Influences of ultrasonic machine settings, transducer frequency and placement of region of interest on the measurement of integrated backscatter and cyclic variation

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Ultrasound 0 1997

in Med. & Biol., Vol. 23, No. 7, pp. 1059- 1070, 1997 World Federation for Ultrasound in Medicine clr Biology Printed in the USA. All rights reserved 0301-56?9/97 $17.00 + .OO

PI1 SO301-5629(97)00117-8

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l Original Contribution INFLUENCES OF ULTRASONIC MACHINE SETTINGS, TRANSDUCER FREQUENCY AND PLACEMENT OF REGION OF INTEREST ON THE MEASUREMENT OF INTEGRATED BACKSCATTER AND CYCLIC VARIATION TAKAHIRO OTA, * DAMIAN M. CRAIG+ and JOSEPH ISSLO * Department of *Medicine and ‘Surgery, Duke University Medical Center, Durham. NC (Received

15 January

1997; in final form

22 January

1997)

Abstract-Integrated backscatter and its cyclic variation are potentially important parameters to diicriminate normal from diseased myocardium. Cyclic variation of integrated backscatter is expected to be independent of machine settings. Backscatter images of swine hearts were taken using a two-dimensional backscatter system while acoustic power was varied at diierent time gain control (TGC) settings. Cyclic variation was measured in viva with various acoustic power and TGC settings using different transducer frequencies. Three different regions were analyzed. For any given TGC setting, the relationship between acoustic power and integrated backscatter in vitro was linear only over a narrow range. In vivo, cyclic variation was present at all regions studied in both long- and short-axis views. However, lower acoustic power (<15 dB) and TGC ( ~20 dB), or excessive settings of acoustic power (>35 dB) and TGC (>50 dB), produced minimal cyclic variation. Appropriate acoustic power (20-35 dB) and TGC (30-50 dB) produced larger and more consistent cyclic variation at the posterior region of the left ventricle. These data indicate that each region has specific, appropriate machine settings to maximize the magnitude of cyclic variation. 0 1997 World Federation for Ultrasound in Medicine & Biology. Key Words: Ultrasound tissue characterization, Integrated backscatter, Cyclic variation, Acoustic power, Time gain control, Transducer frequency, Myocardial region of interest. tensity of the myocardium varies according to physiological contractile state during the cardiac cycle, with the maximal level at relaxation and minimal level at contraction (Fitzgerald et al. 1986; Madaras et al. 1983). Some articles have indicated that the magnitude of cyclic variation of integrated backscatter (cyclic variation) is decreased with ischemia (Barzilai et al. 1984; Lythall et al. 1992; Milunski et al. 1989a; Vered et al. 1989; Vitale et al. 1995), cardiomyopathy (Lattanzi et al. 1991; Skorton et al. 1988; Tanaka et al. 1985; Vered et al. 1987), hypertrophic heart (Masuyama et al. 1989), diabetic heart and acute cardiac rejection (Dibello et al. 1995; Masuyama et al. 1990). Integrated backscatter has been considered independent of postprocessing settings but dependent on the preprocessing machine settings and transducer frequency (Stuhlmuller et al. 1992; van der Steen et al. 1991) . On the other hand, the magnitude of cyclic variation was expected to be independent of machine settings such as acoustic power and time gain control (TGC) and to be used without calibration. This study was designed to determine systemati-

INTRODUCTION In recent years, ultrasonic tissue characterization has been proposed as a method to measure the structural and functional properties of cardiovascular tissue. Integrating the radio frequency backscatter waveforms provides a potentially useful measurement for tissue characterization (Cohen et al. 1982; Perez et al. 1994; Schnittger et al. 1985). To date, quantitative analysis of regional two-dimensional ultrasonic integrated backscatter intensity has been used experimentally and clinically for the noninvasive discrimination of normal from diseased myocardium (Skorton et al. 1987). Despite this significant progress, the measurement of integrated backscatter may be influenced by a number of patient- and/or machine-related factors making comparisons between patients or between serial studies of a single patient unreliable (Cohen et al. 1982; Skorton et al. 1987). It has been demonstrated that the backscatter inAddress correspondence to: Dr. Takahiro Ota, Duke University Medical Center, Division of Cardiology, P.O. Box 3818, Durham, NC 27710, USA. 1059

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Fig. I. Block diagram showing the signal processing path for the two-dimensional integrated backscatter system. The acoustic densitometry signal is measured at the dotted arrow point for integrated backscatter (AD/IBS) images and at the arrow for conventional (AD/US) images, respectively. The beam-formed signal at the receiver is not rectified, log-compressed. The integrated backscatter image data are independent of the compression control and video postprocessing functions. A/D = analog-to-digital conversion; CLR = continuous loop review; D/A = digital-to-analog conversion; DSR = digital storage/retrieval; IF = intermediate frequency; RF = radio frequency signal; TGC = time gain control; VCR = video tape recorder.

tally the effects of changes in acoustic power, TGC settings and transducer frequency on the measurement of integrated backscatter irz vitro and on the magnitude of the cyclic variation in viva. These experiments were also designed to distinguish whether and how the placement of region of interest affects the measurement of these parameters.

