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1 All authors: Department of Radiology, University of Wisconsin Hospital & Clinics, 600 Highland Ave., Madison, WI 53792-3252.
Received March 28, 2002;
accepted after revision September 17, 2002.
Address correspondence to F. T. Lee, Jr.
Abstract
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SUBJECTS AND METHODS. We evaluated 86 hypoattenuating liver metastases in 26 patients. Patients underwent CT in two sessions separated by a mean of 85 days: one time with 150 mL of contrast material and the other time with 100 mL of contrast material followed by a 50-mL saline chaser. The order of the sessions was randomized. Contrast material was administered via power injector and matched for injection rate and delay time. Attenuation values were obtained from normal liver tissue and metastases and from the spleen, kidney, aorta, and inferior vena cava.
RESULTS. The 150 mL dose of contrast material caused slightly greater liver and tumor attenuation than 100 mL of contrast material with a chaser (mean hepatic attenuation, 95.6 vs 89.8 H, respectively; p < 0.03, paired t test; mean tumor attenuation, 53.2 vs 49.1 H, respectively; r = 0.71, p = 0.09). The difference in conspicuity of liver lesions was slightly greater with 150 mL than with 100 mL with a chaser (46.8 H vs 44.2 H; r = 0.46, p = 0.08, paired t test), but was of doubtful clinical significance (2.6 H). Kidney, spleen, and vascular structures enhanced more with 150 mL than with 100 mL and a chaser.
CONCLUSION. Using 100 mL of contrast material and a saline chaser did not result in a meaningful difference in liver parenchyma attenuation or lesion conspicuity compared with using 150 mL of contrast medium alone. Routine use of a chaser for abdominal CT may yield cost savings and a decreased risk of contrast nephropathy.
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All medical specialties, including radiology, are experiencing cost containment pressures. Although the introduction of nonionic contrast material has positively affected patient comfort and decreased the frequency of reactions to contrast material [5], it has added a societal cost burden [6]. In 1997, Hopper et al. [7] described a saline chaser technique for reducing both contrast material use and beam hardening artifact during thoracic CT. This strategy consists of injecting a 100-mL bolus of nonionic iodinated contrast material followed immediately by a 50-mL saline chaser, in lieu of the standard 150-mL bolus of contrast material. By replacing the last third of the standard contrast material bolus with saline, the chaser decreases the beam-hardening artifact and pushes the bolus farther along in the circulation, which reduces the amount of contrast material remaining in the brachiocephalic vein and superior vena cava (Fig. 1). Other benefits of this technique are the substantial cost savings and potential increase in safety inherent in replacing 50 mL of nonionic contrast material with 50 mL of sterile saline solution.
The use of a saline chaser in abdominal CT scanning has intuitive appeal in that it would decrease the amount of contrast material in anatomic locations where contrast material is not needed, provide substantial cost savings, and possibly reduce nephrotoxicity [8, 9]. However, it is important to show that liver enhancement and tumor conspicuity are not adversely affected by the lower dose of contrast material. In this study, we compared liver and tumor enhancement in patients with hypovascular hepatic metastatic disease using two bolus contrast enhancement protocols: 150 mL of contrast material versus 100 mL of contrast material followed immediately by a 50-mL chaser of sterile saline.
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Study Design
The study was conducted between November 1998 and May 2000. All data were
gathered in paired fashion: patients received both contrast material regimens
(on separate days), all scanning and contrast material administration
parameters were identical for each patient between studies, and
region-of-interest measurements were performed by the same observer in
identical portions of tumors and normal liver. Twenty-six consecutive patients
with known hepatic metastatic disease were identified. Prior CT scans acquired
either at our institution or elsewhere were reviewed. Exclusion criteria
included age of less than 18 years; diffuse disease, infiltrating disease, or
both; hyperattenuating metastases; and lesion size smaller than 1 cm on both
CT scans.
