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Thoracic Imaging |
1 From the Departments of Radiology (M.P.R., D.P., A.H., C.L, G.F.) and Pneumology (G.M.), Georges Pompidou European University Hospital, 20 rue Leblanc, 75015 Paris, France. Received November 21, 2003; revision requested January 29, 2004; revision received March 11; accepted April 12. Address correspondence to M.P.R. (e-mail: marie-pierre.revel@hop.egp.ap-hop-paris.fr).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Institutional review board approval and patient consent were not required. A total of 220 consecutive CT angiography studies, 124 (56%) of which involved inpatients, were assessed. Thoracic CT angiography was performed in 216 patients; there were 101 male (age range, 25–93 years; median, 66 years) and 115 female (age range, 15–98 years; median, 67 years) patients. Contiguous 1.25-mm sections were acquired through the entire thorax after injection of 140 mL of contrast material at a rate of 4 mL/sec. CT venography was combined with thoracic CT angiography in 178 patients over 40 years of age. CT studies were interpreted first in the emergency setting and subsequently by two experienced chest radiologists. Untreated patients with normal results were contacted by telephone after 3 months. Proportions were compared with the 
2 test, and agreement was assessed by calculating the 
statistic (for thoracic CT angiography).
RESULTS: Concordance between the two reading sessions was good ( = 0.88; 95% confidence interval: 0.77, 0.98). The proportion of nondiagnostic thoracic CT angiography studies was 9% (20 of 220). PE was found in 54 (24.5%) of 220 cases; eight (15%) of 54 patients had only subsegmental PE, which was associated with a calf vein thrombosis in two patients, and six patients (11%) had chronic PE. CT venography demonstrated venous thrombosis in 15% (26 of 178) of the patients thus studied, as well as in 45% (21 of 47) of patients with positive results at thoracic CT angiography and 4% (five of 131) of patients with negative results at thoracic CT angiography. The 3-month rate of thromboembolic events after negative results was 1.8% (two of 111) (95% confidence interval: 0.2%, 6.4%).
CONCLUSION: Multi–detector row CT enables diagnosis in 91% of cases and identification of isolated subsegmental or chronic PE in a relatively high proportion of patients.
© RSNA, 2005
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The thinner section thickness helps to avoid volume-averaging pitfalls and also offers better depiction of small subsegmental pulmonary arteries (4,5). Because the entire lung is scanned with a section thickness of 1 mm or less, the multi–detector row CT technique can also provide thin-section images of the lung parenchyma. This allows the recognition of subtle changes such as mosaic attenuation of the pulmonary parenchyma, which is suggestive of, although not specific to, chronic thromboembolic pulmonary hypertension (6).
These theoretical advantages of multi–detector row CT over single–detector row CT have been dealt with in detail in previous publications (1–5), but few precise data have been published on the effect of these technical improvements on diagnostic performance. Except for a publication by Remy-Jardin et al in 2002 (1), in which they reported the positive effect of multi–detector row CT on image quality for patients with underlying respiratory disease, to our knowledge there are no other large clinical series and no precise data on the proportion of nondiagnostic images obtained with multi–detector row CT. The frequency of isolated subsegmental pulmonary embolism (PE) and chronic PE, which should theoretically be better identified at multi–detector row CT, is not well known. It is remarkable that there were no cases of isolated subsegmental PE in the group of patients examined with multi–detector row CT in the series results published by Remy-Jardin et al (1).
Thus, the purpose of our study was to prospectively evaluate multi–detector row helical CT for the diagnosis of PE, with focus on the proportion of diagnostic studies and the frequency of subsegmental and chronic PE.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients
During a 6-month period (January through June 2001), all consecutive patients referred to undergo thoracic CT angiography for suspicion of PE were included in this prospective study. At our institution, CT angiography is the first-line examination for patients suspected of having PE, except for the following: patients in whom contrast medium injection is contraindicated, patients with previous PE and prior ventilation-perfusion scanning, and young patients free of prior cardiopulmonary disease who have a low clinical suspicion of PE and normal chest radiographs. These categories of patients are generally referred to undergo first-line ventilation-perfusion scanning, and they represent less than 15% of patients.
The 216 patients were 15–98 years of age (median, 66.5 years), and there were 101 male (age range, 25–93 years; median, 66 years) and 115 female (age range, 15–98 years; median, 67 years) patients. The difference in age between the sexes was not statistically significant (Mann-Whitney test, P = .8).
Four patients were examined twice, because they each had two episodes suspicious for PE during the study period; thus, there were a total of 220 CT examinations. One hundred twenty-four (56%) examinations concerned inpatients and 96 (44%) concerned outpatients.