METHODS

excised swine hearts. The hearts were suspended in degassed water inside a Plexiglas 40-L chamber lined with SOAB rubber to minimize reflected signals. The transducer was fixed to a stand to maintain a constant range (6.0 cm between transducer face and anterior surface of the heart) and position of the hearts within the ultrasound field. The excised hearts were positioned to provide a two-dimensional echocardiographic image of the short-axis view at the papillary muscle level. All experiments were conducted with the water at room temperature (about 25°C).

Integrated backscatter images Integrated backscatter images were collected using a real-time two-dimensional ultrasound backscatter imaging device (Sonos 1500, Hewlett-Packard Co., Andover, MA, USA) equipped with an acoustic densitometry measurement package for the analysis of backscatter signal. The block diagram of the ultrasonic integrated backscatter measurement and acquisition system used in this study outlines where the signal was derived for analysis in the ultrasound imaging system (Fig. 1) . The raw radio frequency signal was sampled before the postprocessing and logarithmic compression pathway of the two-dimensional echocardiographic instrument. Calculation of integrated backscatter has been previously described in detail (Miller et al. 1985; Rijsterborgh et al. 1993). The digitized radio frequency images were recorded via the continuous loop review (tine loop format).

In vitro protocol. The experiments consisted of four series of measurements during which certain controls were fixed and others were varied. Integrated backscatter images were obtained while varying the acoustic power between O-40 dB in 5-dB steps using a broad-band transducer with a center frequency of 2.5 MHz while holding the TGC fixed at 40 dB. Next, backscatter images were taken while varying the TGC from O-60 dB ( lo-dB steps incrementally) while holding the acoustic power fixed at 25 dB. Then, images were obtained using various transducers (2.0, 2.5, 2.7, 3.5 and 5.0 MHz) while the previous two procedures were repeated. Three regions of interest (the anterior, inferior and posterior wall of the two-dimensional echocardiographic short-axis image ) were examined at each system setting.

In vitro experimental set-up. Integrated backscatter of myocardial tissue was measured in five freshly

In vivo animnl preparation. ( 25 - 3 I kg ) were premeditated

Sixteen adult swine with intramuscular

Acoustic densitometry of integrated backscatter l T.

acepromazine ( 1.1 mg/kg) and ketamine (22 mg/kg). After intravenous access was obtained, each animal received a sodium thiopental bolus injection (25 mg/ kg) and was ventilated with a respirator (Harvard model 900). Anesthesia was maintained throughout the study with continuous infusion of fentanyl through a catheter in the femoral vein. A thoracotomy was performed using a midsternal split, the pericardium was incised and the heart was suspendedin the pericardial cradle. The ECG (limb lead II) was monitored throughout the experiment. The study was approved by the Institutional Review Board of the Duke University Medical Center and was in compliance with the Position of the American Heart Association on Research Animal Use. In vivo protocol. After the heart was exposed and systemic hemodynamics had been stable for at least 20 min, the transducer was placed on the epicardial surface of the heart. The images were taken for 3-6 cardiac cycles and stored on optical disk. First, cyclic variation was obtained while acoustic power was varied from O-40 dB in 5-dB steps with fixed TGC of 40 dB. Images were taken in the left ventricular short-axis view at upper-papillary muscle levels. To assessthe variability of cyclic variation between the long- and short-axis views, 10 of 16 swine were imaged in both views using a 5.0-MHz transducer. Second, backscatter images were taken while TGC was varied from O-60 dB in lo-dB steps with fixed acoustic power of 25 dB. Images were obtained in the short-axis view using a 5.0-MHz transducer. Finally, integrated backscatter imageswere taken using various transducers (2.0, 2.5, 2.7, 3.5 and 5.0 MHz) in the short-axis view, while acoustic power was varied from O-40 dB in 5-dB steps with TGC of 30 and 50 dB. Measurement of cyclic variation was performed using several different regions of interest for each system setting and transducer series in both views (Fig. 2 ). During the study, each TGC was adjusted to the samesettings from the near gain to the far gain control. Ultrasonic data acquisition and analysis A nongated capture mode was selected to digitize every frame within the cardiac cycle. Configured software allowed computer control of region of interest size, shapeand placement. The sizes of region of interest selected were 41 X 41 or 3 1 X 3 1 pixels, and the shapeswere elliptical or crescentic. The sizes and shapesof the regions of interest were carefully selected so that the regions of interest could be positioned well within the myocardium, excluding epicardial and endocardial specular reflections. All image data were recorded in a digital format on optical disk for off-line acoustic densitometry analysis. The system was con-

