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1
Service de Radiologie du Centre Hospitalier Lyon Sud, EA 643, Chemin du Grand
Revoyet, 69495 Pierre-Benite Cedex, France.
2
Unité de Pharmacologie Clinique,
Université Claude-Bernard Lyon 1.8, Ave.
Rockefeller, 69373 Lyon, Cedex 08, France.
Received March 22, 1999;
accepted after revision August 9, 1999.
Address correspondence to P. Loubeyre.
Abstract
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SUBJECTS AND METHODS. One hundred twenty patients (60 in their fourth decade malignancies of life and 60 in their seventh decade of life) referred for contrast-enhanced thoracic CT for malignancies or infections prospectively entered the study. They were randomly assigned to be given one of three iodine concentrations of a nonionic contrast material: 250 mg/ml (I250), 300 mg/ml (I300), and 350 mg/ml (I350). Two radiologists independently graded perivenous artifacts and arterial enhancement of mediastinal and hilar vessels on a 4-point scale: 1, poor; 2, fair; 3, good; and 4, excellent. Measurements of arterial attenuation values (quantitative assessment) were obtained on the aorta and pulmonary artery.
RESULTS. Mean scores were equal to or greater than 3 for all vessels only using I350. The higher the iodine concentration was, the higher the mean score, but there was a statistically significant difference only between scores obtained with I350 and those obtained with I300 or I250. Mean scores were higher for the patients in their seventh decade of life than those in their fourth decade; however, there was no statistically significant difference between scores of the two decade groups. We found a highly significant statistical relationship between scores and arterial attenuation values.
CONCLUSION. During contrast-enhanced helical CT examinations for general thoracic evaluations, good opacification of central vascular structures is obtained with a low volume of high iodine concentration nonionic contrast medium.
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Obtaining concomitant opacification of all arterial and venous hilar and mediastinal structures during the whole scan using a low amount of contrast material requires a relatively slow injection rate. We assessed three iodine concentrations on vascular enhancement in two populations with different physiologies (age range of one population, fourth decade; age range of the other population, seventh decade), using a small amount of nonionic contrast material, injected at a relatively low flow rate, without saline dilution of the contrast material. Qualitative and quantitative assessments of thoracic vascular enhancement were performed.
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Patients who required helical CT for detection of pulmonary embolism, had undergone a lung resection, had a history of stenosis or occlusion of the subclavian veins or superior vena cava, and could not hold their breath for the entire scan were excluded from the study (only three patients could not hold their breath and did not enter the study).
Patients in each population were randomly assigned to be given one of the three iodine concentrations (250 mg/ml, 300 mg/ml, and 350 mg/ml; n = 20 patients for each concentration).
Injection
Eighty milliliters of iomeprol (Iomeron, Laboratoires Byk, Paris, France)
was administered. The iodine concentration was 250 mg/ml (I250), 300 mg/ml
(I300), or 350 mg/ml (I350). Osmolality (mosm/kg water) was 435, 521, and 618
for I250, I300, and I350, respectively. Viscosity (mPa/sec) measured at
37°C was 2.9, 4.5, and 7.5 for I250, I300, and I350, respectively. An
injection duration of 40 sec was selected to obtain optimal contrast
enhancement within both arteries and veins during the entire course of the 25-
to 30-sec duration of the entire scan. The injection rate was 2 ml/sec. Left
antecubital venous access was achieved for all patients with a 20-gauge venous
catheter, with the patient's arms positioned beside the head. Contrast medium
was administered using a power injector (Multilevel CT Injector; Medrad,
Pittsburgh, PA).
Helical CT
Twenty-five seconds after initiation of the contrast medium injection,
helical CT was performed using a Somatom Plus S CT scanner (Siemens Medical
Systems, Erlangen, Germany) with a 10-mm collimation, a pitch of 1.0, a
1.0-sec gantry rotation period of the scanner, 145 mA, and 120 kVp.
The entire thorax was imaged within a single 25- to 30-sec breath-hold from the lung apices to lateral costophrenic sulci. Scanning was performed in a craniocaudal direction. Images were reconstructed using a 180° linear interpolation algorithm at 8-mm intervals.
All images were printed on hard-copy films at a window level appropriate for vascular visualization (level, 50 H; width, 400 H) [2].
For each CT examination, a single vascular region of interest was positioned within the ascending aorta, the descending aorta, and the pulmonary trunk at the origin of the left pulmonary artery. The three measurements were obtained on the same scan.
Qualitative Assessment
Two experienced thoracic radiologists independently evaluated helical CT
examinations, which had been randomized and presented to reviewers in a
different order. Reviewers graded perivenous artifacts and arterial
enhancement on a 4-point scale adapted from Rubin et al.
