DOI: 10.1148/radiol.2373041619
(Radiology 2005;237:1063-1067.)
© RSNA, 2005
Bolus versus Continuous Infusion of Microbubble Contrast Agent for Liver US: Initial Experience1
Masahiro Okada, MD,
Christian W. Hoffmann, MD,
Karl J. Wolf, MD and
Thomas Albrecht, MD, FRCR
1 From the Department of Radiology and Nuclear Medicine, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany. Received September 19, 2004; revision requested November 24; revision received January 31, 2005; accepted February 28.
Address correspondence to M.O., Department of Radiology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan (e-mail: mokada{at}rad.med.kindai.ac.jp).
 |
ABSTRACT
|
|---|
Institutional review board approval and informed consent were obtained. To prospectively assess if continuous infusion of galactose-palmitic acid can prolong the duration of hepatic enhancement at ultrasonography over bolus injection, 11 patients received two injections—one bolus injection (2 mL/sec) and one continuous infusion (1.5 mL/min)—with the same dose of galactose-palmitic acid (4 g, 300 mg/dL). Two unenhanced baseline sweep scans (mechanical index of 0.7 and 1.3) of the relevant liver lobe were acquired followed by contrast-enhanced sweeps after bolus injection and continuous infusion. Each sweep was saved as cine loops and analyzed with a personal computer. Duration of enhancement more than 3 dB was prolonged by continuous infusion from 4.3 minutes ± 2.4 (±standard deviation) at bolus injection to 10.1 minutes ± 3.0 (P < .005). Maximal parenchymal enhancement was 11.0 dB ± 3.2 (bolus injection) and 9.2 dB ± 3.8 (infusion, P < .05). Peak liver-to-lesion contrast was 14.2 dB ± 6.3 (bolus injection) and 13.2 dB ± 7.1 (infusion, not significant). Continuous infusion of galactose-palmitic acid markedly prolongs but slightly diminishes hepatic enhancement; liver-to-lesion contrast remains unchanged.
© RSNA, 2005
|
INTRODUCTION
|
|---|
Microbubble contrast agents for ultrasonography (US), in particular those used to image focal liver lesions, have been receiving increasing attention recently. All microbubble agents are considered blood pool agents, because they do not leave the intravascular space. In addition to manifesting during the blood pool phase, some microbubble agents—such as galactose-palmitic acid—manifest during a liver-specific late phase, after the agent has cleared from the blood pool (1). This means that the contrast agent accumulates in normal liver parenchyma after the dwell time of a few minutes in the blood has elapsed (2,3). This liver-specific enhancement spares malignant focal liver lesions, in particular metastases. This enhancement pattern increases liver-to-lesion contrast and allows more and smaller lesions to be detected than are detected at conventional US (4–8).
The depiction of late phase enhancement with galactose-palmitic acid requires microbubble-specific US imaging techniques, such as pulse or phase inversion imaging with a high transmit power, since the enhancement is dependent on microbubble destruction. A previous study has shown that a mechanical index (MI) of 0.5 or more is required to yield visually appreciable enhancement with galactose-palmitic acid and phase inversion US (9). (The MI is a relatively inaccurate calculation of the energy transmitted into the tissue, which varies among transducers and manufacturers but has proved a useful and important estimate for predicting the degree of microbubble destruction in clinical practice.) As a result of bubble destruction, late phase liver enhancement after the vascular phase is highly transient: The stationary microbubbles are rapidly destroyed and are not replenished from the blood pool. To account for this transience of the late phase enhancement, the so-called sweep technique is commonly used: One or two fast imaging sweeps of each entire lobe of the liver are performed, and the images are reviewed on the cine loop. During these imaging sweeps almost all microbubbles are destroyed, which precludes further contrast material–enhanced imaging unless more microbubbles are injected (4). While this technique is feasible and is now used in many centers, it represents a clear limitation of late phase imaging with galactose-palmitic acid.
