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Vascular and Interventional Radiology |
1 From the Department of Radiology (D.F., A.A.B., K.H.) and the Division of Angiography and Interventional Radiology (K.H.), University of Vienna, AKH, Währinger Gürtel 18-20, A-1090, Austria, and the Department of Radiology, Stanford University Medical Center, Stanford, Calif (D.F., G.D.R.). Received February 5, 1999; revision requested April 2; revision received May 3, 1999; accepted August 1. D. F. supported by a "Schrödinger Stipendium" grant by the Austrian Science Fund, Vienna, Austria. Manuscript preparation was supported in part by the Ludwig Boltzmann Institute for Radiological Sciences, Vienna, Austria. Address reprint requests to D.F. (e-mail: dominik.fleischmann@univie.ac.at).
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Abstract |
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MATERIALS AND METHODS: Thirty-two patients with an abdominal aortic aneurysm underwent CT angiography. In 16 patients (group 1), 120 mL of contrast material was administered at a flow rate of 4 mL/sec. In the other 16 patients (group 2), biphasic injection protocols were computed by using mathematic deconvolution of each patient's time-attenuation response to a standardized test injection. Attenuation uniformity was quantified as the "plateau deviation" of enhancement values, which were calculated as the SD of the time-contiguous attenuation values observed during the 30-second scanning period.
RESULTS: Group 2 patients received between 77 and 165 mL (mean, 115 mL) of contrast medium. Initial flow rates ranged from 4.1 to 10.0 mL/sec (mean, 6.8 mL/sec) for the first 4–6 seconds; continuing flow rates ranged from 2.0 to 4.8 mL/sec (mean, 3.1 mL/sec) for the remaining 24–26 seconds. The plateau deviation was significantly smaller in group 2 patients (19 HU) versus group 1 patients (38 HU, P <.001).
CONCLUSION: At CT angiography, tailored biphasic injections led to more uniform aortoiliac enhancement, compared with standard uniphasic injections of contrast medium.
Index terms: Aneurysm, aortic, 98.73, 98.12912, 98.12916 • Aorta, CT, 98.73, 98.12912, 98.12916 • Arteries, CT, 98.12912, 98.12916 • Arteries, iliac, 98.12912, 98.12916 • Computed tomography (CT), angiography, 98.73, 98.12912, 98.12916 • Computed tomography (CT), contrast enhancement, 98.12912, 98.12916
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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This phenomenon is not at all surprising when the recent pharmacokinetic, observational, and experimental data in the radiology literature regarding contrast medium dynamics are taken into account (1–4,9–13). The intravenous administration of the contrast material at a constant rate leads to a progressive increase in arterial opacification over time, with the maximum opacification achieved at the end of the injection period (13). After peak enhancement is achieved, arterial opacification is characterized by a comparably rapid decrease.
As a consequence, even with correct timing of the scanning delay (8,14,15), vascular enhancement is lowest at the beginning and at the end of scanning and is highest at the middle or middle-to-late portion of scanning. Although this consequence has been noted in the literature, it has not been addressed explicitly (7,8,10,13,16).
The nonuniformity of arterial enhancement over time has obvious disadvantages. Inadequate vascular opacification on nondiagnostic images may result, and the heterogeneity of the enhancement substantially complicates the selection of parameters for three-dimensional rendering and quantitation (16).
The problem of nonuniform intraindividual enhancement at CT angiography is further aggravated by a large interindividual variability and by the unpredictability of the overall arterial enhancement. Sheiman et al (8) reported that aortic attenuation values in the middle phase of aortic CT angiography ranged from approximately 140 to 440 HU. Rubin et al (6) reported that for different individuals, the arterial opacification varied between 200 and 400 HU. Both phenomena—the intra- and interindividual variation in vascular opacification—are obstacles to the optimum utilization of contrast media at CT angiography. To date, to our knowledge, systematic attempts to control the uniformity of the enhancement have not been reported.
We recently developed a mathematic technique, which uses a linear systems approach and a Fourier deconvolution of a patient's time-attenuation response to a test bolus, to tailor the injection parameters to achieve near-uniform opacification in the aorta at a predefined level of enhancement (17).
The aim of this study was to quantify the uniformity of aortoiliac opacification during CT angiography and to determine if an individualized biphasic contrast medium injection protocol can be used to achieve greater uniformity in enhancement throughout the imaged volume.