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figured to analyze 30-60 backscatter image frames from continuous loop review memory. The smoothing filter to minimize high-frequency scatter noise and curve fitting options were turned off. Parameters obtained were the peak intensity and peak-to-peak variation of the integrated backscatter signal in each region of interest. The raw data were displayed on a graph preset to span the backscatter intensity values in the range from O-64 dB. Placement of region of interest. The representative value of integrated backscatter was the average of three measurementsof each region of interest in vitro. Integrated backscatter was thus determined at each region of interest and expressed as mean ? SD (in decibels). To compare the uniformity and linearity of the tissue reflectivity for varying acoustic power, a simple linear regression was performed between the magnitude of integrated backscatter and acoustic power at each TGC setting over the whole acoustic power range as well as several specific portions of the range. In vivo, two-dimensional integrated backscatter images of 3-5 consecutive cardiac cycles were stored. Measurements of cyclic variation were performed off-line on each of several region of interests in the left ventricle (LV) Figure 2 shows long- and short-axis images where the highlighted region represents the regions of interest studied. Regions measured in the long-axis view were the basal septum (SEP), basal posterior (b-POST) and mid-posterior (m-POST) wall of the LV. In the short-axis view. measurements were performed on the anteroseptal ( ANT-SEP), midposterior (M-POST) and midinferior (INF) region of the LV. Data sets were stored consecutively using various acoustic power and TGC settings with each transducer frequency. The backscatter value over time within the region of interest was displayed on the right side of the monitor screen, and the curve of integrated backscatter over time was shown on the left side of the screen (Fig. 2 ). The measured cyclic variation values were averaged over at least three cardiac cycles in each region of interest and reported as mean 2 SD (in decibels ). Interobserver and intraobserver variability. Interobserver and intraobserver variability was assessedin five randomly selected subjects in viva. For interobserver variability, images were acquired and traced by operators blinded from each other. For intraobserver variability, the sameoperator reanalyzed images in the same five subjects 2 months after the first analysis. The mean difference between the two observers was described. Statistical analysis. All magnitudes of integrated backscatter and cyclic variation are expressedas mean

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Fig. 2. Two-dimensional integrated backscatter images and regions of interest, where the highlighted region represents those measured in this study. (A) Analysis of cyclic variation was completed on the basal septum (SEP), basal posterior (b-POST) and mid posterior (m-POST) wall of LV in the long-axis view (LAX ), (B ) In short-axis view ( SAX). measurements were performed on the anteroseptal (ANT-SEP), mid posterior (m-POST ) and mid inferior (INF) region of LV, respectively. Data sets were stored consecutively under several acoustic power and TGC settings with each transducer frequency. The relative integrated backscatter number over time within the region of interest was displayed in the right side of the monitor screen. Curve of cyclic variation of integrated backscatter over time was shown in the left side of the screen.

? SD. Differences in the magnitude of cyclic variation between regions of interest in the same subject were determined by paired t-tests and between different machine settings and transducer frequencies by unpaired r-tests. Differences between the range of settings and regions of interest were considered significant when the probability was < 0.01.

RESULTS In vitro study

Acoustic power and TGC. Figure 3 summarizes the relationship between the magnitude of integrated backscatter and acoustic power for TGC from O-60 dB in the anteroseptal region of myocardium. For any given TGC setting, the relationship between acoustic power and integrated backscatter was linear only over a narrow range (Table 1). For example, at 30 dB of TGC, the relationship between integrated backscatter and acoustic power was linear (y = 0.98x + 8.88; r2 = 0.98) only for acoustic power between 15-35 dB. However, the curve derived using 50 dB of TGC was distorted (y = 0.12x + 39.8; r3 = 0.80). The slope

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Fig. 3. The integrated backscatterintensity vs. acoustic power for varied TGC using 2.5-MHz phasedarray transducer in the anterior region of myocardium in vitro. The slopesand patternsof curves varied widely according to TGC settings.

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of this relationship and the degree of linearity varied widely with TGC (Table 1). Excessive settings of TGC resulted in the saturation phenomenon (TGC > 50 dB ) or minimal integrated backscatter signal (TGC < 10 dB ) . Integrated backscatter curves derived by midrange settings were linear only over the narrow ranges of lo-30 dB of TGC and 20-30 dB of acoustic power.

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Transducerfrequency. Figure 4 showed at 30 dB of TGC that the lower frequency transducers produced higher intensity of integrated backscatter, whereas the 5.0-MHz transducer produced lower intensity (Fig. 4). The lower frequency transducers resulted in signal saturation at excessive settings of acoustic power and TGC. Placement of region of interest. Figure 5 shows the effect of region of interest on the mean intensity of integrated backscatter using 2.5- and 5.0-MHz transducers. The highest values of integrated backscatter were measured at the anterior and the lowest at the inferior wall of the two-dimensional short-axis images. The posterior wall region showed intermediate values at each transducer frequency. These differences were larger with the higher frequency (5.0 MHz) transducer and smaller using the lower frequency (2.5 MHz).

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was between 30 and 50 dB. as the cyclic variation WI\ significantly larger and consistent with TGC between 30 and 50 dB than with TGC < 30 dB (r’.~.. 7.9 : I .6 dB at 40 dB of TGC vs. 2.9 ? I .2 dB at 20 dB ot TGC; (7 < 0.005 ). TGC settings > 50 dB also pro-duced minimal cyclic variation.

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Transducer frequenc.~. The 2.0-MHz transducer produced minimal cyclic variation for all regions of interest at fixed acoustic power of 25 dB and TGC of 40 dB. There were no significant differences between the magnitudes of cyclic variation with transducer frequencies between 2.5 and 5 MHz in each region of interest (Fig. 7 )

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Fig. 5. Integrated backscatter (IBS) intensity vs. acoustic power in three regions of interest, anterior, inferior and posterior wall using 2.5- and 5.0-MHz transducers at TGC of 30 dB in vitro. The location of region of interest affected the intensity of integrated backscatter differently for different transducers. ANT = anterior region; INF = inferior region; POST = posterior region of LV.

