Journal of Thoracic Imaging:
Diagnosing Pulmonary Embolism: New Computed Tomography Applications
Nikolaou, Konstantin MD; Thieme, Sven MD; Sommer, Wieland MD; Johnson, Thorsten MD; Reiser, Maximilian F. MD
Department of Clinical Radiology, University Hospitals Munich, Grosshadern Campus, Ludwig-Maximilians-University of Munich, Germany
Reprints: Konstantin Nikolaou, MD, Department of Clinical Radiology, Grosshadern Campus, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377 Munich, Germany (e-mail: email@example.com).
Computed tomographic pulmonary angiography has become the standard of care for the evaluation of patients with suspected pulmonary embolism (PE). In addition to the direct depiction or exclusion of a pulmonary embolus in suspected PE, a number of predictive markers have been established to evaluate the patient's prognosis in acute and in chronic PE. An accurate risk stratification based on CT findings is crucial because optimal management, monitoring, and therapeutic strategies depend on the prognosis. With the recent introduction of the so-called “dual-source” CT scanners, that is, a scanner consisting of 2 tubes and 2 detectors mounted orthogonally to each other, different tube voltages can be used simultaneously, resulting in different energies of the emitted x-ray spectra (dual-energy CT; DECT). Initial results have shown that DECT is capable of iodine mapping of the pulmonary parenchyma, reliably depicting the segmental defects in iodine distribution in locations corresponding to embolic vessel occlusions. This study deals with a number of actual topics on PE imaging with multidetector CT and DECT, including the discussion of the relevant imaging findings to assess the patient's prognosis, the potential and additional benefit of dual-energy information on the parenchymal iodine distribution, the optimization of scan protocols including low-radiation dose chest pain protocols, and the discussion on future perspectives of CT in PE patients, such as the role of computer-aided diagnostic tools or the potential of ventilation imaging with DECT.
Computed tomographic pulmonary angiography (CTPA) has become the standard of care for the evaluation of patients with suspected pulmonary embolism (PE) in most institutions. Acute PE is the third most common acute cardiovascular disease after myocardial infarction and stroke, and results in many deaths each year.1 Typically, the initial diagnostic tests include the D-Dimer essay, with an inherent good sensitivity, but rather poor specificity.2 Ventilation-perfusion scintigraphy (V/Q scan) had represented the standard imaging procedure before the introduction of contrast-enhanced (multi-) spiral CT. However, because of the lower diagnostic accuracy of V/Q scans, with only moderate specificity,3 reduced availability and longer acquisition times needed, CT has become the modality of choice in suspected PE.4 Despite this recent encouraging use of CTPA in PE patients, early meta-analyses on single-slice spiral CTPA have detected strongly varying diagnostic accuracies, with sensitivities ranging from 53% to 100%, and specificities between 83% and 100%.5 With the introduction of the multidetector-row CT (MDCT), diagnostic accuracy has improved consistently over the recent years.6–8 The PIOPED II trial used 4-detector, 8-detector, and 16-detector-row CT scanners in a multicenter setting and reached a combined sensitivity and specificity of CTPA and CT venography of 90% and 95%, respectively,9 establishing the important role of MDCT angiography as the main diagnostic test in PE.
Obviously, the diagnostic features as assessed by CTPA can be helpful in acute PE, and in patients suffering from chronic pulmonary hypertension, potentially leading to pulmonary arterial hypertension in the latter course of the disease, referred to as chronic thrombembolic pulmonary hypertension. Acute PE may manifest as complete arterial occlusion, with the affected artery often being enlarged, or as partial filling defects that are often centrally located. Chronic PE can manifest as complete occlusive disease in vessels that are smaller than adjacent patent vessels. Other CT pulmonary angiographic findings in chronic PE include evidence of recanalization, webs or flaps, and partial filling defects.
In addition to the direct depiction or exclusion of a pulmonary embolus in suspected PE, a number of predictive markers have been established to evaluate the patient's prognosis in acute and chronic PE. Accurate risk stratification based on the CT findings is crucial because optimal management, monitoring, and therapeutic strategies depend on the prognosis.10 Most important, acute right-sided heart failure is known to be responsible for circulatory collapse and death in patients with severe PE. That is why a number of studies have elaborated on the detailed assessment of the right heart in acute and chronic PE settings, including morphologic right heart dimensions and functional parameters implementing electrocardiogram (ECG)-gated CT studies in PE patients.11,12
In 2006, the first MDCT scanner capable of dual-energy CT (DECT) imaging was introduced. This scanner type is the so-called “dual-source” CT scanner; that is, it consists of 2 tubes and 2 detectors mounted orthogonally to each other. With this type of CT scanner, different tube voltages can be used simultaneously, resulting in different energies of the emitted x-ray spectra.13 Initial results have shown that DECT is capable of iodine mapping of the pulmonary parenchyma, reliably depicting segmental defects in iodine distribution in locations corresponding to embolic vessel occlusions.14,15
The following study will deal with a number of actual topics on PE imaging with MDCT and DECT, including the discussion of relevant imaging findings to assess the patient's prognosis, the potential and additional benefit of dual-energy information on the parenchymal iodine distribution, the optimization of scan protocols including low-radiation dose chest pain protocols, and the discussion on future perspectives of CT in PE patients, such as the role of computer-aided diagnostic (CAD) tools or the potential of ventilation imaging with DECT.
