British Journal of Radiology (2004) 77, S39-S45
© 2004 British Institute of Radiology
doi: 10.1259/bjr/17627958
Multislice CT pulmonary angiography and CT venography
J H Reid, MBChB, FRCR, DMRD
Radiology Department, Borders General Hospital, Melrose TD6 9BS, UK
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Abstract
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Pulmonary embolism (PE) is a common and potentially lethal complication of deep venous thrombosis. Clinical diagnosis is difficult and treatment carries significant potential side effects. High sensitivity and specificity of any diagnostic modality for PE are desirable. Helical CT pulmonary angiography (CTPA) offers this by direct visualization of embolic material within the pulmonary arteries. For a number of reasons, including the mobility and orientation of the pulmonary vessels and the peripheral nature of some emboli, the accuracy of CTPA is directly related to the spatial resolution of the technique used. The advent of multislice technology lends itself to improved spatial and temporal resolution and has led to a significant improvement on earlier CTPA results. Indirect CT venography may also be performed as an adjunct to CTPA to help demonstrate culprit thrombus within the lower limbs.
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Introduction
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The last 20 years have seen a wide array of imaging modalities brought to bear on the diagnostic problem of pulmonary embolism (PE) and there is little doubt that in the last decade helical CT has assumed an increasingly central role. Radiological investigation of venous thromboembolic disease represents a significant proportion of the activity of many general radiological departments and, as further clinical confidence and reliance are placed upon CT, the introduction of multislice technology has come as a welcome advance. By the time this article goes to press, most significant sized departments will either have, or will be planning to install, a multislice CT unit. This paper reviews the pathophysiology of venous thromboembolism, helical CT pulmonary angiography (CTPA) in general and the specific advantages conferred by multislice technology. The article will also briefly review the place of CT venography (CTV), which may be performed as an adjunct to CTPA.
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Natural history and pathophysiology of venous thromboembolism
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An understanding of the pathophysiology of venous thromboembolic disease is useful in maximizing the diagnostic potential of multislice CT. The exact incidence of thromboembolic disease in the general population is unknown, but best estimates suggest that approximately 60 to 70 new cases of PE occur per 100 000 of the population each year [1]. Since most large studies show that roughly one in three investigations for PE are positive, it follows that a general hospital serving a population of 200 000 can expect to perform at least 200 investigations for PE per year. Risk factors are well recognized and there is a positive correlation with increasing age and immobility [2]. Presentation and clinical findings associated with PE are related both to the final position and size of the thrombus load as well as the pre-existing cardiopulmonary status of the patient [3, 4]. It is convenient to think of two broad groups. First, the small to moderate embolus that may lodge in one or more subsegmental vessels and often gives rise to the syndrome of pulmonary infarction, which includes pleuritic chest pain, cough and haemoptysis. The second main group of more immediate clinical importance is that of massive PE. In this scenario the patient often presents with marked and inappropriate dyspnoea, pre-syncope and collapse. These are the features of acute right ventricular failure caused by obstruction of more than 50% of the pulmonary vascular bed. Syncope when associated with thromboembolic disease indicates that the cardiac output is precariously balanced and such patients must be diagnosed and treated with a degree of urgency and caution [5]. In cases of massive PE, the sudden rise in right heart pressure leads to right ventricular dilatation that may be seen both on CT and echocardiography [6, 7]. The presence of right ventricular compromise is an indication for consideration of pulmonary thrombolysis [8].
The resolution rate of PE even with anticoagulation is variable and is frequently longer than clinically apparent. In a recent study utilizing CTPA, only one-third of patients had normalization of the pulmonary arteries at 30 days [9]. It is highly unlikely that a patient with anything other than the smallest peripheral embolus will clear their pulmonary vascular bed on conventional heparin therapy within 72 h. This confers something of a breathing space to allow sensible planning of investigations. It is reasonable to assert that, in the absence of clinical findings which suggest massive PE and in the presence of adequate interim heparinization, radiological investigation of PE may be scheduled for the next available session. Indications for out-of-hours imaging should be limited to those patients with suspected massive PE or a strong contraindication to anticoagulation [10].