[2]
(Table 1). To establish a
baseline for scoring the images, before the study was initiated the two
reviewers graded by consensus perivenous artifacts and vascular enhancement on
30 thoracic helical CT scans obtained for general thoracic evaluations, using
a 4-point scale. Arterial opacification was considered poor (score, 1 point)
(Fig. 1A), fair (score, 2
points) (Fig. 1B), good (score,
3 points) (Fig. 1C), or
excellent (score, 4 points) (Fig.
1D).
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Anatomic regions for qualitative assessment of arterial enhancement were the ascending aorta, the descending aorta, the right pulmonary artery (main artery and interlobar artery), the left pulmonary artery (main artery and interlobar artery), the right superior pulmonary vein, and the left superior pulmonary vein (hilar and mediastinal portions of the veins). These regions were selected because they are particularly relevant for clinical interpretation of CT images.
The anatomic regions chosen to assess perivenous artifacts (i.e., blooms and streaks) were the regions adjacent to the superior vena cava and the left innominate vein.
When there was discordance between scores of the two reviewers, the lower score was considered the final score.
Quantitative Assessment
Images were reviewed on a viewing console. Regions of interest were
positioned on each previously defined location and were selected to minimize
the influence of volume averaging on measurements. For each patient and each
measurement location, an arterial attenuation value and its standard deviation
were recorded. For each measurement location, the mean and standard deviation
of arterial attenuation values were calculated for each iodine concentration
in the total population and for each decade group.
Statistical Analysis
Agreement between observers.—Agreement between scores of the
two reviewers was calculated with the Kappa test of concordance. Kappa value
was calculated for each test of concordance. Concordance between observers was
considered fair (0.05 < 
0.6), good (0.6 <
0.8), or excellent ( > 0.8).
Agreement between the scores of the two reviewers for each vessel was calculated for the total population of patients (n = 120), each decade group (n = 60 patients per decade), and each iodine concentration (n = 40 patients per iodine concentration). Agreement between scores of the two observers when considering both patient age and iodine concentration was not calculated because too few patients comprised each group (20 patients per group).
Comparison of final scores and arterial attenuation
values.—In the total population of patients (n = 120),
comparison of arterial attenuation values in the ascending aorta, descending
aorta, and pulmonary artery trunk and comparison of final scores of each
vessel for the three different iodine concentrations were performed using a
Kruskal-Wallis nonparametric test (a p value of <0.05 was
considered a significant difference), and a Student-Newman-Keuls test
(multiplied and adjusted comparison of means, 
= 0.05) which enables
classification of significantly different groups.
When considering the two patient populations, comparisons of arterial attenuation values and of final scores of each vessel were performed using a Student's t test (a p value of <0.05 was considered significant).
Comparisons of scores and arterial attenuation values for each vessel, each iodine concentration, and each decade group were not performed because too few patients comprised each group (20 patients per group).
The relationship between final scores and arterial attenuation values was evaluated using logistic regression (a p value of <0.05 was considered significant).
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When considering each decade.—There was no concordance for scores of perivenous artifacts, concordance for the scores of the right pulmonary artery and of the left pulmonary artery in the seventh decade was fair, concordance for the ascending aorta and descending aorta in the seventh decade group was excellent, and concordance in all other patients was good.
When considering the three different iodine concentrations (40 patients per iodine concentration).—Concordance for the scores of perivenous artifacts with I350 was only fair, concordance for the scores of the ascending aorta with I350 was fair, concordance for the scores of the right pulmonary artery and left pulmonary artery with I300 was fair, concordance for the scores of the ascending aorta and descending aorta with I250 was excellent, and concordance was good in all other cases.
Comparison of Final Scores and Comparison of Arterial Attenuation
Values
When considering the total population of patients and the three iodine
concentrations scores.—No significant difference was noted for
scores of perivenous artifacts. For all other vessels, the higher the iodine
concentration was, the higher the mean score
(Table 3); however, the only
statistically significant difference was between the scores for I350 and those
for I300 or I250. The difference between scores for I300 and those for I250
was not statistically significant (Student-Newman-Keuls test).
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The higher the iodine concentration was, the higher the mean arterial attenuation value was in the ascending aorta, descending aorta, and the pulmonary artery trunk (Table 4), but a statistically significant difference was noted only between arterial attenuation values obtained with I350 and those obtained with I300 or I250. There was no statistically significant difference between arterial attenuation values obtained with I300 and arterial attenuation values obtained with I250 (Student-Newman-Keuls test).
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When only considering the two decade groups (adding up for each decade group the data about the three different iodine concentrations).—Mean scores were higher in the seventh decade group, but there was no statistically significant different final scores between the two decade groups for any of the vessels.
Mean arterial attenuation values were higher, independent of which vessel was evaluated, in the seventh decade group, but there was no significant difference between arterial attenuation values measured in each decade group.