PROGNOSTIC VALUE OF CT IN PE PATIENTS
Risk stratification is important in patients with PE because optimal management, monitoring, and therapeutic strategies depend on the prognosis. Acute right-sided heart failure is known to be responsible for circulatory collapse and death in patients with severe PE. If untreated, PE is fatal in up to 30% of patients, but the death rate can be reduced to 2% to 10% if PE is diagnosed and treated promptly.16 When PE is fatal, patients usually die after right ventricular (RV) failure and circulatory collapse, which frequently occur within the first hours after admission. This suggests that RV dysfunction (RVD) should be diagnosed rapidly to identify patients who could benefit from fibrinolytic therapy.17
Acute right-sided heart failure can be assessed at CTPA by measuring the dimensions of right-sided heart cavities or upstream venous structures, such as the superior vena cava or azygos vein. The magnitude and severity of PE can be calculated by applying clot load scores in the pulmonary arteries (Miller and Walsh scores18,19) or by applying adapted or dedicated CT angiographic scores (Qanadli, Bankier, and Mastora scores20–22). The advent of modern MDCT scanners allows for CTPA to be performed with electrocardiographic gating, permitting new advances in the assessment of acute right-sided heart failure, such as measurement of the left ventricular (LV) and RV ejection fraction.
The typical CT-based cardiovascular parameter measurements that can be derived from a standard, nondual-energy, non-ECG-triggered CTPA data set include RV and LV short-axis measurements; RV short-axis to LV short-axis (RV/LV) ratios; main pulmonary artery (PA), ascending aorta, azygos vein, and superior vena cava diameters; and main PA diameter to aorta diameter ratios. Reflux of contrast medium into the inferior vena cava, leftward bowing of the interventricular septum, pleural or pericardial effusion, pulmonary consolidation, infarct, plate-like atelectasis, and mosaic ground-glass opacity can also be recorded. Ghaye et al23 have retrospectively evaluated PA clot load scores and the above-mentioned CT parameters in 82 consecutive PE patients. RV and LV short axis; RV/LV ratio; azygos vein, superior vena cava, and aorta diameters; and contrast medium reflux into the inferior vena cava were significantly different between survivors and nonsurvivors after an acute PE event. No significant relationship was found between PA clot load and mortality rate. RV/LV ratio and azygos vein diameter allowed correct prediction of survival in 89% of patients. Quiroz et al24 described the additional benefit of dedicated 4-chamber view reconstructions in PE patients. Their study on 63 PE patients concluded that RV enlargement on the reconstructed CT 4-chamber views predicts adverse clinical events in patients with acute PE and that these data are superior to those from axial views for identifying high-risk patients. Kamel et al25 compared the indices of RVD obtained from axial transverse images with those derived from the reconstructed 4-chamber and short-axis views in patients with acute PE. In the study cohort, RV/LV diameters and RV/LV areas obtained from axial transverse images and the reconstructed 4-chamber views were not statistically different. The investigators concluded that in patients with acute PE, the indices of RVD derived from axial transverse images and the reconstructed 4-chamber views yield comparative values. Given the simplicity of the axial analysis, without the need of time-consuming post-processing for reconstruction of short-axis 4-chamber views and area measurements, the axial diameter measurements and RV/LV ratios as derived from the source data could serve as a routine screening tool for risk stratification in acute PE.
In conclusion, risk stratification of patients with PE is important because optimal management, monitoring, and therapeutic strategies depend on prognosis. The above-mentioned studies have shown that CTPA not only allows the diagnosis of PE by directly depicting the clots, but also enables an assessment of PE severity. Cardiovascular CT findings, such as the RV/LV diameter ratio, have shown a significant correlation with fatal outcome, whereas quantification of PA clot load remains controversial.26,27 Many CT findings that may allow refinement of the risk stratification are still under evaluation. Although more complex morphologic and functional findings may be useful for the assessment of treatment effectiveness, their effect on prognosis in patients with severe PE is today still being debated in the literature.