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Conventional pulmonary angiography
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Conventional pulmonary angiography has long been considered the gold standard in the diagnosis of PE and historically it is the technique against which all other modalities have been measured. This position has now been seriously challenged by helical CTPA [11]. In addition, the number of centres that now regularly perform conventional pulmonary angiography has dwindled dramatically to the extent that experience with the technique is now rare in many large departments. This is partly due to the time consuming nature of the technique and the relative reluctance of radiology departments to offer this type of imaging. There is also a long held belief that conventional angiography is dangerous, although large studies have shown that in experienced hands even patients with markedly elevated pulmonary artery pressures suffer little in the way of morbidity or mortality [12]. Suffice it to say that at the current rate of atrophy of catheter angiography, CTPA is set to replace it as the new gold standard.
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CTPA
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Direct visualization of thrombi within the pulmonary arteries by helical CT revolutionized the diagnostic approach to PE over a decade ago. Although previous reports using non-spiral scanners date back to the early 1980s, it was 1992 that saw the first significant publication of CTPA using helical technology [13]. Sensitivities and specificities for early CTPA series varied greatly owing to experience, scanner design and, particularly, the degree of collimation. A meta-analysis of these previous studies was published in 2000 [14]. Rathbun and colleagues concluded that "anti-coagulation cannot be safely withheld on the grounds of a negative CTPA" [14]. Time and technology have moved on since then and the advent of multislice CT has allowed the use of progressively thinner collimation. This has resulted in an incremental improvement in sensitivity and specificity to the extent that it now seems likely that the negative predictive value of CTPA is at least as high as any other currently available technique. In a publication from 2002, Swensen and colleagues [15] looked at outcomes in 1512 patients, 1010 of whom had negative CTPAs. 993 of these were not anticoagulated and were monitored for further events during a 3 month follow-up period. The negative predictive value of CTPA in this group was 99.5%.
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Multislice CTPA
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Simultaneous utilization of more than a single row of detectors, commonly 4, 8 or 16 rows, confers a number of major advantages (Table 1
), including thinner collimation, increased z-axis resolution, decreased examination time, decreased partial volume averaging and increased total scan volume. With a 16 slice machine, the whole thorax can now be scanned in submillimetre resolution in less than 10 s. Since the peripheral pulmonary vascular tree is a dynamic and mobile vascular structure, all of the above features can be seen to be important to varying degrees for the improved resolution of peripheral pulmonary vessels. In particular, narrower collimation has had a dramatic impact on sensitivity, which has risen from approximately 55% for 5 mm collimation on single slice scanners to 95% for 2 mm collimation on multislice systems. It has also significantly improved interobserver agreement, particularly in those difficult areas where vessels run oblique to the axial plane, commonly the middle lobe and lingula. A study by Schoepf et al [16] showed that reduction from 3 mm thick sections to 1 mm sections yielded an average increase of 40% in the rate of detection of emboli in subsegmental pulmonary arteries. The number of indeterminate cases in this study decreased by 70%. Another study by Remy-Jardin and colleagues [17] compared single slice with multislice CTPA and included patients with coexisting respiratory disease. This group showed that the proportion of examinations interpretable down to segmental level was dramatically higher in the multislice group (57% vs 13%). Other workers have confirmed objective improvements in CTPA when multislice technology is employed [18, 19].
Solitary subsegmental emboli have been cited in the past as a difficult diagnosis for CTPA despite accounting for less than 10% of all embolic events. With multislice technology, it has become routine to be able to clearly visualize vessels down to sixth order [20].