Imaging
All CT examinations were performed by using a multi–detector row helical scanner (Lightspeed; GE Medical Systems, Milwaukee, Wis) with four detector arrays. Patients were scanned from the lower lobes to the apices during a single breath hold. Retrograde acquisition was chosen to minimize artifacts from high contrast material concentration in the superior vena cava. The entire thorax was included in the CT acquisitions. Patients who were unable to hold their breath were asked to breathe as shallowly as possible during the acquisition.
The following parameters were used for thoracic CT angiography: collimation, 1.25 mm (four detectors with 1.25-mm section thickness [4 x 1.25 mm]), 7.5-mm table movement per gantry rotation, 0.80 second per rotation, 80–140 mAs, and 100–140 kV according to the patient’s weight. A mechanical injector (Medrad, Pittsburgh, Pa) was used for intravenous injection of iodinated contrast material at a rate of 4 mL/sec. All patients received 140 mL of 64% iohexol (Omnipaque 300; Nycomed Ingenor, Paris, France). The start delay time was empirically determined according to age and general status, and it ranged from 18 to 25 seconds. The delay was 18 seconds for patients who were younger than 60 years and free of heart failure, and the delay was increased to 25 seconds for older patients and patients with impaired cardiac function.
Contiguous transverse 1.25-mm-thick images were routinely reconstructed at mediastinal (width, 400 HU; center, 0 HU) and lung (width, 1600 HU; center, –600 HU) window settings.
The radiologists were free to modify the window settings during their reading at the picture archiving and communication workstations. CT venography was performed following CT angiography, except in patients younger than 40 years, to avoid increasing the radiation dose. The following parameters were used: collimation of 5 mm (4 x 5 mm), 22.5-mm table movement per gantry rotation, 0.80 second per rotation, 80 mAs, and 100 kV. Images were reconstructed at 5-mm contiguous intervals. Two separate helical acquisitions were used—one for the abdomen and pelvis and the other for the legs. Acquisition through the abdomen and pelvis started 2.5 minutes after injection of contrast material, and scanning of the lower limbs (including the calves) started 3 minutes after injection.
Image Interpretation
All CT aquisitions were read twice. A resident aided by a senior radiologist (not necessarily a chest radiologist) read the images first in the emergency setting. Ten residents and 15 senior radiologists participated. The level of experience ranged between 1 and 4 years (mean, 2 years) among residents and between 5 and 15 years (mean, 8 years) among senior radiologists. The acquisitions were then read again, within 72 hours, by two chest radiologists (M.P.R., A.H.; 7 and 15 years of experience in chest CT interpretation, respectively) blinded to the initial readings; images were read first independently and then in consensus. In case of disagreement, the results of the second (consensus) reading were indicated to the referring physician to guide patient care.
Both reading sessions were performed in cine mode at a picture archiving and communication workstation (Impax 4.1; Agfa HealthCare, Mortsel, Belgium). Agreement between the two readings for thoracic CT angiography results was assessed by calculating the statistic.
The diagnostic criteria for PE and deep venous thrombosis were the same for the two readings. The diagnosis of acute PE was based on the presence of filling defects within pulmonary arteries, or global hypoattenuation of enlarged arterial sections, on at least two contiguous sections. PE was then classified as either central (up to the first division of a segmental artery) or subsegmental (beyond the first division of a segmental artery) if the two chest radiologists’ independent readings agreed on the presence and site(s) of subsegmental clots. We considered isolated subsegmental PE as PE limited to the subsegmental level, whatever the numbers of occluded subsegmental branches. All readers used the nomenclature outlined by Remy-Jardin et al (7) for the description of pulmonary arterial branches.
The diagnosis of chronic thromboembolism was based on the presence of marginal clots with contrast enhancement centrally within the affected vessel and/or occluded pulmonary arteries with caliber reduction compared with their accompanying bronchi, which is associated with enlargement of the pulmonary trunk (6) and dilation of bronchial systemic arteries with a diameter greater than 1.5 mm (8). Images obtained with lung window settings were analyzed for the presence of mosaic attenuation.
Thoracic CT angiography was considered nondiagnostic, as in the Evaluation du Scanner Spirale dans l’Embolie Pulmonaire (or ESSEP) study (9), if enhancement of pulmonary arteries was insufficient compared with that of pulmonary veins or if it was inhomogeneous; if breathing, motion artifacts, or underlying lung disease hindered examination of at least one segmental artery; or if an image did not lead to a definite conclusion, whatever its location. CT findings were considered normal when there were no signs of PE on images that were judged technically adequate. Diagnosis of proximal deep venous thrombosis was based on the total absence of enhancement of the venous lumen with enhancement of the venous wall and/or on the presence of intraluminal hypoattenuation (10,11) that persisted when the window setting was modified, while diagnosis of distal deep venous thrombosis relied only on the former sign. Proximal deep venous thrombosis, according to the generally used definition, included the popliteal level, while distal deep venous thrombosis referred to the calf veins (12).
