ORIGINAL ARTICLE
ACTA RADIOLOGICA
Low-High and High-Low Biphasic Injection Forms in Computed Tomography Examinations of the Upper Abdomen L. MARTı´-BONMATı´, E. ARANA, E. TOBARRA & C. SIERRA Department of Radiology, Clı´nica Quiro´n, Valencia, Spain Martı´-Bonmatı´ L, Arana E, Tobarra E, Sierra C. Low-high and high-low biphasic injection forms in computed tomography examinations of the upper abdomen. Acta Radiol 2006;47:10–14. Purpose: To analyze the influence of different biphasic and monophasic injection rate protocols in abdominal computed tomography (CT). Material and Methods: A randomized, consecutive, parallel group study was designed and conducted in 60 patients studied with the same CT helical protocol. Patients were randomly distributed into three groups: (A) monophasic (120 ml at 2.5 ml/s); (B) lowhigh biphasic (120 ml, first 60 ml at a rate of 2 ml/s, the other 60 ml at 2.5 ml/s); and (C) high-low biphasic (120 ml, first 60 ml at a rate of 2.5 ml/s, the other 60 ml at 2 ml/s). All patients were injected with 300 mg I/ml non-ionic contrast media at a fixed delay time of 55 s. Contrast enhancement efficacy was evaluated by attenuation coefficient measurements. Results: Although non-significant, monophasic protocol enhancements were higher than biphasic protocol enhancements in all measurements except aortic bifurcation (p50.003). At this level, biphasic protocols obtained an increased mean enhancement from 7.6% to 2.5% compared to monophasic protocols. Conclusion: Monophasic contrast agent injection in helical CT of the upper abdomen produces a higher enhancement of parenchymal and venous structures. No significant difference was observed between low-high and high-low biphasic protocols. Key words: Computed tomography (CT), contrast enhancement; computed tomography (CT), helical technology; abdomen, CT Dr Luis Martı´-Bonmatı´, Department of Radiology. Clinica Quiro´n, E-46010 Valencia, Spain (fax. +34 963 39 1147, e-mail.
[email protected]) Accepted for publication 2 September 2005
In helical computed tomography (CT) examinations of the abdomen, the form or geometry of the bolus injection of the contrast media has a major influence on parenchymal and vascular enhancement. Monophasic injection of the contrast agents in helical CT of the abdomen is routinely used in most centers. Biphasic injection can have either low-high (LH) or high-low (HL) flow rates. A comparison of these techniques with monophasic injection rates in upper abdominal CT examinations has not been reported. Contrast-enhanced CT in the portal venous phase is the most commonly used phase acquisition in studies of the abdomen. At this time-point, most parenchymal structures are at the peak of their enhancement and most lesions will be seen as hypovascular masses. The technique-related factors that have great influence on the degree of organ enhancement in dynamic contrast-enhanced CT
include the contrast material volume, rate, and type of injection. However, controversy persists regarding the effect that the injection rate of contrast material has on hepatic enhancement (2, 5, 16). Our objective was to analyze the influence of two different biphasic injection rate protocols in contrast-enhanced abdominal CT and to compare with a standard monophasic injection rate.