In vivo study Acoustic power and TGC. The cyclic variation was present in all regions of interest examined in both long- and short-axis views. The effects of acoustic power on cyclic variation between long- and shortaxis views for several regions of interest are illustrated in Fig. 6. At constant TGC, the magnitude of cyclic variation was smaller with acoustic power < 15 dB in both short- and long-axis views. In the shortaxis view at the posterior region, the cyclic variation was significantly larger with acoustic power between 20 and 35 dB than with acoustic power < 15 dB (e.g., 7.2 t- 1.6 dB at 30 dB of acoustic power vs. 4.2 +- 1.5 dB at 15 dB of acoustic power: p < 0.005; Fig. 6). There were no significant differences between the magnitude of cyclic variation of integrated backscatter in the posterior region at acoustic power between 20 and 35 dB. In the long-axis view, the magnitude of cyclic variation was significantly larger with acoustic power between 20 and 40 dB than with acoustic power 15 dB or less in the basal-posterior and mid-posterior. No significant differences were observed between the magnitudes of cyclic variation in the posterior region for acoustic power between 25 and 35 dB. The magnitude of cyclic variation changed greatly with TGC (Fig. 7). In the short-axis view. the best setting for cyclic variation of the midposterior region

Region of’ interest. In the short-axis view, cyclic variation was significantly larger and more consistent in the posterior region with acoustic power between 20 and 35 dB compared to the anteroseptal and inferior regions (Fig. 6). In the anteroseptal region, intermediate acoustic power (between 20 and 25 dB) and TGC (between 30 and 50 dB) settings provided larger cyclic variation than lower or higher acoustic power and TGC settings, whereas, in the inferior region, higher acoustic power (> 25 dB) and TGC (40-50 dB) settings provided relatively larger cyclic variation than lower machine settings (Figs. 6 and 7). In the long-axis view, the magnitude of cyclic variation was consistently larger in the basal-posterior and mid-posterior wall than in the basal septal region with acoustic power between 25 and 35 dB (Fig. 6). There were no significant differences of cyclic variation in the posterior regions between long- and short-axis views. Interobserver and intraobserver variabi&v and reproducibility The mean interobserver difference of the magnitude of cyclic variation of integrated backscatter was 0.6 + 0.5 dB. This difference amounted to a 9% variability in the quantitative measurement. The intraobserver mean difference was 0.4 ? 0.5 dB, which amounted to a 7% variability in the measurement.

DISCUSSION There have been several reports about the utility of myocardial tissue characterization using integrated backscatter. One possible reason for this conjectures that conventional echocardiography takes advantage of the specular reflection occurring at acoustic impedance interfaces whose boundaries are much larger than the wavelength of the applied ultrasound, ultrasonic backscatter is produced by structures within the myocardium that are much smaller than the wavelength of ultrasound (Miller et al. 1985; Perez et al. 1994; Skorton et al. 1987). Integrated backscatter results from the

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Fig. 6. Effect of acoustic power on cyclic variation in short-axis view (top) and long-axis view (bottom). Top: Measurements were done for three regions of interest. In general, cyclic variation is smaller at acoustic power ( AP) < 15 dB. The greatest cyclic variation was in the POST region (filled bar). The cyclic variation of POST is larger and more consistent,plateauat AP between20 and 35 dB more than that of ANT-SEP, INF of region of interest.The cyclic variation of ANT-SEP region (open bar) waslarger at lower AP settingssuchas20 to 35 dB than that of POST region. Bottom: The magnitude of cyclic variation of b-POST (filled bar), and m-POST (hatched bar), is larger and more consistent than that of SEP (open bar), between AP of 20 and 35 dB. Abbreviations as in Fig. 2. TGC was fixed at 40 dB using a S.O-MHz transducer.

interactions between ultrasound and heterogeneities of the tissue structure and consists of the component of omnidirectional scattering energy redirected back to the transducer. Myocardial integrated backscatter Over the past few years, a number of investigators have analyzed reflected ultrasound waves from the myocardium in an effort to characterize the presence of cardiac pathology (Lythall et al. 1993; Picano et al. 1990; Shaw et al. 1984). Previous reports indicate that integrated backscatter levels measured in tissues with acute ischemic myocardial injury and necrosis are

higher compared to integrated backscatter levels in normal myocardium (Barzilai et al. 1984; Cohen et al. 1982; Schnittger et al. 1985). In theory, the energy level of backscatter power is partly determined by the density and orientation of the scatterers within the myocardium and the frequency of the applied ultrasound (Miller et al. 1985; Perez et al. 1994; Skorton et al. 1987; Wickline et al. 1985). The raw radio frequency analog signal, containing all the information describing the biological structure examined, is believed to be a useful tool for the noninvasive discrimination of normal from abnormal myocardial tissue (Miller et al. 1985; Mimbs et al. 1981; Schnittger et

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Fig. 7. Effect of TGC (top) and transducerfrequency (bottom) on the cyclic variation in short-axisview. Top: The magnitudeof cyclic variation largely varied by TGC. Best setting for cyclic variation of M-POST was between 30 and 50 dB, because,betweenthis range, cyclic variation of M-POST (filled bar), was larger and more consistentthan that of ANT-SEP (open bar) and INF (dotted bar) region. Acoustic power was fixed at 25 dB usinga 5.0-MHz transducer.Bottom: Thereare no significantdifferencesof cyclic variation betweentransducersexcept for 2.0-MHz frequencytransducer.The 2.0-MHz frequencyproducedminimalcyclic variation. Abbreviationsas in Fig. 2. Acoustic power wasfixed at 25 dB, TGC at 40 dB.

