Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results

Harmonic Power Doppler Contrast Echocardiography: Preliminary Clinical Results HARALD BECHER, M.D., KLAUS TIEMANN, M.D., REINHARD SCHLIEF, M.D., PH.D.,* BERNDT LUDERITZ, M.D., and NAVIN C. NANDA, M.D."" Department of Cardiology, University of Bonn, Germany, *Clinical Research Department, Schering AG, Berlin Germany, and the **Division of Cardiovascular Disease University of Alabama, Birmingham, Alabama Background: I n fundamental and second harmonic echocardiography new contrast media opacify the cavities and reduce the difference in the gray level between the cavity and the myocardium thus obscuring the borders of the myocardium. Objectives: The aim of the study was to examine the potential usefulness of second harmonic power Doppler imaging (HPD) in providing adequate delineation of the myocardium from the left ventricular (LV) and right ventricular (RV) cavities during intravenous contrast echocardiography. Using HPD, microbubbles in a cavity or a tissue are imaged as colored pixels superimposed on a conventional B-scan image. Methods: I n a pilot study, three healthy volunteers and two patients with ischemic heart disease were investigated using a n ATL-HDI 3000 echo system. Four chamber views were obtained using fundamental B-scan, harmonic B-scan two-dimensional echocardiography (H2D) and HPD following intravenous injections of 3 g Levovist? Results: Using intermittent scanning I recording, H2D and HPD provided intensive and homogenous contrast effects i n the RV and LV cavities. Good delineation of the myocardium was found in all subjects using HPD, whereas in two of three volunteers and in one of two patients ventricular septa1 and apical endocardia1 borders were obscured during H2D. No obvious change i n myocardial backscatter was visually found with H2D. However, in all three healthy volunteers and in one of two patients, HPD recordings demonstrated patchy and reticular patterns in the myocardium, which were different from the homogenous signals in the LV cavity. These are consistent with imaging of intramyocardial coronary vessels. Conclusions: HPD with intravenous Levovist is feasible, This technique demonstrated good delineation of ventricular cavities from the myocardium as well as presence of visible contrast i n the myocardium. This pilot study justifies further clinical trials to evaluate the clinical benefit of this approach. ( E C H O C A R D I O G W m , Volume 14,November 1997) harmonic imaging, power Doppler, harmonic power Doppler, contrast echocardiography

Harmonic imaging takes advantage of the fact that when microbubbles are insonated, they begin to resonate and generate harmonics of the transmitted frequency. Blood and tissue are Address for correspondence and reprints: Priv. DOZ.Dr. Harald Becher, Medizinische Klinik und Poliklinik, Kardiologie, Sigmund-Freud Str, 25, 53105 Bonn, Gemany.

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thought to produce less harmonic effects when insonated. Thus the harmonic mode attenuates tissue signals and enhances flow signa1s.l For many of the known contrast agents, resonance is observed with frequencies that are close to the frequencies of custom scanheads. In these cases, second harmonic frequency is transmit frequency. To twice the take advantage of this effect, an echocardio-

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graphic system has to be modified to transmit at a fundamental frequency and to receive at the second harmonic. Under these conditions the received signals should be mainly caused by micro bubble^.^^^ Harmonic imaging can be performed with two-dimensional echocardiographic scans and with Doppler signals. There are several theoretical advantages of Doppler imaging for left ventricular (LV) cavity opacification as well as for myocardial opacification. First, the sensitivity for microbubbles is much higher using the Doppler than the B - ~ c a nThis . ~ is particularly important for achieving myocardial contrast effects when using intravenous injections of contrast media. Since only 6% of the myocardial volume is blood, there is a substantial decline in signal intensity from the cavity to the myocardium. The second advantage concerns the delineation of endocardia1borders. Using two-dimensional echocardiography, intravenous contrast may result in similar gray levels in the cavities and in the myocardium thus obscuring the endocardial borders. Thus, there is a need to examine other techniques in harmonic imaging. The aim of this study was to evaluate the potential usefulness of harmonic power Doppler (HPD) imaging in delineating the myocardium from LV and right ventricular (RV) cavities during intravenous contrast echocardiography.