Material and Methods A randomized, parallel group study was designed and conducted in 73 consecutive patients. Patients who did not consent were excluded (5 patients) because they (i) had a history of allergy, (ii) had a bad hemodynamic and cardiovascular profile, or (iii) they were unconscious or non-cooperative. In addition, eight patients with solid liver and kidney DOI 10.1080/02841850500335283
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Biphasic and Monophasic Injection Rate in Abdominal CT
tumors were excluded because tumors may alter the hemodynamics within the parenchyma. The patients were free to withdraw from the trial at any moment, in accordance with the Helsinki Declaration. A total of 60 adult patients were included in the study and referred for abdominal contrast-enhanced helical CT examination. All the patients signed an informed consent form (31 M and 29 F, mean age 57 years, range 27–90 years). The patients were homogeneously distributed according to gender, age, and weight; mean weight was 74¡16 kg. The patients were randomly distributed with the aid of a computer program into three injector protocol groups: (A) monophasic (120 ml at 2.5 ml/s); (B) low-high biphasic (120 ml, the first 60 ml at a rate of 2 ml/s, the other 60 ml at 2.5 ml/s); and (C) highlow biphasic (120 ml, the first 60 ml at a rate of 2.5 ml/s, the other 60 ml at 2 ml/s) (Fig. 1). The power injector (Tomojet CT; Bruker, Zurich, Switzerland) was a peristaltic pump with two connections allowing the injection of saline to push the contrast agent (40 ml, 2.5 ml/s). All patients were injected through an antebrachial route; the same amount (120 ml) of non-ionic contrast media (300 mg I/ml) was used (ImagopaqueH; Amersham Health, Buckinghamshire UK). The patients fasted for 6 h before the CT examination. Oral water was administered to every patient at a volume around 1500 ml to ensure bowel analysis. Scanning was performed with a single detector CT helical protocol (craniocaudal acquisition rotation time: 1 s, collimation: 7 mm, nominal slice thickness: 5 mm, pitch 1.5, 100 mAs, 120 kV) in the same scanner (Philips CT Aura; Best, The Netherlands). Scans were obtained with the patient in suspended respiration. The average abdominal helical CT examination lasted 21¡4 s. A portal phase was obtained for all patients at a fixed delay time of 55 s after the start of the contrast delivery, when there is high enhancement of the liver and portal vein. In order to minimize bias, the time was not changed between groups. The recorded variables were patient’s gender, age, and weight. Contrast enhancement efficacy was measured using attenuation coefficients. Liver, superior abdominal aorta, aortic bifurcation, extrahepatic inferior vena cava just caudal to the entrance of the renal veins, horizontal main portal vein, and right renal cortex attenuation coefficients were obtained by operator-defined manually placed regions-of-interest (ROIs) and expressed in Hounsfield units (HU). A radiologist with experience in abdominal CT, blinded to the injection protocol, located the ROIs, with a size between 350
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and 450 mm2. At least three values were averaged for each variable in order to obtain the mean measurement and minimized error in sampling. Within the liver, ROIs were situated in central areas at three different locations (right posterior segment, right anterior segment, and left lobe), excluding vascular and biliary structures. Furthermore, in the right kidney, the cortico-medullary differentiation was classified as either well defined or poorly defined.
Fig. 1. Injection protocols. A. Monophasic. B. Biphasic low-high. C. Biphasic high-low. Acta Radiol 2006 (1)
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Statistical analysis was performed for the three groups with the Pearson chi-square test for contingency tables (gender, cortico-medullary differentiation) and, after testing the normal distribution with the Kolmogorov-Smirnov test, an ANOVA with the Student–Newman–Keuls test (age, weight, and attenuation measurements). The results are expressed as mean¡standard error of the mean. A statistical significance was established with a Pv0.05. Results There were no statistically significant differences among the three evaluated injection protocols in the mean enhancement of most evaluated abdominal organs and vascular structures (Table 1, Fig. 2). In particular, no difference was found between the attenuation coefficients of the liver (P50.15), the superior abdominal aorta (P50.73), extrahepatic inferior vena cava (P50.2), main portal vein (P50.38), and right renal cortex (P50.82). Although the groups did not statistically differ, the HU obtained with the monophasic injection rate always reached slightly higher values than the biphasic rates, with an increased mean enhancement from 7.6% with the LH and 2.5% with the HL biphasic protocol. Only at the aortic bifurcation was a statistically significant difference observed (P50.003), the values with the biphasic injection rates being consistently higher than those obtained from the monophasic injection. Renal cortico-medullary differentiation was well defined in most cases (49 cases, 82%), with no significant difference in the proportions between the injection protocols (P51.0). Discussion In abdominal CT, a parenchymal phase obtained 50 to 70 s after the start of the contrast administration will ensure a high parenchymal enhancement (2, 4, 6, 14). Keeping the acquisition delay time after the start of the contrast agent administration constant,
there are several technique-related factors influencing enhancement in helical CT. The most important are related to the contrast material volume, injection rate, and form or type of injection. Regarding the bolus geometry, in most centers helical CT scanners use a high monophasic injection rate followed by a saline flush with the same flow rate. In monophasic protocols, the contrast medium is injected at a constant rate, ensuring a steady increase of vascular enhancement profile followed by parenchymal enhancement. Studies concerning biphasic and sigmoid injection flows have not been widely published (4, 7, 10, 11, 15). Most biphasic injection protocols employ a high velocity at the beginning of the injection, followed by a slower injection rate. Most of these studies have shown discordant results. Uniform vascular and parenchymal enhancement during only one acquisition after contrast administration renders different phases superfluous, consequently decreasing the patient’s radiation dose. A high level of parenchymal and vascular enhancement is desirable to increase the radiologist’s performance. CT angiography levels of enhancement above 200 HU are therefore recommended (2). Our randomized study design was conducted to assess the differences in vascular and parenchymal enhancement after different flow protocol rates of injection (monophasic, LH, and HL biphasic rates) observed during a single CT acquisition of the abdomen in the portal phase. Although patients were homogeneously distributed according to gender, age, and weight, this does not imply equality. Differences in body weight and cross-sectional dimension can therefore influence the image quality of abdominal CT scans (13). In the present study, liver parenchymal enhancement showed no statistically significant differences among the different monophasic and biphasic protocols. One reason may be found in the simulation by BAE et al. (2): peak hepatic enhancement increases substantially with a rise in injection rates only at low injection rates, i.e. below 2 ml/s. The use of injection rates above 2 ml/s did not substantially increase hepatic peak enhancement but
Table 1. Data from all the study groups (HL: high-low flow rate; LH: low-high injection flow rate). Values are expressed as mean¡standard deviation.
