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Thromboembolic Disease Detection at Indirect CT Venography versus CT Pulmonary Angiography¹

¹ From the Department of Radiology, Strong Memorial Hospital–University of Rochester School of Medicine and Dentistry, 620 Park Ave, PMB 244, Rochester, NY 14607 (M.D.C.); and Department of Radiology, New York Presbyterian Hospital–Weill Medical College at Cornell University, New York, NY (D.F.Y., C.I.H.). From the 2002 RSNA Annual Meeting. Received December 9, 2002; revision requested February 6, 2003; final revision received April 12, 2004; accepted April 28. Address correspondence to M.D.C. (e-mail: matthew_cham@urmc.rochester.edu).

	ABSTRACT

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PURPOSE: To assess the incremental increase in thromboembolic disease detection at indirect computed tomographic (CT) venography versus CT pulmonary angiography and to determine the importance of scan interval for indirect CT venography on the basis of thrombus length.

MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was not required. The study included 1590 consecutive patients undergoing CT pulmonary angiography for the suspicion of pulmonary embolism. Two minutes after completion of pulmonary angiography, a contiguous indirect CT venography was performed from the iliac crest to the popliteal fossa. The presence of pulmonary embolism or deep venous thrombosis (DVT) was recorded for all patients. The lengths of all deep venous thrombi found in the first 378 consecutive patients were recorded.

RESULTS: Pulmonary embolism was detected in 243 (15%) of 1590 patients at CT pulmonary angiography, and DVT was detected in 148 (9%) patients at indirect CT venography. Among 148 patients with DVT, pulmonary embolism was detected in 100 patients at CT pulmonary angiography. Thus, the addition of indirect CT venography to CT pulmonary angiography resulted in a 20% incremental increase in thromboembolic disease detection compared with that at CT pulmonary angiography alone (99% confidence interval: 17%, 23%). Among the 378 patients, DVT was present in 33 patients at indirect CT venography. Two (6%) of 33 patients had clots measuring 2 cm or less, six (18%) had clots measuring 3–4 cm, and 25 (76%) had clots measuring more than 4 cm in length.

CONCLUSION: The addition of indirect CT venography to CT pulmonary angiography incrementally increases the detection rate of thromboembolic disease by 20%. Performance of indirect CT venography by using contiguous section intervals, with a section width of 1 cm, is recommended to accurately detect DVT.

© RSNA, 2005

	INTRODUCTION

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Pulmonary embolism is a life-threatening disease that affects between 40 000 and 200 000 patients annually in the United States alone (1–3). Pulmonary embolism is a well-recognized sequela of deep venous thrombosis (DVT) of the lower extremities (4,5). Findings of studies have shown that inadequately treated DVT is associated with recurrent pulmonary embolism (6–8). To accurately diagnose thromboembolic disease in patients suspected of having pulmonary embolism, several investigators have developed helical computed tomographic (CT) protocols that depict both pulmonary embolism and lower extremity DVT (9,10). This technique has been referred to as combined CT pulmonary angiography and indirect CT venography.

Indirect CT venography allows examination of the pelvis and lower extremities by using only the contrast material already in circulation from the preceding CT pulmonary angiography, thus obviating additional contrast material, which is associated with both traditional and direct CT venography (9,10).

The addition of indirect CT venography to the standard CT pulmonary angiographicprotocol requires only an additional 3 minutes to perform, potentially obviating a separate lower extremity examination that can further delay the turnaround time of results (9,10). In our prior study, we compared indirect CT venography with lower extremity sonography in 116 patients and found a disagreement rate of only 3% (11). Authors of a double-blinded prospective study involving 70 consecutive patients undergoing both lower extremity sonography and combined CT pulmonary angiography and indirect CT venography reported a sensitivity and specificity of 100% and 97%, respectively, for indirect CT venography (12). Authors of other nonrandomized retrospective studies have reported sensitivities of 71%–94% and specificities of 93%–94% for indirect CT venography (13,14).

Several investigators have also noted that, like CT pulmonary angiography, indirect CT venography also has the potential to provide alternative nonvascular diagnoses for the patient’s clinical presentation (15–17). The widespread use of this examination has been further supported by studies in which a moderately good interobserver agreement, a consistently high level of venous enhancement, and a low radiation risk were reported (18–21).

Authors of several large prospective multicenter studies have found that the addition of indirect CT venography to the basic CT pulmonary angiographic protocol increased the diagnosis of thromboembolic disease by 15%–38% (11,17,22).

Another consideration in the increasingly common use of combined CT pulmonary angiography and indirect CT venography is the optimization of the indirect CT venographic portion of the examination. From a technical standpoint, it is necessary to consider two important parameters: the time delay prior to initiating indirect CT venography and the section intervals. We previously evaluated the former and found that the 2-minute delay following CT pulmonary angiography produced near maximum opacification in the majority of patients (11). Consideration of the latter necessitates obtaining information about thrombi length, because long (ie, 5-cm) section intervals would potentially miss small thrombi. On the other hand, increasing the section interval reduces radiation exposure, which is currently slightly lower than that of a standard pelvic CT (21).

