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Thoracic Imaging |
1 From the Departments of Clinical Radiology (U.J.S., R.B., H.K., C.R.B., J.W., P.H., A.H., M.F.R.) and Internal Medicine I-Cardiology (A.K., O.M., R.H.), Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Germany. Received October 14, 1999; revision requested November 18; final revision received February 23, 2000; accepted February 28. Address correspondence to U.J.S. (e-mail: schoepf@ikra.med.uni-muenchen.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Twenty-two patients suspected of having acute pulmonary embolism underwent contrast material–enhanced thin-section electron-beam CT angiography of the pulmonary arteries. In addition, in each patient, a dynamic multisection blood flow CT study was performed on a 7.6-cm lung volume with electrocardiographic gating. Pulmonary blood flow was calculated, and perfusion parameters were visualized on color-coded maps. The color-coded maps and CT angiograms were independently evaluated, segment by segment, by two readers for perfusion deficits and the presence of clots, respectively. The results were compared.
RESULTS: Mean pulmonary blood flow was 0.63 mL/min/mL in the occluded segments versus 2.27 mL/min/mL in the nonoccluded segments (P = .001). The sensitivity and specificity of perfusion maps for the presence of segmental pulmonary embolism compared with those of CT angiography were 75.4% and 82.3%, respectively, with positive and negative predictive values of 79.6% and 84.7%, respectively. The false-negative findings were caused mainly by partial occlusion of vessels. In eight patients, a substantial alternative or additional pathologic entity was diagnosed.
CONCLUSION: By combining CT angiography and dynamic CT imaging, a comprehensive and noninvasive diagnosis of thoracic structure and function is feasible with a single modality.
Index terms: Computed tomography (CT), angiography, 60.12116 • Computed tomography (CT), electron beam, 60.12112, 60.12113, 60.12116, 60.12118 • Computed tomography (CT), perfusion study, 60.12112, 60.12113, 60.12116, 60.12118 • Embolism, pulmonary, 60.72 • Lung, CT, 60.12112, 60.12113, 60.12116, 60.12118 • Lung, perfusion
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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At many institutions, ventilation-perfusion scanning remains the method of first choice for the detection of suspected pulmonary embolism. Although planar scintigraphy is a very sensitive but fairly nonspecific examination for the detection of pulmonary embolism (10), scintigraphic methods enable a reliable functional evaluation of lung perfusion.
A valuable feature of electron-beam CT is that it can be used both for volume scanning to depict structure (1) and for functional analyses by acquiring high-temporal-resolution data sets simultaneously on multiple sections of an organ. Thus, both function and anatomy can be imaged with the same modality. Electron-beam CT has been used successfully for perfusion measurements in the heart (11–13), brain (14), and kidneys (15). The feasibility of pulmonary blood flow (PBF) measurements with electron-beam CT has been validated in a number of controlled animal studies (16,17). However, to our knowledge, the value of this method in the diagnostic work-up of patients suspected of having pulmonary embolism has never been assessed. Therefore, the purpose of this prospective study was to use electron-beam CT as the single modality to image both thoracic structure and function in patients suspected of having acute pulmonary embolism.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Twenty-two consecutive patients (12 women, 10 men; mean age, 58 years; age range, 29–72 years) referred for suspected acute pulmonary embolism were included. Inclusion criteria were high suspicion of pulmonary embolism and a stable cardiac and respiratory status. High suspicion of pulmonary embolism was based on the results of physical examination, electrocardiography, echocardiography, venous ultrasonography, or chest radiography or on elevated dimerized plasmin fragment D levels. Exclusion criteria were age younger than 18 years, pregnancy, renal insufficiency (serum creatinine level >1.5 mg/dL [132.6 µmol/L]), history of anaphylactic reactions to contrast material, heart rate greater than 115 beats per minute, systolic blood pressure lower than 90 mm Hg, or partial arterial pressure of oxygen less than 80 mm Hg breathing room air. Two patients were examined twice—at initial referral and after anticoagulation therapy (Figs 1, 2).
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Functional Scanning
The technical design of the electron-beam CT scanner is described in detail elsewhere (18,19). We used the multisection mode of the scanner to acquire eight sections in a 7.6-cm volume at 20 consecutive time points without patient table movement to monitor the passage of the contrast material bolus through the lung parenchyma. Routinely, the scanning level was adjusted to ensure coverage of the main pulmonary arteries and the central subsegments of most of the upper-, middle-, and lower-lobe lung segments. To improve the quality of the data, the scanning was electrocardiographically triggered to the quiet diastolic phase of the heart at 80% of the cardiac cycle. For the first 16 scans, scanning was performed at every heartbeat to image the ascending slope and the peak of the contrast curve with high temporal resolution, and for the remaining four scans, scanning was performed at every second heartbeat to enable prolonged sampling of the tail of the curve.