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MATERIALS AND METHODS |
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Imaging Technique
Each examination began with the acquisition of a series of nonenhanced contiguous 8-mm conventional CT images (210 mA, 120 kVp) from the celiac axis to the level of the iliac bifurcation. After these images were reviewed, a scanning volume of 18 cm in length was localized; this usually ranged from the level of the superior mesenteric artery to the level of the common iliac arteries.
Next, a test bolus of contrast medium was injected to determine the individual delay time (group 1) or to calculate the individualized biphasic injection parameters (group 2). A 17-gauge plastic cannula was inserted into the largest cubital vein. Before the contrast material was administered, saline injections were manually administered at a high rate of flow, with the patient's arms in the scanning position. This was done to ensure the successful cannulation of the vein. In addition, the injection site was inspected and/or palpated during the first seconds of the automated administration of the contrast agent. The test bolus consisted of 16 mL of the contrast medium, which was automatically injected at a rate of 4 mL/sec. This was followed immediately by a 20-mL saline bolus, which was manually injected.
Single-level CT imaging of the juxtaceliac aorta was performed every 2 seconds after an 8-second delay at the start of the injection. A total of 21 images (40 mA, 120 kVp) were obtained during quiet breathing to avoid a Valsalva maneuver. Thus, the individual aortic time-attenuation response to the test injection was monitored for 8–50 seconds after the beginning of the test injection. A time-attenuation curve was generated from the circular regions of interest placed within the aorta. All patients subsequently underwent CT angiography with a 3-mm collimation and a 6 mm/sec table feed for a 30-second acquisition (165 mA, 120 kVp) during quiet breathing. Sections were reconstructed by using 180° linear interpolation at 1-mm intervals.
In group 1, the delay time was the contrast agent transit time, which was defined as the time to peak enhancement on the time-attenuation curve obtained with the test injection. All patients of group 1 received a total of 120 mL of contrast medium, which was injected at a flow rate of 4 mL/sec.
In group 2, the volume of contrast medium and the injection flow rates were set according to the values calculated by using a mathematic technique based on a Fourier analysis of the patient's time-attenuation response to the test injection. The algorithm for the calculations was previously reported (17). In short, the parameters for the test injection, the subsequently measured time-attenuation values for the enhancement from the test bolus, the anticipated duration of CT angiography, and the desired plateau of enhancement (200 HU above baseline) were entered into a standard microcomputer (150 MHz Pentium [Intel, Santa Clara, Calif] processor). The scanning delay time, the contrast medium volume, the two injection flow rates, and the duration of both phases of the injection were calculated from these data by using a commercially available software program (Mathematica for Windows; Wolfram Research, Champaign, Ill).
Data Analysis
For each patient, the arterial attenuation values were measured in the center of the aorta and the iliac arteries by using circular regions of interest that contained 300 (aortic) or 50 (iliac) pixels every 6 mm (every second) along the z axis. Attenuation values in the left and right iliac arteries were averaged. All densitometric measurements were obtained by the same experienced CT technologist. Baseline attenuation values from the nonenhanced localized sections were subtracted from those of the enhanced sections to give the aortoiliac enhancement profiles (expressed as a change in Hounsfield units over time) for each patient.
The uniformity of the aortoiliac enhancement over time was quantified by measuring the variability in the attenuation values within the 30-second scanning time as the SD of the enhancement values. The SD of the individual enhancement profiles thus served as a measure of the deviation in enhancement from an ideal (perfectly uniform) 30-second plateau of enhancement. We referred to this measure as the plateau deviation.
Magnitude and Interindividual Variability in Aortoiliac Enhancement
For each patient, the mean aortoiliac enhancement value (for 30 seconds) was computed, and an overall mean enhancement value was derived for the group. Interindividual enhancement variability was expressed as the variance in the mean attenuation values for patients in group 1 or group 2.
Statistics
The measures of enhancement uniformity and magnitude were compared between the groups by using a two-tailed t test. The interindividual variance in the mean enhancement value between the groups was compared by using the F test. The mean and relative enhancement values (enhancement per volume of contrast agent [Hounsfield units per milliliter]) were correlated with body weight and contrast agent transit time by using a linear regression analysis. For all statistical analyses, a P value less than .05 was considered to indicate a significant difference.
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RESULTS |
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Overall, the contrast agent transit times were longer in group 1 patients (22 seconds; range, 16–29 seconds) than in group 2 patients (19.3 seconds; range, 16–24 seconds; P = .048). The delay times, as computed for group 2 patients, were similar (within 2 seconds) to the contrast agent transit times (Table 3).
