Coronary Tree Assessed With Contrast Harmonic Imaging

Transcription

1 J Echocardiogr Vol.5, No.1, (2007) Coronary Tree Assessed With Contrast Harmonic Imaging Young-Jae Lim, MD PhD*, Hitoshi Yamaguchi, MD PhD*, Masayoshi Mishima, MD PhD*, Minoru Ichikawa, MD PhD*, Akio Iwata, MD*, Takaharu Hayashi, MD*, Tsuyoshi Nakata, MD*, Fuminobu Ishikura, MD PhD** and Shintaro Beppu, MD PhD** *Cardiovascular Center, Kawachi General Hospital, Higashi-Osaka, Japan **School of Allied Health Sciences, Faculty of Medicine Osaka University, Suita, Japan Abstract Background. There have only been a few studies that visualized the human coronary tree continuously from coronary arteries to capillaries in the clinical setting. The purpose of this study was to visualize the human coronary tree noninvasively with myocardial contrast echocardiography (MCE) by changing frame rates. Methods. MCE was performed intravenously using TM Levovist. Study population consisted of 20 patients with ischemic heart disease. We performed 3 kinds of MCE: intermittent, semi-real, and real-time harmonic imaging. Results. 1. Myocardial blood flow velocity and volume were obtained from the time-intensity replenishment curve with intermittent imaging. Curve fitting was possible in 75% of the targeted region of interest. 2. Semi-real-time perfusion image was obtained with a frame rate of 5/sec. We observed a cyclic variation of echo-intensity in one cardiac cycle in only viable region (Peak subtracted signal intensity: in end-diastole and in end-systole, p<0.05). This phenomenon may result from the compression of arterioles according to cardiac beat. 3. Real-time perfusion image was obtained at a rate of 26 frames/sec. We observed line-form small artery flows in 80 % of the viable area. Conclusions. Thus, coronary tree following major epicardial coronary arteries was visualized non-invasively from the small artery to the capillary bed with 3-staged intravenous-mce in the clinical setting. (J Echocardiogr 2007; 5: 21-27) Key words: Coronary tree, Intermittent imaging, Myocardial contrast echocardiography, Real time imaging Background Received December 18, 2007; revision received February 11, 2007; accepted March 7, 2007 Address for correspondence: Young-Jae Lim, M.D. Cardiovascular Center, Kawachi General Hospital, 1-31 Yokomakura, Higashi-Osaka, , Japan. Telephone: Fax: rin-eisai@s5.dion.ne.jp 2007 Japanese Society of Echocardiography The assessment of perfusion by myocardial contrast echocardiography (MCE) has evolved from the early contrast agents, including agitated urografin, to the newer contrast agents improving microbubble persistence. Newer contrast agents are capable of transpulmonary passage and myocardial microcirculation after intravenous administration. Also, innovative imaging techniques using harmonics and intermittent imaging have minimized tissue signal and improved signal-tonoise ratio, making the assessment of myocardial perfusion possible [1-3]. Recently real-time MCE has been possible using higher harmonic imaging, which is an advanced harmonic imaging technique and is very sensitive to the signal from microbubbles. The coronary vessel system consists of epicardial coronary arteries, intramyocardial small arteries, arterioles, capillaries, venules, intramyocardial small veins, and coronary veins. To date, many investigations have been performed about the coronary vessel system, which is also known as the coronary tree[4, 5]. However, there have only been a few studies that visualized the human coronary tree continuously from coronary arteries to capillaries in the clinical setting. We hypothesized that it may be possible for MCE to image coronary flow at different flow velocities using different frame rates. Purpose of this study is to visualize human coronary tree non-invasively with MCE by changing the frame rates. 21