DECT OF LUNG PERFUSION
CT Pulmonary Perfusion Imaging: Background
In the diagnostic workup of PE or pulmonary arterial hypertension, the assessment of regional lung perfusion is an important part of diagnostic imaging. The established imaging methods of pulmonary perfusion are nuclear medicine modalities, that is, planar lung perfusion scintigraphy or single photon-emission computed tomography (SPECT). In addition, magnetic resonance imaging (MRI) of lung perfusion has emerged as an alternative tool. When compared with nuclear medicine imaging methods, lung perfusion MRI offers the advantage of a time-resolved quantification of regional lung perfusion, allowing for the calculation of semiquantitative (time-to-peak) and absolute perfusion parameters (pulmonary blood flow and volume, mean transit time).28–31 However, today, CTPA is the method of choice in the diagnosis of acute PE, as outlined above. Interestingly, the decisive criterion for the diagnosis of PE differs between nuclear medicine methods and CTPA. In V/Q (ventilation/perfusion) planar scintigraphy or SPECT, the diagnosis of PE is made on the basis of a characteristic ventilation and perfusion mismatch, that is, on a visualization of functional parameter changes with a reduced perfusion in lung areas that are normally ventilated. In CTPA, in contrast, PE is primarily diagnosed on the basis of embolic clot detection in the pulmonary arterial vasculature, that is, on morphologic changes. This basic difference in the underlying principle for the diagnosis of PE partially accounts for differences in the diagnostic performance of CTPA and nuclear medicine methods. Although both SPECT of pulmonary ventilation and perfusion and CTPA could be shown to have a higher diagnostic accuracy when compared with planar ventilation/perfusion (V/Q) scintigraphy,32–34 SPECT has shown slightly higher sensitivity in the detection of peripherally located PE when compared with CTPA by visualizing peripheral perfusion defects resulting from tiny clots at the subsegmental arterial level that are too small to be detected in CT. Thus, it seems that despite the quoted advantages of CT in the field of lung imaging, the lack of functional information regarding pulmonary parenchymal perfusion remains a potential drawback of conventional CT. In the past, the only viable method for lung perfusion imaging with CT was a dynamic CT scan of selected lung regions during parenchymal contrast material uptake. Although this method allows for an assessment of dynamic, that is, time-resolved, perfusion parameters, the main disadvantage with dynamic scanning is an increased radiation dose and a limited coverage of the lungs, further complicated in patients who are unable to hold their breath during the time-resolved data acquisition.35,36
DECT of the Lung: Methods
With the introduction of DSCT and DECT, the concept of iodine distribution mapping, that is, functional imaging of organ “perfusion” and material differentiation, is now accessible for clinical examinations, as initially shown by Johnson et al.13 In principle, DECT imaging allows for material differentiation based on the different absorption characteristics of different types of tissue. Compared with subsequent scans of the same volume at 2 energy levels, the use of this technique enables simultaneous dual-energy image acquisition in the same phase of contrast enhancement. Iodine, a commonly used CT contrast material, is generally known to produce higher attenuation at lower tube voltage settings.37 Because of this effect, the spectral information on images obtained at different voltage settings allows for the differentiation of iodine from materials that do not exhibit this behavior. Selective visualization of iodine distribution in body tissues such as the pulmonary parenchyma is, therefore, a potential advantage of dual-energy imaging. In fact, real “perfusion” imaging would be based on a dynamic, repetitive, that is, time-resolved, acquisition of the lung after intravenous administration of contrast medium.38 DECT images do not yield this type of dynamic perfusion information because they display iodine distribution at only a single time point, providing an iodine map of the lung microcirculation (Fig. 1).15 Within normal lung parenchyma, the iodine content of the capillary bed can thus be compared with the “parenchymal” phase of a conventional or digital angiogram. However, the enhancement within the lung microvessels depends on a number of factors, such as the volume and flow rate of the contrast agent administered, and on the site of its administration.14 In addition, all the anatomic structures through which the iodinated contrast agent travels before and after the pulmonary capillary level will affect iodine distribution within the lung microcirculation, such as the systemic venous return, the right side of the heart, large pulmonary arteries and veins, the left side of the heart, the aorta, and peripheral arteries. Finally, the anatomic status of the lung parenchyma needs to be included in the analysis of DECT iodine maps. For example, an atelectatic lung zone may remain perfused to a certain degree, but less perfused than normally ventilated areas. Despite these potential limitations of a single-time-point, DECT iodine map of the lung, a good correlation between vessel occlusion depicted at CTA and defects in the iodine distribution on dual-energy scans could be found.39 In conclusion, initial results indicate that iodine distribution in the pulmonary parenchyma is closely related to pulmonary perfusion, for example, as assessed by scintigraphy. In addition, even if dual-energy acquisition does not correspond to true perfusion imaging, as it visualizes only blood volume and not blood flow, several advantages of this imaging technique can be underlined. Compared with scintigraphy and MRI, it is the only imaging modality able to provide high-quality morphologic analysis and functional information on the pulmonary circulation from the same data set.
The first generation of DSCT scanners, introduced in 2005, had a rather small field of view of the second detector. Therefore, in up to 80% of the cases, a small portion of the peripheral lungs could not be assessed in the reconstructed dual-energy images.40 The recently introduced second generation of DSCT systems provides a field of view of the second detector of 33 cm, enabling the depiction of the whole lungs in most patients (Fig. 2). With regard to the radiation dose of dual-source, DECT scans, the dose values for dual-energy protocols have been reported to range from 229 to 382 mGy cm for chest/abdomen examinations.13 Investigating a cohort of 117 patients in the clinical context of acute PE, Pontana et al41 reported a mean dose-length product of 280 mGy cm for DECT angiograms of the chest, corresponding to an average effective patient dose of about 5 mSv. This value is even lower than the European reference value of 650 mGy cm. Thus, even if the dose of DECT of the thorax can be a little bit higher than the dose values reported for a standard, single-source, single-energy thoracic CT, the above-mentioned benefits of DECT of the lung in patients with suspected PE seem to justify the moderate increase in the overall radiation dose. It is the only technique allowing for a direct comparison of CT angiograms acquired at different energies in the same patient, at the same time point after the injection of the contrast medium, and within strictly similar hemodynamic conditions.
