CT Venography Compared with
Single–Detector Row CT
Pulmonary Angiography?
1
Benoit Ghaye, MD Alain Nchimi, MD Charlemagne T. Noukoua, MD Robert F. Dondelinger, MDPurpose: To compare retrospectively the incremental value of
indi-rect computed tomographic (CT) venography performed after multi– detector row CT pulmonary angiography and single– detector row CT pulmonary angiography for the diagnosis of venous thromboembolism (VTE).
Materials and Methods:
The institutional ethics committee approved this study; informed consent was not required. The authors retro-spectively reviewed results of 1100 combined single– de-tector row CT pulmonary angiographic and indirect CT venographic examinations (542 men, 558 women; mean age, 61 years ⫾ 17 [standard deviation]) (group 1) and 308 combined multi– detector row CT pulmonary angio-graphic and indirect CT venoangio-graphic examinations (150
men, 158 women; mean age, 62 years⫾ 18) (group 2),
performed in 1408 patients suspected of having pulmonary embolism (PE). Frequency of deep venous thrombosis (DVT), PE, and VTE, and the incremental value of indirect CT venography were recorded in both groups. Data were compared by means of the Student t test for continuous data and z statistics for independent proportions.
Results: VTE, PE, and DVT were found in 23.3% (n⫽ 256), 19.9%
(n⫽ 219), and 18.3% (n ⫽ 201) of the 1100 patients in group 1, respectively, and in 23.7% (n⫽ 73), 17.2% (n ⫽ 53), and 18.8% (n ⫽ 58) of the 308 patients in group 2, respectively (P values ranging from .273 to .876). The incremental value of indirect CT venography was 14.4% (37 of 256 patients) in group 1 and 27.4% (20 of 73 patients) in group 2.
Conclusion: Despite potential improved accuracy of multi– detector
row CT pulmonary angiography for the diagnosis of PE, the addition of indirect CT venography increased the diag-nosis of VTE in 27.4% of patients.
娀 RSNA, 2006
1From the Department of Medical Imaging, University
Hospital Sart-Tilman, Domaine Universitaire du Sart-Til-man B 35, B-4000 Lie`ge, Belgium (B.G., C.T.N., R.F.D); and the Department of Medical Imaging, Clinique Saint Joseph, Lie`ge, Belgium (A.N.). From the 2004 RSNA An-nual Meeting. Received March 1, 2005; revision re-quested April 26; revision received July 4; accepted July 21; final version accepted September 8. Address corre-spondence to B.G. (e-mail: bghaye@chu.ulg.ac.be). 姝 RSNA, 2006
ORIGINAL
V
enous thromboembolism (VTE) is a major health problem, with an incidence of approximately 1.5 per 1000 person-years and a 10% mor-tality rate (1). Early diagnosis and treat-ment substantially improve survival in patients with VTE (2). Although clots in the pulmonary arteries influence pa-tients’ cardiopulmonary status, the ma-jor risk of death is from recurrent pul-monary embolism (PE), which arises from deep veins of the lower limbs and the pelvis in more than 90% of cases (2,3). Therefore, imaging of lower-limb veins has been advocated in PE diagnos-tic algorithms for patients in whom in-vestigations at the level of the pulmo-nary arteries do not allow for a definite diagnosis of PE (4–6). Ultimately, the detection of VTE is used to determine patient care.Computed tomographic (CT) pul-monary angiography has progressively gained acceptance as the frontline imag-ing modality for the diagnosis of PE, replacing ventilation-perfusion lung scintigraphy and pulmonary angiogra-phy (7–9). Indirect CT venograangiogra-phy, per-formed immediately after CT pulmo-nary angiography in patients suspected of having VTE (10), provides results similar to those of lower-limb ultra-sonography (US) for the diagnosis of deep venous thrombosis (DVT) in the femoropopliteal veins (11–16). The in-cremental value of indirect CT venogra-phy is in the range of 8%–27% in pa-tients with negative findings at 3- to 5-mm-collimation CT pulmonary an-giography (12,15–19).