Influence of Body Weight and Time to Peak Enhancement
In group 1 patients, all of whom received the same amount of contrast medium (120 mL), aortoiliac enhancement decreased significantly with body weight (y = 394 - 1.7x, r = -0.57, P = .025). In group 2 patients, who received tailored injections with individually calculated amounts of contrast medium, enhancement was not significantly associated with body weight (y = 234 - 0.3x, r = -0.15, P = .58) (Fig 5a). When the relative enhancement values were plotted against body weight, however, an association between the magnitude of enhancement and body weight was disclosed for both injection protocols (group 1, r = -0.57, P = .025; group 2, r = -0.77, P < .001) (Fig 5b).
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DISCUSSION |
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Ongoing progress in the development of tube and scanner technology, such as the development of fast multidetector array scanners, will make the delivery of contrast material at CT angiography even more challenging in the near future (19–21). By allowing wider or narrower time windows that are less error-tolerant, these technical advantages will require more precision in the administration of contrast media.
In this study, we primarily aimed to improve the uniformity of arterial enhancement achieved during scanning at CT angiography. In addition, we hoped to decrease the variability in the arterial enhancement between patients. Our results confirm the theoretic and experimental data: A uniphasic injection of a contrast agent does not lead to a plateau of vascular enhancement, as is desired at CT angiography, but to a hump-shaped time-attenuation curve.
In our patients with aortic aneurysms, the time course of arterial enhancement was variable and ranged from 16 to 29 seconds. This underscored the fact that correct timing, as determined by adjusting the delay time to the contrast agent transit time, is mandatory in these patients. Even with the correct timing of the scanning delay, the time course of enhancement is far from optimum. As expected, maximum enhancement occurred at the middle or end of the aquisition of CT images, whereas the most proximal (visceral and renal arterial) and distal (iliac arterial) portions of the vascular region of interest shared an increased risk of being poorly opacified. Poor arterial opacification limits the quality of CT angiographic images. Furthermore, rapid, steep changes in the attenuation in the target vasculature within the scanned volume poses a problem for threshold-dependent automated tools for vascular segmentation and for quantitative measurement, as well as for three-dimensional rendering techniques (16).
Clearly, timing of the scanning delay alone cannot be the ultimate technique for optimizing vascular opacification at CT angiography. This motivated our attempts to develop a technique that enabled us to calculate individualized injection parameters on the basis of a mathematic deconvolution of the information contained in a patient's time-attenuation response to a standardized test bolus (17). With this information, we can customize the volume of the contrast medium and the biphasic injection rate to achieve near-uniform arterial enhancement at a predefined level.
Our data show that, at CT angiography of the abdominal aorta, individually customized biphasic injection of the contrast medium results in arterial enhancement that is significantly more homogeneous than that obtained with standard uniphasic injection. This is clearly recognized on the maximum intensity projection images (Figs 1–3), the summation plots (Fig 4), the significantly different measurements of plateau deviation, and the differences in the maximum and minimum attenuation values between the series of images.
Our expectations to reduce the interindividual variability in arterial enhancement, however, were not fully satisfied. Despite the fact that the volume of contrast material was individualized for each patient on the basis of the enhancement from the test bolus, interindividual variation was reduced only moderately and not significantly. Whereas this may, in part, be due to the systematic limitations of the mathematic model, we speculate that the major reason for this imprecision is the technique used in administering the test bolus.
Our approach was necessarily sensitive to the inaccuracies associated with the peripheral intravenous injection of a test bolus. Despite an attempt to standardize the test bolus by flushing the vein immediately after the automated injection, the saline bolus could be administered only manually. Small amounts of contrast material may have remained in portions of the arm veins (probably due to backflow) and, thus, may not have contributed to the measurement of the time-attenuation response. Respiratory effects on the venous blood flow also may have played a role. Automated programmable injection systems, which allow the administration of a saline bolus immediately before and after the administration of the contrast agent, are becoming available. These might improve the accuracy of our model in predetermining the level of enhancement, even with a peripheral injection site.
One unexpected finding in our series was that the mean arterial enhancement value achieved in the group 2 was significantly lower (207 HU) than that of group 1 (251 HU), despite only a small difference in the mean volume of contrast material administered (115 vs 120 mL). While we cannot definitively explain this discrepancy, it may, in part, be attributed to the fact that with individual tailoring, a greater proportion of the contrast material is injected into those patients whose physiologic characteristics cause poor arterial contrast enhancement.
