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DOI:10.2214/AJR.06.1240
AJR 2007; 189:156-161
© American Roentgen Ray Society

Original Research

CT Pulmonary Angiography and CT Venography: Factors Associated with Vessel Enhancement

Hiroaki Arakawa1, Tatsuo Kohno1, Taro Hiki1 and Yasushi Kaji1

1 All authors: Department of Radiology, Dokkyo Medical University, 880, Kita-Kobayashi, Mibu, Tochigi, 321-0293 Japan.

Received September 20, 2006; accepted after revision February 5, 2007.

 
Address correspondence to H. Arakawa.


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. The objective of our study was to determine factors associated with enhancement on CT pulmonary angiography and CT venography.

MATERIALS AND METHODS. Two hundred forty-two cases (83 men and 159 women; mean age, 63 years; age range, 21-92 years) underwent CT pulmonary angiography using a bolus-tracking technique; 189 cases subsequently underwent CT venography 3 minutes after the start of the contrast injection. Two different amounts of nonionic iodine contrast medium were administered: patients weighing > 50 kg who were undergoing both CT pulmonary angiography and CT venography received 450 mg I (group B), whereas all other patients received 300 mg I (group A). The enhancement of vessels was subjectively estimated using a four-point scale, and attenuation values were measured at predetermined levels. Multiple regression analyses were performed with attenuation as the dependent variable and patient age, sex, and weight; amount of contrast medium; scanning delay; and presence of embolism as the independent variables.

RESULTS. The scanning delay for CT pulmonary angiography ranged from 10 to 31 seconds (mean, 19 seconds; SD, 3.3). Subjective estimates of enhancement quality on CT venography were significantly better for group B than for group A (p < 0.001). Multiple regression analyses revealed that body weight and age were the only significant and consistent independent variables associated with enhancement of the pulmonary arteries. The amount of contrast medium, body weight, and scanning delay were the independent variables that were consistently associated with enhancement of the deep veins.

CONCLUSION. The bolus-tracking technique showed relatively small variations in the scanning delay time. Patient age, body weight, and the amount of contrast medium were the important factors associated with vessel enhancement in combined CT pulmonary angiography and CT venography.

Keywords: contrast media • CT angiography • CT venography • deep vein thrombosis • embolism • hemodynamics • pulmonary embolism


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
With the advent of MDCT scanners, CT pulmonary angiography has almost replaced ventilation-perfusion scanning as the initial screening test for patients with suspected pulmonary embolism [1-4]. Because deep vein thrombosis is a possible cause of pulmonary embolism, evaluation of the deep veins has been reported to increase the diagnostic accuracy and is performed at the time of CT pulmonary angiography in many institutions [5-8]. A recent systematic review of the studies of CT pulmonary angiography for the diagnosis of pulmonary embolism revealed a sensitivity of 53-100%, a specificity of 79-100%, and a false-negative rate of 1.0-10.7%; in one study, the false-negative rate was reduced to 1.5% (95% CI, 1.0-1.9%) when CT venography of the lower extremities was combined with CT pulmonary angiography [9].

Radiologists are responsible for the selection of contrast medium and for the scanning start time because vessel enhancement is crucial for diagnosis. In a recent report of 3,612 patients who underwent CT pulmonary angiography, poor contrast enhancement (40%) was the second most frequent reason for an indeterminate CT study after motion artifact (74%) [10]. Poor opacification is also the most frequent reason for failure in the diagnosis of deep vein thrombosis with CT [11, 12].

To achieve optimal vessel opacification, investigators have introduced and reported several techniques to improve diagnostic accuracy. For example, the use of isosmolar contrast medium, which reduces the osmotic diuresis and hemodilution, is reported to show modest improvement of venous opacification at the equilibrium phase [13, 14]. The use of a tourniquet or stockings for CT venography significantly increases vessel opacification by reducing the venous return to the superficial veins of the extremities [15, 16]. For CT pulmonary angiography, determining the optimal scanning delay after injection of contrast medium is crucial; thus, several techniques have been introduced [17, 18]. The bolus-tracking technique, which is widely used in clinical imaging, including abdominal [19, 20] and pediatric [21] imaging, is commonly used in CT pulmonary angiography, but a fixed scanning delay based on the radiologist's experience is also commonly applied. Despite the common use of this technique, there has been only one report [18] discussing the validity of this technique in CT pulmonary angiography in the literature, to our knowledge.