Results of previous in vitro, animal, and human studies have shown that continuous infusion of a US contrast agent can markedly prolong vascular Doppler US enhancement with a plateaulike enhancement profile that lasts until the end of the infusion (10–15). Thus, the purpose of our study was to prospectively assess if continuous infusion of galactose-palmitic acid can prolong the duration of liver enhancement at US over that with bolus injection.
|
Materials and Methods
|
|---|
Subjects
Institutional review board approval was obtained, and all patients gave informed written consent. From October 2000 to March 2001, we studied 11 consecutive patients (three men and eight women; mean age, 54 years; age range, 37–78 years; mean body weight, 70.0 kg; body weight range, 52–102 kg; mean height, 170.2 cm; height range, 150–180 cm) who had confirmed primary malignancies: colorectal carcinoma in seven patients, breast carcinoma in two, laryngeal carcinoma in one, and uterine cervical carcinoma in one. No patient had a clinical history of heart disease. The patients had either biopsy-proved metastatic tumors (eight patients) or typical findings of metastases depicted at computed tomography (CT) and magnetic resonance (MR) imaging according to established image interpretation criteria (three patients) (16). Lesion diameter range was 1.5–4.7 cm, and lesions were hypoechoic in 10 patients and hyperechoic in one patient before administration of contrast material. Multiple metastases (up to four lesions) were noted in five of 11 patients.
Injection Protocol
Galactose-palmitic acid (Levovist; Schering, Berlin, Germany) was administered intravenously via an 18- or 20-gauge cannula in the antecubital fossa. Each patient received two injections, one bolus injection and one continuous infusion, both with the same dose of galactose-palmitic acid (commercial preparation of 4 g; mixed at a concentration of 300 mg/mL; total volume, 13.3 mL). Bolus injections were given by hand (M.O., T.A., or C.W.H.) at a rate of approximately 2 mL/sec, and continuous infusions were given with a pump injector (Pulsar; Medrad, Indianola, Pa) at a rate of 1.5 mL/min (total volume of galactose-palmitic acid was 13.3 mL; therefore, the duration of the infusion was approximately 8.9 minutes), and both were followed by a manual flush with 10 mL of normal saline solution. The second injection was given 5 minutes after the signal enhancement from the first had completely disappeared as judged by two observers (M.O., 2 years of experience with galactose-palmitic acid; T.A., 7 years of experience with galactose-palmitic acid) by consensus to avoid any carryover effects.
Imaging Protocol
All liver imaging was performed with pulse inversion US by using the sweep technique. Fast but controlled sweeps of one entire lobe of the liver were performed, as has been described previously (4), by one of two examiners (M.O. or T.A.). The rationale for the sweeps was to image new and undestroyed microbubbles with each new US frame. Only one lobe (right lobe in nine patients, left lobe in two patients) of the liver was imaged according to the study protocol: This was either the lobe that contained the lesion that was visualized (in cases of a single lesion) or the lobe that provided the best sonographic access and depiction of lesions. The right lobe was scanned in the transverse plane from the diaphragm to a lower pole. The left lobe was imaged in the longitudinal plane, from left to right.
Two unenhanced baseline sweep scans of the relevant lobe of the liver were performed. This was followed by administration of a bolus injection of contrast material and US at one sweep per minute, starting at 1 minute after injection. Then, after continuous infusion of the contrast material, US at one sweep per minute was performed, starting at 2 minutes after the start of the infusion. Imaging was started later with the continuous infusion because only a relatively small amount of microbubbles had reached the liver by the 1st minute after infusion, which in our previous experience did not produce apparent enhancement. The examinations were terminated 2 minutes after the signal enhancement in the hepatic parenchyma had completely disappeared at maximum MI as judged by two observers (M.O. and T.A.) by consensus.
All examinations were performed with an HDI 5000 scanner (Philips Ultrasound, Bothell, Wash) and a C5-2 transducer (Philips Ultrasound). The baseline sweeps were performed with MIs of 0.7 and 1.3. The first sweeps after contrast material administration were performed at an MI of 0.7. When the signal enhancement obtained at this intermediate MI started to fade (as judged by the two observers), the MI was increased to 1.3 and kept at this level until the end of the enhancement; this usually yielded further signal enhancement. Experience has shown that an intermediate MI of approximately 0.7 is often sufficient to provide good signal enhancement with galactose-palmitic acid. However, bubble destruction is not complete at an intermediate MI, so the portion of the bubbles in the liver that remain intact can be used for signal enhancement during further sweeps, thus increasing the temporal imaging window. Once the signal enhancement becomes weak after a few sweeps at the intermediate MI, further enhancement can be obtained by increasing the MI to its maximum (1.3 for the transducer and settings used in this study), since this will lead to far more complete destruction of the relatively few remaining bubbles and thus provide further enhancement even when imaging at an intermediate MI was ineffective.
