Comparison of Power Doppler and B-Scan Sonography for Renal Imaging Using a Sonographic Contrast Agent

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1 Comparison of Power Doppler and B-Scan Sonography for Renal Imaging Using a Sonographic Contrast Agent Chandra M. Sehgal, PhD, Peter H. Arger, MD, Charles R. Pugh, DVM, James I. Kirchofer, DVM, Elon Y. Kotlar, BA, Kenneth C. Bovee, DVM The goal of this study was to evaluate the relative performance of power Doppler and B-scan imaging modes in detecting vascular perfusion changes resulting from injection of a contrast agent. To allow this comparison the imaging plane and the contrast agent injection must be the same for both modes. We achieved this by using a rigid transducer holder and simultaneously recording power Doppler and B- scan images on separate videotapes. The kidneys of five adult beagles were scanned to allow a comparison of how power Doppler and B-scan imaging methods monitor changes during the injection of 0.1 ml/kg of a contrast agent, EchoGen emulsion (Sonus Pharmaceuticals, Bothell, WA). The changes in the images were assessed qualitatively by three radiologists and quantitatively using a customdesigned image analysis software. All of the radiologists agreed that no visually detectable changes occurred in B-scan images but that significant changes could be observed in power Doppler images. Image analysis also indicated a difference between power Doppler and B-scan images. The change in mean color level of power Doppler images could be displayed as an indicator dilution curve with a peak enhancement of 46 ± 16 above the preinjection value. The time at which mean color level peaked was 18 ± 13 s. The mean color level returned to half of the peak value by 69 ± 42 s and returned to the preinjection baseline value by 148 ± 73 s. Conversely, B-scan images showed statistically insignificant changes, and time measurements could not be made. By all measures used to evaluate images, power Doppler imaging had a greater sensitivity in detecting changes resulting from contrast agent injection than B-scan imaging. This finding indicates that power Doppler imaging of contrast agent injections can be used to map regional differences in flow as well as quantitative measurements of a contrast agent s transit time and has the potential to assess kidney abnormalities associated with renal blood flow. KEY WORDS: Kidney; Contrast agent; Power Doppler sonography; Perfusion, renal. ABBREVIATIONS ROI, Region of interest; MCL, Mean color level; MGL, Mean gray scale level; SD, Standard deviation. Received May 5, 1998, from the Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania. Revised manuscript accepted for publication September 4, Address correspondence and reprint requests to Chandra M. Sehgal, PhD, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA With the development of new sonographic contrast agents, new applications for diagnostic ultrasonography may become available. Gray scale imaging, color flow Doppler imaging, and power Doppler imaging of the kidneys are all modalities that have been shown to be enhanced with the use of contrast agents. 1 8 However, it is less clear how these various modes of imaging compare in performance relative to one another. A common difficulty in making such comparisons is that separate injections are used for each mode of imaging. Under these circumstances it is difficult to determine if the observed changes are 1998 by the American Institute of Ultrasound in Medicine J Ultrasound Med 17: , /98/$3.50