The purposes of the present study were to measure the time between the injection of contrast medium and the start of scanning in CT pulmonary angiography using the bolus-tracking technique, to evaluate the validity of this technique, to evaluate the enhancement of the pulmonary vessels and deep veins using different quantities of contrast medium, and to determine which factors control vessel enhancement.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Population
We retrospectively identified patients who underwent CT pulmonary angiography between October 2004 and March 2006 based on a search of the radiology information database at our hospital. One patient was excluded because the contrast medium used did not meet the study protocol. We reviewed 242 cases (159 women and 83 men; mean age, 63 years; age range, 21-92 years) of CT pulmonary angiography performed in 152 patients (98 women and 54 men). Repeated CT pulmonary angiography was performed to assess therapeutic results in 54 patients. In 189 cases, CT venography followed CT pulmonary angiography. All patients had a suspected or known history of pulmonary or deep vein thrombosis.

Our institutional review board approved this retrospective study, and written informed consent from the patients was waived.

CT Pulmonary Angiography
All the CT scans were obtained using an MDCT scanner (VolumeZoom, Siemens Medical Solutions) with four detector arrays. We used the following parameters for thoracic CT pulmonary angiography: 1.25-mm collimation, 7.5-mm table movement per gantry rotation, 0.5 second per rotation, 120 mAs, and 120 kV with a scanning direction of caudad to cephalad.

Either 100 (Group A) or 150 (Group B) mL of iohexol (Omnipaque 300, Daiichi Pharmaceutical) was injected at a rate of 3 mL/s via an antecubital vein. Group A included patients who underwent only CT pulmonary angiography and patients who underwent both CT pulmonary angiography and CT venography and whose body weight was 50 kg or less. Group B included only patients who underwent both CT pulmonary angiography and CT venography and who weighted more than 50 kg.

We determined the delay time before scanning (scanning delay) after injecting contrast medium using the bolus-tracking technique (CARE bolus software, Siemens Medical Solutions). This technique is based on real-time monitoring of the main bolus during injection by acquiring a series of dynamic low-dose monitoring scans (120 kV, 20 mAs every 1.25 seconds) at the level of the main pulmonary artery. It is possible to start the main scanning automatically with a predetermined threshold trigger. In the present study, the threshold trigger was set at 100 H and scanning started 5 seconds after that threshold had been reached.

Contiguous transverse 1.0-mm-thick images were routinely reconstructed at mediastinal (width, 350 H; center, 50 H) and lung (width, 1,400 H; center, 650 H) window settings. The radiologists were free to modify the window settings during review at PACS workstations. CT venography was performed after CT pulmonary angiography 3 minutes after the start of the contrast injection to cover the region from the top of the diaphragm to below the knee joint. The following parameters were used: 5-mm collimation (4 x 5 mm), 25-mm table movement per gantry rotation, 0.5 second per rotation, 120 mAs, and 100 kV. Images were reconstructed at 8-mm contiguous intervals.

Image Interpretation
The images were interpreted on a two-monitor system of the PACS network in our department. One board-certified thoracic radiologist and another attending radiologist evaluated the images in consensus while being blinded to the amount of contrast medium used, scanning delay, and final diagnosis. The reviewers worked together initially to assess for the presence or absence of a clot after reviewing all the images from the main pulmonary trunk to the subsegmental arteries and from the inferior vena cava to the distal popliteal vein.

The global quality of enhancement was determined as excellent, good, fair, or poor by consensus. Enhancement was considered excellent when all the pulmonary arteries from the main trunk to the subsegmental levels were clearly visualized and enabled confident observation. Enhancement was considered good when most but not all of the subsegmental arteries were clearly visualized and all the segmental arteries were visible. Enhancement was considered fair when many of the subsegmental arteries were not clearly visualized but all the segmental arteries were visible. Enhancement was considered poor when the segmental arteries were not clearly visualized.