Patients were enrolled prospectively and randomized to receive either a 150-mL contrast material bolus or a 100-mL bolus of contrast material with a 50-mL saline chaser. Those who received the bolus plus chaser had the scanning parameters matched with their most recent scan at our institution, and that scan (using a 150 mL saline bolus) was used for comparison. Those who had not been scanned previously at our institution and those receiving the 150-mL bolus were followed, and the subsequent CT was performed using the identical technical parameters and injection rate, albeit with the other bolus technique. Ten patients (37 tumors, 3.7 tumors per patient) were scanned initially using the 150-mL regimen, and 16 patients (49 tumors, 3.1 tumors per patient; p = 0.41 versus 150 mL, Mann-Whitney U test) received 100 mL of contrast material and a saline chaser on the initial scan (no significant difference in scanning order, p > 0.05, binomial test). Intervals between examinations for each patient ranged from 29 to 232 days, with a mean interval between scans of 85 days.
Scanning Parameters and Contrast Material Injection
Contrast-enhanced helical CT was performed using a CT/i scanner (General
Electric Medical Systems, Milwaukee, WI) with 7-mm collimation and a pitch of
1.4:1. Rates of contrast material administration and delay times were
initially optimized according to each patient's vascular access and then held
constant for each patient. Rates varied from patient to patient, depending on
the type of venous access, and ranged from 1.0 to 3.0 mL/sec. All contrast
material injections were performed using a power injector (Envision; Medrad,
Indianola, PA). The contrast material used for all patients was iohexol
(Omnipaque 300; Nycomed, New York, NY) at 300 mg I/mL, for a total iodine dose
of either 30 g (100 mL iohexol plus a saline chaser) or 45 g (150 mL iohexol).
Scanning delay time was calculated using an automated bolus-tracking device
(SmartPrep; General Electric Medical Systems). Scanning was initiated when the
liver parenchyma enhanced 50 H over baseline. Once a delay time was
established for an individual patient, the identical delay time was used for
the subsequent examination. Delay times ranged from 30 to 97 sec, with a mean
delay time of 56 sec.
Saline Chaser
The saline chaser technique has been described in detail by Hopper et al.
[7]. In summary, contrast
material is first drawn into the power injector reservoir with the tip
pointing up, so that the contrast material pools dependently in the reservoir.
Sterile saline (50 mL) is then drawn into the syringe. Because the density of
saline is less than that of the contrast material, the saline floats on the
surface with minimal mixing (Fig.
2). The power injector is inverted into the ready position (tip
down) in a single smooth motion. This action causes the saline and contrast
material to invert in position. Thus, the contrast material is injected first,
followed by the saline chaser. If the technique is performed correctly, a
border between saline and contrast material is clearly visible. It is
important to load the saline and contrast material as near as possible to the
time of injection to decrease mixing over time.
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Mixing of Contrast Material and Saline in the Injector
To show the extent of mixing that occurs after loading the contrast
material and saline into the injector, we obtained CT scans of the saline, the
contrast material, and a loaded power injector (before and after inversion).
Hounsfield unit values were obtained of each specimen using a
107.9-mm2 area of interest.
Data Collection and Statistical Analysis
A single observer performed all attenuation value measurements using a
10-mm2 circular region of interest. For normal liver, a mean value
was obtained by making three measurements at separate locations within the
liver parenchyma. In general, measurements from normal liver came from the
left lobe, mid liver, and right lobe—modified as necessary by the
presence of metastases. Care was taken to avoid vascular structures,
artifacts, and bile ducts. Attenuation values from as many as five liver
metastases per patient were obtained in a similar fashion. Measurements for
metastases were taken from the central hypoattenuating zone rather than at the
enhancing rim found in some lesions. Areas of calcification, necrosis, or
liquefaction were avoided. Special attention was given to obtaining
measurements from identical areas of normal liver and metastases in the same
patient in both studies so that the validity of using paired statistics was
preserved. Attenuation measurements were also obtained from the spleen, renal
cortex, aorta, and inferior vena cava for each examination.
Previous studies have shown that reviewers are not able to consistently detect attenuation differences of less than 10 H [10, 11]. Therefore, a Hounsfield unit value difference between examinations of 10 or greater was considered clinically relevant.
Comparisons of attenuation values were performed using paired t tests and simple regression, computed using commercially available statistical software (Statview; Abacus Concepts, Berkeley, CA). Results were expressed as p values and correlation coefficients (r). We considered p values below 0.05 to be significant, and r values above 0.75 signified a good relationship between data sets [12].
