|
|
|
 |
|
 |
| Dr Simon Padley FRCP, FRCR
is Consultant Radiologist at the
Chelsea and Westminster Hospital
and the Royal Brompton Hospital.
Following a fellowship in Vancouver
in 19912 he has maintained a
longstanding interest in all aspects
of thoracic imaging and is widely
published in the field. |
Imaging of pulmonary embolism
Simon PG Padley,1 Kapila Jain2
1 Department of Radiology, Chelsea and Westminster
Hospital, London, UK;
2 Department of Radiology, Royal Brompton Hospital,
London, UK
Address for correspondence:
Dr Simon PG Padley
Consultant Radiologist,
Royal Brompton Hospital, Sydney Street,
London, SW3 6NP, UK
Tel: +44 (0)20 8746 8562
Fax: +44 (0)20 8746 8588
Email: s.padley@ic.ac.uk
Abstract
If a diagnosis of pulmonary embolism (PE) has not been
excluded after the initial clinical assessment and chest
X-ray, the options for further evaluation include V/Q
scintigraphy and CT. CT pulmonary angiography allows
the pulmonary arterial system to be visualised and
inter-observer agreement is generally very good for a
diagnosis of PE. The advantage of CT over other imaging
techniques is that it also demonstrates other aspects
of the thoracic anatomy and facilitates alternative
diagnoses. This is important since up to two-thirds of
patients with suspected PE may eventually receive a
different diagnosis. The advent of spiral MDCT provides
a powerful tool for diagnosis of PE that is currently
being compared with various combinations of tests in
the PIOPED II study. CT is undoubtedly very valuable
for the diagnosis of PE, but in order to reduce radiation
exposure, it should be the last step in a sequential
clinical evaluation.
| Abbreviations |
|
| CT |
Computed Tomography |
| CTPA |
Computed Tomography
Pulmonary Angiogram |
| DVT |
Deep Vein Thrombosis |
| ECG |
Electrocardiogram |
| ELISA |
Enzyme-Linked
Immunosorbent Assay |
| MDCT |
Multidetector Computed
Tomography |
| PE |
Pulmonary Embolism |
| PIOPED |
Prospective Investigation of
Pulmonary Embolism Diagnosis |
| V/Q scintigraphy |
Ventilation-perfusion
Scintigraphy |
Introduction
Pulmonary embolism is a major cause of morbidity
and mortality and, despite much research, remains a
diagnostic challenge due to its non-specific presentation.
Any diagnostic strategy for acute pulmonary embolism
has two main goals:
| • |
Firstly, the strategy must identify those patients
who have had a thromboembolic event and hence
are at risk of a second event. These patients require
long-term anticoagulant therapy. |
| • |
Secondly, but of equal importance, is the need
to identify patients who have not developed a
thrombus and in whom anticoagulation can be
safely withheld. |
Diagnostic protocols
Ideally, there is a progression from clinical assessment
to basic non-imaging tests before imaging of the
pulmonary arteries ensues. Clinical models have been
described and validated that predict the probability of
pulmonary embolism from a patients clinical history,
physical examination, ECG, arterial blood gases and
chest radiography.3 This diagnostic process can help
identify other conditions such as myocardial infarction,
pneumonia or pneumothorax. The addition of the
plasma D-dimer (a degradation product of cross-linked
fibrin) assay provides a highly sensitive test with a
high negative predictive value. It has become clear
that the highest utility of the D-dimer test is derived
from its use as the principal screening blood test in
emergency department patients. The test is less useful
for patients who are already in hospital since D-dimer
levels can be elevated in many pathological conditions
such as malignancy and infection, in the absence of
venous thrombosis. In a recent study by Dunn et al.,
the sensitivity of the D-dimer assay was 97% and
the negative predictive value for suspected PE was
99.6%.4 In this and other studies, the combination
of a normal ELISA D-dimer level and a low clinical
probability has been shown to be accurate in ruling
out pulmonary embolism,5,6 with a 3-month risk of
subsequent thromboembolism in patients who were not
anticoagulated in these studies between 0 and 1.5%.
The chest radiograph is usually obtained at the time of
initial assessment and may demonstrate abnormalities including regional oligaemia, pleural-based densities,
and lung volume loss. However, these findings are nonspecific
for PE.7 The chest radiograph may be normal,
even in patients with massive PE although usually at
least some changes are evident. The main benefit of
a chest radiograph in patients with suspected PE is its
ability to demonstrate a non-embolic aetiology for the
patients symptoms, and its added value in the decision
to undertake and subsequent interpretation of the
V/Q scintigraphy.