After the first scan of the series had been acquired, contrast material was injected at a flow rate of 10 mL/sec for 4 seconds. Again, scanning was performed during a single breath hold. The total room time for performing both volume and dynamic CT scanning averaged 15 minutes.
Morphologic Image Analysis
The images obtained with volume scanning were evaluated in an individual window setting that was adjusted to the degree of contrast enhancement according to recommendations outlined in the study by Brink et al (20). For this initial feasibility study, consensus reading by two observers (R.B., U.J.S.) was used to perform the following analyses: First, the volume scans that had been acquired in our study population of 22 patients were evaluated for the overall presence of pulmonary embolism. For the purpose of the study, a diagnosis of pulmonary embolism was made when at least one embolus was clearly visualized in a segmental or larger vessel at volume scanning. Alternative or concomitant disease, when present, was noted.
In four of the 22 patients, extensive pleural effusions (n = 2), parenchymal consolidation (n = 1), or a mediastinal mass (n = 1) (Fig 3a) were present and hampered the analysis of the pulmonary vessels on a segmental level. After exclusion of these patients, a population of 18 patients in whom a detailed analysis of the segmental pulmonary arteries could be performed was left. For this analysis, each of the 360 segmental arteries was classified as open, containing thrombus, or indeterminate. In the two patients who underwent scanning twice, the pretreatment images were used for this part of the analysis. For nomenclature of segmental arteries, a description as outlined in the study by Remy-Jardin et al (21) was used.
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With guidance from PBF maps, a quantitative analysis for the assessment of regional PBF (16) was performed. To this end, time-attenuation curves were generated by one of two authors (U.J.S., H.K.), who manually traced on the dynamic functional scans regions of interest over the lung segments that showed flow deficits (Fig 1c). The size and shape of the regions of interest were adjusted to include the entire lung segment of interest. To test the feasibility of quantitatively assessing regional PBF in occluded versus nonoccluded vessels with functional electron-beam CT, 29 pairs of segments in 12 patients were chosen. These segments were occluded in one lung and not occluded in the contralateral lung, as demonstrated at both volume and functional electron-beam CT. In two patients, there were no occluded segments with corresponding patent segments on the contralateral side. Thus, region of interest–based estimations of regional PBF were available for 58 segments. Corresponding contralateral segments were chosen as intraindividual controls to avoid bias from gravity-related regional differences in PBF between ventral and dorsal or between cranial and caudal portions of the lung.
For assessment of the variance of PBF in a normal population, additional measurements were performed in four patients who showed no evidence of pulmonary embolism or structural lung changes. In these patients, PBF values were determined in eight representative segments: right lung, segment 2 and left lung, segment 2 (cranial, ventral); right lung, segment 3 and left lung, segment 3 (cranial, dorsal); right lung, segment 8 and left lung, segment 8 (caudal, ventral); and right lung, segment 10 and left lung, segment 10 (caudal, dorsal). For each study, another region of interest was placed over the main pulmonary artery or the right ventricle. Regional PBF in each segment was then assessed according to the indicator dilution theory (22,23) by using the following basic flow equation (11,16): PBF/V = 
pul/
CRCdt, where PBF/V is the PBF per unit volume of lung tissue; pul, the peak attenuation change during contrast material injection; and CRCdt, the area under a 
variate fit of a time-attenuation curve of the right side of the circulation.
Differences in PBF between corresponding occluded and nonoccluded segments were tested for statistical significance by using the Wilcoxon matched-pair signed rank test. The Mann-Whitney-Wilcoxon two-sample statistic was used to compare the mean PBF in the occluded versus nonoccluded vascular territories. Because of the small sample size, PBF parameters in the four healthy patients were not analyzed statistically.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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When PBF parameters in the occluded versus nonoccluded segments were compared, the mean PBF (± SD) was significantly lower (Mann-Whitney-Wilcoxon two-sample statistic, P = .001) in the occluded segments, 0.63 mL/min/mL ± 0.37, versus in the nonoccluded vascular zones, 2.27 mL/min/mL ± 0.74. Highly significant differences were also found when the PBF values in the corresponding occluded and nonoccluded segments were compared separately (Wilcoxon matched-pair signed rank test, P = .002). In the four patients without pulmonary embolism, the total mean PBF in all segments was 2.31 mL/min/mL ± 0.48. In these patients, PBF was higher in the caudal segments (2.42 mL/min/mL) than in the cranial segments (2.19 mL/min/mL) and higher in the dorsal segments (2.44 mL/min/mL) than in the ventral segments (2.18 mL/min/mL). There was no substantial difference between the left (2.311 mL/min/mL) and right (2.305 mL/min/mL) lung segments.