Materials and Methods Three healthy male volunteers (22-, 24-, and 25-years old) with good acoustic windows and two male patients (71- and 79-years old) with known ischemic heart disease were included in this pilot study. Both patients had been previously examined with contrast echocardiography using Levovist@(Schering AG, Berlin, Germany) to evaluate the severity of mitral regurgitation, which could not be adequately assessed with noncontrast enhanced conventional and color Doppler. Informed consent was obtained from all subjects. Following completion of clinical studies, two further injections of Levovist were given using HPD. All examinations were performed with the patient positioned in the left lateral decubitus. A commercially available ultrasound imager

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(ATL-HDI 3000, Advanced Technology Laboratories, Bothell, WA, USA) with a 2.5 MHz transducer was used. This echo system provides conventional or fundamental B-scan and Doppler imaging, harmonic B-scan two-dimensional echocardiography (H2D) and HPD imaging. A commercial digital color flow system is modified for harmonic mode to transmit at 1.7 MHz and to receive at the second harmonic frequency of 3.4 MHz. Standard apical four-chamber views were first obtained in each volunteer and patient using two-dimensional echocardiography and then the HPD mode was activated. The wall filter was fixed at the highest possible level, and the pulse repetition frequency set at 3000hecond. No persistence of frames was used, the emission power was kept at the highest level (mechanical index 0.9-1.1) and the frame rate was 8 Hz during continuous recordings. The ultrasound machine provides a variable sector over which harmonic Doppler interrogation can be performed. This sector was positioned to achieve Doppler-signals from the complete LV myocardium. Electrocardiographic (ECG) trigger points were set on the peak of the R wave. Gain was adjusted to the highest level with wall motion signals still absent. In this setting contrast microbubbles are imaged as colored pixels superimposed on a conventional B-scan. All recordings were stored on a super VHS videotape. Recordings were begun at least 10 seconds before the contrast agent was injected, initially in a nontriggered mode. As soon as contrast echoes were noted in the left ventricle, the volunteer or patient was asked to hold his breath and examination was then performed in a triggered mode with one frame taken during insonication at each R wave peak and at the end of the T wave. There was no transmission of ultrasound to the patient during the remainder of the cardiac cycle. Video recordings were continued until LV contrast became inhomogenous and incomplete.

Contrast Agent Levovist was prepared in the standard manner as a solution of 300-mg microparti-

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cles in sterile water and hand-injected into an antecubital vein as a bolus through a 29gauge canula. This was followed by a normal saline flush of 5 mL. A second similar injection of Levovist was given after 10 minutes, at which time the contrast effects from the first injection had disappeared from the LV cavity.

Results Contrast injections in all patients were well tolerated without any adverse reactions. No significant changes in heart rate or blood pressure were observed.

Harmonic Two-Dimensional Echocardiography Continuous scanning resulted in incomplete opacification of the LV cavity in all subjects. Opacification was particularly poor in the apex. ECG triggering with one or two frames/ cardiac cycle (endsystole/enddiastole) provided complete and dense LV opacification. But in two volunteers and one patient, the gray level in the LV cavity visually approximated the gray level in the adjacent myocardium obscuring the endocardial borders especially in the region of the ventricular septum and apex. This effect could not be eliminated by reducing

Figure 1. Comparison of various imaging modalities in a 79-year-oldpatient with ischemic heart disease. (A) Fundamental mode shows an enlarged LV (end-diastolicframe) whose endocardial borders are not completely displayed. (B) Harmonic two-dimensional echocardiography, performed following intravenous injection of 3 g Levovist demonstrates good LV cavity opacification but the endocardial borders are obscured. (C) On the other hand, harmonic power Doppler recording, also performed with the same intravenous dose of Levovist clearly delineates the LV endocardium. LV = lefr ventricular.