DECT of the Lung: Available Data and Clinical Indications
To validate the diagnostic accuracy of DECT in the detection of PE against pathologic analysis with the use of an animal model, Zhang et al42 have evaluated the feasibility and added value of DECT in the diagnosis of PE in an animal model. After the injection of gelatin sponge particles into the pulmonary artery, 8 rabbits underwent contrast-enhanced dual-source CTPA from which blood flow and fusion images were created. Immediately after CT, the rabbits were killed, and a detailed pathologic determination of the location and number of lung lobes with PE was performed. On the dual-energy blood flow images, segments with an embolic region showed low perfusion compared with segments with a normal pulmonary region. The investigators concluded that DECT improved the detection of acute PE in rabbits compared with CTPA alone. Fused images (images that are a combination of blood flow images and CT pulmonary angiograms), which simultaneously provide morphologic and functional information, provided complementary information that maximized the accuracy of CT in the detection of PE. In addition, it has already been shown by several investigators that DECT can detect endoluminal clots in patients on averaged images of tubes A and B as efficiently as single-source CTA.41 In this study, the authors have also validated the detectability of perfusion defects beyond obstructive clots. Perfusion defects in the adjacent lung parenchyma have the typical territorial triangular shape well known from pulmonary angiographic, scintigraphic, and MRI perfusion studies (Figs. 3, 4). DECT angiography can lead to the depiction of perfusion defects without direct identification of peripheral endoluminal clots located within the subsegmental or more distal branches. Another advantage of DECT is the ability to use the diagnostic information available from tube B, set at 80 kV. As this tube voltage optimizes the contrast-to-noise ratio within pulmonary vessels, it can help detect peripheral endoluminal clots known to be better visualized than on images acquired at 120 or 140 kV.43,44 The iodine map can also be used as an additional parameter in the assessment of pulmonary artery obstruction score in the clinical context of acute PE.
In another pilot study, Thieme et al45 compared the diagnostic value of DECT in the assessment of pulmonary perfusion with reference to pulmonary perfusion scintigraphy. For this purpose, 13 patients were included, who underwent DECT and scintigraphy. The results were compared by patient and by segment, and the diagnostic accuracy of DECT perfusion imaging in the detection of PE was calculated with regard to scintigraphy as the standard of reference. The diagnostic accuracy of DECT pulmonary iodine maps showed 75% sensitivity, 80% specificity, and a negative predictive value of 66% per patient. Sensitivity per segment amounted to 83% with 99% specificity, with 93% negative predictive value. CTPA identified corresponding emboli in 66% of patients with concordant perfusion defects in DECT and scintigraphy. The investigators concluded that DECT perfusion imaging is able to display pulmonary perfusion defects with good agreement with scintigraphic findings.
Chronic PE and Other Indications
DECT pulmonary angiography can also allow for the depiction of perfusion defects in patients with chronic PE or patients with chronic thrombembolic pulmonary hypertension. A typical imaging characteristic of chronic PE can be mosaic patterns of lung attenuation, that is, areas of ground-glass attenuation mixed with areas of normal lung attenuation, suggesting a redistribution of blood flow. Here, DECT could help to differentiate ground-glass attenuation of vascular origin in PE patients (by means of the high iodine content within the areas of ground-glass attenuation) from ground-glass attenuation secondary to bronchiolalveolar diseases.46 In addition, chronic PE can lead to the development of calcifications within partially or completely occlusive chronic clots and within pulmonary artery walls when chronic PE is complicated by longstanding and/or severe pulmonary hypertension. Such calcifications within the pulmonary arteries can be detected and differentiated from contrast within these vessels by means of “virtual noncontrast imaging,” that is, subtraction of iodine from the contrast-enhanced data sets, a function that is always accessible from DECT data.
Besides acute and chronic PE, alterations in pulmonary perfusion are present in numerous stages of smoking-related respiratory diseases. Several structural changes in the early stages of chronic obstructive pulmonary disease have been described in experimental models, including proliferation of smooth muscle fibers within peribronchiolar arterioles and deposition of collagen and elastin in the thickened intima.47 In preliminary studies, Hoffman et al48 have shown increased heterogeneity of local mean transit times of the contrast agent within the pulmonary microvasculature of smokers with normal pulmonary function tests. Recently, Pansini et al49 have assessed the pulmonary perfusion on a lobar level in smokers, using DECT. Forty-seven smokers and 10 nonsmokers underwent a DECT of the chest. Emphysema was present in 37 smokers and absent in 10 smokers. Smokers with an upper lobe predominance of emphysema (n=8) showed a significantly lower contrast enhancement in the upper lobes compared with smokers without emphysema. In addition, a correlation was found between the difference in the percentage of emphysema between the upper and lower lobes and the difference in contrast attenuation in the corresponding lobes. Thus, regional alterations of lung perfusion can be depicted by DECT in smokers with emphysema.
CT IN PATIENTS WITH ACUTE CHEST PAIN
The diagnosis of patients with acute chest pain remains a challenging problem. There are approximately 6 million chest-pain-related emergency department visits annually in the United States alone.50 Approximately 5.3% of all emergency department patients are seen because of chest pain, and reported admission rates are between 30% and 72% for these patients.51 Comprehensive CTA protocols for a complete assessment of the thoracic vessels, often referred to as “triple rule-out” protocols, are increasingly used in the differential diagnosis of chest pain. These protocols aim to opacify pulmonary and coronary arteries and the aorta simultaneously to rule out PE, coronary artery disease, and aortic aneurysm or dissection in a single examination. Currently, there are no guidelines that have been published for the use of CT for acute chest pain. Initial appropriateness criteria have recently been published.52 More general guidelines are currently under development. In a recent consensus paper, the investigators discussed the available evidence for the use of CT in chest pain patients, to provide guidance to the practitioner and to provide a basis for practice with evolving technologies.53 The authors of this paper state clearly that in the emergency department setting, the symptoms and clinical signs of patients with chest pain are variable, but it is important to distinguish life-threatening causes that need rapid or immediate intervention from those that are less likely to be fatal but still need in-patient treatment, and those that can be managed supportively on an out-patient basis.54 Patients who present to the emergency department with a suspected PE can be risk-stratified using the Wells clinical decision rule. The likelihood of PE is low if the score is 4 or less and the D-dimer is negative.55 If the patient has a score greater than 4, then further investigations are required to exclude the diagnosis of PE. Hence, the most commonly used imaging technique is a contrast-enhanced chest CT. A negative CT study is associated with a low risk for subsequent fatal and nonfatal venous thromboembolism. Therefore, in the patient with undifferentiated chest pain and a moderate-to-high probability of PE, a CT is indicated.
