Applied Radiology

Dr. Farag is a Clinical Fellow in the Thoracic Radiology Division of Brigham and Women's Hospital and Harvard Medical School, and Dr. Costello is Associate Professor of Radiology at Harvard Medical School and Director of the Thoracic Radiology Division of Brigham and Women's Hospital, Boston, MA.

Pulmonary embolism (PE) is a common cause of death in hospitalized patients with clinical manifestations that are protean and nonspecific. Patients can present with symptoms ranging from minimal dyspnea to sudden death. Most often, symptoms and signs include dyspnea, pleuritic chest pain, cough, hemoptysis, tachypnea, hypotension, fever, and tachycardia. Given the non-specific gamut of signs and symptoms, the diagnosis of PE can easily be overlooked. Standard laboratory tests are also non-specific with diminished arterial PO ₂ and a widened alveolar-atrial gradient. More recently, D-dimer, a blood test that measures fibrin degradation products, has been found to be helpful but remains in development. ^1,2

The classical clinical approach to a patient with suspected PE is to combine the degree of clinical suspicion with ventilation-perfusion (V/Q) scintigraphy, and to perform pulmonary angiography in cases that remain unclear. The problem arises in that approximately 75% of patients fall within the "indeterminate" V/Q category of "diagnosis," requiring pulmonary angiography for a definitive diagnosis. ³ Pulmonary arteriography is invasive, has an associated small but measurable morbidity, and is costly. Over the past few years, the introduction of spiral CT angiography (spiral CTA), a more direct and relatively non-invasive technique for the diagnosis of PE, has become generally available. ^4-7

The addition of spiral CT to the diagnostic armamentarium has the potential to dramatically alter the approach taken when assessing patients for PE. Because of the wide availability of spiral CT systems, CT is generally an easier study to obtain than a V/Q scan or pulmonary angiogram. With careful attention to CT technique, direct visualization of the clot in the pulmonary arteries down to the level of segmental, and even subsegmental, vessels is possible. ^8-10 Additionally, spiral CTA is capable of demonstrating a variety of thoracic pathologies that can "mimic" PE, and may establish an alternative diagnosis for the patient's symptoms. ¹¹

This review will explore the current role of spiral (helical) CT scanning in the diagnosis of PE. We will also attempt to evaluate where this technique stands with regard to the conventional methods of diagnosing PE. A brief review of the pitfalls in the diagnosis with spiral CTA will be given. Finally, diagnostic future techniques will be examined briefly.

Evaluation

Spiral CT and PE--Over the past 8 years, it has been suggested that spiral CT can replace V/Q scanning and pulmonary angiography for the diagnosis of PE. CT criteria for diagnosing acute PE are similar to criteria used with pulmonary angiography. Clots can be directly visualized as partial or complete filling defects within opacified vessels. ^8-10 Several studies have reported high sensitivities and specificities in the identification of PE down to the segmental arterial level ^12-17 (Table 1).

Coche et al ¹¹ have reported the value of associated pleural and parenchymal findings that aid in the diagnosis of pulmonary embolism. Ancillary signs such as wedge-shaped pleural based consolidation, linear bands, and dilated central or segmental pulmonary arteries can be associated with the diagnosis of PE and are statistically significant findings. As such, the detection of these findings may direct further investigations particularly if a study is "suboptimal" for assessment of central or segmental vessels.

CT technique--With spiral CT, the x-ray tube and detector revolve around the patient generating a helix of data while the patient moves through the gantry. Most newer CT systems have cycle times of <1 second and have tube capacities that allow the entire thorax to be examined in <25 seconds. ¹⁸ Recently introduced multi-detector array CT scanners will have a major influence on PE detection. Through the simultaneous acquisition of four slices with a rotation speed of 0.5 seconds, even higher resolution studies of the chest can be acquired with short breathhold intervals. The shorter scan time reduces cardiac and respiratory motion artifacts, making vessels adjacent to the heart easier to visualize.

Intravenous contrast can be administered at low-concentration/high-flow rate protocols (i.e., 30% concentration at 5 to 6 mL/sec) or standard concentration and a flow rate of 3 mL/sec can be used for PE detection. Artifacts produced with high-concentration low-flow rate protocols due to contrast in the superior vena cava can slightly degrade evaluation of the right main and right upper lobe pulmonary arteries. Low-concentration/high-flow rate contrast administration may limit the evaluation of more distal subsegmental vessels because of suboptimal vessel opacification. Our protocol uses 100 mL of 60% iodine concentration infused at 3 mL/sec through an antecubital vein with a 15-second delay to scan start.