2 22 Lim et al. Methods Study population consisted of 20 patients with ischemic heart disease. Mean age was 63 years (35 ~ 82). Five patients were female. All patients gave informed consent for all MCE procedures. TM Levovist (Schering), a suspension of monosaccharide (galactose) microparticles in sterile water, was used as the ultrasound contrast agent in this study and was administered as either a continuous infusion or slow bolus injection. For the intermittent imaging, continuous infusion was performed at a concentration of 125mg/ml and speed of 5ml/min using an infusion pump. Slow bolus injection was performed at a concentration of 250 mg/ml and a speed of 0.5ml/sec in the semi-real-time and real-time imaging. TM Sonos 5500 (Philips) was used as the echo equipment for this study with TM S3 transducer. All imaging were performed using TM Ultra harmonic (Philips), in which ultrasound was transmitted at 1.3 MHz and received at 3.6 MHz. The mechanical index was set at high ranging from 1.4 to 1.6. Three kinds of frame rate dependent MCE were performed: intermittent imaging by low frame rate, semi-real-time imaging by intermediate frame rate, and real-time imaging by high frame rate. The identification of the infarct region was performed with 2D echocardiography. We defined the infarct region as that showing more severe asynergy than hypokinesis. Blood flow is visualized because microbubbles in the contrast agent are of strong echo origin in the blood. Ultrasonic transmission destructs microbubbles. Transmission with higher frame rate destructs more bubbles. Therefore, higher frame rate imaging visualizes only faster blood flow due to the destruction of almost all microbubbles in the slower blood flow. Thus circulation of the coronary tree can be visualized at several different levels by changing frame rate. 1.Evaluation with intermittent imaging Intermittent MCE was designed to reduce the destruction of microbubbles using a low frame rate and to visualize slow capillary circulation. MCE was performed by changing the pulsing interval from 1:1 to 1:8 in end-systole. Peak background-subtracted contrast intensity of myocardium versus pulsing interval plots were fitted to an exponential function: y = A (1 - exp t ), where A is the plateau contrast intensity reflecting the myocardial blood volume, and reflects the rate of raise of contrast intensity and, hence, blood flow velocity [6]. We measured A and in the normal segments from the time-intensity replenishment curve using an on-line image analyzer. 2. Evaluation with semi-real-time imaging This MCE was designed using the intermediate frame rate of 5 frames per second (fps) to visualize precapillary circulation including arterioles that have more rapid flow than capillary. Peak background-subtracted contrast intensity of myocardium was obtained in both end-systole and end-diastole at 55 normal and 11 infarcted segments. Frames acquired over 3 entire cardiac cycles were transferred to an on-line image analyzer. A region of interest (ROI) was placed over the mid myocardium of normal and infarcted segments. Pre-contrast intensity obtained from end-systolic and end-diastolic frames before microbubble administration were subtracted from their respective contrast-enhanced values. 3. Evaluation with real-time imaging Using a high frame rate of 26 fps, this MCE was designed to visualize intramyocardial small arteries that have more rapid flow and to destruct more microbubbles within slow flow such as capillary or precapillary circulation. It was evaluated that real-time MCE could detect intramyocardial arterial flow in normal segments. Results 1. Assessment with intermittent perfusion imaging Curve fitting was possible in 15 of 20 (75%) ROIs for the equation of y = A (1 - exp t ) in the time-intensity replenishment curve (Fig. 1). Value A was measured to be AU, and the rate constant was measured to be in the normal 15 segments expressed by mean SD, respectively. Capillary circulation was assessed with myocardial perfusion image obtained with low frame rate. 2. Assessment with semi-real-time perfusion imaging Myocardial opacification was good in the normal segment and poor in the infarcted segment. Therefore, it was possible to differentiate the infarcted region from the normal region with MCE by intermediate frame rate. Moreover, we observed phasic changes of echo-intensity in one cardiac cycle in viable myocardium (peak background-subtracted signal intensity: in end-diastole and in end-systole, p<0.05) (Fig. 2). Echo intensity that increased in diastole and decreased in systole might reflect the pha-

3 Coronary Tree With Contrast Echo 23 Fig. 1. Measurement of myocardial blood volume (A) and velocity (ß) with intermittent imaging. This is a MCE image of a patient with anterior myocardial infarction in the chronic stage. Intermittent MCE was performed changing pulsing interval from 1:1 to 1:8 in end-systole. Peak background-subtracted contrast intensity of myocardium versus pulsing interval plots is fitted to an exponential function: y = A (1 - exp ßt ). A and ß were measured from the replenishment curve in the normal segment of this patient. Fig. 2. Visualization of infarcted area with semi-real time imaging This is a MCE image of the same patient as Figure 1. Phasic changes of echo-intensity in one cardiac cycle were observed in viable myocardium. Contrast intensity increased in diastole (arrow in the left panel) and decreased in systole (arrow in the right panel) that might reflect the phasic changes of pre-capillary circulation. Fig. 3. Phasic changes of contrast-intensity in the normal segment and infarcted segment Pre-capillary circulation was assessed with myocardial perfusion image obtained with intermediate frame rate. Phasic changes of contrast intensity were less prominent in the infarcted region than in the normal region. SI= signal intensity/256 sic changes of pre-capillary circulation. Phasic changes were less prominent in the infarcted region than in the normal region (Fig. 3). Pre-capillary circulation was assessed with myocardial perfusion image obtained with intermediate frame rate. 3. Assessment with real-time vascular imaging We observed intramyocardial line-form small artery flows in high frame B-mode images in 80 % of the viable myocardium (Fig. 4). The linear structures traversing the myocardium represent the intramyocardial small arteries that have a velocity high enough to fill in 40 ms. It was possible to assess intramyocardial arterial flow with pulse Doppler technique in 25% of those small arteries. Small artery flow was assessed with