Technical Aspects and Optimization of Protocols
MDCT is currently the diagnostic test of choice for the diagnosis of PE and acute aortic syndrome. As mentioned above, alternative diagnoses may also be found or excluded as causes of chest pain. If MDCT was robust enough to additionally exclude an acute coronary syndrome in patients without ST elevation, and sensitive enough to indicate which patients with non-ST-elevation myocardial infarction are likely to have treatable coronary disease, it might be used to shorten the observational period for patients with chest pain and suspected acute coronary syndrome to either rule out cardiac causes for chest pain or ensure timely institution of specific therapy. However, as of today, there are no large prospective studies where “triple rule-out” MDCT has been used for this purpose, and further research is desirable to better define the role for these protocols. Quite a few studies have meanwhile shown the feasibility of a simultaneous evaluation of these vascular territories in 1 single breath-hold scan with good sensitivity in the identification of the cause of chest pain.56–60 However, a major limitation of initial MDCT chest pain studies, especially in acutely ill patients, is the restricted image quality of the coronary arteries in high heart rates.61 With the advent of DSCT, cardiac imaging has shown robust image quality and very good diagnostic accuracy of coronary CTA, even in high heart rates.62,63 However, in first-generation DSCT scanners, triple rule-out protocols have been associated with rather high volumes of contrast (up to 150 mL) and highly effective radiation doses in the range of 15 to 20 mSv.57 These facts were considered as significant drawbacks of initial 64-slice CT and first-generation DSCT triple-rule-out protocols.
With the recently introduced second-generation DSCT, a new high-pitch dual spiral technique offers the possibility to acquire an ECG-gated synchronized data set of the whole chest in less than 1 second and at very low radiation doses (Fig. 5). In a first study on the use of this second-generation DSCT in chest pain patients, Sommer et al64 have compared the dose of such a chest pain protocol to a standard, non-ECG-gated chest scan and to a conventional, retrospectively ECG-gated triple-rule-out protocol, in a phantom model and in patients. The efficacy and dose of this dual spiral protocol were compared in patients examined with this high-pitch technique and a matched control group scanned with the conventional technique. The equivalent dose determined with thermoluminescent dosimeter measurements in the phantom model amounted to 2.65, 2.68, and 19.27 mSv, respectively, for the new, high-pitch dual spiral technique; the standard, non-ECG-gated chest scan; and the conventional retrospective technique. There was no significant difference in image noise. In the patient examinations, the dose was 4.08±0.81 mSv with the high-pitch protocol compared with 20.4±5.3 mSv in the matched controls with the conventional technique, and 4.40±0.83 mSv for the non-ECG-gated thorax scan. Scan times were 0.7±0.1 seconds for the high-pitch scan and 15±3 seconds for the conventional chest pain scan. The aorta and pulmonary arteries were shown in diagnostic quality in both groups. Of the coronary artery segments, 95.4% were rated as diagnostic in the high-pitch examinations (in heart rates below 65 bpm), whereas 92.9% of coronary artery segments were of diagnostic image quality with the conventional approach (Figs. 6–8, for clinical examples with this high-pitch protocol). There are other additional advantages in scanning the entire chest with the high-pitch ultra-high temporal resolution protocol; for example, in scanning adult patients with limited ability to cooperate, or in patients from intensive care units because of very short scan time. This fast and low-dose high-pitch triple-rule-out protocol is also of special interest in the diagnosis of PE, as one can exploit the possibility of reduction or suppression of motion artifacts in the heart and the surrounding mediastinal and parenchymal structures. In summary, the high-pitch protocol is a very promising means of scanning the entire thorax and could become the standard CT angiographic protocol for chest pain patients.
PERSPECTIVES AND CONCLUSIONS
Computer-aided Detection in the Diagnosis of PE
New tools could further enhance the diagnostic performance of MDCT in the diagnosis of PE. Earlier studies have evaluated the feasibility and performance of CAD tools for the automated detection of segmental and subsegmental pulmonary emboli. Schoepf et al65 have tested 1 such CAD tool (ImageChecker CT, R2 Technology, Inc) in 23 patients with PE and 13 patients without PE. Data were collected with a 16-slice CT. The performance of the CAD tool for the detection of emboli in the segmental and subsegmental pulmonary arterial tree was assessed. A consensus reading of 2 experienced radiologists revealed 130 segmental pulmonary emboli and 107 subsegmental pulmonary emboli in the 23 patients with PE. All 23 patients with PE were correctly identified as having PE by the CAD system. In vessel-by-vessel analysis, the sensitivity of the CAD algorithm was 92% (119/130) for the detection of segmental pulmonary emboli and 90% (92/107) for subsegmental pulmonary emboli. The overall specificity, positive predictive value, and negative predictive value of the algorithm were 89.9%, 63.2%, and 97.7%, respectively. The average false-positive rate of the CAD algorithm was 4.8 (range, 1 to 9) false-positive detection marks per case. The investigators concluded that CAD of segmental and subsegmental pulmonary emboli based on 1-mm multidetector-row CT studies is feasible. Application of CAD tools may improve the diagnostic accuracy and decrease the interpretation time of CTA for the detection of pulmonary emboli in the peripheral arterial tree and further enhance the acceptance of this test as the first-line diagnostic modality for suspected PE.