In the venous system, excellent enhancement corresponded to entirely homogeneous enhancement comparable to that of the corresponding artery. Good corresponded to inhomogeneous enhancement less strong than that visualized between the corresponding artery and muscle. Fair corresponded to enhancement similar to that of the surrounding muscle. Poor corresponded to enhancement lower than that of the surrounding muscle [22] (Figs. 1, 2, 3, and 4).


Figure 1
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  		Fig. 1 —Global quality of enhancement on CT venography in 76-year-old woman with excellent enhancement of deep veins. Patient weighed 50 kg at time of examination, and 150 mL of contrast medium was administered. Right femoral vein (arrow) shows similar enhancement to accompanying artery, with homogeneous attenuation. Note that there is femoral vein thrombosis with diffuse subcutaneous edema in left thigh.

 

Figure 2
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  		Fig. 2 —68-year-old man with good enhancement of deep veins. Patient weighed 57 kg at time of examination, and 150 mL of contrast medium was administered. Distal femoral veins show attenuation that is intermediate between attenuations of accompanying artery and surrounding muscles (arrows).

 

Figure 3
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  		Fig. 3 —68-year-old woman with fair enhancement of deep veins. Patient weighed 49 kg at time of examination, and 100 mL of contrast medium was administered. Popliteal veins (arrows) show attenuation similar to that of surrounding muscles.

 

Figure 4
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  		Fig. 4 —78-year-old woman with poor enhancement of deep veins. Patient weighed 48 kg at time of examination, and 100 mL of contrast medium was administered. Right common femoral vein (arrow) shows lower attenuation than surrounding muscles. Left femoral vein shows fair enhancement. No embolus was noted in this patient who later underwent lower limb venography (not shown).

 
Several months later, the same thoracic radiologist again evaluated the images. The quality of vascular enhancement was evaluated at five levels of the pulmonary arteries and three levels of the deep veins. The following were evaluated according to Remy-Jardin et al. [23]: pulmonary circulation, the main pulmonary artery trunk and right lower lobe artery at the level of the lobar artery, one segmental (posterobasal) artery, and two subdivisions of this segmental artery (posterior and mediobasal ramus). The venous system was evaluated at the level of the distal inferior vena cava, the right femoral vein at the inguinal ligament, and the right popliteal vein at the popliteal fossa. If an embolus was identified in the vessel of interest, the equivalent contralateral vessel was substituted. The attenuation values (expressed in Hounsfield units) were measured at the center of the vessel lumen at each level as determined by a minimal-sized region of interest. In the subsegmental pulmonary arteries, we used the larger value of the two measurements.

Statistical Analyses
We performed statistical analyses using commercial software (SPSS version 11.0.1J, SPSS). The two groups of patients were compared in terms of demographic and clinical characteristics. At every level of the examined vessels, we used a chi-square test to compare the quality of contrast enhancement between the two groups. A comparison of the mean vascular attenuations (in Hounsfield units) was performed using the Student's t test. Multiple regression analyses were performed to assess the contribution of each variable to vascular enhancement. We used patient age, patient sex, body weight, presence of pulmonary embolism, amount of contrast medium, and scanning delay as the independent variables and attenuation (in Hounsfield units) as the dependent variable. The variables were retained in the stepwise analyses if p < 0.20, whereas they were excluded if p ≥ 0.20. A p value of < 0.05 was considered significant in all statistical analyses.


Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The amount of contrast medium used was 100 mL in 111 cases (group A), whereas 150 mL was used in 131 cases (group B). Demographic data for each group are listed in Table 1. The mean body weight was significantly heavier for group B than group A (mean, 63 vs 52 kg, respectively; p < 0.001). The scanning delay for pulmonary angiography of both groups ranged from 10 to 31 seconds, with a mean of 19 seconds (SD, 3.3): The delay was significantly longer in group A than in group B (mean, 18 seconds; range, 10-26 seconds; and mean, 19 seconds; range, 11-31 seconds, respectively; p < 0.005). However, the difference between the mean values was only 1 second.