2 752 RENAL IMAGING WITH SONOGRAPHIC CONTRAST AGENT J Ultrasound Med 17: , 1998 due to variations in the injections of the contrast agent or actually due to the differences in the sensitivities of the imaging modes. For a comparison of two modes of imaging to be valid they must be performed simultaneously. In particular, the images must correspond to the same image plane and to the same injection of contrast agent. Taking this factor into consideration the present paper evaluates the relative sensitivity of power Doppler sonography and B-scan imaging in visualizing a given dose of microbubbles as they transit through the kidneys. MATERIALS AND METHODS Five healthy adult beagles were anesthetized by intravenous injection of thiopental (15 ml of 2.5% solution). Intermittent boluses of the same agent were used to maintain the animals under anesthesia for 2 h. Hair was clipped from the abdomen to facilitate acoustic coupling. All protocols and procedures were approved by the Institutional Animal Care and Use Committee. The animals kidneys were scanned using a 7-4 MHz transducer and an HDI 9 ultrasound scanner (Advanced Technology Laboratories, Bothell, WA). After preliminary scanning with a hand-held transducer an image plane was chosen and the transducer was locked in position by a specially designed rigid holder. This allowed a fixed plane to be scanned as a function of time throughout the study. The B-scan and power Doppler images were acquired simultaneously by accessing two video signals, one for each mode of imaging, from the scanner. The images were recorded on videotapes with time-address encoded on one of the two audio channels. The time of injection was marked on the B-scan and power Doppler images. The timeaddress of the marked frames was used to synchronize the digitization of the two tapes. This procedure provided a sequence of power Doppler and B-scan images corresponding to the same time period. A bolus injection of the fluorocarbon-based contrast agent EchoGen (Sonus Pharmaceuticals, Bothell, WA) was given intravenously at a dose of 0.1 ml/kg. Images were recorded for approximately 1 min prior to the contrast agent injection and 15 min after the injection. The initiation and completion of the bolus injection were marked on the videotapes. The bolus injection time was determined by counting the number of video frames from the initiation of the injection to its completion. This time ranged between 2 and 5 s for this study. The images were assessed both qualitatively and quantitatively. The qualitative assessment involved review of the tapes by three independent observers. Each reviewer had a priori knowledge that the recorded tapes had images obtained both before and after injection of contrast agent. The changes were characterized by the reviewers as (1) obvious change, (2) possible change, or (3) no change. The quantitative assessment was performed offline. The images were first digitized frame by frame at 24 bit depth. For each contrast agent injection 600 images were obtained per imaging mode. The image in which initiation of contrast agent injection occurred was marked on the tape. The frame addresses of these images were used to synchronize the image sets of the two imaging modes, allowing the individual frames of each data set to correspond to the same time period. Using custom designed software, each image in the two data sets was analyzed globally and regionally as described later. Global Analysis The entire kidney was outlined on both Doppler and gray scale images. The colors in the color bar on the power Doppler images were assigned values between 0 and 100 based on their position in the color bar. The colored pixels within the ROI were identified and assigned values according to their color levels. The MCL for each image was determined by taking the arithmetic mean of the colored pixels within the ROI. B-scan images were analyzed by measuring the MGL of the pixels enclosed within the outlined region. Both MCL and MGL were plotted as a function of time. A five point moving average was taken to filter noise in the curves. The properties of these curves were characterized by measuring three times: the time at which the enhancement peaks, T p ; the time at which the enhancement is reduced to half of its peak value, T 1 / 2 ; and the time at which the enhancement returns to the baseline value before contrast agent injection, T b. Regional Analysis A regional analysis was done by comparing the MGL of an pixel window for images before and after injection of contrast agent. If the difference in the means was statistically significant (P 0.01) the center pixel was stained in color, otherwise it was left unchanged. The window was scanned pixel by pixel and at each step the procedure of measuring MGL, statistical evaluation of the differences in the mean values and pixel staining was repeated. By this procedure a new set of images was constructed with