Dual-energy Xenon Ventilation Imaging of the Lung in PE Patients
In the evaluation of lung function, ventilation assessment is an important component. Presently, ventilation imaging is mainly realized using nuclear medicine methods33 or MRI with the inhalation of polarized noble gases, that is, 3Helium or 129Xenon,66 or gadolinium chelate aerosols.67 A drawback of these methods is the rather limited morphologic information in scintigraphy or SPECT, as well as restricted spatial resolution and lack of information on the pulmonary microstructure in both MRI and nuclear medicine imaging. Whenever high-resolution morphologic information on structural changes of the lung parenchyma is needed, MDCT is the first-line imaging modality that can provide this important morphologic information, applying the so-called high-resolution protocols. In combination with DECT, comprehensive imaging for morphology, angiography, perfusion, and ventilation could become feasible in PE patients. The inert gas xenon has x-ray absorption characteristics that resemble those of iodine and can therefore serve as an inhalative contrast agent for CT ventilation imaging.68,69 Although there have been trials in the past decades to use stable xenon gas for CT ventilation imaging, this method has so far not been used in clinical care. These earlier approaches were based on sequential chest scans, implying an increased patient dose and potential misregistrations because of varying levels of inspiration.70 With dual-source scanners, DECT now has the potential to map xenon distribution patterns by directly visualizing the inhaled xenon gas. Chae et al69 performed xenon-enhanced DECT in 12 patients at an inspiratory xenon concentration of 30%, and showed the technical feasibility of DECT ventilation imaging. Using DECT with inhalation of xenon and intravenous iodine administration, a comprehensive assessment of pulmonary morphology and function, including both ventilation and perfusion imaging, becomes possible with CT. Future studies will deal with the use of DE ventilation imaging in combination with DE perfusion mapping in patients with pulmonary functional impairment, for example, after PE, or in cases of worsening of the gas exchange during intensive care treatment, to evaluate the feasibility of a comprehensive diagnostic evaluation including ventilation, perfusion, morphology, and structure of the parenchyma. However, to differentiate perfusion from ventilation information, 2 DECT scans would have to be performed. The first scan with inhaled xenon, and the second scan after intravenous administration of iodinated contrast material, will have to be performed to map the parenchymal distribution of iodine and to correlate changes in ventilation and perfusion with structural or vascular abnormalities. As inhaled xenon can have anesthetic properties at higher concentrations,25,26 future studies will also have to deal with the optimal inspiratory concentration of the inhaled xenon.
As outlined above, MDCT, and especially DSCT, will remain the most powerful and clinically most important tool in the evaluation of PE patients. Routine MDCT pulmonary angiography offers an accurate and quick depiction of the pulmonary clots, and this method is available nearly everywhere. In addition, MDCT can provide crucial information on the hemodynamic stability and prognosis of a patient suffering from acute PE. New acquisition strategies, such as dual-energy techniques (perfusion imaging, ventilation imaging, direct thrombus imaging) and very fast and low-dose acquisition protocols such as the second-generation DSCT high-pitch chest pain protocol, will further strengthen this position.
1. Wittram C, Maher MM, Yoo AJ, et al. CT angiography of pulmonary embolism: diagnostic criteria and causes of misdiagnosis. Radiographics. 2004;24:1219–1238.
2. Brown MD, Rowe BH, Reeves MJ, et al. The accuracy of the enzyme-linked immunosorbent assay D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Ann Emerg Med. 2002;40:133–144.
3. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753–2759.
4. Costello P, Gupta KB. Pulmonary embolism: imaging modalities—V/Q scan, spiral (helical) CT, and MRI. Semin Vasc Med. 2001;1:155–164.
5. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000;132:227–232.
6. Schoepf UJ, Costello P. CT angiography for diagnosis of pulmonary embolism: state of the art. Radiology. 2004;230:329–337.
7. Schoepf UJ. Diagnosing pulmonary embolism: time to rewrite the textbooks. Int J Cardiovasc Imaging. 2005;21:155–163.
8. Ravenel JG, Costello P, Schoepf UJ. CT in the diagnosis of pulmonary embolism. AJR Am J Roentgenol. 2005;184:1707–1708.
9. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354:2317–2327.
10. Ghaye B, Ghuysen A, Bruyere PJ, et al. Can CT pulmonary angiography allow assessment of severity and prognosis in patients presenting with pulmonary embolism? What the radiologist needs to know. Radiographics. 2006;26:23–39.
11. Lu MT, Cai T, Ersoy H, et al. Comparison of ECG-gated versus non-gated CT ventricular measurements in thirty patients with acute pulmonary embolism. Int J Cardiovasc Imaging. 2009;25:101–107.
12. Revel MP, Faivre JB, Remy-Jardin M, et al. Pulmonary hypertension: ECG-gated 64-section CT angiographic evaluation of new functional parameters as diagnostic criteria. Radiology. 2009;250:558–566.
13. Johnson TR, Krauss B, Sedlmair M, et al. Material differentiation by dual energy CT: initial experience. Eur Radiol. 2007;17:1510–1517.
14. Boroto K, Remy-Jardin M, Flohr T, et al. Thoracic applications of dual-source CT technology. Eur J Radiol. 2008;68:375–384.