A general physiologic and anatomic limitation of the model is that scanning at a constant location for the acquisition of the entire series of images was assumed and, thus, the model does not account for the continuously changing flow dynamics along the aortoiliac axis. In addition, the flow dynamics may have been affected by pathologic conditions, as they were in two of our patients with large perfused aortic aneurysms.
Another limitation inherent in the technique we used is the need for longer monitoring of the enhancement from the test bolus. This increases the patient's exposure to radiation because the monitoring of a test bolus administered for only timing purposes can be stopped as soon as the enhancement peak has been reached. However, with a reduced tube current (40 mA), the imaging of the additional sections account for only a small proportion of the total dose required for the acquisition of a series of CT angiographic images. These usually consist of the acquisition of a nonenhanced image and a series of spiral CT images at 210 and 165 mA, respectively.
The biphasic injections used in this study required flow rates in the initial 4–6 seconds that were higher than those commonly used with the uniphasic injection protocols at CT angiography. Although flow rates of up to 10 mL/sec are commonly used in functional imaging studies (22,23), we took precautions to avoid relevant extravasation of contrast material. These precautions are routinely performed at our institution in all CT angiographic or functional imaging studies. They include the placement of a 17-gauge cannula in a large-caliber cubital vein, the injection of saline to ensure correct catheter placement, and the monitoring of the injection site by means of inspection and palpation during the initial seconds of the injection. If the calculated injection flow rates seem disproportionally high for a patient's physique, it is still possible to select a more shallow increase in enhancement in the mathematic model to lower the initial injection rates and to prolong the optimum delay time.
In contrast to the equal distributions of patient age, sex, and body weight, the contrast agent transit times were unevenly distributed between the two study groups; these times were significantly longer in group 1 (uniphasic injection) than in group 2 (biphasic injection). As longer contrast agent transit times may reflect lower cardiac output, this might be a confounding variable that limits the interpretation of our overall results. Therefore, we reanalyzed our data while excluding that of the three patients in group 1 with the longest contrast agent transit times (>27 seconds). This analysis corrected for the transit times, but it did not affect the statistically significant differences in the main outcome parameters, the plateau deviation, and the maximum-minimum difference. These findings supported the overall validity of our results.
The improved uniformity of the aortoiliac enhancement observed in group 2 patients might suggest that a standardized biphasic injection technique similarly improves the arterial enhancement profiles while eliminating the need for an imperfect test injection and a mathematic deconvolution. On the basis of the doses and injection parameters calculated for our patient cohort, a standardized biphasic protocol for 30-second acquisitions might, for example, consist of the following regimen: The total volume of contrast medium could be individualized according to body weight (eg, 1.5 mL/kg), and then, it could be injected in two phases. During 5 seconds of the initial phase, 30% of the total volume of contrast material might be administered. This would be followed by a 26-second continuing phase in which the remaining 70% would be injected.
That such a standardized approach yields an enhancement similar to that obtained with the mathematically customized technique remains to be proved. This is especially true in light of the variation in the relative percentages of initial-phase volumes versus continuing-phase volumes, which ranged from 24% versus 76% to 37% versus 63% in our patients with aortic aneurysms. In patient cohorts without severe cardiovascular diseases, a standardized biphasic injection technique might, nevertheless, be superior to a standardized uniphasic technique and might be equally simple to perform.
We conclude from our study findings that a uniphasic contrast medium injection protocol does not result in a plateau-like enhancement, which is desirable at CT angiography. Biphasic (high initial flow rate, low continuing flow rate) injection protocols are significantly better for the approximation of a uniform aortoiliac enhancement. Our individually customized technique was not superior to the standard injection technique in its intended ability to predetermine the magnitude of arterial enhancement in different patients, but technical refinements—especially in the administration of the test bolus—have recently been made and might improve this aspect in the future.
Despite the current limitations, we believe that individualized computer-aided techniques for the delivery of contrast material (such as the one proposed in this study) will play a key role in the optimal utilization of contrast media and in the improvement of image quality in the continuously evolving applications of CT angiography.
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Acknowledgments |
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Footnotes |
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) demonstrates a continuous increase in aortic opacification during the first two-thirds of the scanning period, followed by a steep decrease in the last third of the scanning period. The black line indicates the mean enhancement, and the error bar indicates the plateau deviation. The gray lines indicate the contrast agent injection rate. s = second, 
HU = change in Hounsfield units, 
= enhancement achieved with the test bolus.
) and the SDs (error bars) for every second of imaging. Note the hump-shaped profile in a versus the shallow saddle-shaped profile in b.