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Technique
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Acquisition protocols for CTPA will vary between different makes of equipment and will depend on the speed of rotation of the gantry and the number of rows of detectors. However, some factors are common to the technique, and suggested general considerations are outlined in Table 2. Ideally, for the exclusion of thromboembolic disease down to fourth order vessels or smaller, collimation should be set at 2 mm or less (Table 3). Coverage should be as wide as possible, but from at least the level of the upper border of the aortic arch down to the base of the heart is possible. This area will encompass the majority of subsegmental vessels. Many previous protocols have suggested that scanning should be in a caudocranial direction to ensure minimum movement of the most mobile lower lobe vessels at the start of the sequence. This is probably no longer necessary in view of the speed and coverage of multislice equipment. The scan delay time will vary significantly depending on the haemodynamic status of the patient. Scan delays can vary from 10 s to 20 s and bolus tracking may be helpful.
A further potential advantage of multislice CTPA is a reduction in administered contrast medium volume. Until now most studies have employed approximately 120–150 ml of intravenous contrast medium. Experience with multislice systems has suggested that this volume can be reduced to 100 ml or less.
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Image interpretation
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Classical CTPA abnormalities are well described in other larger publications [21]. Positive findings include partial central filling defects (Figure 1) giving rise to the so-called "polo mint" effect (or "tram lining" if parallel to the axial plane), eccentric defects frequently seen at the origin of branches, and abrupt cut-off of vessels that often appear inappropriately enlarged. Distal emboli can give rise to wedge-shaped pleural-based areas of consolidation often with a "feeding" pulmonary artery entering the apex (Figure 2). These are the CTPA equivalent of Hampton's hump. Owing to its dual blood supply, the lung does not often undergo infarction and these areas probably represent focal haemorrhage accompanied by pleural irritation. Unfortunately, wedge-shaped parenchymal changes may be seen with processes other than thromboembolism, such as pneumonia and neoplasia. Similarly, it is not uncommon for peripheral parenchymal changes of PE to be irregular in shape. However, the finding of characteristic parenchymal changes in someone with appropriate symptoms and risk factors should raise suspicion of venous thromboembolism even in the absence of obvious intravascular filling defects. In this scenario, a review of the lower limbs by CTV, phlebography or ultrasound may be helpful.
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Figure 1. CT pulmonary angiography viewed on mediastinal settings showing characteristic filling defects of long segments of leg vein thrombus coiled in the central pulmonary arteries.
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Figure 2. CT pulmonary angiography on lung parenchymal settings showing multiple pleural-based wedge-shaped areas of consolidation in keeping with pulmonary infarcts. This patient had pleuritic chest pain and haemoptysis. Note previous myocardial infarction that has resulted in thinning of the septum of the left ventricle.
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Pitfalls in interpretation are often caused by poor technique, which can give rise to motion artefact, particularly respiratory artefact in the lower lobes. Errors in contrast bolus timing or slow delivery may also give rise to underfilling of target vessels, which can occasionally mimic abrupt vessel cut-off or even pseudo polo mint effect. It is wise to scroll through the images to ensure a continuous adequate bolus has been administered. Hilar lymphadenopathy can cause pseudo filling defects, seen particularly at the bifurcations of the proximal vessels. Partial volume artefact of the fibrofatty node that sits just above the origin of the right main pulmonary artery may also cause confusion but can be resolved by scrolling the images. Artefact caused by dense contrast medium in the adjacent superior vena cava can occasionally give rise to difficulty with interpretation of the right upper lobe vessels. It has been recognized for some time that complex structures are often best viewed in scrolling or "cine" mode and it is recommended that identification or exclusion of PE should only be made on a workstation and not from hard copy. In our institution, the full examination is stored digitally on the picture archiving and communication system (PACS) and no hard copy is made. Workstation review also allows an opportunity to carry out multiplanar reconstruction, which can occasionally be helpful in assessing vessels that run parallel to the axial plane, notably the right middle lobe and lingular arteries. It has recently been suggested that transforming the axial images into a rotated paddle-wheel format can give higher detection of PE than standard coronal reconstructions [22]. Optimum viewing windows should also be selected to be appropriate for the structures being interrogated and the density of contrast medium. It has been suggested that optimum windows for assessment of the pulmonary vessels are centred at a level of –100 Hounsfield units (HU) with a width of 1000 HU [23]. Optimum settings for lung parenchyma may be a level of –600 HU and a width of 1600 HU.