15. Fink C, Johnson TR, Michaely HJ, et al. Dual-energy CT angiography of the lung in patients with suspected pulmonary embolism: initial results. Rofo. 2008;180:879–883.
16. Carson JL, Kelley MA, Duff A, et al. The clinical course of pulmonary embolism. N Engl J Med. 1992;326:1240–1245.
17. Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation. 2000;101:2817–2822.
18. Walsh PN, Stengle JM, Sherry S. The urokinase-pulmonary embolism trial. Circulation. 1969;39:153–156.
19. Miller GA, Sutton GC, Kerr IH, et al. Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism. Br Med J. 1971;2:681–684.
20. Qanadli SD, El Hajjam M, Vieillard-Baron A, et al. New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. AJR Am J Roentgenol. 2001;176:1415–1420.
21. Mastora I, Remy-Jardin M, Masson P, et al. Severity of acute pulmonary embolism: evaluation of a new spiral CT angiographic score in correlation with echocardiographic data. Eur Radiol. 2003;13:29–35.
22. Bankier AA, Janata K, Fleischmann D, et al. Severity assessment of acute pulmonary embolism with spiral CT: evaluation of two modified angiographic scores and comparison with clinical data. J Thorac Imaging. 1997;12:150–158.
23. Ghaye B, Ghuysen A, Willems V, et al. Severe pulmonary embolism: pulmonary artery clot load scores and cardiovascular parameters as predictors of mortality. Radiology. 2006;239:884–891.
24. Quiroz R, Kucher N, Schoepf UJ, et al. Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism. Circulation. 2004;109:2401–2404.
25. Kamel EM, Schmidt S, Doenz F, et al. Computed tomographic angiography in acute pulmonary embolism: do we need multiplanar reconstructions to evaluate the right ventricular dysfunction? J Comput Assist Tomogr. 2008;32:438–443.
26. Engelke C, Rummeny E, Marten K. Acute pulmonary embolism: prediction of cor pulmonale and short-term patient survival from assessment of cardiac dimensions in routine multidetector-row CT. Rofo. 2006;178:999–1006.
27. Engelke C, Marten K. Multidetector-row CT in severe pulmonary embolism: radiologists' help in risk stratification. Radiologe. 2007;47:725–734.
28. Nikolaou K, Schoenberg SO, Brix G, et al. Quantification of pulmonary blood flow and volume in healthy volunteers by dynamic contrast-enhanced magnetic resonance imaging using a parallel imaging technique. Invest Radiol. 2004;39:537–545.
29. Nikolaou K, Schoenberg SO, Attenberger U, et al. Pulmonary arterial hypertension: diagnosis with fast perfusion MR imaging and high-spatial-resolution MR angiography—preliminary experience. Radiology. 2005;236:694–703.
30. Attenberger UI, Ingrisch M, Dietrich O, et al. Time-resolved 3D pulmonary perfusion MRI: comparison of different k-space acquisition strategies at 1.5 and 3 T. Invest Radiol. 2009;44:525–531.
31. Ingrisch M, Dietrich O, Attenberger UI, et al. Quantitative pulmonary perfusion magnetic resonance imaging: influence of temporal resolution and signal-to-noise ratio. Invest Radiol. 2010;45:7–14.
32. Bajc M, Olsson CG, Olsson B, et al. Diagnostic evaluation of planar and tomographic ventilation/perfusion lung images in patients with suspected pulmonary emboli. Clin Physiol Funct Imaging. 2004;24:249–256.
33. Roach PJ, Bailey DL, Harris BE. Enhancing lung scintigraphy with single-photon emission computed tomography. Semin Nucl Med. 2008;38:441–449.
34. Gutte H, Mortensen J, Jensen CV, et al. Comparison of V/Q SPECT and planar V/Q lung scintigraphy in diagnosing acute pulmonary embolism. Nucl Med Commun. 2010;31:82–86.
35. Wildberger JE, Schoepf UJ, Mahnken AH, et al. Approaches to CT perfusion imaging in pulmonary embolism. Semin Roentgenol. 2005;40:64–73.
36. Schoepf UJ, Bruening R, Konschitzky H, et al. Pulmonary embolism: comprehensive diagnosis by using electron-beam CT for detection of emboli and assessment of pulmonary blood flow. Radiology. 2000;217:693–700.
37. Nakayama Y, Awai K, Funama Y, et al. Abdominal CT with low tube voltage: preliminary observations about radiation dose, contrast enhancement, image quality, and noise. Radiology. 2005;237:945–951.
38. Miles KA. Perfusion imaging with computed tomography: brain and beyond. Eur Radiol. 2006;16(suppl 7):M37–M43.
39. Zhang LJ, Yang GF, Zhao YE, et al. Detection of pulmonary embolism using dual-energy computed tomography and correlation with cardiovascular measurements: a preliminary study. Acta Radiol. 2009;50:892–901.
40. Thieme SF, Johnson TR, Lee C, et al. Dual-energy CT for the assessment of contrast material distribution in the pulmonary parenchyma. AJR Am J Roentgenol. 2009;193:144–149.
41. Pontana F, Faivre JB, Remy-Jardin M, et al. Lung perfusion with dual-energy multidetector-row CT (MDCT): feasibility for the evaluation of acute pulmonary embolism in 117 consecutive patients. Acad Radiol. 2008;15:1494–1504.