4 24 Lim et al. Fig. 4. Visualization of intramyocardial small artery with real time imaging This is a MCE image of a patient with anterior myocardial infarction in the chronic stage. Intramyocardial line-form flows were observed in high frame B-mode images in viable myocardium (arrow in the middle panel). The linear structures traversing the myocardium represent the intramyocardial small arteries that disappear in the systolic phase. myocardial vascular image obtained with high frame rate. Discussion 1. The flow that can be assessable with low frame rate MCE Myocardial blood flow can be quantified with MCE during a venous infusion of microbubbles. In high mechanical index ultrasonography, signal intensity has a strong linear correlation with the concentration of the ultrasound contrast agent under conditions of constant applied acoustic pressure. Therefore, we can assess coronary circulation with contrast signal intensity [7-9]. Destruction of microbubbles and measurement of their reappearance rate within the myocardium during a continuous infusion provide an estimation of mean myocardial microbubble velocity. Similarly, the plateau contrast intensity at long pulsing interval reflects myocardial blood volume. Knowing both the mean myocardial microbubble velocity and the myocardial blood volume can then provide a measure of mean blood flow. Excellent correlations were found between flow and, as well as flow and the product of A and [6]. Because 90% of myocardial blood volume resides in capillaries [10,11], contrast intensity at a pulsing interval of more than 5 seconds mostly represents capillary blood volume that does not change between end diastole and end systole when cardiac function and coronary blood flow are normal [12]. However, the correlation between flow and is influenced by several examination variables, including depth, angle, and instrument settings [13, 14]. Therefore, MCE refilling measures are best applied by comparing baseline values with those of stress studies [15]. Thus, myocardial image with low frame rate could assess capillary circulation. 2. The flow that can be assessable with intermediate frame rate MCE Microbubbles fill only arterioles before being destroyed by the next ultrasound pulse because the interval between frames during semi-real-time imaging is only 250msec. Thus, myocardial perfusion image obtained with intermediate frame rate visualized precapillary circulation including arterioles. Full-motion MCE utilizing an intravenous fluorocarbon-based agent and pulse inversion power Doppler techniques identifies stunned myocardium and accurately predicts recovery of segmental left ventricular function in patients with recent myocardial infarction [16,17]. In our study, myocardial opacification decreased significantly in the infarcted segment than in the normal segment which means there was damage to not only capillary circulation but also pre-capillary circulation. Therefore, we can know the damage territory vasculature of coronary tree after reperfusion in myocardial infarction. Phasic changes in intramyocardial arteriolar dimensions have been documented during cardiac contrac-

5 Coronary Tree With Contrast Echo 25 Fig. 5. Visualization of Coronary Tree Coronary tree following major epicardial coronary arteries will be visualized from the small artery to the capillary bed with 3-staged intravenous-mce. tion [18]. This phenomenon may result from the compression of arterioles according to cardiac beat [19, 20]. However, there is controversy regarding changes in capillary dimensions during this period [21-24]. Changes in intramyocardial pressures during the cardiac cycle could potentially affect phasic changes in myocardial contrast intensity because microbubbles are sensitive to ambient pressure [25]. Wei et al [12] showed that phasic changes in myocardial contrast intensity with continuous MCE using high mechanical index allow the detection and quantification of coronary stenosis at rest without need for pharmacological or exercise stress. Thus, the measurement of phasic changes in contrast intensity has the potential to detect myocardial ischemia or myocardial viability. 3. The flow that can be assessable with high frame rate MCE Microbubbles within the myocardium are destroyed by pulses of ultrasound at a sampling rate of 26Hz with real-time imaging using high mechanical index [12]. Any myocardial opacification could occur only from partial or complete filling of vessels whose velocity would allow significant replenishment at 40ms. In this manner, there is no backscatter from capillaries and arterioles. Therefore, only vessels with a high enough velocity could be detected at the high sampling rate used. Doppler technique would be able to assess intramyocardial small artery flow under real-time MCE. Thus, real-time MCE has potential to widen Doppler approach for intramyocadial small artery flow. 4. Each phase of coronary tree We have defined a novel method for visualizing the coronary tree that is based on the bubble destruction by ultrasound. 1. Perfusion image obtained with intermittent MCE using low frame rate visualizes capillary flow of speeds less than 1 mm/sec and does not show phasic change of contrast. 2. Pre-perfusion image obtained with semi-real-time MCE using intermediate frame rate visualizes precapillary circulation including arterioles and shows phasic change of echo intensity depending on cardiac cycle. 3. Vascular image obtained with real-time MCE using high frame rate visualizes intramyocardial small artery flow of speeds more than cm/sec. MCE with different frame rates provides several information about the different levels of the coronary tree using a venous administration of microbubbles that is likely to be a feasible clinical technique. This novel method gives us a new possibility about the identification of myocardial infarction. Namely, we can assess the infarcted region from the view of not only perfusion but also vasculature damage of precapillary using 3 kinds of MCE in the clinical setting. At present, epicardial coronary arteries can be assessable with transthoracic Doppler technique.