Ultrasound examination of the lower extremities is
widely used for detection of presence of DVT in patients
with suspected PE. However, its use in diagnosing DVT
is controversial in asymptomatic patients810 and a
negative leg ultrasound study is an unreliable basis on
which to exclude PE, probably because the DVT has
often completely embolised to the lungs.11
If the initial diagnostic round does not exclude
pulmonary embolism, then historically, nuclear medicine
V/Q scintigraphy has been the imaging mainstay for
further evaluation of suspected PE. More recently,
enthusiasm for the test has waned, despite its high
sensitivity. This is because of the high percentage
of indeterminate scans 73% of all performed V/Q
studies, when the classic PIOPED criteria are applied.12
Furthermore, poor interobserver correlation13 and a poor
spatial resolution detract from the test which provides
only indirect evidence for PE, based on the assessment
of pulmonary perfusion rather than direct visualisation
of the venous thromboembolism. Nevertheless, the
test remains a prime imaging tool in a more selected
population.
Undoubtedly, magnetic resonance imaging produces high
tissue contrast without ionising radiation but, at present,
this technique is less popular for evaluation of an acutely
ill patient with possible PE. This is due to technical
limitations in patient monitoring, higher costs, limited
availability and relatively long examination times.
CT Pulmonary Angiography
 |
 |
 |
| Figure 1. (a) Axial, (b) coronal, and (c) oblique multiplanar reformats
(MPRs) from a MDCT CTPA dataset with a central and lobar pulmonary
embolism. |
CTPA has emerged as a front-line imaging modality
in cases of suspected acute PE in daily clinical practice
in many institutions. One important advantage of
CT over other imaging modalities is its ability to
demonstrate anatomy beyond the pulmonary arteries.
Hence with CT, both mediastinal and parenchymal
structures are evaluated and thrombus is directly
visualised. Studies have shown that up to two-thirds of
patients with an initial suspicion of PE will eventually be
labelled with an alternative diagnosis,14 including aortic
dissection, pneumonia, lung cancer, and pneumothorax.15 Most of these diagnoses are readily apparent on CT and
allow a specific aetiology for the patients symptoms to
be established.16
After contrast administration, CTPA provides
visualisation of the pulmonary arterial system in the
axial plane, and multiplanar and three-dimensional
reconstructions can be generated from raw data
(Figure 1). These have little added diagnostic value but
are useful for the display and demonstration of anatomy
and pathology. Usually for a CTPA study 120140 ml
of intravenous contrast material is injected at a rate
of 35 ml per second, although there is a trend for
concentration of contrast to rise and volumes to fall
as scanners become faster and image detail improves.
The cardinal sign of acute PE on CTPA is an intra-arterial
filling defect that partially or completely occludes the
vessel and may be associated with increased diameter
of the affected vessel. The inter-observer agreement for
spiral CT is better than for scintigraphy.17 In a recent
study, the inter-observer agreement for the diagnosis
of PE was very good for spiral CT angiography (k=0.72)
and only moderate for V/Q lung scanning (k=0.22).13
On comparison with diagnostic algorithms that
are based on other imaging modalities (ultrasound,
scintigraphy and pulmonary angiography) for diagnosis
of PE, spiral CT appears to be the most cost-effective
approach.18
Early studies comparing conventional single slice
spiral CT (using 5 mm thick sections) with selective
pulmonary angiography demonstrated a high accuracy
of spiral CT for detecting PE from the main pulmonary
artery to the segmental arterial level, but less than
ideal sensitivity rates, especially at the subsegmental
level,19,20 due to partial volume effects on small-sized
vessels. The degree of accuracy that can be achieved for
the visualisation of subsegmental pulmonary arteries
and for detection of emboli in these vessels with single
slice, dual slice and electron beam CT scanners was
found to range between 61% and 79%.19,21,22 This low
accuracy has proved to be the main barrier to universal
acceptance of CT as the new approach of choice for the
diagnosis of acute PE.
Concerns over the accurate detection of subsegmental
clots have been a source of controversy, despite the
uncertainty over the clinical significance of small
peripheral emboli. It has been suggested that 630% of
patients with documented PE present with clots only
in subsegmental and smaller arteries.12,23 Controversy
exists concerning the treatment of small emboli and
whether this will result in improved clinical outcome.24,25
Several recent studies23,26,27 have looked at the frequency
of venous thromboembolic episodes in a 312 month
period following a negative CTPA; they have concluded
that patients with a clinical suspicion of acute PE and
stable vital signs but with a negative CTPA may be
safely left untreated.
These studies were performed at between 35 mm
collimation and concluded that the negative predictive
value of a normal CTPA was high, compared favourably
with catheter pulmonary angiography,28 and approached
98%, regardless of whether underlying lung disease was
present.29,30 On the other hand, the value of a negative
CTPA has not been evaluated exhaustively in patients
with poor cardiopulmonary reserve, where the additional
burden of a small PE may be fatal. Indeed, a recent
study by de Monye et al.31 found that 21% of patients with isolated subsegmental clot had a high probability
V/Q scan lending support to the argument that
subsegmental emboli may be physiologically significant.