The advent of multi– detector row technology allows analysis of pulmonary arteries down to the sixth subdivision and substantially helps increase the de-tection rate of clots when 1-mm-colli-mation multi– detector row CT pulmo-nary angiography is used (20,21). Accu-racy of CT pulmonary angiography has therefore increased from greater than 80% with single– detector row CT pul-monary angiography to greater than 90% with multi– detector row CT pul-monary angiography (7,22,23). Thus, the incremental value of indirect CT venography can be questioned if thin-collimation multi– detector row CT pul-monary angiography is being used (24). The purpose of our study, there-fore, was to compare retrospectively the incremental value of indirect CT venography performed after multi– de-tector row and single– dede-tector row CT pulmonary angiography for the diagno-sis of VTE.
Materials and Methods
Patients and CT Image Acquisition
CT pulmonary angiography has been the diagnostic modality of choice in pa-tients suspected of having PE in our in-stitution (University Hospital of Liege) since 1995; diagnostic testing was fur-ther refined by the addition of indirect CT venography in 1998. Only pregnancy or contraindications to injection of io-dinated contrast medium led to evalua-tion with other imaging techniques. Pa-tients younger than 40 years underwent US instead of indirect CT venography to avoid a higher radiation dose. Indirect CT venography was performed in pa-tients younger than 40 years only when previous US of lower-limb veins pro-duced equivocal findings. Oral informed consent was routinely obtained from all patients before combined CT pulmo-nary angiography–indirect CT venogra-phy examinations. An exemption for written informed consent was obtained for our retrospective study from the in-stitutional ethics committee (at Univer-sity Hospital of Liege), which approved the study.
Between 1998 and 2002, 1344
con-secutive patients underwent combined single– detector row CT pulmonary an-giography and indirect CT venography of the lower limbs (group 1). Pulmonary arteries were scanned from 2 cm below the diaphragm to the aortic arch with helical acquisition (PQ 5000; Philips, Eindhoven, the Netherlands) by using 2-mm collimation, 1-mm reconstruction increment, a pitch of 2, 1-second rota-tion time, 100 mAs, and 130 kVp, start-ing 20 –25 seconds after the start of in-travenous injection of 140 mL of 30% iodinated contrast material (Xenetix 300; Guerbet, Aulnay-sous-Bois, France) at a flow rate of 3 mL/sec. CT venogra-phy was performed 210 seconds after the start of injection, from calf to dia-phragm, by using a sequential acquisi-tion of 5-mm-thick secacquisi-tions at 20-mm intervals, 100 –125 mAs, and 130 kVp. CT venography was started at 240 –300 seconds in patients suspected of having low cardiac output (14,25).
Between 2002 and 2004, 329 con-secutive patients underwent combined 16 – detector row CT pulmonary angiog-raphy and indirect CT venogangiog-raphy (group 2). Lungs were scanned from base to apex (Sensation 16; Siemens Medical Solutions, Forcheim, Germany) by using 0.75-mm-collimation helical ac-quisitions, 1-mm-thick reconstruction, 0.7-mm reconstruction increment, 0.5-second rotation time, 100 –140 mAs, and 120 kVp, with the same protocol for contrast material injection as used in
Published online before print 10.1148/radiol.2401050350 Radiology 2006; 240:256 –262 Abbreviations:
DVT⫽ deep venous thrombosis PE⫽ pulmonary embolism VTE⫽ venous thromboembolism Author contributions:
Guarantors of integrity of entire study, B.G., A.N.; study concepts/study design or data acquisition or data analy-sis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, B.G., A.N.; clinical studies, B.G., C.T.N.; statistical analysis, A.N.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
Advances in Knowledge
䡲 Indirect CT venography has an important effect on the diagnosis in patients suspected of having venous thromboembolism. 䡲 The incremental value of indirect
CT venography when combined with CT pulmonary angiography is 17.3%.
group 1. Lower-limb veins were scanned from calf to diaphragm by using 1.5-mm collimation, 5-mm-thick reconstruction, 5-mm reconstruction increment, 100 mAs, and 120 kVp, with the same delay as described in group 1.
Of these 1673 patients, 265 (15.8%) were excluded from the study for the following reasons: DVT documented be-fore combined CT pulmonary angiog-raphy–indirect CT venography (118 pa-tients in group 1 and 16 papa-tients in group 2), follow-up examinations of documented VTE (100 patients in group 1 and four patients in group 2), and examinations unavailable for review (26 patients in group 1 and one patient in group 2). As a result, the final study population comprised 1408 patients; group 1 consisted of 1100 patients (542 men, 558 women; mean age, 61 years⫾ 17 [standard deviation]) and group 2 consisted of 308 patients (150 men, 158 women; mean age, 62 years⫾ 18).