Apart from the MI, all scanner settings remained unchanged during the entire examination. The receive gain was set so that it produced a relatively dark baseline image to allow for the increase in brightness after contrast material arrival. The frame rate was 9–13 Hz depending on the depth of the ultrasound field; the depth was adapted to the size of the liver. We used a single focal zone that was set at the level of the lesion to be analyzed.
Each of the acquired sweeps was saved as cine loops onto a personal computer for quantitative analysis with HDI-Lab software (Philips Ultrasound).
Quantitative Image and Data Analysis
Regions of interest (ROIs) of approximately 1.0 x 1.0 cm were drawn both within a lesion and in normal hepatic parenchyma (Fig 1). Normal hepatic parenchyma was recognized as a lesion-free area on the US images and by correlation with CT or MR images. All ROIs were drawn by one investigator (M.O.), and the positions of the two regions (lesion and parenchyma) were drawn at the same depth from the skin for each patient. The ROIs in the hepatic parenchyma were placed so that they avoided visible vascular structures. The lesion ROIs were placed in the center of the lesion; none of the studied lesions were necrotic. The signal intensity within the ROIs was measured by calculating the average of three consecutive frames at the level of the lesion to account for slight frame-by-frame variation of the signal intensity.
View larger version (148K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1a. Transverse B-mode pulse inversion US scans of liver metastasis in right lobe of liver in 56-year-old woman. ROIs were drawn both within the lesion (R1) and in normal hepatic parenchyma (R0) for measurement of liver signal intensity in parenchyma and the lesion. (a) Unenhanced scan with ROIs drawn in normal hepatic parenchyma (intensity, 5.6 dB) and the lesion (intensity, 4.8 dB). Liver-to-lesion contrast is 0.8 dB. (b) Contrast-enhanced scan obtained 7 minutes after start of infusion, with ROIs drawn in normal hepatic parenchyma (intensity, 20.5 dB) and the lesion (intensity, 8.0 dB). Liver-to-lesion contrast is 12.5 dB.
|
|
View larger version (143K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1b. Transverse B-mode pulse inversion US scans of liver metastasis in right lobe of liver in 56-year-old woman. ROIs were drawn both within the lesion (R1) and in normal hepatic parenchyma (R0) for measurement of liver signal intensity in parenchyma and the lesion. (a) Unenhanced scan with ROIs drawn in normal hepatic parenchyma (intensity, 5.6 dB) and the lesion (intensity, 4.8 dB). Liver-to-lesion contrast is 0.8 dB. (b) Contrast-enhanced scan obtained 7 minutes after start of infusion, with ROIs drawn in normal hepatic parenchyma (intensity, 20.5 dB) and the lesion (intensity, 8.0 dB). Liver-to-lesion contrast is 12.5 dB.
|
|
Enhancement of the hepatic parenchyma and liver-to-lesion contrast were plotted over time for each injection. Enhancement of the hepatic parenchyma was defined as the signal intensity at each time point after contrast material injection minus the signal intensity at baseline at the same location in the liver (in each patient, the intermediate MI baseline sweep was used for the intermediate MI contrast-enhanced sweeps, and the high MI baseline sweep was used for the corresponding contrast-enhanced high MI sweeps). Liver-to-lesion contrast was defined as the absolute difference of signal intensity of normal hepatic parenchyma minus signal intensity within the lesion. If multiple metastases were covered by the sweep, the largest metastasis was selected for the analysis.
From these time-intensity curves, the following five parameters were extracted and compared between bolus injection and continuous infusion: peak enhancement of normal hepatic parenchyma, area under the curve for hepatic parenchymal enhancement, duration of normal hepatic parenchymal enhancement exceeding 3 dB (this threshold was chosen because signal intensity differences less than 3 dB are difficult to detect visually), peak liver-to-lesion contrast, and area under the curve for liver-to-lesion contrast.