Advantages of MDCT
The introduction of multidetector spiral CT has been a
milestone in CTA technology and has helped to dispel
any remaining concerns about the accuracy of spiral CT
for PE detection. The current generation of 4-, 16- and
now 64-slice MDCT scanners allows comprehensive
evaluation of the entire chest with 1 mm or
submillimeter resolution within a short single breath
hold (6 seconds in a 64-slice CT). Shorter breath-hold
times are of benefit for patients with underlying lung
disease and reduce the percentage of non-diagnostic
scans.32 Compared with single slice CT, MDCT can more
precisely delineate clots down to the subsegmental
level: third subsegmental branches can be assessed with
4 x 2.5 mm collimation,33 and delineation of arteries
down to the 5th and 6th order can be achieved with 4
x 1 mm collimation.34 The use of thin (approximately
1 mm) sections significantly decreases the number of
arteries classified as indeterminate by approximately
70% and improves interobserver agreement in
detection of PE.35
The interobserver correlation for confident diagnosis of
subsegmental emboli with high resolution spiral MDCT
far exceeds the reproducibility of selective pulmonary
angiography.3537 Combining such a dedicated
examination protocol with additional 3D shaded surface
display reconstruction images allows precise anatomical
analysis of peripheral pulmonary arteries, together with
the ability to convey information in a more intuitive
display format.38 According to the updated guidelines
of the British Thoracic Society, no further examination
or treatment is needed for patients with a high-quality
negative MDCT pulmonary angiogram.39,40
Because PE and deep venous thrombus are two different
aspects of the same disease, a combined examination including indirect CT phlebography has been suggested
as an option for complete assessment of venous
thromboembolism,41 although uptake of this approach
has been influenced by concerns over increased
radiation exposure in the general population.42,43
The efficacy of spiral MDCT in patients suspected of
having PE is currently being assessed by the PIOPED II
study.44 The performance of CTPA is assessed against a
composite reference test for venous thromboembolism
based on the V/Q lung scan, venous compression
ultrasound of the lower extremities, digital subtraction
pulmonary angiography, and contrast venography in
various combinations, in order to establish the PE status
of the patient. Results are pending but preliminary
indications suggest that MDCT may become the firstline
study in patient evaluation.
MDCT has provided a powerful tool for imaging the
pulmonary arteries. However, it should be remembered
that CT is the most significant source of radiation
exposure for the general population, particularly in
the context of the thin slice acquisitions of extensive
anatomical volumes now routine with MDCT. The
most important step to reduce the overall radiation
burden from CT for suspected PE is the effective
implementation of clinical algorithms where CT is the
endpoint of a progression from clinical assessment
through non-imaging testing, with imaging investigation
being employed only in those patients for whom PE
remains a realistic possibility.
Key Learning
• Pulmonary embolism remains a major healthcare concern and rapid and accurate diagnosis is imperative to
reduce mortality
• Primary aim for diagnosis of suspected PE is to identify patients who would need long term anticoagulant
therapy
• Diagnostic strategy normally proceeds from clinical assessment, D-dimer measurement to imaging modalities
including nuclear medicine, ultrasonography and computed tomography
• CT pulmonary angiography enables direct visualisation of thrombus as an intra-arterial filling defect and has
a high negative predictive value for clinically relevant PE
• An advantage of CT is its ability to look at anatomy beyond the pulmonary arteries
• Wide availability of multidetector-row spiral CT has greatly improved visualisation of peripheral pulmonary
arteries and detection of small emboli not seen with single slice CT, in a short single breath hold
• CT is rapidly becoming the sole imaging modality for the accurate detection of central and peripheral
pulmonary embolism |
References
1. Van Beek EJR, Brouwers E, Song B, et al. Clinical validity of a normal
pulmonary angiogram in patients with suspected pulmonary embolism-a
critical review. Clin Radiol 2001;56:83842.
2. Van Beek EJR, Reekers JA, Batchelor D, et al. Feasibility, safety and clinical
utility of angiography in patients with suspected pulmonary embolism and
non-diagnostic lung scan findings. Eur Radiol 1996;6:4159.
3. Minaiati M, Bottai M, Monti S. Comparison of 3 Clinical Models for
predicting the probability of pulmonary embolism. Medicine 2005;84:
10714.
4. Dunn KL, Wolf JP, Dorfman DM, et al. Normal D-dimer levels in
emergency department patients suspected of acute pulmonary embolism.
J Am Coll Cardiol 2002;40:14758.