Interpretation of CT Scans
Findings from all 1408 examinations had been interpreted on an independent workstation (Voxel Q; Philips) by two readers reaching a consensus. One of them was a chest radiologist with 10 or 20 years of experience in interpreting CT angiograms (B.G. or R.F.D.). The second reader was a staff radiologist with 3– 8 years of experience in reading CT scans. The interpretations were
ret-rospectively collected by A.N. or
C.T.N., who reviewed the reports. Interpretation was formulated ac-cording to a predefined protocol that included, along with positive, negative, or inconclusive findings for PE and DVT, the following parameters: The presence of an arterial clot was as-sessed from the main pulmonary artery down to the subsegmental level for sin-gle– detector row CT pulmonary angiog-raphy and as distal as possible for multi– detector row CT pulmonary an-giography. Inconclusive CT pulmonary angiographic findings were those ob-tained from examinations without evi-dence of PE and in which pulmonary arteries were not assessable beyond the lobar level. Inconclusive indirect CT venographic findings were those
ob-tained from examinations without evi-dence of venous thrombosis and in which one or more venous segments were not assessable. Reasons for incon-clusive findings were systematically re-corded. CT signs of PE and DVT were interpreted according to guidelines pub-lished in the literature and consisted of complete or partial intravascular filling defect surrounded by contrast material that presented the “polo mint” sign, in which sections were perpendicular to the long axis of the vessels, or the “rail-way” sign, in which sections were paral-lel to the long axis. The involved artery or vein is frequently dilated (Figure) compared with similar vessels on the other side (9,26).
Data Analysis
Frequencies of PE, DVT, and VTE (PE and DVT, PE alone, or DVT alone) were calculated in both groups. The incre-mental value of indirect CT venography for diagnosis of VTE, defined as the per-centage of patients with DVT and no PE, was evaluated in both groups. In patients with DVT and no PE, the fre-quency of DVT located in above-knee veins (ie, including and above the level of the popliteal vein) and in below-knee veins (ie, below the level of the popliteal vein) were calculated in both groups. The final result for VTE was considered inconclusive when findings at CT pulmo-nary angiography or indirect CT venog-raphy, or both, were inconclusive and no confident diagnosis of VTE could be made from the examination. The reason for indeterminate examination was sys-tematically noted. The results of CT pul-monary angiography and indirect CT venography in patients with indetermi-nate findings at indirect CT venography or CT pulmonary angiography, respec-tively, were analyzed.
Statistical Analysis
The software used for statistical analy-sis was Systat 9.0 (Systat Software,
Richmond, Calif). Continuous data
were expressed as mean⫾ standard de-viation. The 95% confidence intervals for means and proportions were calcu-lated by using the modified Wald method. Comparisons of continuous
data were performed by means of the unpaired Student t test. Comparisons of
independent proportions were
per-formed with two-tailed z statistics. P⬍ .05 was considered to indicate a signifi-cant difference.
Results
No significant differences were found for patient age, sex, and inpatient or outpatient status between groups (Ta-ble 1).
Of 1408 patients, 272 (19.3%) had PE, 259 (18.4%) had DVT, and 329 (23.4%) had VTE. DVT was found in 74.3% (202 of 272) of patients with PE. The frequencies of PE, DVT, and VTE in groups 1 and 2 showed no significant
difference between groups (P ⬎ .05)
(Table 2). In patients with DVT and no PE, the frequency of DVT located in above-knee veins and in below-knee veins was not significantly different be-tween groups (Table 2).