al. 1985). After digitization, its frequency content, phase and attenuation in tissue still provide information about the tissue studied (Miller et al. 1985; van der Steen et al. 1991) . As in all ultrasound imaging, the intensity of returning backscatter signals may be markedly influenced by acoustic power (system gain) and system control settings (receive gain) but not any postprocessing algorithms (Skorton et al. 1988). Few data have been acquired systematically to quantitate integrated backscatter and cyclic variation for varied settings and transducer frequencies in multiple left ven-

tricular regions imaged from both long- and shortaxis views. Cyclic variation of integrated backscatter

In normal myocardium, end-diastolic integrated backscatter is higher compared to the end-systolic level (Barzilai et al. 1984; Fitzgerald et al. 1986; Madaras et al. 1983). The magnitude of cyclic variation has been recognized as an important parameter to discriminate normal from diseased myocardium. The evaluation of cyclic variation is a potential method of clinical

ultrasonic tissue characterization, because cyclic varia-

Acoustic densitometry of integrated backscatter 0 T. OTA et al.

tion has been reported to be dependent on myocardial contraction (Barzilai et al. 1984; Naito et al. 1996; Wickline et al. 1985). Some articles postulated that cardiac contraction and relaxation alter the reflectivity of the ultrasonic scattering elements within myocardium by changing their size, shape, density and orientation from systole to diastole, which produced a local acoustic impedance mismatches (Lythall et al. 1992; Wickline et al. 1985). The magnitude of cyclic variation is also greatly reduced during coronary occlusion and recovers after reperfusion (Glueck et al. 1985; Milunski et al. 1989a, 1989b). This approach is promising because it is believed to require no external or internal calibration. Therefore, the relative measurement of cyclic variation is expected to be less sensitive to machine settings and other factors. However, the actual influence of these factors on the magnitude of cyclic variation has not been fully assessed. Acoustic power and TGC The in vitro study indicates that there are profound effects on the measurement of integrated backscatter as a result of changes in acoustic power and TGC. Acoustic power is a transmit function and TGC (the ramp) is a receive function, and this study suggestsa narrow range where their effects are linear. As acoustic power or TGC was changed, the resultant integrated backscatter measurement changed. Thus, to some degree, expressions of the magnitude of integrated backscatter must be understood in the context of the acoustic power and TGC settings. The fact that there were extremes on the end of each of these controls where the results were nonlinear implies that huge distortions are possible clinically if system settings are outside the linear range. Within narrow ranges (20-30 dB of acoustic power and lo-30 dB of TGC), the slope of the acoustic power vs. integrated backscatter intensity relationship was approximately equal to 1.0. Therefore, if TGC is constant between two images, the difference in acoustic power levels can be used directly to adjust the difference in integrated backscatter intensity levels. The in vivo study showed that the magnitude of cyclic variation in the posterior wall in long- and shortaxis views was consistently higher only with acoustic power between 20 and 35 dB and TGC between 30 and 50 dB. Lower machine settings (acoustic power < 15 dB and TGC < 20 dB ) produced minimal cyclic variation magnitude in all of the regions studied. We suspectedthat the smaller ultrasound power could not produce sufficient backscatter signals and would result in minimal cyclic variation. Acoustic power > 35 dB and TGC > 50 dB caused image saturation that does not represent tissue properties correctly. As shown in the in vitro study, the relationship between acoustic power or TGC and backscatter intensity was not linear,

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especially near the extremes of acoustic power and TGC. These results indicate that cyclic variation is also dependent on machine settings, and appropriate settings of acoustic power and TGC are necessary to provide maximal and consistent cyclic variation. Placement of region of interest The magnitude of cyclic variation was different for various regions of interest, in both long- and shortaxis views. Real-time integrated backscatter imaging demonstrated a larger cyclic variation in normal posterior wall regions than in anterior, septal or inferior wall region of the LV, similar to the results of other investigators (Lange et al. 1995) . Variation in integrated backscatter intensity between different regions of interest is partly due to the combined effects of attenuation and scatterer orientation. Studies have shown that normal myocardium exhibits the property of ultrasonic anisotropy. That is, the magnitude of ultrasonic energy backscattered from the myocardium, as well as the attenuation, is dependent upon the angle between the sound beam and the predominant orientation of the muscle fibers at selected regions (Mottley and Miller 1988; Picano et al. 1985). It has been reported that integrated backscatter intensity was maximal at an angle of interrogation perpendicular to the myocardial fibers and minimal at those parallel to the orientation of the fibers (Lange et al. 1995; Madaras et al. 1983; Recchia et al. 1993; Vandenberg et al. 1989). In a typical two-dimensional short-axis image, tissues in the anterior and posterior regions would likely be oriented perpendicularly to tissues.The backscatter signal returning from the anterior region of interest would also be subjected to less attenuation. The differences in resolution and signal-to-noise ratio between near field and focusing depth may cause the smaller cyclic variation in the anteroseptal region than in the posterior region. The parallel or oblique orientation of the ultrasound beam to the fibers in the inferior and lateral regions of the myocardium when imaged from the parastemal short-axis view may explain the smaller magnitude of cyclic variation in these regions (Hall et al. 1997; Madaras et al. 1988; Vandenberg et al. 1989). Differences in the magnitude of measured integrated backscatter between regions noted in this study suggestthat: ( 1) actual differences in tissuecharacteristics may exist in these different regions; or ( 2 ) the same tissuesare present but the angle of incidence and distance between the ultrasound beam and the cardiac muscle fibers are of major importance (Madaras et al. 1988; Picano et al. 1985; Recchia et al. 1993). Appropriate settings for cyclic variation measurement in the anterior and septal walls were found to be 20-25 dB for acoustic power and 30-40 dB for TGC levels, which are lower than those of the posterior