The purpose of this study was to assess the incremental increase in thromboembolic disease detection at indirect CT venography versus CT pulmonary angiography and to determine the importance of scan interval for indirect CT venography on the basis of thrombus length.

	MATERIALS AND METHODS

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Patients
Our study included 1590 consecutive patients who had undergone combined CT pulmonary angiography and indirect CT venography between June 2, 1998, and October 31, 2001. Institutional review board approval was obtained for the study (IRB# 0699–746). Informed consent was not required by our institutional review board; patient identifiers were deleted.

Of 1590 patients (age range, 18–99 years), 707 (44%) were men (median age, 64 years; mean age, 61 years) and 883 (56%) were women (median age, 64 years; mean age, 62 years). A total of 1324 (83%) patients were from the inpatient setting, while 266 (17%) were from the emergency department and outpatient setting.

From June 2, 1998, to June 27, 1999, we documented the lengths of deep venous thrombi in 378 consecutive patients. We also recorded whether these 378 patients and an additional 1212 consecutive patients had positive findings for pulmonary embolism or DVT at combined CT pulmonary angiography and indirect CT venography, for a total of 1590 patients.

All patients were referred to the New York Presbyterian-Hospital–Weill Medical College at Cornell University because of the clinical suspicion of pulmonary embolism. All studies were ordered by physicians as clinically indicated and were not influenced by the study protocol. Because no additional contrast agent was necessary to perform indirect CT venography, all patients with a serum creatinine level of less than 1.5 mg/dL (133 µmol/L) were eligible to undergo combined CT pulmonary angiography and indirect CT venography. Patients who could not complete the study because of known allergic reactions, inadequate intravenous access, or renal insufficiency without hemodialysis were excluded from the study.

Imaging
Our imaging protocol was the standard hospital protocol used for routine clinical care, without modifications. All patients underwent combined CT pulmonary angiography and indirect CT venography. A 140 mL dose of iohexol (Omnipaque 300; Nycomed-Amersham, Princeton, NJ) was injected at a rate of 3 mL/sec. Helical CT scanning was performed (Hi-Speed Advantage CT/i; GE Medical Systems, Milwaukee, Wis), with a scan delay of 28 seconds. Images were obtained from the diaphragm to the aortic arch, with a section width of 3 mm and a pitch of 1.6:1. Scanning of the pelvis started from the iliac crest 120 seconds after completion of CT pulmonary angiography and continued to the popliteal fossa, with a section width of 10 mm and a pitch of 1:1. Reconstruction for the CT pulmonary angiographic portion was performed at 1-mm intervals. Indirect CT venography was evaluated by using standard 10-mm-thick nonoverlapping images.

Image Interpretation
Each study had been read by one of six attending chest radiologists (including D.F.Y. and C.I.H.). Each attending radiologist had at least 10 years of experience. For both CT pulmonary angiography and indirect CT venography, thrombi were defined as low-attenuating partial or complete intraluminal filling defects surrounded by a high-attenuating ring of enhanced blood and were seen on at least two consecutive transverse images. If only one transverse image demonstrated a filling defect, then a thrombus would not be diagnosed. Thrombus length was measured by counting the number of consecutive images on which the deep venous thrombus was visible. Because a section width of 10 mm was used for indirect CT venography, each image represents 1 cm of the thrombus length. Findings of the examination were categorized as inconclusive when poor examination quality resulted in a nondiagnostic impression.

Statistical Analysis
The parameter of interest was the incremental increase in detection of thromboembolic disease when combined CT pulmonary angiography and indirect CT venography was performed versus when only CT pulmonary angiography was performed. The 99% confidence interval for this incremental increase was calculated by using the standard approach.

	RESULTS

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A typical example of a deep venous thrombus at indirect CT venography is shown in Figure 1. Among the first 378 consecutive patients, DVT was detected at indirect CT venography in 33 patients, a thrombus was seen on contiguous sections in 21 patients, and two distinct thrombi were seen in 12 patients each.

View larger version (66K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Indirect CT venogram of the left common femoral vein shows a deep venous thrombus (arrow).

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Bar graph illustrates the relative frequency of thrombi of various lengths among 378 consecutive patients suspected of having pulmonary embolism. Among 33 patients with DVT at indirect CT venography, 24% had maximum thrombus lengths of less than 5 cm.

	DISCUSSION

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Over the past years, CT pulmonary angiography has become a commonly ordered examination. In many specific clinical situations, it has replaced ventilation-perfusion scanning as the initial examination in the work-up of pulmonary embolism (23,24). Likewise, combined CT pulmonary angiography and indirect CT venography has become increasingly common, with many institutions worldwide routinely incorporating indirect CT venography into the CT pulmonary angiographic examination (11,21,22).