Statistical Analysis
Because data were normally distributed, the Wilcoxon signed rank test was used to evaluate the differences between bolus injection and continuous infusion for the five parameters. The Statistical Package for Social Science programming (version 11.0; SPSS, Chicago, Ill) was used for analysis. A P value less than .05 was considered to indicate a statistically significant difference.
|
Results
|
|---|
After bolus injection, we used the intermediate MI (ie, 0.7) for a mean of 3.8 minutes ± 0.7 (standard deviation). At these time points, the initial enhancement at intermediate MI had faded and we had to change to high MI (ie, 1.3) to obtain further contrast-enhanced liver images. After infusion, we could use intermediate MI for a mean of 9.5 minutes ± 2.3 (range, 7–15 minutes), and we changed to high MI thereafter. Infusion with a pump injector continued for 9 minutes in all cases. With both bolus injection and continuous infusion, enhancement of the hepatic parenchyma increased in all cases after MI was changed from intermediate to high.
Hepatic Parenchymal Enhancement
In 10 of the 11 patients, the hepatic parenchyma enhanced markedly with both continuous infusion and bolus injection of contrast material. Only one patient showed almost no signal enhancement at the level of the lesion, due to its deep location (>12 cm). The contrast-enhanced effect was limited to a band of approximately 6–8 cm around the focal zone as described previously (9).
Average peak enhancement of normal hepatic parenchyma (Table) was 11.0 dB ± 3.2 for bolus injection and 9.2 dB ± 3.8 for continuous infusion (P < .05). In eight patients, peak enhancement after bolus injection was reached at 1 minute with the initial intermediate MI; in the remaining three patients, peak enhancement was maximal at the first sweep performed after switching to high MI at 4–7 minutes. After the peak, there was a gradual decrease in the signal intensity, which returned to normal within 14 minutes (an example is shown in Fig 2a).
View larger version (21K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2a. Graph shows (a) enhancement of normal hepatic parenchyma and (b) liver-to-lesion contrast plotted over time for bolus injection and continuous infusion in a 52-year-old woman with metastasis from colon carcinoma. Arrows indicate time at which MI was increased from 0.7 to 1.3.
|
|
View larger version (22K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2b. Graph shows (a) enhancement of normal hepatic parenchyma and (b) liver-to-lesion contrast plotted over time for bolus injection and continuous infusion in a 52-year-old woman with metastasis from colon carcinoma. Arrows indicate time at which MI was increased from 0.7 to 1.3.
|
|
The continuous infusions produced a different enhancement profile (Fig 2a). The rise of the time-intensity curve was more gradual, and in nine cases we observed a plateau (defined as a horizontal curve over a period of at least 4 minutes with less than 4-dB variation) of the curve starting after 3.8 minutes ± 1.1 (range, 3–6 minutes) and lasting until the end of the continuous infusion. Peak enhancement was reached after a mean of 8.5 minutes ± 3.8 (range, 2–14 minutes). Peak enhancement occurred at the initial intermediate MI in four patients and on the first sweep after changing to high MI in seven. When the signal enhancement of normal liver parenchyma obtained at intermediate MI had visually faded, however, there was persistent enhancement in four of 11 patients on actual measurement of signal intensity.
The areas under the curves were increased with continuous infusion from 38.0 dB/min ± 23.5 (bolus injection) to 72.9 dB/min ± 36.8 for normal hepatic parenchymal enhancement (P < .005) (Table).
Duration of Hepatic Parenchymal Enhancement Exceeding 3 dB
The duration of normal hepatic parenchymal enhancement exceeding 3 dB, and thus the visually appreciable enhancement, was markedly prolonged with continuous infusion, from 4.3 minutes ± 2.4 with bolus injection to 10.1 minutes ± 3.0 (P < .003) (Table).
After the switch to high MI, the duration of enhancement exceeding 3 dB was short (bolus injection, 1.7 minutes ± 1.1; continuous infusion, 2.5 minutes ± 1.5) due to extensive bubble destruction.
Contrast between Normal Hepatic Parenchyma and Lesion
Ten of the 11 metastases studied were hypoechoic on baseline scans and became more hypoechoic after both bolus injection and continuous infusion of contrast material, which increased their conspicuity. One metastasis was hyperechoic on baseline scans. This lesion showed reversed echogenicity and became relatively hypoechoic after bolus injection of contrast material, whereas it was isoechoic during continuous infusion with decreased conspicuity compared with baseline.