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Tumor Size
Mean tumor size on the initial CT scans was 2.3 ± 1.1 cm (range,
0.5–5.8 cm) compared with 2.5 ± 1.2 cm (range, 0.6–6.1 cm)
on the follow-up scan (p = 0.19, paired t test). Some
lesions were smaller than 1 cm on one of the two scans because of either
growth or shrinkage in the interval between scans.
Liver and Tumor Attenuation
The Hounsfield values that we found in normal liver and in the liver
metastases are summarized in Table
2. Briefly, using 150 mL of contrast material resulted in slightly
greater liver attenuation than using 100 mL with a saline chaser (mean
attenuation, 95.6 vs 89.8 H, respectively; p < 0.05, paired
t test). We found a good correlation between groups (r =
0.78). Tumor attenuation measured slightly less when we used 100 mL of
contrast material with a saline chaser as compared with using 150 mL of
contrast material alone (49.1 vs 53.2 H; r = 0.71, p <
0.05). The conspicuity of liver lesions was slightly greater with 150 mL of
contrast material than with 100 mL of contrast material and a saline chaser
(46.8 vs 44.2 H; r = 0.46, p > 0.05, paired t
test) (Fig. 3). However, the
difference in attenuation (2.6 H) between the two regimens was not important
clinically and would be unlikely to be noticeable in clinical practice.
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We found no statistically significant difference in the mean conspicuity of the hepatic metastases in patients who received each contrast material regimen, regardless of whether they received 100 mL of contrast material with a saline chaser or 150 mL of contrast material as the first injection (Fig. 4A, 4B). For scans obtained with 100 mL and a chaser, tumor conspicuity for the two groups was 46.1 ± 15.3 H versus 41.6 ± 16.7 H, respectively (p = 0.72, paired t test). For scans obtained with 150 mL of contrast material, tumor conspicuity was 47.9 ± 22.2 H versus 45.4 H (p = 0.61, paired t test).
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Kidney and Spleen Enhancement
The attenuation values from the kidney and the spleen obtained after
contrast material injection are also summarized in
Table 2. Both the renal cortex
and the splenic parenchyma were enhanced more when we used 150 mL of contrast
material than when we used 100 mL of contrast material and a saline chaser.
This difference may be important depending on the clinical indication (Fig.
5A,
5B).
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Vascular Enhancement
Vascular structures enhanced to a greater degree with 150 mL of contrast
material than with 100 mL of contrast material and a saline chaser
(Table 2). This difference was
more marked in the abdominal aorta (193.3 vs 151.0 H; r = 0.43,
p < 0.05, paired t test) than in the inferior vena cava
(111.2 vs 96.3 H; r = 0.61, p < 0.05, paired t
test).
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Our research is based on the observation that a substantial amount of contrast material remains in the veins of the upper extremity and central circulation during the performance of helical CT of the chest and abdomen (Fig. 1). Optimal use of all injected contrast material requires either using a longer delay time (which would result in equilibration of contrast material into the extracellular space and decreased tumor conspicuity) [10, 14] or "pushing" the contrast material into the heart with a saline chaser after contrast injection [7, 15]. This study shows that it is possible to replace the last 50 mL of a contrast material bolus with saline and still preserve liver opacification and tumor conspicuity by more efficiently using the first 100 mL of contrast material.
The possibility that replacement of 50 mL of contrast material with the same volume of saline would merely dilute the administered 150 mL volume and decrease tumor conspicuity is a real concern [16]. However, as we have shown, very little mixing occurs when the injection is properly prepared; thus the saline is enabled to truly act as a chaser during injection of the bolus (Table 1). The use of a dual injector could further eliminate the possibility of contrast material mixing with saline. Dual injectors were not available for CT when our study was performed.
Several studies have evaluated the effect of simply decreasing the amount of contrast material injected for helical CT of the abdomen (performed without a saline chaser). These researchers found that lesser volumes of contrast material yielded decreased hepatic attenuation, resulting in decreased tumor conspicuity [2, 3, 4]. With decreased injection volumes, a relatively larger proportion of contrast material is unavailable to the liver for parenchymal opacification due to venous pooling compared with what is available with a higher-volume injection.