CT venography was considered nondiagnostic if venous enhancement was less than that of neighboring arteries or if it was inhomogeneous; if artifacts due to orthopedic material prevented proper visualization of a proximal venous segment; or if there was an image that did not lead to a definite conclusion within a vein regarding flow artifact or clot, whatever its location. Results at CT venography were considered normal if no venous abnormalities were found on technically adequate CT images.
Follow-up in Patients with Negative Results
Three months after examination, untreated patients with negative results were contacted by telephone by one of the investigators (D.P.) to identify any thromboembolic events. Hospital charts were systematically consulted in addition to the telephone contacts. When potential recurrence of thromboembolism was suspected on the basis of telephone interview, the referring physician was contacted.
Statistical Analysis
The Mann-Whitney test was used to compare age between male and female patients. Proportions were compared by using 2 analysis. Agreement between the two reading sessions was assessed for thoracic CT angiography results by calculating the statistic. In accordance with the literature (13), we considered a index above 0.8 to indicate very good agreement between the two readings.
A P value less than .05 was considered to indicate a significant difference. We used statistical software (StataCorp, College Station, Tex) for all calculations.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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index of 0.88 (95% confidence interval: 0.77, 0.98). The 13 cases of disagreement were as follows: the chest radiologists’ reading was nondiagnostic in five cases, while the emergency setting reading was normal; the emergency setting reading was positive in three cases, while the chest radiologists’ reading was normal; two emergency setting readings were considered nondiagnostic, while the chest radiologists’ readings were normal in one case and positive in one case; and three emergency setting readings that were normal were considered positive at the chest radiologists’ reading (Table 1).
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The chest radiologists’ readings were used for subsequent analysis. Of the 220 thoracic CT angiography examinations, 200 were considered diagnostic; the images showed the presence or absence of clots within the pulmonary arteries. The proportion of nondiagnostic CT aquisitions was 9% (20 of 220) overall (9.7% in inpatients and 8.3% in outpatients, P = .7). Of the 20 nondiagnostic CT acquisitions, 13 were blurred due to respiratory motion artifacts, two were blurred due to a poor level of enhancement, and five were blurred due to both of these problems. Nine of the 18 CT acquisitions with respiratory artifacts showed abundant unilateral or bilateral pleural effusion.
Images from 54 thoracic CT angiography examinations revealed clots within pulmonary arteries, which equals a prevalence of PE of 24.5% (54 of 220) overall (24% [30 of 124] for inpatients and 25% [24 of 96] for outpatients; P = .89). Thirty-seven acquisitions showed multiple segmental PEs (Fig 1), three showed clots within a single segmental artery, and eight (15%) showed PE limited to the subsegmental level (Table 2) (Figs 2–4). In four patients, subsegmental PE was seen in a single pulmonary segment, while in the other four patients, there were two (in two patients) or three (in two patients) involved pulmonary segments. The distribution of the eight subsegmental PEs was similar in inpatients and outpatients (four vs four identified).
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The proportion of diagnostic acquisitions was 94% (167 of 178). CT venography studies demonstrated lower-limb deep venous thrombosis in 26 cases (of 178, 15%), of which 17 (65%) were proximal and nine (35%) were limited to the calves (Table 3). Deep venous thrombosis was detected in 46% (21 of 47) of the patients with positive results at thoracic CT angiography who underwent CT venography. Seven patients with PE did not undergo CT venography because they were younger than 40 years of age. Two of the eight patients with PE limited to the subsegmental level had positive results at CT venography, which demonstrated clots in the calf veins. The other six patients either had normal (three patients) or nondiagnostic (two patients) results at CT venography or did not undergo this examination (one patient).
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Among 135 patients with negative results at thoracic CT angiography and CT venography who did not undergo anticoagulation therapy, 3-month follow-up information was obtained for 111 patients. For 109 patients, no thromboembolic events were reported, while the other two patients reported deep venous thrombosis with ultrasonographic (US) confirmation. Thus, the rate of venous thromboembolic events in patients with negative results at CT examinations who were followed up was 1.8% (two of 111; 95% confidence interval: 0.2, 6.4). Fourteen patients died, of causes other than thromboembolic disease, during the 3-month follow-up period. The last 10 patients could not be contacted by phone and were lost to follow-up.