The curves for liver-to-lesion contrast were very similar to the curves for parenchymal enhancement in 10 of the 11 metastases (Fig 2), since the signal intensity within the lesions changed very little after contrast material injection. The changes in liver-to-lesion contrast were a function mainly of the signal intensity changes in the hepatic parenchyma.
Average peak liver-to-lesion contrast was very similar with both bolus injection and continuous infusion (14.2 dB ± 6.3 for bolus injection vs 13.2 dB ± 7.1 for continuous infusion; not significant, P = .24) (Table). It was substantially increased with both injection methods compared with baseline (4.3 dB ± 4.5; P < .001 compared with bolus injection and continuous infusion).
The area under the curve for liver-to-lesion contrast was increased with continuous infusion from 46.6 dB/min ± 32.2 for bolus injection to 107.5 dB/min ± 60.5 (P < .005) (Table).
|
Discussion
|
|---|
US contrast agents for hepatic imaging, such as galactose-palmitic acid, are traditionally injected as a bolus. Use of destructive intermediate or high MI imaging techniques (which are mandatory with the use of galactose-palmitic acid) results in a short window for imaging, during which only a few contrast-enhanced sweeps of the liver are possible. The results of our study show that the duration of hepatic contrast enhancement after administration of galactose-palmitic acid can be significantly prolonged with the use of continuous infusion. The number of sweeps that produce visually appreciable contrast enhancement could be doubled with the use of continuous infusion from a mean of four to almost 10 with the same single dose of contrast agent. At the same time, peak hepatic enhancement was only slightly reduced by a mean of 2.8 dB. More important, peak liver-to-lesion contrast was not substantially decreased with the use of infusion. This suggests that the number of sweeps can be doubled without loss of image quality with regard to lesion conspicuity. Continuous infusion is thus well suited to improve the most important limitation of galactose-palmitic acid-enhanced liver imaging—that is, the short duration of contrast enhancement.
Imaging of liver metastases with galactose-palmitic acid is usually performed several minutes after a bolus injection during the so-called liver-specific late phase (2,4–7), because it is assumed that most of the microbubbles will have disappeared from the blood pool and thus from metastases while the microbubbles persist in hepatic parenchyma. Our results show that a bolus injection is not necessary: Liver-to-lesion contrast was almost the same during continuous infusion as it was after bolus injection, despite a relatively high microbubble concentration in the blood pool and thus in metastases during infusion. The fact that this did not reduce liver-to-lesion contrast suggests that, even during the blood pool phase, selective hepatic contrast material uptake is dominant, and the microbubble concentration in normal liver exceeds that within the metastasis. In other words, we speculate that the liver-specific effect begins much earlier than previously thought and is already dominant during the blood pool phase. This appears to work in favor of the continuous infusion method when using galactose-palmitic acid for the detection of metastases. The majority of the metastases in our study were hypovascular, but the continuous infusion provided the same results in the two patients with deposits from carcinoma of the breast. Whether this applies to hypervascular metastases in general should be the subject of further studies. The origin of the liver specificity of galactose-palmitic acid remains uncertain, but some interaction with the reticuloendothelial system appears likely.
Our study has some limitations. It was designed as a pilot study to test the feasibility of continuous infusion for liver imaging on a limited number of patients. We did not assess the effect of different infusion rates, and we used only one time interval between sweeps. On the basis of previous experience, we chose an interval of 1 minute to allow for sufficient microbubble replenishment after a destructive sweep. Our results show that this interval was sufficiently long, but a shorter interval might have further increased the number of possible sweeps.
The potential clinical application of the continuous infusion technique in the liver is detection of hypovascular metastases. The technique may be less useful for detecting hypervascular lesions, such as liver metastasis of renal cell carcinoma, carcinoid, and hepatocellular carcinoma, and this should be the subject of further studies. For other applications such as characterization of focal liver lesions, bolus injection should be preferred so that lesions can be studied dynamically during the different phases (arterial, portal venous, and late) of contrast enhancement.