Liver (HU) Superior aorta (HU) Aortic bifurcation (HU) Inferior vena cava (HU) Portal vein (HU) Right renal cortex (HU)
Acta Radiol 2006 (1)
Monophasic injection
LH biphasic injection
HL biphasic injection
P-value
112.8¡15.6 264.6¡56.2 182.7¡37.1 135.9¡24.7 180.8¡37.7 214.2¡48.9
99.1¡25.7 256.0¡47.6 229.9¡57.1 121.3¡29.4 166.2¡38.5 206.2¡38.1
112.7¡31.6 252.6¡45.7 239.1¡65.7 128.3¡22.9 180.3¡33.8 210.6¡32.9
NS NS 0.003 NS NS NS
Biphasic and Monophasic Injection Rate in Abdominal CT
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Fig. 2. Example of scans with monophasic (A), low-high (B), and high-low (C) biphasic protocols at the pancreas level. Examples of ROIs have been placed at the liver, portal vein, and superior aorta.
helped increase the magnitude of arterial enhancement and temporal separation of arterial and venous phases of enhancement for dual-phase spiral CT (2). As none of our protocols injected less than 120 ml at 2.0 or 2.5 ml/s, no such differences were found. Among the factors defining the contrast injection protocol, an increase in the injection rate alone exerted less effect on the enhancement of the portal venous system and hepatic parenchyma (9). In most studies, biphasic protocols have performed less well than monophasic protocols in parenchymal and vascular enhancement. It has been shown that enhancements obtained with the monophasic protocol are always equal or higher than those obtained with the biphasic LH protocol in every anatomic level measured except in the superior aorta and aortic bifurcation (15). BIRNBAUM et al. (4) found higher enhancement with uniphasic than biphasic protocols, although with more delay time and larger contrast volume. KOPKA et al. (14) also found that high flow (4 ml/s) rates produced
higher enhancement of the parenchyma and portal vein than a HL biphasic protocol (4 ml/s followed by 2 ml/s). We have shown that a monophasic protocol produces a higher enhancement of parenchymal and venous structures than either a LH or HL biphasic protocol. Moreover, we did not find any significant difference between these latter protocols. Regarding vascular enhancement, it has been observed that biphasic injection results in more prolonged aortic enhancement than uniphasic injection (13). Our monophasic injection produced degradation of the contrast column morphology with relevant differences between superior aorta and bifurcation, a recognized drawback of this injection scheme (3). Even tailored biphasic injections led to more uniform aortoiliac enhancement compared with standard uniphasic injections. However, biphasic protocols tend to generate two enhancement peaks with a valley in between (3). This valley of enhancement decrease can be avoided with Acta Radiol 2006 (1)
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multiphasic injections. A HL biphasic protocol could be an alternative for abdominal studies with a desirable aortic enhancement (3). One of the inherent limitations in devising a universal scanning protocol is that biological variability cannot be taken into account. Although we did not analyze the circulation time, for a contrast medium volume of 120 ml a scanning delay of approximately 65 s ensures depiction of the portal hepatic and pancreatic phases. A similar scanning delay (60 s) has proved to be the best compromise for determining the short gap between pancreatic and hepatic peaks using a single acquisition (15). Because of individual variation in circulation time, slower injection (2–3 ml/s) of a large amount of contrast medium (longer injection) and an optimized CT protocol may be an effective method of obtaining good quality abdominal CT images (8). Another bias is our velocity regarding single helical CT. With the increased availability of multidetector CT, flow velocities are higher and these results should be transferred to new administration schemes. Moreover, use of a monophasic injection rate with dose and rate of the contrast material tailored to the patient’s weight (0.056 ml/s per kg injected in 25 s) has been shown to produce a uniform temporal scan window as compared with an injection protocol with a fixed injection rate (1). The influence of different injection geometries with this tailored approach has not been published. In conclusion, a monophasic injection of contrast agents in helical CT of the upper abdomen consistently showed a higher enhancement of parenchymal and venous structures than biphasic protocols. No significant difference was observed between LH and HL biphasic protocols. Acknowledgment This work was presented as a scientific exhibit at the European Congress of Radiology, 5–9 March 2004, Vienna, Austria. References 1. Awai K, Hori S. Effect of contrast injection protocol with dose tailored to patient weight and fixed injection duration on aortic and hepatic enhancement at multidetector-row helical CT. Eur Radiol 2003;13: 2155–60.