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  		TABLE 1: Demographic Data for Groups A and B

 

Global quality of pulmonary artery enhancement was obtained in 233 of the 242 cases; the remaining nine cases were excluded because respiratory motion was significant. There was no significant difference in the subjective estimates of the global enhancement quality of the pulmonary arteries between the two groups (p = 0.778) (Table 2). For groups A and B, excellent enhancement was obtained in 79.3% and 76.6%, respectively. The mean enhancement of the pulmonary artery trunk was 359 and 331 H at the main trunk, 380 and 334 H at the lobar level, 411 and 371 H at the segmental level, and 416 and 375 H at the subsegmental level for groups A and B, respectively (Table 3). All the differences were significant (p < 0.05).


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  		TABLE 2: Enhancement Quality Assessments for Pulmonary Arteries and Deep Veins on CT Angiography and Indirect CT Venography

 

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  		TABLE 3: CT Attenuation Measurements with Contrast Media

 

Subjective estimates of global enhancement quality of the deep veins were significantly better in group B than in group A (p < 0.001): Excellent enhancement was obtained in 51.2% and 23.3%, respectively (Table 2). Furthermore, the mean enhancement (in Hounsfield units) was significantly higher at all levels in group B than in group A: The mean enhancements were 130 and 113 H for groups A and B, respectively, at the level of the distal inferior vena cava; 122 and 107 H at the femoral vein; and 125 and 104 H at the popliteal vein (Table 3).

Multiple regression analyses revealed that body weight and patient age were the only significant and consistent independent variables associated with enhancement of the pulmonary artery branches (Table 4). For example, at the segmental artery, the model is expressed as follows: CT attenuation (H) = 474.728 - [3.005 x body weight (kg)] + [1.341 x age (years)].


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  		TABLE 4: Results of Multiple Stepwise Regression Analyses: Contrast Enhancement and Independent Variables

 

The amount of contrast medium, body weight, and scanning delay are the independent variables that were consistently associated with enhancement of the deep veins. For example, at the popliteal vein, the model is expressed as follows: CT attenuation (H) = 183.362 + [39.506 x contrast medium] - [0.843 x body weight (kg)] - [2.209 x scanning delay (seconds)] - [8.920 x sex], where contrast medium is 0 for group A and 1 for group B and sex is 0 for female and 1 for male.


Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In our study, we used two different quantities (100 and 150 mL) of contrast medium of the same concentration (300 mg I/mL). The mean body weight was significantly heavier for group B, who received 150 mL of contrast medium, and the measured attenuation in Hounsfield units in all of the pulmonary arteries was significantly lower in group B than group A. We consider that the global quality of the pulmonary arteries did not differ between the two groups because the differences in the mean attenuations were small (range, 28-46 H) compared with their absolute values (> 300 H). This finding has also been suggested in previous reports that used 16-MDCT [24, 25].

In the multiple regression analyses, the body weight and age of the patient were the only independent variables that were associated with measured enhancement of the pulmonary arteries. The effect of the larger amount of contrast medium may have been cancelled out because group B included heavier patients. It is noteworthy that higher patient age was clearly associated with better contrast enhancement; the unstandardized regression coefficient ranged from 0.791 to 1.669. The reason for this trend is not clear, but it may be associated with changes that occur in cardiopulmonary circulation with aging [17, 26, 27]. Pulmonary artery pressure has been reported to increase with patient age [26, 27]. Hartmann et al. [17] confirmed that the transit time of a small amount of contrast medium through the pulmonary circulation became significantly longer with increased patient age after adjustments for differences in blood pressure, body surface area, heart rate, and cardiac function. The pulmonary blood pool may be stagnant in older subjects, and the contrast medium is better visualized in those patients while performing CT pulmonary angiography.

