultrasound systems employed in referral centers for fetal CHD should be equipped with THI. 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