Pulmonary angiography--Pulmonary angiography has long been considered the "gold standard" for true diagnosis of PE, with a high spatial resolution that allows for detection of emboli to the subsegmental level. ¹⁹ However it is invasive, with morbidity and mortality rates quoted as 1% to 3% in patients having pulmonary angiograms. ^20,21 Given its invasive and costly properties, some clinicians are reluctant to refer all patients with intermediate-probability V/Q scans for pulmonary angiography, despite the fact that one-third of these patients will have PE. ³

Most importantly, the interobserver variability for pulmonary angiography is significant, and Stein et al ²⁰ has documented an overall interobserver agreement of only 81%, the agreement is even lower at the level of the subsegmental vessels.

V/Q scintigraphy--The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study has evaluated the usefulness of V/Q scintigraphy in the diagnosis of PE. ³ In this study, V/Q scans were split into four categories with regard to the findings and the likelihood of acute PE (normal, low, intermediate, or high probability). Patients with normal V/Q scans were shown to have a 2% to 4% chance of having clinically significant acute PE. ³ Patients with high-probability V/Q scans were shown to have a 96% probability of acute PE. ³ In these settings, clinicians are comfortable with the results and will withhold or administer anticoagulant therapy correspondingly.

Problems arise with studies that fall within the low- and intermediate-probability categories. These V/Q diagnoses occur in up to 75% of patients, and 16% of patients with low probability and 33% of patients with intermediate probability scans will have angiographically proven PE. ³ Because of a reluctance to perform pulmonary angiography, this can translate into patients not receiving needed anticoagulant therapy, or patients receiving unnecessary anticoagulant therapy. Interobserver disagreement in the PIOPED study for low- and intermediate-probability scans was quoted as 25% and 30%, respectively. ³

Compression Doppler ultrasound--Patients with clinically suspected PE have also been shown to benefit from compression and color Doppler venous ultrasound of the legs to evaluate for deep venous thrombosis (DVT). ^22,23 If DVT is discovered, the patient is treated regardless of the V/Q scan result. The limits of Doppler ultrasound lie within the deep pelvic veins, which cannot be assessed adequately. Recently Loud et al ^24,25 described CT evaluation for DVT as an extension of the spiral CT exam of the chest. Venous phase imaging of the pelvis and upper legs at the time of spiral CTA was shown to be comparable to venous sonography for the evaluation of femoropopliteal DVT. ²⁵ In addition, this technique proved to be useful for evaluation of clots in the vena cava and iliac veins (vessels poorly assessed sonographically).

Spiral CT compared with pulmonary angiography and V/Q scans--Several studies have compared spiral CT with pulmonary angiography for the diagnosis of acute PE with reported high sensitivities and specificities in the identification of PE down to the segmental level. ^12-17,26 Data from these studies demonstrates a sensitivity range of 53% to 100% and a specificity of 78% to 100% for spiral CT. Range variations can be explained by differences in equipment, scanning protocols, contrast administration, study design, and radiologist experience. However, when only central or segmental emboli are considered, sensitivity and specificity of spiral CT approaches 90% ⁴ (figure 1).

The European Multicenter Trial (ESTIPEP) is a prospective study of 401 patients that compared spiral CT with pulmonary angiography. ²⁷ Clinical probability for PE was estimated, and all patients underwent spiral CT and V/Q scanning. Pulmonary angiography was performed in cases of low- and intermediate-probability V/Q scans, and if spiral CT and V/Q diagnoses were contradictory. The study demonstrated sensitivity of spiral CT to vary between 75% to 92%.

Sensitivity of V/Q scans in this study ranged from 36% to 65%. ²⁷ Spiral CT had the advantage of performing fewer non-diagnostic exams than V/Q, since the lung parenchyma, mediastinum and chest wall structures were also assessed resulting in alternative diagnoses for patient's symptoms. Equally important is the fact that the interobserver agreement between readers was greater for CT than for V/Q scanning (*72% versus *39%) ²⁷ and even better than pulmonary angiography (46%). ²⁷ The European Multicenter trial also showed interobserver agreement for CT to be dependent on the quality of the study. For V/Q scans, interobserver agreement was neither due to study quality nor the use of PIOPED criteria. ²⁷

One recently published study highlights the importance of technical factors when performing spiral CT for PE. Drucker et al ²⁶ described the sensitivity and specificity of two groups of readers for detecting PE by spiral CT to be 53% to 60% and 87% to 97%, respectively. These results, which were significantly worse than other studies, may be explained by several factors. First, relatively thick slices were used (5 mm, while most current techniques utilize 2-mm slice thickness). Second, hard-copy interpretation makes it difficult to recognize small clots, as many can only be recognized by varying window levels and tracing vessels on sequential images. Soft-copy workstation interpretation improves image viewing since it is interactive and allows for easy window leveling and vessel tracking.