All eight patients with subsegmental PE were followed up. Of these eight patients, five underwent anticoagulation therapy: In two patients, deep venous thrombosis was seen at CT venography; in one patient, blood test results disclosed a clotting disorder; and in two patients, therapy was performed for reasons other than thromboembolic disease (heart failure with arrhythmia). The other three patients were not treated because they had a low clinical probability of PE and low-probability lung scan results. They all remained well after 3 months of follow-up.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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More recently, multi–detector row helical CT has been introduced into clinical practice; this technique allows acquisition of contiguous sections with a section thickness of 1 mm or less throughout the thorax, with a reduced acquisition time (15). The reduced acquisition time yields optimal contrast enhancement on all acquired sections, and the narrow collimation increases spatial resolution and reduces partial volume averaging. Thus, multi–detector row helical CT should reduce the proportion of inconclusive results at thoracic CT angiography. However, the proportion of indeterminate results in our study was not lower than that reported with single–detector row CT. Indeed, 9% of studies in our series were nondiagnostic, while the reported percentage of indeterminate CT studies is usually between 2% and 10% (16,17). It is noteworthy that only two CT studies in our series were nondiagnostic because of poor vascular opacification alone; the remaining eighteen nondiagnostic studies were caused by respiratory motion artifacts, which were associated with abundant pleural effusion in eight patients. Clearly, despite the shorter acquisition time, multi–detector row CT cannot provide high-quality images in highly dyspneic patients with large respiratory movements. The agreement between the initial and subsequent (chest radiologists’) readings was good in our study, as it was in studies based on single–detector row helical CT (18). Half of the discrepancies (six of 13 cases) between the two readings concerned normal versus nondiagnostic studies, which underlines the fact that the limit between a diagnostic and a nondiagnostic study is sometimes difficult to define. The chest radiologists, who were likely to have been more demanding, disqualified five studies that were judged as normal at the initial reading.
The 24.5% prevalence of PE in our series is at the lower end of the usually reported values (generally around 35% in nonbiased series) (9,19–21). This may reflect the fact that CT angiography, a minimally invasive procedure, is now more widely used to investigate clinically suspected PE. The clinical probability of PE was not evaluated in our study, in which all consecutive patients suspected of having PE were referred for CT angiography. Thus, we were unable to determine the proportion of our patients with a low clinical probability of PE, in whom the prevalence of PE is known to be low (22).
We observed a higher proportion of PE limited to the subsegmental level than is usually reported. For example, the proportion of patients with isolated subsegmental PE was only 3% in the Musset et al series (9) based on single–detector row helical CT; 2% in the Remy-Jardin et al study (1), of 125 patients explored with single–detector row CT; and 0% in the same study by Remy-Jardin et al, of 134 patients studied with multi–detector row CT.
Stein and Henry (23) reported a 6% prevalence of PE limited to the subsegmental level in the Prospective Investigation of Pulmonary Embolism Diagnosis, which was based on results at angiography, while the estimated proportion of PE limited to subsegmental or smaller arteries was 30% in the Oser et al angiography series (24). Thus, it is difficult to estimate the precise frequency of isolated distal PE, because the reported frequency differs widely from one study to another and probably depends on the study population. Because of the poor interobserver agreement (25), pulmonary angiography is no longer considered the standard for diagnosis of subsegmental PE. Moreover, it has been experimentally demonstrated that angiography is not superior to CT angiography for the diagnosis of distal PE (26).
Two of our eight patients with isolated subsegmental PE also had deep venous thrombosis, thus confirming the presence of thromboembolic disease. The remaining six patients had no other test results to confirm the CT findings, so it is not possible to assert that the CT findings were true-positive; however, it is noteworthy that the two chest CT radiologists were required to agree on the diagnosis and on the number and sites of involved subsegmental arteries.
In regard to the question of whether subsegmental PE necessitates anticoagulation therapy, the number of untreated patients in our study is too small to draw a conclusion, but it must be underlined that all three untreated patients remained well after 3 months of follow-up.
If the high frequency of isolated subsegmental PE is confirmed in future studies, the lack of consensus regarding the need for treatment will become more acute (27). Remy-Jardin et al (3) suggested that CT venography combined with thoracic CT angiography can help with therapeutic decision making by demonstrating or ruling out the presence of thrombotic material that could re-embolize into the lungs.
We found no difference between inpatients and outpatients regarding the proportion of diagnostic versus nondiagnostic studies or the prevalence of proximal and distal PE. This is an important result, as most published study results concerning PE predominantly or exclusively concerned outpatients (9,19).