Continuous infusion of galactose-palmitic acid markedly prolongs but slightly diminishes hepatic enhancement; liver-to-lesion contrast remains unchanged. However, because of a limited number of patients, further studies are needed to determine when the continuous infusion technique is preferable.
|
ACKNOWLEDGMENTS
|
|---|
We thank Tohru Takebayashi, MD, of the Department of Statistics in Keio University for the advice of statistical analysis. Philips Ultrasound, Bothell, Wash, supplied the US system and the software for signal intensity analysis.
|
FOOTNOTES
|
|---|
Abbreviations: MI = mechanical index • ROI = region of interest
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, T.A.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, T.A.; clinical studies, M.O., C.W.H., T.A.; statistical analysis, M.O.; and manuscript editing, K.J.W., T.A.
|
References
|
|---|
- Blomley M, Albrecht T, Cosgrove D, Jayaram V, Butler-Barnes J, Eckersley R. Stimulated acoustic emission in liver parenchyma with SHU 508A. Lancet 1998;351:568.[Medline]
- Albrecht T, Blomley MJ, Heckemann RA, et al. Stimulated acoustic emissions with the ultrasound contrast medium SHU 508A: a clinically useful contrast effect with liver-specific properties. Rofo 2000;172:61–67.[Medline]
- Blomley MJ, Albrecht T, Cosgrove DO, et al. Stimulated acoustic emission to image a late liver and spleen-specific phase of SHU 508A in normal volunteers and patients with and without liver disease. Ultrasound Med Biol 1999;25:1341–1352.[CrossRef][Medline]
- Albrecht T, Hoffmann CW, Schmitz SA, et al. Phase-inversion sonography during the liver-specific late phase of contrast enhancement: improved detection of liver metastases. AJR Am J Roentgenol 2001;176:1191–1198.[Abstract/Free Full Text]
- Dalla Palma L, Bertolotto M, Quaia E, Locatelli M. Detection of liver metastases with pulse inversion harmonic imaging: preliminary results. Eur Radiol 1999;9(suppl 3):S382–S387.[Medline]
- Harvey CJ, Blomley MJ, Eckersley RJ, et al. Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SHU 508A—early experience. Radiology 2000;216:903–908.[Abstract/Free Full Text]
- Harvey CJ, Blomley MJ, Eckersley RJ, Heckemann RA, Butler-Barnes J, Cosgrove DO. Pulse-inversion mode imaging of liver specific microbubbles: improved detection of subcentimetre metastases. Lancet 2000;355:807–808.[CrossRef][Medline]
- Albrecht T, Blomley MJ, Burns PN, et al. Improved detection of hepatic metastases with pulse-inversion US during the liver-specific phase of SHU 508A: multicenter study. Radiology 2003;227:361–370.[Abstract/Free Full Text]
- Albrecht T, Hoffmann CW, Schettler S, et al. B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans. Radiology 2000;216:273–278.[Abstract/Free Full Text]
- Kuntz-Hehner S, Goenechea J, Pohl C, et al. Continuous-infusion contrast-enhanced US: in vitro studies of infusion techniques with different contrast agents. Radiology 2001;220:647–654.[Abstract/Free Full Text]
- Correas JM, Burns PN, Lai X, Qi X. Infusion versus bolus of an ultrasound contrast agent: in vivo dose-response measurements of BR1. Invest Radiol 2000;35:72–79.[CrossRef][Medline]
- Kratzer W, Kachele V, Merkle E, et al. Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent SHU 508A. Rofo 2000;172:443–448.[Medline]
- Kaps M, Seidel G, Algermissen C, Gerriets T, Broillet A. Pharmacokinetics of echocontrast agent infusion in a dog model. J Neuroimaging 2001;11:298–302.[Medline]
- Albrecht T, Urbank A, Mahler M, et al. Prolongation and optimization of Doppler enhancement with a microbubble US contrast agent by using continuous infusion: preliminary experience. Radiology 1998;207:339–347.[Abstract/Free Full Text]
- Albrecht T, Cosgrove DO, Butler-Barnes J, et al. Comparison of bolus and infusion of the ultrasound contrast media SHU 508A for color Doppler ultrasound of renal arteries. Rofo 2000;172:824–829.[Medline]
- Heiken JP. Liver. In: Lee JKT, Sagel SS, Stanley RJ, Heiken JP, eds. Computed body tomography with MRI correlation. 3rd ed. Philadelphia, Pa: Lippincott-Raven, 1998; 701–777.
TOP
ABSTRACT
INTRODUCTION