Three hundred sixty segmental arteries on 18 volume scans were individually evaluated. Thirteen (4%) vessels were coded as indeterminate; 133 (37%) vessels, as containing thrombus; and 214 (59%) vessels, as open. On the corresponding functional scans, 295 segments (82%) could be evaluated, because 65 (18%) segments in the peripheral upper or lower lobes of the lung were not covered at dynamic CT scanning. Of these 295 segments, 17 (6%) were interpreted as indeterminate; 108 (37%), as showing perfusion deficits on a segmental level; and 170 (58%), as open.
The functional scans were then compared with the volume scans, which were the standards of reference, in 270 segments. Twenty-five (8%) of the 295 segments could not be compared because of indeterminate findings on the volume or functional scans or on both. Of the remaining segments, 86 (32%) with flow deficits at functional scanning showed pulmonary embolism at volume scanning and were considered to be true-positive findings. In 144 (53%) segmental vascular zones, no flow voids were found on functional scans and no signs of pulmonary embolism were found on volume scans; these were considered to be true-negative findings. Thus, there was good correlation between volume and functional scanning, with agreement in 85% (230 of 270) of segments.
In 19 (7%) segments, flow deficits at functional scanning could not be substantiated at volume scanning; thus, these were considered to be false-positive findings. Twenty-one (8%) segments that were classified as open on the functional scans showed pulmonary embolism on the volume scans. However, at retrospective review, 11 of these 21 segments were only partially occluded and had signs of reperfusion at volume scanning (Fig 4). After exclusion of the 65 (18%) segments that were not covered at dynamic scanning, the overall sensitivity of functional scanning for the presence of segmental pulmonary embolism was 75.4%, and the specificity was 82.3%. The positive and negative predictive values were 79.6% and 84.7%, respectively. There was no obvious pattern in the distribution of segments with false-negative or false-positive findings (eg, nondependent versus dependent lung sections).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Several imaging modalities are available to address these questions. Although pulmonary angiography is considered to be the reference standard for the detection of emboli, it is used infrequently because it is invasive and not free of complications (24). In addition, its ability to depict isolated peripheral emboli does not seem to exceed the accuracy of CT (8,9). Scintigraphy enables a reliable functional assessment of lung ventilation and perfusion, but it lacks spatial resolution (10). Thus, potentially life-threatening alternative causes of the patient’s clinical signs and symptoms are easily missed.
Magnetic resonance (MR) imaging may be a promising tool for the diagnosis of pulmonary embolism (25) and enables functional analyses (26), but to date it has not had widespread use in emergency medicine, mainly because of its long examination times and the difficulties in patient monitoring. CT provides high spatial resolution and enables objective noninvasive visualization of thoracic anatomy. Sources of chest pain other than pulmonary embolism can be identified. The location of emboli and the extent of disease can be assessed to determine the need for and feasibility of anticoagulation therapy, thrombolysis, or more invasive measures. In addition, CT appears to be the most cost-effective tool in the diagnostic algorithm of pulmonary embolism (27).
To our knowledge, however, to date, CT has not permitted the functional evaluation of pulmonary microcirculation during pulmonary embolism. The functional scanning method presented here may represent a valuable adjunct to CT pulmonary angiography by enabling both structural and functional information to be obtained with the same modality. The well-established accuracy of CT in the depiction of emboli and thoracic anatomy is thus supplemented by an effective means of quantitatively assessing the functional effect of thromboembolism on lung perfusion. This way, a comprehensive diagnosis is feasible within a few minutes without having to subject the patient to multiple expensive and time-consuming tests that necessitate transportation and advanced logistics.
In our study, the PBF in the dorsal and caudal lung segments appeared to be slightly higher than that in the ventral and cranial segments; this is consistent with the results of earlier experimental studies (11,16) that demonstrated the influence of gravity on lung perfusion. In occluded segments, the mean PBF was significantly reduced, 0.63 mL/min/mL, versus 2.27 mL/min/mL in nonoccluded vascular zones. Functional analysis of PBF therefore enables one to differentiate segments with normal capillary perfusion from those with reduced capillary perfusion and to estimate the percentage of lung parenchyma with impaired microcirculation. Thus, a decision as to whether thrombolysis is warranted is facilitated. During the course of treatment, the effect of therapy may be monitored by comparing the pre- and posttherapy PBF values by means of repeat scanning (Figs 1, 2).
Up to two-thirds of patients who are initially suspected of having pulmonary embolism receive other diagnoses, including unknown malignancies or life-threatening conditions such as aortic rupture or dissection (28). By initially performing a contrast-enhanced thin-section CT volume study, the presence of pulmonary embolism can be verified and other or additional underlying diseases can be readily recognized. The case of the patient with previously unknown small-cell lung cancer in our study (Fig 3) illustrates the importance of a thorough analysis of thoracic structure. Further studies are needed to investigate the influence of structural lung changes, such as emphysema, on perfusion. However, when input from both structural and functional scanning is used to make a comprehensive diagnosis, altered perfusion parameters based on structural lung changes can be recognized as such and therefore should not impair the utility of perfusion electron-beam CT.