3 J Ultrasound Med 17: , 1998 SEHGAL ET AL 753 color superimposed on the original gray scale image, with color representing a statistically significant difference in image brightness owing to the presence of contrast agent. These images, referred to as statmaps, were obtained for B-scan and power Doppler modes. For the purpose of comparison, the power Doppler images were converted into gray scale images with a 0 to 255 scale prior to regional measurements. RESULTS Figure 1 shows a characteristic power Doppler image obtained under the described experimental conditions. Renal, interlobar, arcuate, and cortical blood vessels as well as their branching patterns can be seen clearly. Furthermore, a sharp distinction can be noted between the cortical and medullary regions. Although these images provide a vascular pattern with high resolution they do not differentiate between arterial and venous flow. In the qualitative assessment of the videotapes all three observers identified the changes as obvious on power Doppler sonographic images and as no change on B-scan images (Figs. 2, 3). The numbers shown on each panel represent seconds after contrast injection. Both power Doppler and B-scan images correspond to the same contrast agent injection. Although significant enhancement of color level occurred in the power Doppler sonographic images, no detectable difference was found in the gray scale images. The color level of the power Doppler images returned to the preinjection level by 240 s (compare panels 1 and 6 of Fig. 2). All the dogs studied showed the same pattern of change. Quantitative measurements of the MCL of the power Doppler images and Figure 1 Power Doppler image of a dog kidney obtained by a fixed transducer. of the MGL of B-scan images as a function of time are shown in Figures 4 and 5. A rapid increase in MCL occurred immediately after contrast agent injection, which peaked at approximately 20 s and then decayed exponentially. Conversely, the mean gray level of the B-scan images remained constant with time at an approximate MGL value of 75. In Figure 5, a small peak appears to be present in the MGL-time curve at about 20 to 30 s after contrast agent injection, the time period in which the corresponding power Doppler image shows a significant enhancement. When displayed on an expanded scale (Fig. 6) the same data show a small peak corresponding to three units of gray scale change. Although computer measurements could detect these changes, identifying them visually on a videotape with any level of confidence was difficult. It was not feasible to make transit time measurements on MGL-time curves derived from the B-scans, whereas these measurements could be made easily on MCL-time curves derived from power Doppler sonographic images. Table 1 summarizes the characteristic time measurements made on power Doppler sonograms of the five dogs. On average the MCL peaked at T p = 18 ± 13 s and was reduced to half its original value at T1/ 2 = 69 ± 42 s. The power Doppler sonographic signal returned to the original baseline value at T b = 148 ± 73 s, which corresponded to the contrast enhancement time. The peak enhancement difference in MCL relative to the baseline value was 46 ± 16. Figures 7 and 8 show the statmap images comparing the regional changes in power Doppler and B-scan images. The changes in the power Doppler images are marked and spread over the entire kidney, including the medulla. Conversely, the changes in the B-scan images are sparse and correspond to the lower end of the color scale, which demonstrates its lack of sensitivity in detecting bubbles at relatively low doses of contrast agent injected. DISCUSSION Significant differences are noted in the structures visualized on B-scan and power Doppler images even though they both correspond to the same image plane. Whereas the vasculature in the power Doppler images is well defined, these vessels cannot be seen in B-mode images. In addition, a marked difference occurs in the response of the two imaging modes to the injection of a contrast agent. All measures used in this study to evaluate the two modes of imaging demonstrate the presence of a significant increase in the color level of the power Doppler

4 754 RENAL IMAGING WITH SONOGRAPHIC CONTRAST AGENT J Ultrasound Med 17: , 1998 Figure 2 Effect of injection of a contrast agent on the power Doppler images of dog kidneys. The numbers on each panel represent time relative to the contrast agent injection. Figure 3 Effect of injection of a contrast agent on the B-scan images of dog kidneys. The numbers on each panel represent time relative to contrast agent injection. These images were obtained simultaneously to the power Doppler images shown in Figure 2 and thus correspond to the same contrast agent injection and the same plane of imaging. images as low doses of contrast agents transit through the kidney. This enhancement is uniformly distributed over the entire kidney. However, the same bubble population of the contrast agent when observed simultaneously by B-scan imaging did not produce an appreciable change in the gray scale images. These results demonstrate that power Doppler imaging is more sensitive in detecting changes due to a contrast agent injection than B-scan imaging. One common problem experienced in using power Doppler imaging is the flash artifact due to the motion of the transducer. Our study shows that this effect can be controlled to a significant extent by holding the transducer fixed and by using a high persistence setting on the scanner. Figure 4 Change in MCL of the power Doppler images enhanced by the injection of 0.1 ml/kg of contrast agent. Figure 5 Time intensity plot of the gray scale (B-mode) images enhanced by the injection of contrast agent. These data correspond to the same injection as that shown for Figure 4.