6 26 Lim et al. Coronary tree following major epicardial coronary arteries will be visualized from the small artery to the capillary bed with 3-stage intravenous-mce (Fig.5). 5. Limitation A large dose of ultrasound contrast agent needs to be injected to be able to detect small arterial flow. This amount of microbubbles caused significant far-field shadowing that makes assessment of the posterior wall impossible. Therefore, we could not assess myocardial perfusion with short axis view or parasternal view in MCE. The sensitivity of harmonic imaging has to improve in order to obtain the same information from a continuous infusion of a small dose of microbubbles without producing far-field attenuation [12]. Imaging at higher harmonics improves sensitivity because the tissue signal is less and it is easier to filter the second harmonics. Therefore, we used TM Ultra harmonic imaging technique in this study, but we could not completely neglect far-field shadowing. Recently, several advanced harmonic imagings that use high or sub-harmonics have emerged as new harmonic technologies. These new imaging technologies will overcome a problem of far-field attenuation and bring us marked improvement of signal to noise ratio [26]. In this study, we did not measure direct blood velocity of capillary, arteriole and small artery using Doppler signal. Therefore we do not have clear proof that our findings indicate coronary tree circulation. References 1. Porter T, Xie F: Transient myocardial contrast after initial exposure to diagnostic ultrasound pressures with minute doses of intravenously injected microbubbles. Demonstration and potential mechanisms. Circulation 1995; 92: Kaul S: Myocardial contrast echocardiography. 15 years of research and development. Circulation 1997; 96: Mayer S and Grayburn PA: Myocardial contrast agents: Recent advances and future directions. Progress in Cardiovascular Diseases 2001; 44: Estes EH, Enlman ML, Dixon HB, Hackel DB: The vascular supply of the left ventricular wall. Am Heart J 1966; 71: Baston OV and Bellet S: The reversal of flow in the cardiac veins. Am Heart J 1930; 6: Wei K, Firoozan S, Jayaweera AR, et al: Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a continuous infusion. Circulation 1998; 97: Skyba DM, Jayaweera AR, Goodman NC, et al: Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast: implications for venous injection. Circulation 1994; 90: Kaul S, Jayaweera AR: Coronary and myocardial blood volumes: noninvasive tools to assess the coronary microcirculation? Circulation 1997; 96: Yamada S, Komuro K, Mikami T, et al: Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography. Heart 2005; 91: Kassab GS, Lin DH, Fung YB: Morphometry of pig coronary venous system. Am J Physiol 1994; 267: H Kassab GS, Lin DH, Fung YB: Topology and dimensions of pig coronary capillary network. Am J Physiol 1994; 267: H319-H Wei K, Le E, Jayaweera AR, Bin JP, Goodman NC, Kaul S: Detection of noncritical coronary stenosis at rest without recourse to exercise or pharmacological stress. Circulation 2002; 105: Otani K, Masuda K, Asanuma T, et al: Complete bubble destruction is essential for quantitative assessment from the replenishment curve in real-time myocardial contrast echocardiography. J of Echocardiography 2005; 3: Otani K, Masuda K, Asanuma T, et al: Destruction of microbubbles in the ventricular cavities affects the quantitative assessment of myocardial perfusion during realtime myocardial contrast echocardiography. J of Echocardiography 2006; 4: Lafitte S, Masugata H, Peters B, et al: Accuracy and reproducibility of coronary flow rate assessment by realtime contrast echocardiography: In vitro and in vivo studies. J Am Soc Echocardiogr 2001; 14: Main ML, Magalski A, Chee NK, Coen MM, Skolnick DG, Good TH: Full-motion pulse inversion power Doppler contrast echocardiography differentiates stunning from necrosis and predicts recovery of left ventricular function after acute myocardial infarction. J Am Coll Cardiol 2001; 38: Shimoni S, Zoghbi WA, Xie F, et al: Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: Comparison with single photon emission computed tomography. J Am Coll Cardiol 2001; 37: Yada T, Hiramatsu O, Kimura A, et al. :In vivo observations of subendocardial microvessels of the beating porcine heart using a needle-probe videomicroscope with a CCD camera. Circ Res 1993; 72: Goto M, VanBavel E, Giezeman JMM, Spaan JAE: Vasodilator effect of pulsatile pressure on coronary resistance vessels. Circ Res 1996; 79:

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