The third major result of our study is the relatively high frequency of chronic PE. Chronic thromboembolism is usually considered to be infrequent (6,28). However, six patients examined during this 6-month study period were found to have subclinical chronic thromboembolic pulmonary hypertension. The frequency of chronic thromboembolic pulmonary hypertension in patients suspected of having acute PE has not previously been examined, but our data suggest that this entity may have been underdiagnosed prior to the advent of multi–detector row CT, as the symptoms are nonspecific and pulmonary angiography is rarely performed. Multi–detector row CT is likely to facilitate this diagnosis by providing thin-section images of the lung parenchyma that can reveal both mosaic attenuation of the lung parenchyma (28) and small segmental and subsegmental vessels compared with their accompanying bronchi. Strong contrast enhancement, combined with the reduced section thickness, is also likely to improve the detection of bronchial and nonbronchial systemic hypervascularization.
Our last major result concerns the effect of combining CT venography with thoracic CT angiography, which was systematically performed except in those patients who were younger than 40 years of age (to avoid increasing their radiation dose) (29). We found a global deep venous thrombosis prevalence rate of 15%, a rate similar to that of positive CT venography results reported in other studies (30). This percentage is also similar to that of deep venous thrombosis found globally in US imaging studies in patients suspected of having PE (29). In our subgroup of patients with PE, CT venography demonstrated deep venous thrombosis more frequently than in the global population, as 49% of patients with PE were found to have lower-limb thrombosis. This value is also similar to the percentage of positive US findings in patients with confirmed PE (31). We did not compare our CT venography findings with those of US studies, as this was outside the scope of our study. It has been shown that the results at multi–detector row CT, like those at single–detector row CT, correlate well with Doppler US findings (29).
Our study had several limitations. First, the clinical probability of PE was not assessed at baseline; it was only determined secondarily in patients with negative CT results to assess the need for additional diagnostic testing. This could have lowered the prevalence of PE in our series. The follow-up interview at 3 months did not include all patients with negative CT results who were untreated, because 10 of the 135 patients concerned were lost to follow-up. Thus, the rate of venous thromboembolic events at 3 months could have been underestimated, and our data do not, therefore, show the sensitivity of multi–detector row CT for the detection of PE. However, this was not an objective of our study.
Another limitation was that no other tests were used to confirm our results. Pulmonary angiography is no longer routinely performed, since it is invasive and unreliable for the diagnosis of distal PE because of poor interobserver agreement (25). Thus, our data, except for those concerning patients with chronic PE, which received further confirmation, were based mainly on agreement between independent readings by two experienced chest radiologists. However, the lack of comparison with a reference standard is common in studies dealing with the use of spiral CT for diagnosis of PE, since CT is increasingly accepted as the best modality for this diagnosis. The fact that the proportion of positive CT venography results agreed well with data from US studies, both in the overall study population and in patients with confirmed PE, tends to validate our data.
The last limitation was that four–detector row CT scanners are no longer the most advanced CT technology, as 16– and 64–detector row devices are now available and provide submillimeter sections of the entire thorax in less than 10 seconds. Use of a 16–detector row scanner could modify the proportion of conclusive results at multi–detector row CT, but this is likely to depend most on the characteristics of the study population and especially on the proportion of highly dyspneic patients.
In conclusion, multi–detector row CT was diagnostic in 91% of cases in this series, which was composed of 56% inpatients. The overall 24.5% prevalence of PE was lower than that in previous series, which probably reflects a broadening of the indications of this minimally invasive technique. The relatively high proportion of PE limited to the subsegmental level in our series may be explained in the same way, but this must be confirmed with additional prospective studies. The adjunctive use of CT venography was helpful in this situation; it demonstrated deep venous thrombosis in two of the eight patients who had PE limited to the subsegmental level. Whether such patients should be treated in the absence of deep venous thrombosis remains to be determined, but this question will become more acute if the high frequency of isolated subsegmental PE is confirmed. Last, chronic thromboembolic pulmonary hypertension was identified in six cases in which it was unsuspected, which suggests that this entity is far from rare and may be underdiagnosed.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, M.P.R., D.P.; study concepts, M.P.R.; study design, M.P.R., G.F., G.M.; literature research, M.P.R., D.P.; clinical studies, M.P.R., D.P., A.H.; data acquisition, M.P.R., D.P., A.H.; data analysis/interpretation, M.P.R., D.P.; statistical analysis, M.P.R., C.L.; manuscript preparation and editing, M.P.R., C.L.; manuscript definition of intellectual content, revision/review, and final version approval, all authors
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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