42. Zhang LJ, Zhao YE, Wu SY, et al. Pulmonary embolism detection with dual-energy CT: experimental study of dual-source CT in rabbits. Radiology. 2009;252:61–70.
43. Hoey ET, Gopalan D, Ganesh V, et al. Dual-energy CT pulmonary angiography: a novel technique for assessing acute and chronic pulmonary thromboembolism. Clin Radiol. 2009;64:414–419.
44. Gorgos A, Remy-Jardin M, Duhamel A, et al. Evaluation of peripheral pulmonary arteries at 80 kV and at 140 kV: dual-energy computed tomography assessment in 51 patients. J Comput Assist Tomogr. 2009;33:981–986.
45. Thieme SF, Becker CR, Hacker M, et al. Dual energy CT for the assessment of lung perfusion-correlation to scintigraphy. Eur J Radiol. 2008;68:369–374.
46. Remy-Jardin M, Faivre JB, Pontana F, et al. Thoracic applications of dual energy. Radiol Clin North Am. 2010;48:193–205.
47. Santos S, Peinado VI, Ramirez J, et al. Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:1250–1256.
48. Hoffman EA, Simon BA, McLennan G. State of the Art. A structural and functional assessment of the lung via multidetector-row computed tomography: phenotyping chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:519–532.
49. Pansini V, Remy-Jardin M, Faivre JB, et al. Assessment of lobar perfusion in smokers according to the presence and severity of emphysema: preliminary experience with dual-energy CT angiography. Eur Radiol. 2009 Jun 16. [Epub ahead of print].
50. Zalenski RJ, Rydman RJ, Ting S, et al. A national survey of emergency department chest pain centers in the United States. Am J Cardiol. 1998;81:1305–1309.
51. Graff LG, Dallara J, Ross MA, et al. Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study. Am J Cardiol. 1997;80:563–568.
52. Hendel RC, Patel MR, Kramer CM, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac computed tomography and cardiac magnetic resonance imaging: a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group, American College of Radiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, American Society of Nuclear Cardiology, North American Society for Cardiac Imaging, Society for Cardiovascular Angiography and Interventions, and Society of Interventional Radiology. J Am Coll Cardiol. 2006;48:1475–1497.
53. Stillman AE, Oudkerk M, Ackerman M, et al. Use of multidetector computed tomography for the assessment of acute chest pain: a consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology. Eur Radiol. 2007;17:2196–2207.
54. Jeudy J, Waite S, White CS. Nontraumatic thoracic emergencies. Radiol Clin North Am. 2006;44:273–293, ix.
55. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416–420.
56. Johnson TR, Nikolaou K, Wintersperger BJ, et al. Optimization of contrast material administration for electrocardiogram-gated computed tomographic angiography of the chest. J Comput Assist Tomogr. 2007;31:265–271.
57. Johnson TR, Nikolaou K, Becker A, et al. Dual-source CT for chest pain assessment. Eur Radiol. 2008;18:773–780.
58. Savino G, Herzog C, Costello P, et al. 64 slice cardiovascular CT in the emergency department: concepts and first experiences. Radiol Med. 2006;111:481–496.
59. White CS, Kuo D, Kelemen M, et al. Chest pain evaluation in the emergency department: can MDCT provide a comprehensive evaluation? AJR Am J Roentgenol. 2005;185:533–540.
60. Raptopoulos VD, Boiselle PB, Michailidis N, et al. MDCT angiography of acute chest pain: evaluation of ECG-gated and nongated techniques. AJR Am J Roentgenol. 2006;186(6 suppl 2):S346–S356.
61. Leschka S, Wildermuth S, Boehm T, et al. Noninvasive coronary angiography with 64-section CT: effect of average heart rate and heart rate variability on image quality. Radiology. 2006;241:378–385.
62. Johnson TR, Nikolaou K, Wintersperger BJ, et al. Dual-source CT cardiac imaging: initial experience. Eur Radiol. 2006;16:1409–1415.
63. Scheffel H, Alkadhi H, Plass A, et al. Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control. Eur Radiol. 2006;16:2739–2747.
64. Sommer WH, Schenzle JC, Becker CR, et al. Saving dose in triple-rule-out computed tomography examination using a high-pitch dual spiral technique. Invest Radiol. 2010;45:64–71.
65. Schoepf UJ, Schneider AC, Das M, et al. Pulmonary embolism: computer-aided detection at multidetector row spiral computed tomography. J Thorac Imaging. 2007;22:319–323.
66. Kauczor HU. Hyperpolarized helium-3 gas magnetic resonance imaging of the lung. Top Magn Reson Imaging. 2003;14:223–230.
67. Mosbah K, Ruiz-Cabello J, Berthezene Y, et al. Aerosols and gaseous contrast agents for magnetic resonance imaging of the lung. Contrast Media Mol Imaging. 2008;3:173–190.
68. Goo HW, Chae EJ, Seo JB, et al. Xenon ventilation CT using a dual-source dual-energy technique: dynamic ventilation abnormality in a child with bronchial atresia. Pediatr Radiol. 2008;38:1113–1116.
69. Chae EJ, Seo JB, Goo HW, et al. Xenon ventilation CT with a dual-energy technique of dual-source CT: initial experience. Radiology. 2008;248:615–624.
70. Gur D, Drayer BP, Borovetz HS, et al. Dynamic computed tomography of the lung: regional ventilation measurements. J Comput Assist Tomogr. 1979;3:749–753.
pulmonary embolism; computed tomography; dual-source computed tomography; dual-energy computed tomography
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