Inconclusive Findings
Inconclusive findings for VTE and DVT were seen in 15% (211 of 1408) and 12.7% (179 of 1408) of patients, re-spectively, with no significant difference
between groups (Table 2). Inconclusive findings at indirect CT venography were due to poor venous opacification (75% [103 of 137] of patients in group 1 and 79% [33 of 42] of patients in group 2), beam-hardening artifacts caused by or-thopedic hardware (16% [22 of 137] of patients in group 1 and 17% [seven of 42] of patients in group 2), and low signal-to-noise ratio or venous segments out of acquisition range (9% [12 of 137] of patients in group 1 and 5% [two of 42] of patients in group 2). The poor venous opacification was located exclu-sively at the level of the calf in 97% (100
of 103) of patients in group 1 and 97% (32 of 33) of patients in group 2. The remaining four patients (3% in both groups) had poor venous opacification in veins located both above and below the knee.
Inconclusive findings for PE were seen in 10.4% (146 of 1408) of patients. There were significantly fewer inconclu-sive CT pulmonary angiographic find-ings in group 2 (7.5% of patients [23 of 308]) than in group 1 (11.2% of patients [123 of 1100]) (P⫽ .036). Inconclusive CT pulmonary angiographic findings were due to breathing motion artifacts
(81% [100 of 123] of patients in group 1 and 74% [17 of 23] of patients in group 2), poor arterial opacification (9% [11 of 123] in group 1 and 13% [three of 23] in group 2), cardiac motion artifacts (6% [seven of 123] in group 1 and 4% [one of 23] in group 2), and low signal-to-noise ratio or arterial segments out of acquisition range (4% [five of 123] in group 1 and 9% [two of 23] in group 2). Regarding inconclusive findings at CT pulmonary angiography and indirect CT venography, positive results at CT pulmonary angiography were found in 28% (30 of 109) and 33% (12 of 36) of the patients with inconclusive findings at indirect CT in groups 1 and 2, respec-tively (P⫽ .495) (Table 3). Positive in-direct CT venographic findings were seen in 35% (33 of 95) and 29% (five of 17) of patients with inconclusive CT pul-monary angiographic findings in groups 1 and 2, respectively (P ⫽ .710) (Ta-ble 3).
Incremental Value
The incremental value of indirect CT venography was 17.3% (57 of 329 pa-tients; 95% confidence interval: 13.6%, 21.8%) in the whole study group and was significantly higher in group 2 (27.4% [20 of 73 patients; 95% confidence interval: 18.5%, 38.7%]) than in group 1 (14.4% [37 of 256 patients; 95% confidence inter-val: 10.6%, 19.3%]) (P⫽ .005).
Discussion
We found that, despite the potentially improved sensitivity of multi– detector row technology (ie, 16 – detector row CT) for the diagnosis of PE, indirect CT venography remains highly valuable. The mean incremental values of adding indirect CT venography to CT pulmo-nary angiography in our study were 17% (95% confidence interval: 13.6%, 21.8%) in patients with VTE, 14% (95% confidence interval: 10.6%, 19.3%) with use of single– detector row CT pul-monary angiography, and 27% (95% confidence interval: 18.5%, 38.7%) with use of multi– detector row CT pul-monary angiography. The incremental values lie within the range (8%–27%) of those reported in other published series
Table 1
Patient Characteristics
Variable Group 1 (n⫽ 1100) Group 2 (n⫽ 308) P Value
Sex .859* Male 542 (49) 150 (49)
Female 558 (51) 158 (51)
Age (y) .937†
Range 19–100 28–86 Mean⫾ standard deviation 61.2⫾ 16.9 62.0⫾ 17.9
Origin .303* Inpatient 251 (23) 62 (20)
Outpatient 849 (77) 246 (80)
Note.—Unless otherwise indicated, data are numbers of patients, and numbers in parentheses are percentages. * Two-tailed z statistics.
†Student t test.