Relationship Between Scores and Arterial Attenuation Values
There was a highly significant relationship between scores of the ascending
aorta, descending aorta, right pulmonary artery, and left pulmonary artery
with arterial attenuation values measured respectively in the ascending aorta,
descending aorta, and pulmonary trunk. The p value was 0.0001 in all
cases.
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In our study, only one parameter was evaluated: iodine concentration. Three increasing iodine concentrations were evaluated. The range of iodine concentrations encompasses most of the iodine concentrations used in thoracic helical CT [1,2,3]. Because evaluating the influence of age on the vascular enhancement would have required a very large number of patients so that all the age groups would be statistically significantly represented, we elected to only evaluate two decades in which the physiologic conditions are supposed to be different (during the fourth decade versus seventh decade).
We elected to inject a small amount of contrast material using a relatively low rate of injection (2 ml/sec) to preserve venous access, limit potential local brachial extravasation of contrast material, and reduce the cost of the examination. The question addressed in this study focused on whether this protocol of contrast material injection for thoracic helical CT could maintain adequate mediastinal and hilar vascular enhancement.
This study was exclusively performed using a nonionic contrast medium to reduce potential morbidity and mortality and movement artifacts related to nausea [4]. We did not attempt to dilute the contrast medium solution because it is not always possible to guarantee the efficacy and sterility of the diluted solution. This technique has been evaluated [2]. Moreover, we did not attempt to push the contrast material with saline solution to simplify the procedure, although this technique has been proved to provide satisfactory thoracic vascular enhancement [1].
Our results show that the higher the iodine concentration, the higher the enhancement of the vessels. The amount of iodine entering the central blood volume per unit of time is a fundamental variable that influences vascular enhancement after IV administration of contrast medium [5]. However, a statistically significant difference was only noted for the higher iodine concentration (I350). With this iodine concentration, the mean enhancement scores were good (3.1-3.2) for all vessels; obscuring perivenous artifacts that could degrade quality of CT images were not seen. The few perivenous artifacts can be explained in part by the low flow rate of injection and the low viscosity of the contrast material (one of the lowest of all contrast media available). We found that this protocol of injection, with a high iodine concentration, is sufficient for general thoracic applications. We did not encounter major interpretation-solving problems, and we believe that no significant abnormality was missed.
The vascular enhanced scores were higher in the older population compared with those of the younger population, but the difference in the scores between the two decade groups was not statistically significant. Although physiologic conditions of patients in the two group are supposed to be different, this result is in accordance with the results of a previous study in which parameters such as age, weight, and heart rate did not correlate with the time of maximum enhancement [3].
There are some limitations in this study. Only two age groups encompassing two decades were studied. Patients older than 70 years did not enter the study. We chose the seventh decade because this age group represented most of our patients. The effect of factors such as cardiac output, heart rate, central blood volume, osmolality of the contrast media, inotropic or chronotopic effect on the myocardium of the contrast material, and the flow-rate—dependent temporal on enhancement has not been evaluated. We do not know whether our results can be extrapolated to ionic contrast media (nonionic contrast media are retained in the vascular space better than ionic media and selfdilute to a lesser degree by a factor of approximately a quarter) [5, 6]. Our results cannot be extrapolated to specific thoracic CT indications such as detection of pulmonary embolism, but this injection protocol should not be adapted for this specific thoracic CT indication because a high degree of enhancement of the pulmonary vessels is mandatory in all patients for detection of pulmonary artery thrombi. These results are valid for the collimation and pitch used in this study. The influence of the window settings on image scores has not been evaluated. We selected a window setting currently used for mediastinal visualization [2].
To avoid overestimating the final scores, we chose to take into account the lower score of the two reviewers when there was discordance between them. In the whole population of patients, a statistically significant discordance between reviewers was noted only when assessing artifacts between moderate and minimal (scores of 2 and 3) and between minimal and no artifacts (scores of 3 and 4). This discrepancy in scores can be explained by the fact that the qualitative score is subjective. When reviewing the scores of cases of discordance between the two reviewers for vessel enhancement, the scores of one reviewer were higher that those of the other reviewer in most cases. This difference can be explained by the years practicing as a radiologist.
More studies are needed to optimize the delay between initiation of the contrast medium injection and initiation of the scan to further reduce the injected volume or increase the rate of injection without increasing the injected volume. For general thoracic CT indications, in particular for cancer staging, a high or even good degree of aortic enhancement is probably not mandatory in most patients. The main issue is to obtain good opacification of the pulmonary vessels, particularly of the hilar vessels.
In conclusion, during contrast-enhanced helical CT for general thoracic indications, good opacification of central vascular structures was obtained with a low volume of nonionic contrast medium, with a high iodine concentration.
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