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region. Thus, in order to measure the cyclic variation of integrated backscatter of anterior and septal wall regions, TGC levels need to be set below those of posterior region by lo-20 dB. Transducer frequency Reportedly, transducer carrier frequency can also profoundly influence the final calculation of integrated backscatter magnitude (Hall et al. 1997; Skorton et al. 1987; van der Steen et al. 1991; Wear et al. 1991). In vitro study showed small differences of backscatter intensity between transducer frequencies, except for the 5.0-MHz transducer, which produced a much smaller integrated backscatter magnitude. The highest frequency transducer (5.0 MHz) produced lower integrated backscatter intensity, particularly in the posterior region, and the lower frequency transducer (2.0 MHz) produced larger integrated backscatter intensity but resulted in minimal cyclic variation, partly because of saturation effects. Except for the 2.0-MHz transducer, the effect of transducer frequency on cyclic variation was small. It is well known that integrated backscatter is dependent upon applied transducer frequency, but the influence of transducer frequency on the magnitude of cyclic variation may be less than that of machine settings. Real-time two-dimensional integrated backscatter image There are some reports of radio frequency signal analysis throughout the cardiac cycle for normal and diseased myocardial tissue, mostly by M-mode cursor (one scan line) (Masuyama et al. 1990; Milunski et al. 1989b: Schnittger et al. 1985; Stuhlmuller et al. 1992; Wickline et al. 1986). The real-time two-dimensional integrated backscatter images have an advantage over M-mode images because the M-mode technique does not allow perfect geometric location of the structure and the two-dimensional approach provides for spatial averaging under examination (Barzilai et al. 1988). By including backscatter data over the entire cardiac cycle, integrated backscatter imaging with acoustic densitometry is a promising method of assessing myocardial tissue in the clinical situation. Clinical

implications

Integrated backscatter. The integrated backscatter data itself may not be useful for either inter- or intrapatient study, even when acoustic power, TGC, transducer frequency or location of region of interest are fixed. Currently, only a few manufacturers have made measurement of integrated backscatter available. If more manufacturers do the same, differences in slope and break points of these various measurement systems

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might further confound interpretation. Results of integrated backscatter studies can be interpreted only in the context of absolute settings for acoustic power. TGC, carrier frequency and location of region of interest. Indeed, these absolute settings would likely be different for every patient. A possible solution could be to standardize the integrated backscatter measurement by using normal tissues ( scatterers ) as an internal reference. Relative integrated backscatter measurement using the pericardial reflection or other specular reflection as a reference has been reported as a basis for measurement correction (Douglas et al. 1994: Lattanzi et al. 1991; Tanaka et al. 1985 ). Such an approach may not be valid, because pericardium may be saturated with high-amplitude specular reflectors and is different in character than the scattered reflection derived from the myocardium. The calibration from blood in the LV of the heart may be valid only for exclusion of the noise level (Naito et al. 1995 ) . Cyclic variation of integrated backscatter. We observed a large variation of the cyclic variation for different levels of insonification and regions measured during normal contractile performance in ~ivo. As changes in acoustic power and TGC alter the magnitude of cyclic variation, the adjustment of these settings can be critical for optimizing the tissue characterization and minimizing the data variability. The current study indicates several clinical implications for use of cyclic variation. First, cyclic variation data may be useful in a clinical study only when acoustic power, TGC and transducer frequency are appropriate. Second. special caution should be used to compare cyclic variation between different regions of interest. The ability to demonstrate cyclic variation only in selected views and regions of interest may limit the clinical utility of a real-time backscatter imaging system (Vandenberg et al. 1989). However, we described that each region studied has a substantial magnitude of cyclic variation and each region has specific, appropriate machine settings to maximize the magnitude of cyclic variation. Under these conditions, it may be possible to compare each cyclic variation with the corresponding region of interest or compare combined multiple regions of interest to evaluate myocardial tissue (Lange et al. 1995; Ota et al. 1995). The current study raises the possibility that. if acoustic power and/or TGC are set at the low or high settings where the functions are nonlinear, one may possibly observe cyclic variations of considerably different magnitude than when these settings are within the linear ranges. Some solutions may be the development of backscatter calibration curves that could be used to compensate for variations in acoustic power and TGC settings among different images or the expansion of the dynamic range of the