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CTPA vs other modalities
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Some authors have advocated CTPA as a single first line imaging test based on its high sensitivity and specificity. This approach assumes that small peripheral emboli are unimportant if overlooked. This seems to be borne out by the high negative predictive value of CTPA, which compares favourably with a negative Q scan (previously the best negative predictor). At a clinical level, the incidence of subsequent events following a negative scan is very low [24]. The direct-to-CTPA algorithm, however, assumes adequate resources to dedicate enough CT time to the pursuit of thromboembolic disease. In practice there is often intense pressure to deal with other urgent cases including trauma, neurovascular disease and acute abdominal pathology, not to mention the massive load generated by cancer imaging. It is therefore necessary in many departments to filter cases to alternative modalities. The British Thoracic Society has in the past advocated echocardiography as a frontline test for suspected massive PE [25]. This technique may itself be in short supply and gives only indirect confirmation of thromboembolic disease. Scintigraphy is usually the main complementary technique and attempts have been made to help identify its optimum role. In radiological terms, patients with peripheral emboli present a more difficult challenge for CTPA since sensitivity not surprisingly falls off in subsegmental vessels. In contrast, lung scintigraphy is relatively sensitive to peripheral vascular occlusion. Studies have shown that if the chest radiograph is clear and there is no prior history of significant lung disease, a radioisotope perfusion lung scan may be considered a useful first line investigation [26]. Whenever the chest radiograph is abnormal and there is a background of chronic lung disease such as chronic obstructive pulmonary disease (COPD) and asthma, CTPA may yield a significantly higher diagnostic result.
The British Thoracic Society guideline referred to above has been reviewed and re-released as a result of recent advances in diagnosis and therapy [27]. This new guideline makes a number of recommendations that have implications for radiology. First, it is suggested that there is proper clinical review of the patient and that a clinical probability score accompanies any radiology request. This simple scoring system is based on the Wells' criteria [28]. In a patient with compatible clinical features, probability of PE is high if: there is no other demonstrable cause for symptoms and there is a major risk factor. If only one of these is true the probability is intermediate and if neither is true then the probability is low. These criteria help convey to the radiologist the degree of clinical suspicion accompanying any particular case. It has also been suggested that clinical probability scoring may substantially reduce the need for imaging if used in conjunction with D-dimer assay [29]. However, practical experience with this combination suggests that it can lead to an increase in radiological activity rather than the converse owing to the poor positive predictive value of D-dimer assay. In one study, researchers found a doubling of the total number of patients requiring imaging tests because of the high number of false positive D-dimer tests [30].
Importantly, the guideline recommends that CTPA should be the first choice imaging modality in non-massive PE and, if a good quality examination is negative, no further imaging is required. It goes on to recommend that scintigraphy is acceptable if the chest radiograph is normal and, if it is non-diagnostic, further imaging should always be performed. It also states that a single normal leg ultrasound should not be relied upon to exclude culprit deep venous thrombosis in an asymptomatic limb.
A significant major advantage of multislice CTPA over all other modalities is that non-embolic abnormalities that may be responsible for either symptoms or for incidental disease are frequently demonstrated [31]. Several studies have confirmed that up to three-quarters of all patients suspected of PE will have an alternative diagnosis [32]. A particular benefit of the temporal and spatial resolution of multislice systems has been the demonstration of mediastinal and cardiac structures that may reveal the correct diagnosis (Figure 3).
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Figure 3. This 36-year-old man presented with pleuritic type chest pain. CT pulmonary angiography demonstrated the presence of a significant pericardial effusion, later confirmed as viral pericarditis.
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In pregnant patients, CTPA may be used as the first line test, having an advantage over scintigraphy in terms of the absorbed dose to the fetus [33]. An alternative approach is to utilize a half-dose perfusion lung scan when performed in the presence of a normal chest radiograph. If the chest radiograph is abnormal, CTPA remains the best option.