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Figure 2. Harmonic power Doppler imaging in a 24-year-old healthy man. (A) The precontrast endsystolic frame shows no colored pixels in the ventricular cavities or the myocardium. (B,C) Following a n intravenous injection of 3 g Levovist intense and complete opacification of the RV and LV cavities occurred. I n addition, patchy pink signals appeared in the myocardium consistent with imaging of intramyocardial coronary vessels. LV = left ventricular; RV = right ventricular.

the gain by 50%. No change in the gray level of the myocardium was noted, when the precontrast frames were visually compared with the frames taken at full opacification of the LV cavity. Harmonic Power Doppler Imaging

As with HZD, only incomplete opacification of the LV cavity was observed in the non-ECG triggered mode. However, the intensity of the

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Doppler signals was brighter as compared to the B-scan. On the other hand, ECG triggered recordings demonstrated dense and complete opacification of the LV cavity. In addition, in all subjects the myocardium was well delineated from the LV and RV cavities. In the three volunteers and in one of two patients, patchy and reticular Doppler signals were noted within the myocardium, both in the ventricular septum and free wall. No homogenous patterns were found in any patient. In the re-

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maining patient, no patchy or reticular signals were noted in the myocardium with HPD following contrast injection. Discussion Although H2D has been shown t o enhance the effects of several contrast agents, there are no reports in the literature assessing the usefulness of harmonic imaging during power Doppler examination. The present study demonstrates that HPD is feasible and offers advantages in comparison to H2D. First of all, unlike H2D, HPD provided clear delineation of the LV endocardium. Secondly, HPD demonstrated discrete, reticular Doppler signals within the myocardial wall consistent with imaging of intramyocardial coronary vessels. This is not surprising since previous experimental and clinical studies using fundamental and harmonic modes have shown the Doppler imaging to be more sensitive than two-dimensional echocardiography in the assessment of contrast e c h o e ~In . ~ our study, the inhomogenous pattern of myocardial contrast was an unexpected finding since in previous studies intracoronary injections of various contrast agents have resulted in homogenous opacification of the myocardium.6 It is possible that power Doppler imaging displays blood flow in the larger intramyocardial vessels and not the smaller vessels or capillaries. This will explain our findings of only patchy, reticular, and incomplete opacification of the myocardium. To assess this effect, new algorithms will be needed since conventional videodensitometric methods that have been used in two-dimensional contrast echocardiography may not be useful or appropriate.

Harmonic imaging, particularly harmonic Doppler is a new imaging technique that has not been standardized so far. Ultrasound machine settings for recording and displaying power Doppler signals have not been optimized. By modifying the system settings further, improvement in the delineation of the LV cavity from the myocardium may be possible. A preliminary result using color coded display is show in Figure 3. In the present preliminary study adjustment of gain, wall filters, etc. was based on our knowledge from fundamental imaging, but these may not necessarily represent ideal settings for harmonic imaging.

Conclusion HPD with intravenous Levovist is feasible. This technique demonstrated good delineation of ventricular cavities from the myocardium as well as presence of visible contrast in the myocardium consistent with imaging of intramyo-

Study Limitations

All patients included in this study had good acoustic windows. Further studies are required to evaluate the feasibility and limitations of HPD in patients with poor acoustic windows. In this situation, at least theoretically, a benefit is anticipated because contrast media have been shown to improve the signalto-noise ratio in Doppler echocardiography.

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Figure 3. Harmonic power Doppler imaging: color-coded display. Blue colors indicate high Doppler power values present within LV and RV cavities caused by high concentrations of Levovist in this individual. Different hues of yellow represent low power signals anticipated within the tissue (such as myocardium). Note the clear delineation of the lateral papillary muscle. LV = left Ventricular; RV = right ventricular.

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cardial coronary vessels. This pilot study justifies further clinical trials to evaluate the clinical benefit of this approach.

References 1. Burns PN: Harmonic imaging with ultrasound contrast agents. Clin Radiol 1996;51:50-55. 2. Porter TR, Xie F, Kricsfeld D, et al: Improved myocardial contrast with second harmonic transient ultrasound response imaging in humans using intravenous perfluorocarbon-exposed sonicated dextrose albumin. J Am Coll Cardiol 1996;27:1497-1501.

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3. Chang PH, Shung KK, Wu S, et al: Second harmonic imaging and harmonic Doppler measurements with albunex. IEEE Trans Ferroelect 1995;42:1020-1027. 4. Becher H, Schlief R: Improved sensitivity of color Doppler by SH U 454. Am J Cardiol 1989;64:374377. 5 . Schlief R. Developments in echo-enhancing agents. Clin Radiol 1996;51:5-7. 6. Villanueva FS, Camarano G, Ismail S, et al. Coronary reserve abnormalities in the infarcted myocardium. Assessment of myocardial viability immediately versus late after reflow by contrast echocardiography. Circulation 1996;94:748-754.

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