Table 2
VTE Findings in Group 1 versus Group 2
Finding
Group 1 (n⫽ 1100) Group 2 (n⫽ 308)
P Value*
No. of Patients 95% CI (%) No. of Patients 95% CI (%) VTE 256 (23.3) 20.7, 25.7 73 (23.7) 18.9, 28.4 .876 PE 219 (19.9) 17.6, 22.2 53 (17.2) 12.9, 21.4 .273 DVT 201 (18.3) 15.9, 20.5 58 (18.8) 14.4, 23.2 .824 DVT and PE 164 (14.9) 12.8, 17.0 38 (12.3) 8.6, 16.0 .234 PE without DVT 55 (5.0) 3.7, 6.2 15 (4.9) 2.4, 7.2 .926 DVT without PE 37 (3.4) 2.3, 4.4 20 (6.5) 3.7, 9.2 .038 Below knee 29 (2.6) 1.7, 3.6 15 (4.9) 2.5, 7.3 .090 Above knee 8 (0.7) 0.2, 1.2 5 (1.6) 0.2, 3.0 .241 Inconclusive findings At CT pulmonary angiography 123 (11.2) 9.3, 13.0 23 (7.5) 4.5, 10.4 .036 At indirect CT venography 137 (12.4) 10.5, 14.4 42 (13.6) 9.8, 17.4 .590 For VTE 169 (15.3) 13.2, 17.5 42 (13.6) 9.8, 17.4 .440
(12,15–19). Similar to findings in other studies, 5% (57 of 1136) of our patients with negative results at CT pulmonary angiography would have been wrongly classified as not having VTE if no further testing was performed (12,15).
Our incremental value of 14% with use of single– detector row CT pulmo-nary angiography is close to values in the largest, to our knowledge, study published to date (19). In a study of 1590 patients, Cham et al (19) reported a 16% incremental increase in VTE de-tection after the addition of 10-mm-col-limation indirect helical CT venography to 3-mm single– detector row CT pul-monary angiography. On the other hand, the 27% incremental value we ob-tained with use of 16 – detector row CT pulmonary angiography is higher than the 17% incremental increase found by Richman et al (17), who reported their experience with four– detector row CT in 800 outpatients suspected of having PE. Nevertheless, that study involved a greater reconstruction thickness than did our study: 3-mm-thick sections for CT pulmonary angiography and 10-mm-thick sections at 20-mm increments for indirect CT venography (17).
Schoepf et al (21) demonstrated that decreasing the section thickness from 3 to 1 mm resulted in a higher rate of detection of clots and in fewer incon-clusive findings for PE. Indeed, we found a significant decrease in inconclu-sive findings for PE with use of multi– detector row compared with single– de-tector row CT pulmonary angiography (7.5% vs 11.2%; P ⫽ .036). Neverthe-less, we found no significant difference in the rate of isolated PE (ie, patients with CT results positive for PE but
with-out CT evidence of DVT) between pa-tients who underwent testing with both technologies.
Similarly, a recent study (23) sug-gested that in routine practice, four– detector row CT pulmonary angiogra-phy may still have limitations in demon-strating small peripheral emboli in comparison with pulmonary angiogra-phy. On the other hand, the percentage of our patients with isolated DVT (ie, patients with CT results positive for DVT but without CT evidence of PE) was higher in the multi– detector row
CT group (6.5% vs 3.4%; P ⫽ .038).
Therefore, the increase in incremental value of indirect CT venography with multi– detector row CT in our study may be related to the use of contiguous thcollimation (5-mm) sections for in-direct CT venography. Indeed, short segmental DVT may be overlooked when sequential scanning is used be-cause the risk increases with larger in-tersection gaps (12,27). When a helical acquisition is used, even small venous clots can be diagnosed during assess-ment of consecutive images (19). Fur-thermore, pseudo–filling defects (ie, flow-related artifacts or volume averag-ing around venous valves) are more confidently recognized with indirect he-lical CT venography (13,26). Finally, the addition of indirect CT venography still decreased, by 29%, the rate of in-conclusive results for VTE that would have been obtained with CT pulmonary angiography alone when multi– detector row CT was used, compared with 34.7% when single– detector row CT was used.
Unlike with CT pulmonary angiogra-phy, the rate of indeterminate results
for indirect CT venography was similar with both technologies. Inconclusive in-direct CT venographic findings resulted mainly from poor venous enhancement, particularly at the level of the calves in most patients (97% in both groups). This may explain our higher rate of in-conclusive findings at indirect CT venog-raphy (12.7%) compared with rates in other studies (1%–3%) that did not in-clude the calf in the acquisition range (16,19,27,28).
So far, insufficient venous enhance-ment has not been compensated by the improvement in CT technology. The use of compressive elastic stockings or isos-molar contrast material (compared with low-osmolar contrast media, which are hyperosmolar to blood) has recently been shown to significantly increase de-layed venous enhancement (29–31). Additional studies are needed to investi-gate whether such refinements can de-crease the rate of inconclusive indirect CT venographic findings. Nevertheless, final and positive results for VTE were obtained with a positive result at CT pulmonary angiography in 28% and 33% of patients with inconclusive find-ings at indirect CT venography acquired with single– and multi– detector row CT, respectively.