There are a number of limitations to this technique: To obtain good-quality images, the patient needs to be able to cooperate to some degree. At our institution, critically ill patients who are in unstable cardiac or respiratory condition usually do not undergo diagnostic imaging, and such patients were excluded from this study. Therefore, patient cooperation did not pose an obstacle.
A major limitation is that the 7.6-cm scanning volume in the dynamic study does not cover the entire chest. However, this range is still within the recommended z-axis coverage in electron-beam CT (3,4) or spiral CT (21) scanning for suspected pulmonary embolism.
The speed of the electron-beam CT scanner enables imaging of the thoracic vessels during optimal contrast opacification (6,29). Therefore, excellent enhancement can be achieved with 100 mL of contrast material. With the inclusion of an additional 40 mL in one dynamic study in the current series, the total of 140 mL of contrast material was well within the range of the amount of contrast material that is usually administered during spiral CT for suspected pulmonary embolism.
The additional radiation dose used in the dynamic study was measured in a pilot study (data not shown) and amounts to an effective dose equivalent of 7.2 mSv. This equals the radiation exposure usually applied during scintigraphy (30).
The high accuracy of CT in the detection of emboli in segmental arteries is well established (2,5,6,8,31,32), and the sensitivity and specificity exceed 90% in most studies, especially when thin collimation is used (21), as in our study. The accuracy of CT in the detection of emboli in subsegmental or smaller vessels, however, is currently under investigation. In our patient cohort, we did not have the opportunity to compare our findings with those of other imaging modalities. Therefore, we had to restrict our evaluation to segmental or larger vessels. Thus, for the purpose of this study, emboli in subsegmental or smaller vessels were not considered to be proof of the presence of pulmonary embolism, although suspicion of isolated peripheral emboli, if any, was included in the written report. In times, however, when pulmonary angiography, the reference standard for the detection of emboli, is increasingly being replaced by noninvasive modalities (8,9, 24,33), electron-beam CT angiography should provide reasonable correlation— at least on a segmental level.
According to the results of previous studies (8,9), the depiction of small peripheral emboli at pulmonary angiography appears to be limited. In light of these results, an assessment of intra- and interobserver variability in the detection of segmental and subsegmental perfusion defects on CT perfusion maps, which was not performed in this initial feasibility study, will be of special interest.
Although there was good correlation (34) between volume and functional scan findings, with agreement on the detection of segmental emboli in 85% of cases, a perceived limitation of this technique arises from the partial occlusion of vessels with maintained blood flow on a capillary level despite the presence of thrombi. Such findings were classified as false-negative results in our study (Fig 4). However, valuable information can be gained by assessing the actual effect of small emboli on lung microcirculation. Completely or partially maintained perfusion despite the presence of emboli at functional scanning may influence the decision of whether to start thrombolytic therapy in a patient, which carries a small but definite risk (35,36). Thus, the quantitative assessment of the effect of pulmonary embolism on tissue perfusion may provide information that is more important for patient treatment than the direct visualization of emboli at CT angiography alone.
Nonoccluding emboli are also a well-known problem in lung scintigraphy, in which even extensive central emboli frequently go undiagnosed when they are only partially occluding and do not cause localized perfusion defects. Similar pitfalls can be avoided by the combined use of CT angiography and CT perfusion measurement for a comprehensive diagnosis.
Our model for the assessment of PBF in patients suspected of having pulmonary embolism has been previously described (11,16,22). However, numerous different models have been developed in the past, with the aim of determining different blood flow parameters at noninvasive imaging. Our method enabled a quantitative estimate of PBF in occluded versus nonoccluded lung segments and was sensitive enough to monitor the effect of therapy (Figs 1, 2). Further studies are warranted to compare the accuracies of different models in determining actual tissue perfusion.
We conclude that electron-beam CT enables a comprehensive diagnosis of pulmonary embolism by combining CT angiography with PBF evaluation on a microvascular level. Thus, thoracic structure and function can be assessed noninvasively with use of a single modality.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, U.J.S., R.H., M.F.R.; study concepts and design, U.J.S., R.B., M.F.R.; definition of intellectual content, U.J.S., R.B., H.K.; literature research, U.J.S., H.K., O.M.; clinical studies, U.J.S., C.R.B., A.K., O.M., R.H.; data acquisition, U.J.S., C.R.B.; data analysis, U.J.S., H.K., J.W., P.H.; statistical analysis, U.J.S., A.H.; manuscript preparation, U.J.S., R.B.; manuscript editing, U.J.S., R.B., C.R.B.; manuscript review, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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) has been placed in the main pulmonary artery to measure the arterial input for estimation of PBF. Data from the time-attenuation curve were fit by using a 