In previous studies, indirect CT venography has been shown to increase the diagnosis of thromboembolic disease by 15%–38%, compared with the basic CT pulmonary angiographic examination (11,17,22). In this study, we found that combined CT pulmonary angiography and indirect CT venography increases thromboembolic disease detection by 20% (99% confidence interval: 17%, 23%) compared with CT pulmonary angiography alone. This result is similar to our previous findings, where the detection rate of thromboembolic disease was increased by 18% with use of indirect CT venography in 541 patients (11). Our current results lend further support to the consistent diagnostic yield that can be expected from indirect CT venography.

There were several limitations in our study. First, only one radiologist read each image from the combined CT pulmonary angiography and indirect CT venography. However, this replicates real-world conditions. Second, our criterion for thrombus diagnosis requires that filling defects are seen on at least two consecutive sections; otherwise, possible filling defects seen on only one section would be attributed to partial volume averaging. Thus, there is potential for small clots of less than 1 cm to be undiagnosed. Such an underestimation of clot length would however only add credence to the need for contiguous section intervals. Third, there were no standard comparisons performed in this study. Findings of published prospective studies in which indirect CT venography was directly compared with sonography have confirmed our initial findings that indirect CT venography is similar to sonography in sensitivity and specificity (11,12,18).

As indirect CT venography becomes increasingly used at more institutions, there is great need to optimize its effectiveness (11). The radiation dose to the pelvis and gonads is an important consideration when performing indirect CT venography. Using a combined CT pulmonary angiographic and indirect CT venographic protocol similar to ours, Rademaker et al (21) measured patient gonadal doses on the order of 2.1–10.7 mSv, with variation between individuals and sex. They found that the addition of indirect CT venography increases the gonadal radiation dose by 500- to 2000-fold compared with CT pulmonary angiography alone. Fortunately, this increase in gonadal dose is well below the thresholds for deterministic radiation effects provided in the International Commission on Radiological Protection Publication 60, or ICRP-60, guidelines (25). There are several stochastic effects that may arise from irradiation of the pelvis during indirect CT venography, such as leukemia and heritable genetic disease. Given the ICRP-60 stochastic risk estimate of 5% per sievert and a calculated effective dose of about 2.5 mSv for indirect CT venography, the risk of radiation-related death from leukemia is on the order of 1:8000 (21). Given the ICRP-60 stochastic risk estimate of 1% per sievert, this corresponds to a genetic risk of about 1:15 000 among patients in the reproductive age group undergoing indirect CT venography (21). This genetic risk does not exist for the majority of patients undergoing indirect CT venography who, on average, are older than 60 years. Like all other forms of x-ray–based imaging, the risk of mortality and morbidity from thromboembolic disease should be considered in the context of these risks, especially for patients in the reproductive age group.

Some investigators have suggested the use of discontinuous transverse sections, with 5-cm gaps between sections (9,22). The use of discontinuous sections can reduce the integral dose by as much as 80% but has the potential to decrease specificity owing to interpretive pitfalls (16,26,27). Noncontiguous section intervals can adversely affect the interpretation of images along the iliac and popliteal veins that run oblique to the transverse plane and are thus prone to partial volume artifacts that mimic a clot. Since contrast enhancement in the legs can be relatively low and there are subtle differences in the attenuation distribution, it is useful to see if a subtle filling defect persists on more than one image. This approach is used routinely in the interpretation of CT pulmonary angiographic studies, where it is often necessary to identify a clot on two or more consecutive images for a definitive diagnosis.

Even in the absence of interpretive pitfalls, our current data suggest that use of a 5-cm scan interval would result in a 40% chance of missing the thrombi that measure less than 5 cm. The lengths of deep vein thrombi among patients suspected of having pulmonary embolism strongly favor the use of contiguous indirect CT venography for the pelvis and lower extremities.

Some investigators have found that the frequency of isolated pelvic DVT is relatively uncommon, comprising 1%–4% of all cases positive for DVT (22,28). Thus, another possible imaging option would be to scan only the legs in patients who are in the reproductive age group.

Several new technologies have the potential to decrease the radiation dose during combined CT pulmonary angiography and indirect CT venography, while hopefully maintaining diagnostic effectiveness. Most multi–detector row CT scanners are now equipped with dose-reducing applications that automatically modulate the tube current in the z-, x-, or y-axis. Depending on patient’s body habitus, this technology can reduce radiation dose by as much as 50%. In the future, clinical studies will be needed to determine whether a small reduction in radiation dose, at the expense of a slightly increased noise, will adversely affect the detection of thromboembolic disease.

	FOOTNOTES

 
Abbreviation: DVT = deep venous thrombosis

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, D.F.Y., M.D.C., C.I.H.; study concepts and design, D.F.Y., C.I.H.; literature research, M.D.C., D.F.Y., C.I.H.; clinical studies, D.F.Y., M.D.C.; data acquisition, M.D.C., D.F.Y.; data analysis/interpretation, M.D.C., D.F.Y., C.I.H.; statistical analysis, C.I.H., M.D.C., D.F.Y.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, M.D.C., D.F.Y., C.I.H.

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cham, M. D. Articles by Henschke, C. I. Search for Related Content PubMed PubMed Citation Articles by Cham, M. D. Articles by Henschke, C. I.