We found a high frequency of DVT (74%; 95% confidence interval: 68.7%, 79.1%) with indirect CT venography in patients with PE. Despite being higher than the 36% frequency (95% confi-dence interval: 22%, 52%) reported in a meta-analysis by van Rossum et al (32), our results are in agreement with those of more recent studies reporting prevalence of DVT ranging from 66% to 83% with use of ascending venography
Table 3
Inconclusive Findings at CT Pulmonary Angiography and Indirect CT Venography
Group
Inconclusive CTPA Finding Inconclusive Indirect CTV Finding No. of Patients with Inconclusive Findings at Both No. of Patients Positive CTV Finding Negative CTV Finding No. of Patients Positive CTPA Finding Negative CTPA Finding Group 1 (n⫽ 232) 95 33 (35) 62 (65) 109 30 (28) 79 (72) 28 Group 2 (n⫽ 59) 17 5 (29) 12 (71) 36 12 (33) 24 (67) 6 P value* .710 .495 .671
(33,34), US (35), or indirect CT venog-raphy (12). To avoid selection bias, we excluded patients who were known to have venous thrombosis before indirect CT venography; thus, our results con-firm that the clinical diagnosis of DVT is difficult and that all patients suspected of having VTE would require assess-ment of the lower-limb veins.
Although multi– detector row tech-nology has greatly expanded our diag-nostic capabilities in patients suspected of having VTE, the use of thin collima-tions often results in an increase in the radiation dose (21). The radiation dose delivered to the gonads and pelvis has to be cautiously considered when indirect CT venography is performed. With use of four– detector row indirect CT venog-raphy, researchers from two studies (28,36) reported median cumulative ef-fective doses of 8.3–9.3 mSv and me-dian effective gonadal doses of 3.4 – 4.4 mSv, with variations between individu-als and according to sex. Nevertheless, VTE is a disease that primarily affects an elderly population, as confirmed by a mean age greater than 60 years in our patients and in most study populations (11–14,16–19,22,28). Furthermore, as a rule, we rarely perform indirect CT venography in patients younger than 40 years unless findings from previous US of the lower limb were inconclusive. Therefore, the risk-to-benefit ratio is rather low in the context of potential morbidity and mortality related to VTE
(19,37). Dose modulation systems,
which minimize the radiation dose re-quired without compromising image quality, are being developed by all de-vice manufacturers and could reduce the radiation dose by 35%– 60% (38).
Our study had limitations. First, the retrospective analysis may lead to unin-tentional selection bias. In particular, we could not compare indirect CT venography with an independent refer-ence test. However, indirect CT venog-raphy has been demonstrated to have results similar to those of US for the diagnosis of DVT (11–16,26). Second, patients were not classified according to symptoms of DVT. Nevertheless, pa-tients who presented with symptoms of DVT as their chief complaint underwent
US before CT and therefore were ex-cluded from the study. Third, we did not specifically track the minority of pa-tients who had clinical symptoms of PE but underwent other diagnostic tests, because CT pulmonary angiography has been the diagnostic modality of choice in our institution since 1995 (further refined by the addition of indirect CT venography in 1998).
Fourth, rare cases of isolated PE lo-cated distal to the subsegmental level may have been overlooked because we have restricted the interpretation to subsegmental pulmonary arteries with use of single-section CT pulmonary an-giography. Nevertheless, authors of large studies have questioned the accu-racy of positive findings determined at single-section CT pulmonary angiogra-phy at the subsegmental level (39). This may, however, have slightly increased the incremental value of single-section indirect CT venography. Finally, we did not examine interobserver agreement, which has been reported as good to ex-cellent for CT pulmonary angiography (18,22,23) and as moderately good to excellent for indirect CT venography (15,27) in other studies.
Despite the theoretically improved accuracy of multi– detector row over single– detector row CT pulmonary an-giography, the addition of multi– detec-tor row indirect CT venography still re-sults in an increase of VTE diagnosis in 27% of patients.
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