5 J Ultrasound Med 17: , 1998 SEHGAL ET AL 755 Figure 6 Gray scale changes observed in Figure 5 on an expanded scale. In the experiments described, the dose of contrast agent used was smaller than that used earlier. 4 The dose-image enhancement relationship is complex and nonlinear. 4,9,10 Therefore, the results of this study should not be applied to higher doses. Our previous studies with an earlier version of the same contrast agent at a dose 6.5 times greater produced a demonstrable enhancement of gray scale images. 4 Figure 9 shows the statmap images constructed from one such injection. Interestingly, even at this high dose the enhancement of the kidney was limited to the cortical region, unlike the situation with power Doppler images, which showed enhancement throughout the organ. In accordance with the indicator dilution theory, 11 the increase in color levels in the power Doppler images with time followed a well-defined pattern. It is of interest to note that T p, T1/ 2, and T b derived from the power Doppler imaging in this study were consistently and significantly shorter than the transit times determined from the gray scale enhancement in our previous study. 4 Specifically, T p was on average 20 s versus 70 s and T b was 170 s versus 700 s for power Doppler and gray scale imaging, respectively. The reason for this difference is not fully understood. One likely explanation is that the two modes of imaging correspond to different portions of the total flow through the kidneys. Although the transit time measures derived from power Doppler images emphasize flow through relatively larger blood vessels (e.g., interlobar, arcuate, and cortical arteries), the measures derived from B-scan images correspond to total flow through all blood vessels, including slow flow through the capillaries. Owing to the weighting from the slow blood flow, the transit time measures should be expected to be longer for B-scan images than those derived from power Doppler images. Thus, although contrast agent enhanced B-scan imaging may be less sensitive it may have an advantage over power Doppler imaging in estimating slower flow. This study demonstrates that power Doppler imaging is more sensitive than B-scan imaging in detecting the flow of a contrast agent through the kidneys. The flash artifact commonly experienced in power Doppler imaging can be minimized to a significant extent by an appropriate choice of exper- Figure 7 Statmap images show regional enhancement of power Doppler images by the contrast agent at a dose of 0.1 ml/kg. Panels a through f represent times 0 s, 6 s, 8 s, 16 s, and 240 s after injection of the contrast agent. Table 1: Characteristics of MCL-Time Curves for Contrast Agent Injection in Individual Dogs MCL Difference* Dog T p (s) T 1/ 2(s) T b (s) (peak baseline) Mean SD T p = Time at which MCL peaks; T 1/ 2 = time taken for MCL to return to half the peak value; T b = time taken for MCL to return to the baseline value after injection of contrast agent. *Difference between the peak enhancement and the baseline (before contrast agent injection) value.

6 756 RENAL IMAGING WITH SONOGRAPHIC CONTRAST AGENT J Ultrasound Med 17: , 1998 Figure 8 Statmap images show regional enhancement of B- scan images by the contrast agent at a dose of 0.1 ml/kg. Panels a through f represent times 0 s, 6 s, 8 s, 16 s, and 240 s after injection of a contrast agent. Figure 9 Statmap images show regional enhancement of the gray scale images by the contrast agent at the dose of 6.5 ml/kg. Data for this figure were obtained from the study by Seghal and associates. 4 imental conditions. The use of a contrast agent in combination with power Doppler imaging can be employed to map regional differences in flow and to assess the transit time of the contrast agent quantitatively. These measures have potential for assessing kidney abnormalities associated with acute renal failure and kidney transplant rejection. REFERENCES 1. Coley BD, Mattrey RF, Roberts A, et al: Potential role of PFOB enhanced sonography of the kidney. II. Detection of partial infarction. Kidney Int 39:740, Munzing D, Mattrey RF, Reznick VM, et al: Potential role of PFOB enhanced sonography of the kidney. I. Detection of renal function and acute tubular necrosis. Kidney Int 39:733, Pugh CR, Arger PH, Sehgal CM, et al: Enhancement of Doppler, color flow and power Doppler by a new ultrasound contrast agent. Radiology 193:366, Sehgal CM, Arger PH, Pugh CR: Sonographic enhancement of renal cortex by contrast media. J Ultrasound Med 14:741, Pugh CR, Arger PH, Sehgal CM: Power, spectral, and color flow Doppler enhancement by a new ultrasonographic contrast agent. J Ultrasound Med 15:843, Taylor GA, Ecklund K, Dunning PS: Renal cortical perfusion in rabbits: Visualization with color amplitude imaging and an experimental microbubble based US contrast agent. Radiology 201:125, Lang RM, Feinstein SB, Powsner SM, et al: Contrast ultrasonography of the kidney: A new method for evaluation of renal perfusion in vivo. Circulation 75:229, Abilgaard A, Klow NE, Jackobsen JA, et al: Effects of ultrasound contrast medium in color Doppler and power Doppler visualization of blood flow in canine kidneys. Acta Radiol 38:445, Sehgal CM, Arger PH, Pugh CR: Influence of postprocessing curves on contrast-echographic imaging. J Ultrasound Med 14:735, Sehgal CM, Arger PH: Mathematical modeling of the dilution curves for ultrasonographic contrast agents. J Ultrasound Med 16:471, Grodins FS: Basic concepts in the determination of vascular volumes by indicator dilution methods. Circ Res 10:429, 1962

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