We observed that global deep vein enhancement was significantly better when the larger amount of contrast medium was used. Although poor enhancement was seen in only 0.8% of group B and 1.7% of group A patients, good or excellent enhancement (attenuation higher than the musculature) was seen in 81.1% and 61.6% in groups B and A, respectively. This was confirmed by measurements of vessel attenuation that ranged from 104 to 113 H in group A and from 122 to 130 H in group B.

In previous reports, investigators who used various combinations of quantities and concentrations of contrast media (range in iodine content, 360-420 mg) described a range in mean venous attenuation of 91-115 H on CT venography [22, 28-30] and revealed a trend of improved vessel enhancement when a contrast medium with greater iodine content was used. We obtained greater venous attenuation in our present study than that described in previous reports by investigators who used a contrast medium with a similar iodine content. These differences may be explained by the relatively small size of the Asian patients in our study compared with North American patients, although the patients' weights in the previous studies were not indicated [22, 28, 31].

Although there is no consensus about the adequate venous opacification to diagnose deep venous thrombosis on CT, the difference in attenuation between the vein and the clot should be large enough for confident diagnosis. The attenuation of clot has been reported to be variable; for example, Loud et al. [32] reported a mean of 31 H (SD, 10), and Cham et al. [22] reported a mean attenuation of 51 H (95% CI, 45-57 H). Baldt et al. [33] reported that the attenuation of clot showed a trend of negative correlation with days after the onset of disease. Clots imaged within 8 days of disease onset showed an average attenuation of 66 H (SD, 7), whereas those that had been present more than 8 days showed an average attenuation of 55 H (SD, 11) [33]. In keeping with these data, Goodman et al. [14] suggested that the optimal venous enhancement should be more than 80 H.

We used multiple regression models for analyses and found that the independent variables associated with enhancement of the deep veins were amount of contrast medium; body weight; and, less importantly, scanning delay. The results are understandable considering that the venous system is the site of blood pooling. For example, from the equation drawn from the analyses at the level of the popliteal vein, we can expect an increase in enhancement of approximately 39 H when using 150 mL of contrast medium compared with that expected when using 100 mL. We can also expect a decrease in enhancement of 8 H if the weight of the patient is increased by 10 kg. These values are not small considering their absolute value of approximately 100 H.

We used the bolus-tracking method to determine the scanning delay for CT pulmonary angiography. The scanning delay in our series ranged from 10 to 31 seconds, with a mean of 19 seconds (SD, 3.3). Using this technique, we judged 4.8% of group A and 3.9% of group B to have poor contrast enhancement. In a previous study, investigators used single-detector CT for CT pulmonary angiography to compare enhancement of the pulmonary vessels in 57 patients using the test bolus technique and in 50 patients for whom the scanning delay was fixed at 20 seconds [17]: They found no significant differences in image quality between the two methods and insisted that a fixed scanning delay was valid in helical CT pulmonary angiography. Our results agree with their observations, anslthough we believe that the bolus-tracking method is preferable because the appropriate scanning delay differs substantially in a minority of patients.

One of the limitations of this study is that the enhancement of vessels was evaluated in patients with different physiologic conditions. Some patients had severe derangement in cardiopulmonary circulation or respiratory status that could have affected vessel enhancement, whereas others were relatively stable. For this problem, we excluded cases that showed obvious and significant motion artifact in evaluating global enhancement quality and measurement of enhancement in CT pulmonary angiography. To avoid incorrect results, we also did not measure the enhancement of a vessel when the vessel in question had a clot or was occluded proximally.

In conclusion, the contrast enhancement of CT pulmonary angiography is independently associated with the weight and age of the patient, whereas contrast enhancement of CT venography is independently associated with patient weight, quantity of injected contrast medium, and scanning delay time. The use of 450 mg I of contrast medium significantly improved enhancement of the deep veins in the lower extremities. A relatively minor variation in scanning delay was observed for CT pulmonary angiography using the bolus-tracking technique; however, the bolus-tracking technique is preferable because a wide range of scanning delays is seen in a small number of patients.


References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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