Acoustic

densitometry

of integrated

integrated backscatter processing hardware by manufacturers. Prior to the study, one can make sure to use the appropriate settings of acoustic power and TGC that work within the linear range for several regions. Acoustic densitometry and digital storage. Digital acoustic densitometry systems have the advantage of decreasing the integrated backscatter analysis complexity and time with appropriate configuration menu selection compared to complex off-line data processing. Acoustic densitometry provides the integrated on-line capability to measure, display and analyze the average backscatter image intensity within the userspecified region of interest at the user-specified triggered intervals. Image storage on optical disks has the major advantage of largely preserving the information of the original radio frequency signal. The digitized image quality is much higher than that of the analog video image and allows fast random access to the data. An off-line computed analysis using video-taped data loses original important information and reduces dynamic range due to the signal processing, log compression and the rectification of the analog video signal performed prior to recording, leaving only the amplitude information. The sensitivity of ultrasound equipment has continuously increased the potential of myocardial tissue characterization in the diagnosis and management of patients with impaired myocardium. Technological advances suggest that the resolution can be improved to utilize the lateral gain control and near gain adjustment system (Recchia et al. 1993 ) . No measurement of lateral gain control was performed in this study. Limitations. Some limitations of the specific methodology and/or technology used in the present study should be acknowledged. This study did not exactly represent the clinical situation, as epicardial imaging eliminated the attenuation caused by the chest wall thickness. Ultrasound must traverse body tissue to reach the target organs, so the transmit power will be absorbed and weakened through transthoracic passage. The appropriate setting in the clinical situation may not be the same as in this study. Further studies into these relationships would help to bring these methods to more certain clinical utility. Summary Consistent measurement of tissue reflectivity existed only when acoustic power and TGC settings were within appropriate ranges in vitro and in vivo. The cyclic variation of integrated backscatter was present at regions examined in this study and influenced by the acoustic power, TGC and transducer frequency as well as placement of the region of interest. Minimal

backscatter

0 T. OTA et al.

1069

settings of acoustic power and TGC did not produce enough signal to create a significant magnitude of cyclic variation, while excessive settings caused signal saturation that masked integrated backscatter variation in the myocardium. There is a limited range of appropriate machine settings that may be used for quantitative tissue characterization. This study indicates that proper transducer selection and setting of acoustic power and TGC, as well as an understanding of region of interest, are necessary and critical for interpretation of integrated backscatter and its cyclic variation.

REFERENCES Barzilai B, Madaras EI, Sobel BE, Miller JG. Perez JE. Effects of myocardial contraction on ultrasonic backscatter before and after ischemia. Am J Physiol 1984;247:H478-H483. Barzilai B, Thomas LJ, Glueck RM, et al. Detection of remote myocardial infarction with quantitative real-time ultrasonic characterization. J Am Sot Echocardiogr 1988; 1: 176- 186. Cohen RD. Mottley JG. Miller JG. Kumik PB, Sobel BE. Detection of ischemic myocardium in vivo through the chest wall by quantitative ultrasonic tissue characterization. Am J Cardiol 1982:50:838-843. Dibello V, Talarico L. Picano E. et al. Increased echodensity in myocardial wall in the diabetic heart: An ultrasound tissue characterization study. J Am Co11 Cardiol 1995;25: 140% 1415. Douglas PS, D’Sa A. Katz S. Howell S. Ultrasonic integrated backscatter: A new method for imaging and analysis (abstract). Circulation 1994;90:1-326. Fitzgerald PJ, MacDaniel MD, Rolett EL, James DH, Strohbehn JW. Two-dimensional ultrasonic variation in myocardium throughout the cardiac cycle. Ultrason Imaging 1986; 8:241-25 1. Glueck RM. Mottley JG, Miller JG, Sobel BE, Perez JE. Effects of coronary artery occlusion and reperfusion on cardiac cycledependent variation of myocardial ultrasound backscatter. Circ Res 1985;56:683-689. Hall CF, Verdonk ED. Wickline SA, Perez JE. Miller JG. Anisotropy of the apparent frequency dependence of backscatter in formalin fixed human myocardium. J Acoust Sot Am 1997; 101:563-568. Lange A. Moran CM, Palka P. et al. The variation of integrated backscatter in differing ultrasonic transthoracic view q;. J Am Sot Echocardiogr 1995;8:830-838. Lattanzi F, Spirit0 P, Picano E. et al. Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy. J Am Co11 Cardiol 1991; 17:1085-1090. Lythall DA. Gibson DG. Kushwaha SS, et al. Changes in myocardial echo amplitude during reversible ischemia in humans. Br Heart J 1992;67:368-376. Lythall DA, Bishop J. Greenbaum RA, et al. Relationship between myocardial collagen and echo amplitude in non-fibrotic hearts. Em Heart J 1993; 14:344-350. Madaras EI, Barzilai B. Perez JE, Sobel BE, Miller JG. Changes in myocardial backscatter throughout the cardiac cycle. Ultrason Imaging 1983;5:229-239. Madaras EL Perez J, Sobel BE, Mottley JG, Miller JG. Anisotropy of the ultrasonic backscatter of myocardial tissue: II. Measurements in I’~L’o. J Acoust Sot Am 1988;83:762-769. Masuyama T. Gore FG, Tye TL. et al. Ultrasonic tissue chardcterization of human hypertrophied hearts in rii~j with cardiac cycledependent variation in integrated backscatter. Circulation 1989; 80:925-934. Masuyama T. Valantine HA. Gibbons R. Schnittger I. Popp RL. Serial measurement of integrated ultrasonic backscattrr in human cardiac allografts for the recognition of acute rejection. Circulation 1990;81:829-839. Miller JG. Perez JE. Sobel BE. Ultrasonic characterization of myocardium. Prog Cardiovas Dis 1985; 18:85- 1 IO. Milunski MR. Mohr GA. Wear KA. et al. Early identitication with