The recognized limitation of spiral CT for the detection of subsegmental emboli continues to be debated. ^12,14,15 Isolated subsegmental PE are likely infrequent, as most PE split into an average of 6 to 8 fragments, ^13,28,29 of which in most patients one or more should be large enough to be detected by spiral CT.

In the PIOPED study, 5.6% of PE were limited to subsegmental arteries. ³ In four studies comparing spiral CT to pulmonary angiography, 0% to 36% of pulmonary emboli were isolated and subsegmental. ^12,14,15,26 Spiral CT demonstrated between 0% to 50% of these isolated subsegmental emboli.

Although early results showed limitations of spiral CT in the detection of subsegmental emboli, ^12,15,30,31 earlier scan protocols (e.g., 5-mm collimation with pitch of 1) have been surpassed by technological improvements in CT systems. Narrower collimation (2-mm, and even 1-mm with multi-detector CT systems) and reconstruction intervals have improved visualization of peripheral pulmonary arteries (figure 2). Remy-Jardin et al ³² described a group of 370 patients that demonstrated the percentage of analyzable subsegmental arteries to be statistically significantly higher when patients are scanned with 2-mm collimation and pitch of 2 rather than with 3-mm collimation and a pitch of 1.7 (65% versus 43%, respectively). ³²

The clinical significance of subsegmental emboli remains uncertain, ³³ but probably depends on a patient's cardiopulmonary reserve. ^15,30 In otherwise healthy patients, subsegmental emboli may be insignificant clinically. However, occlusion of several subsegmental vessels perfusing the normal lung tissue in a patient with pre-existing lung disease can lead to respiratory failure. ^15,30

Pitfalls of spiral CT angiography--Spiral CT and conventional pulmonary angiography have similar rates of diagnostically suboptimal examinations, between 2% and 4% of spiral CT studies and 3% of pulmonary angiograms. ^20,32 Suboptimal exams are most often due to poor image quality arising from motion related to patient dyspnea. ^15-17,30 Breathing artifacts are seen as pseudo-filling defects, mostly at the level of obliquely oriented arteries due to variable position of the vessel in the section width in two successive scans. In this instance, a decrease in attenuation can be seen at the level of the arterial bifurcation.

Routes of intravenous contrast delivery, flow rates, catheter size and position, and short or long scanning delays may all affect the quality of pulmonary artery opacification. With prolonged scan delays, there may not be adequate contrast available to opacify the vessels at the end of the scanned volume. With short scan delays, insufficient time has elapsed to allow appropriate opacification of the pulmonary arteries (especially on the earlier images of the scanned volume). As such, appropriate consideration must be given to patient cardiovascular physiology (particularly cardiac output), anatomy, and the cardiac output. In general, a 15-second delay to scan initiation is used, but in patients with poor cardiac function a delay of 20 seconds may be used.

Similarly, increased pulmonary vascular resistance due to parenchymal abnormalities can lead to false-positive studies. Additional limitations and possible sources of error in interpreting spiral CT exams involve elements related to the interpreter's experience. Confusion of pulmonary veins, hilar lymph nodes, and mucous-filled bronchi (figure 3) with poorly opacified pulmonary arteries is often less problematic when the reader is more experienced.

MRI diagnosis of pulmonary embolism

Gefter et al ³⁴ advocates the utility of pulmonary magnetic resonance an-giography (MRA) to evaluate the pulmonary arterial system for PE. The use of pulmonary MRA is attractive because of its non-invasiveness, and its ability to provide a three-dimensional evaluation of pulmonary vasculature. The combination of pulmonary MRA with MR venography of the pelvis and lower extremities makes the technique more appealing because of its comprehensive nature. ³⁴ The role of pulmonary MRA in the clinical algorithm to diagnose PE has yet to be established, and its cost-effectiveness as a routine examination is debatable.

Conclusion

Spiral CT angiography is a widely available and cost-effective technique for the evaluation of the pulmonary arterial system, and assessment for pulmonary embolism. With improvements in CT technology (faster gantry speeds and multi-row detector CT), techniques and protocols are evolving that will lead to a higher sensitivity and specificity of spiral CTA for PE. Combining spiral CTA and compression Doppler ultrasound of the legs seems the most cost-effective method. This technique can also suggest alternate diagnoses that cannot be established by conventional V/Q scintigraphy or by pulmonary arteriography. AR

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