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Severity stratification
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It is well recognized that perfusion defects demonstrated on scintigraphy can significantly underestimate the volume of thrombus. Significant work has been carried out using helical CT in terms of attempting to quantify and stratify thrombus load. Bankier and colleagues [34] have adopted a modified Miller score, which was originally developed for conventional pulmonary angiography. This technique attributes a score of 1 for the presence of thrombus in each of the pulmonary segments, irrespective of the percentage of obstruction in that segment. This system appears to correlate well with clinical findings. A more refined scoring system has been developed by Mastora and colleagues [9]. Further work has been carried out to determine the prognostic value of these scoring systems [35]. It has also been noted that some assessment can be made of right ventricular overload at the time of CTPA [7]. This may give significantly useful information that may be comparable with echocardiographic assessment of the afterload effect of massive embolism on the right heart [36, 37].
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CT venography
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It has been recognized for some time that thrombosis of the inferior vena cava and lower limb veins could be visualized by contrast-enhanced CT (Figure 4). A more recent innovation has been the suggested routine use of follow-on (indirect) CTV using the same contrast bolus injected for the primary CTPA [38–40]. This technique visualizes the inferior vena cava (IVC), pelvic veins and leg veins in an attempt to demonstrate culprit thrombus at source. It has also been suggested that assessment of the volume of residual lower limb thrombus may be helpful in management planning, e.g. the potential placement of a caval filter. To achieve the necessary density of contrast medium at 3 min (the average time of starting the lower limb scan post injection for CTPA), it is recommended that an adequate bolus (120–150 ml) be administered for the CTPA (Table 4). Like any imaging procedure, follow-on CTV also has recognized pitfalls [41]. Difficulty may be experienced because of heterogeneous venous enhancement caused by inadequate mixing and scanning too early or by layering in dilated vessels. Failure to recognize anatomical variants such as duplication of the IVC and the deep thigh veins is especially problematic, particularly if there is complete occlusion of one channel of the duplication. Other potential pitfalls include confusion with thrombosed native arteries, lymph nodes, haematomas, neurinomas and Baker's cysts.
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Figure 4. This patient presented with bilateral leg swelling and chest pain. CT pulmonary angiography confirmed a small embolus and CT venography showed inferior vena cava thrombus (arrow).
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It may not be immediately obvious why the addition of indirect CTV could be an advantage in light of the sensitivity and negative predictive value mentioned above for CTPA alone. However, it appears that CTV can increase the number of cases of thromboembolism detected by up to 26% by demonstrating residual lower extremity thrombus in those with a negative or equivocal CTPA [42]. Although the optimum use of indirect CTV has not yet been defined, these data would suggest that it should be employed in conjunction with every CTPA that is equivocal or negative. However, unless the CT scanner being used has real-time image reconstruction, the 3 min injection/scan delay can be too short to allow adequate review of the CTPA, necessitating the employment of CTV with all CTPAs, positive or otherwise. Therefore, from a practical viewpoint (taking into consideration the added examination time, complexity, pitfalls and radiation burden), the author would not recommend the routine application of this follow-on technique until studies of sufficient power confirm its added diagnostic advantage. The author would recommend its use if the patient was required to have a second CTPA either because the initial study was technically unsatisfactory or was equivocal.
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Conclusion
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Helical CTPA is now rightly acknowledged as the premier radiological modality for diagnosis of PE [27]. Direct visualization and quantification of thromboembolic material is the major advantage of this technique. This advantage is significantly enhanced by the advent of multislice technology, mainly by virtue of the excellent spatial resolution offered by narrow collimation. The high specificity of the technique will ensure its continued popularity with clinicians. Recent studies confirming its high negative predictive value have been useful in allaying fears over how to treat patients with a negative CTPA. Further research is required to determine whether the technology needs to be pushed further to ensure that all subsegmental emboli are identified. Follow-on CTV could prove to be a promising addition to the technique (once its place has been more clearly defined) by helping to stratify further the risk of patients who have either a negative or indeterminate CTPA.
Received for publication August 25, 2003.
Revision received November 6, 2003.
Accepted for publication November 17, 2003.
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Abstract
Introduction