I(170

Ultrasound

in Medicine

and

Biology

ultrasonic integrated backscatter of viable but stunned myocardium in dog. J Am Co11 Cardiol 1989a; 14:462-471. Milunski MR, Mohr GA, Perez JE, et al. Ultrasonic tissue characterization with integrated backscatter: Acute myocardial ischemia, reperfusion, and stunned myocardium in patients. Circulation 1989b; SO:49 I-503. Mimbs J. Bauwens D, Cohen RD, et al. Effects of myocardial ischemia on quantitative ultrasonic backscatter and identification of responsible determinants. Circ Res 1981;49:89-96. Mottley JG. Miller JG. Anisotropy of the ultrasound backscatter of myocardial tissue: I. Theory and measurement in vitro. J Acoust Sot Am 1988;83:755-761. Naito J, Masuyama T. Mano T, et al. Validation of transthoracic myocardial ultrasonic tissue characterization: Comparison of transthoracic and open chest measurements of integrated backscatter. Ultrasound Med Biol 1995;21:33-40. Naito J. Masuyama T, Mano T, et al. Influence of preload and afterload and contractility on myocardial ultrasonic tissue characterization with integrated backscatter. Ultrasound Med Biol 1996;22:305-312. Ota T, Heinle SK, Evans W, Higgenbotham M, Kiss10 J. Echocardiographic cardiac rejection surveillance using acoustic densitometry of two dimensional ultrasound backscatter imaging: Multiple views and regions of interest (abstract). J Am Co11 Cardiol 1995;25(Suppl):289A. Perez JE, Miller JG. Holland MR, et al. Ultrasonic tissue characterization: Integrated backscatter imaging for detecting myocardial structural properties and on-line quantification of cardiac function. Am J Card Imaging 1994:8:106-l 12. Picano E, Landini L, D&ante A, et al. Angle dependence of ultrasonic backscatter in arterial tissue: A study in vitro. Circulation 1985;12:572-576. Picano E, Pelosi G, Marzilli M, et al. In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans, Circulation 1990;81:58-64. Recchia D, Miller JG, Wickline SA. Quantification of ultrasonic anisotropy in normal myocardium with lateral gain compensation of two-dimensional integrated backscatter images. Ultrasound Med Biol 1993: 19:497-505. Rijsterborgh H, Mastik F, Lancee CT, et al. Ultrasound myocardial integrated backscatter signal processing: Frequency domain versus time domain. Ultrasound Med Biol 1993; 19:211-219. Schnittger I, Vieli A, Heiserman JE, et al. Ultrasonic tissue character-

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ization: Detection of acute myocardial ischemia in dogs. Circulation 1985;72:193-199. Shaw TRD. Logan-Sinclair RB, Surin C, et al. Relation between regional echo intensity and myocardial connective tissue in chronic left ventricular disease. Br Heart J 1984; 5 I:46653 Skorton DJ, Chivers RC, Collins SM. Ultrasonic tissue characterization in cardiology. Am J Noninvas Cardiol 1987: 1:88-97. Skorton DJ, Collins SM. Clinical potential of ultrasound tissue characterization in cardiomyopathies. J Am Sot Echocardiogr 1988; 1:69-77. Stuhlmuller JE, Skorton DJ, Burns TL, Melton HE. Vandenberg BF. Reproducibility of quantitative backscatter echocardiographic imaging in normal subjects. Am J Cardiol 1992;69:542546. Tanaka M, Nitta S, Nitta K, et al. Non-invasive estimation by cross sectional echocardiography of myocardial damage in cardiomyopathy. Br Heart J 1985;53:137-152. van der Steen AFW, Rijsterborgh H, Mastik F, et al. Influence of attenuation on measurements of ultrasonic myocardial integrated backscatter during cardiac cycle ( an in vitro study). Ultrasound Med Biol 1991; 17:869-877. Vandenberg BF. Rath L, Shoup TA, et al. Cyclic variation of ultrasound backscatter in normal myocardium is view dependent: Clinical studies with a real-time backscatter imaging system. J Am Sot Echocardiogr 1989;2:308-314. Vered Z, Barzilai B, Mohr GA, et al. Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging, in normal human subjects and patients with dilated cardiomyopathy. Circulation 1987:76:10671073. Vered Z, Mohr GA, Barzilai B, et al. Ultrasound integrated backscatter tissue characterization of remote myocardial infarction in human subjects. J Am Co11 Cardiol 1989; 13:84-91. Vitale DE, Bonow RO, Gerund0 G, et al. Alterations in ultrasonic backscatter during exercise-induced myocardial ischemia in humans. Circulation 1995;92: 1452- 1457. Wear KA. Milunski MR, Wickline SA, et al. The effect of frequency on the magnitude of cyclic variation of backscatter in dogs and implications for prompt detection of acute myocardial ischemia. IEEE Trans 199l;UFFC-38:498-502. Wickline SA, Thomas LJ, Miller JG, Sobel BE, Perez JE. Sensitive detection of the effects of reperfusion on myocardium by ultrasound tissue characterization with integrated backscatter. Circulation 1986;74:389-400. Wickline SA, Thomas LJ, Miller JG, Sobel BE, Perez JE. A relationship between ultrasonic integrated backscatter and myocardial contractile function. J Clin Invest 1985; 76:215 l-21 60.