Using a saline chaser has several potential benefits. The most obvious advantage is marked cost savings as a result of using less contrast material. However, this savings is dependent on the prepackaged volumes that each institution uses (e.g., using a prepackaged 150 mL volume of contrast material may be only slightly more expensive than using two 50 mL packages plus a saline chaser). If contrast material is priced strictly by volume, a hospital that buys nonionic contrast material at $0.25/mL can save $12 per patient (including $0.50 for the cost of the saline dose) or $60,000 per year if 5000 contrast injections are performed. Savings will increase if more expensive contrast materials are used or more injections are performed. It should be noted that with increased experience of the technology staff, the addition of a saline chaser takes only a few extra seconds compared with preparing for a conventional contrast material injection, and thus it has no substantial impact on patient through-put.
Because the use of a saline chaser also appears to improve image quality in thoracic CT [7], there should be no reduction in imaging quality with chaser use when combined chest and abdomen examinations are performed. Another advantage of chaser use in combination with a reduced volume of contrast material injection is a potential (but not quantified) decrease in nephrotoxicity, particularly in patients with preexisting renal insufficiency or other risk factors [8, 9].
Two main disadvantages are associated with saline chaser use in the abdomen. First, when 100 mL of contrast material is used with a saline chaser, opacification of the aorta, inferior vena cava, and other vascular structures is decreased in comparison with their opacification when 150 mL of contrast material is used. This reduction would be a disadvantage for CT angiography. However, if the scanning protocol were tailored for CT angiography, we believe that the vascular attenuation would be comparable. In fact, we routinely use a 150-mL bolus of contrast material with a saline chaser for CT angiography in our practice. Second, other solid organs (spleen, renal cortex) were not as well opacified with the lower dose of contrast material plus saline chaser. Unlike the liver, nonhepatic solid organs have a single arterial supply, and they are maximally enhanced shortly after contrast material is delivered—well before peak hepatic enhancement [17]. Our protocol was tailored for maximal hepatic enhancement: the longer the time that contrast material continues to enter the spleen and kidney when 150 mL of contrast material is used, the higher the attenuation of these organs at the delay times used in this study. In most patients, opacification of these organs is of secondary importance to hepatic opacification, but in patients who have suspected primary kidney or splenic abnormality (e.g., renal or splenic trauma, infarction, infection), increased attenuation of the parenchyma may be desirable.
This study represents a cross-section of the population of patients with cancer encountered in our tertiary care practice. The long delay between scanning sessions in some patients was a result of the clinical needs of the patient rather than a study-design issue. Despite this varied interval between scan acquisitions, the mean tumor size increased by only 0.1 cm (some tumors shrunk with treatment), and the tumor conspicuity did not appear to change substantially. The patients in the study group often had undergone multiple venous punctures and chemotherapeutic regimens; as a result, these patients had poor venous access. This problem is reflected in the variety of injection rates that we used. For each patient, an individualized injection rate was selected on the basis of the manufacturer's recommendations for the specific venous access set. The injection rates in this study reflect the maximum tolerable rate for each patient, up to 3 mL/sec for an 18- or 20- gauge peripheral IV line. Some patients received their injections at a suboptimal rate, but we think this is typical in follow-up of patients with known metastatic disease, as opposed to what occurs in the initial cancer-staging workup. Nonetheless, this study is not meant as a liver metastases detection study but rather was intended to compare the conventional and saline-chaser techniques. We believe that the results of our study suggest that lower contrast material injection volumes may be used with a saline chaser in patients with abdominal cancer without the loss of important diagnostic information.
In summary, we found that decreasing the administered volume of IV contrast material from 150 mL to 100 mL and adding a 50 mL saline chaser did not substantially decrease liver parenchyma enhancement or lesion conspicuity. If the use of a chaser is adopted for abdominal CT scanning, cost savings can be anticipated, depending on the contrast material packaging for individual institutions. A potential decrease in contrast nephropathy may be an additional benefit of decreased contrast material usage.
Acknowledgments
We gratefully acknowledge the assistance of the CT technology crew, under
the leader-ship of Thomas Lanoway and Heidi Knuteson; Carrie Poole, for
assistance with manuscript preparation; and Christopher D. Johnson, for the
figure preparation.
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) and
after injection of 150 mL of contrast material (•).