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2. Bae KT, Heiken JP, Brink JA. Aortic and hepatic peak enhancement at CT: effect of contrast medium injection rate – pharmacokinetic analysis and experimental porcine model. Radiology 1998;206:455–64. 3. Bae KT, Tran HQ, Heiken JP. Multiphasic injection method for uniform prolonged vascular enhancement at CT angiography: pharmacokinetic analysis and experimental porcine model. Radiology 2000;21:872–80. 4. Birnbaum BA, Jacobs JE, Yin D. Hepatic enhancement during helical CT: a comparison of moderate rate uniphasic and biphasic contrast injection protocols. Am J Roentgenol 1995;165:853–8. 5. Garcia PA, Bonaldi VM, Bret PM, Liang L, Reinhold C, Atri M. Effect of rate of contrast medium injection on hepatic enhancement at CT. Radiology 1996;199:185–9. 6. Gocke P, Gocke C, Neumann K, Henseke P, Langer R, Muller RD. Prospective randomized study for an injection protocol for intravenous contrast media in abdominal and pelvic helical CT. Acta Radiol 1999;40:515–20. 7. Foley WD, Hoffmann RG, Quiroz FA, Kahn CE Jr, Perret RS. Hepatic helical CT: contrast material injection protocol. Radiology 1994;192:367–71. 8. Han JK, Choi BI, Kim AY, Kim SJ. Contrast media in abdominal computed tomography: optimization of delivery methods. Korean J Radiol 2001;2:28–36. 9. Han JK, Kim AY, Lee KY, et al. Factors influencing vascular and hepatic enhancement at CT: experimental study on injection protocol using a canine model. J Comput Assist Tomogr 2000;24:400–6. 10. Heiken JP, Brink JA, McClennan BL, Sagel SS, Forman HP, DiCroce J. Dynamic contrast-enhanced CT of the liver: comparison of contrast medium injection rates and uniphasic and biphasic injection protocols. Radiology 1993;187:327–31. 11. Hoeffel C, Legmann P, Girardot C, Bunouf P, Mezzi K, Bonnin A. Contrast material injection for hepatic helical computed tomography. Comparative study of five protocols. Invest Radiol 1996;31:467–71. 12. Kalra MK, Maher MM, Prasad SR, Hayat MS, Blake MA, Varghese J, et al. Correlation of patient weight and cross-sectional dimensions with subjective image quality at standard dose abdominal CT. Korean J Radiol 2003;4:234–8. 13. Kim T, Murakami T, Takahashi S, Tsuda K, Tomoda K, Narumi Y, et al. Effects of injection rates of contrast material on arterial phase hepatic CT. Am J Roentgenol 1998;171:429–32. 14. Kopka L, Funke M, Vosshenrich R, Hagemann A, Oestmann JW, Grabbe E. Helical CT of the liver: evaluation of injection flow rate, mode, and scan delay with a reduced-volume contrast medium bolus. J Comput Assist Tomogr 1995;19:406–11. 15. Marti-Bonmati L, Tobarra E, Manjon JV, Robles M, Arana E, Molla E, et al. Comparison of different injection forms in CT examination of the upper abdomen. Abdom Imaging 2003;28:799–804. 16. Tublin ME, Tessler FN, Cheng SL, Peters TL, McGovern PC. Effect of injection rate of contrast medium on pancreatic and hepatic helical CT. Radiology 1999;210:97–101.