5. Marieke JHA, Monique GLL, Leclecq, MD et al. Diagnostic strategies for
excluding pulmonary embolism in clinical outcome studies. A systematic
review. Ann Intern Med 2003;138:94151.
6. Perrier A, Roy PM, Aujesky D, et al. Diagnosing pulmonary embolism
in outpatients with clinical assessment, D-dimer measurement, venous
ultrasound, and helical computed tomography: a multicenter management
study. Am J Med 2004;116:2919.
7. Elliott CG, Goldhaber SZ, Visani L, et al. Chest radiographs in acute
pulmonary embolism: results from the International Cooperative
Pulmonary Embolism Registry. Chest 2000;118:338.
8. Jongbloets LM, Lensing AW, Koopman MM, et al. Limitations of
compression ultrasound for the detection of symptomless postoperative
deep vein thrombosis. Lancet 1994;343:11424.
9. Wells PS, Lensing AW, Davidson BL, et al. Accuracy of ultrasound for
the diagnosis of deep venous thrombosis in asymptomatic patients after
orthopedic surgery: a meta-analysis. Ann Intern Med 1995;122:4753.
10. Mac Gillavry MR, Sanson BJ, Bόller HR, et al. Compression
ultrasonography of the leg veins in patients with clinically suspected
pulmonary embolism: is a more extensive assessment of compressibility
useful? Thromb Haemost 2000;84:9736.
11. Turkstra F, Kuijer PM, van Beek EJ, et al. Diagnostic utility of
ultrasonography of leg veins in patients suspected of having pulmonary
embolism. Ann Intern Med 1997;126:77581.
12. PIOPED Investigators. Value of the ventilation/perfusion scan in acute
pulmonary embolism. JAMA 1990;95:498502.
13. Blachere H, Latrabe V, Montaudon M, et al. Pulmonary embolism
revealed on helical CT angiography: comparison with ventilation-perfusion
radionuclide lung scanning. AJR Am J Roentgenol 2000;174:10417.
14. Hull R, Raskob GE, Ginsberg JS, et al. A non invasive strategy for the
treatment of patients with suspected pulmonary embolism. Arch Intern
Med 1994;154:28997.
15. van Rossum AB, van Erkel AR, van Persijn van Meerten EL, et al.
Accuracy of helical CT for acute pulmonary embolism: ROC analysis
of observer performance related to clinical experience. Eur Radiol
1998;8:11604.
16. Garg K, Welsh CH, Feyerabend AJ, et al. Pulmonary embolism:
diagnosis with spiral CT and ventilation-perfusion scanning- correlation
with pulmonary angiographic results or clinical outcome. Radiology
1998;208:2018.
17. van Rossum AB, Pattynama PM, Mallens WM, et al. Can helical CT
replace scintigraphy in the diagnostic process in suspected pulmonary
embolism? A retrospective-prospective cohort study focussing on total
diagnostic yield. Eur Radiol 1998;8:906.
18. van Erkel AR, van Rossum AB, Bloem JL, et al. Spiral CT angiography
for suspected pulmonary embolism: a cost-effective analysis. Radiology
1996;201:2936.
19. Goodman LR, Curtin JJ, Mewissen MW, et al. Detection of pulmonary
embolism in patients with unresolved clinical and scintigraphic diagnosis:
helical CT versus angiography. AJR Am J Roentgenol 1995;164:136974.
20. van Rossum AB, Pattynama PMT, Ton ER, et al. Pulmonary embolism:
validation of spiral CT angiography in 149 patients. Radiology
1996;201:46770.
21. Mayo JR, Remy-Jardin M, Muller NL, et al. Pulmonary embolism:
prospective comparison of spiral CT with ventilation-perfusion
scintigraphy. Radiology 1997;205:44752.
22. Qanadli SD, Hajjam ME, Mesurolle B, et al. Pulmonary embolism
detection: prospective evaluation of dual-section helical CT versus
selective pulmonary arteriography in 157 patients. Radiology
2000;217:44755.
23. Oser RF, Zuckerman DA, Gutierrez FR, et al. Anatomic distribution
of pulmonary emboli at pulmonary angiography: implications for cross
sectional imaging. Radiology 1996;199:315.
24. Cauvain O, Remy-Jardine M, Remy J, et al. Spiral CT angiography in the
diagnosis of central pulmonary embolism: comparison with pulmonary
angiography and scintigraphy. Rev Mal Respir 1996;13:14153.
25. Novelline R, Baltarowich O, Athanasoulis C, et al. The clinical course of
patients with suspected pulmonary embolism and a negative pulmonary
angiogram. Radiology 1978;126:5617.
26. Nilsson T, Olausson A, Johnsson H, et al. Negative spiral CT in acute
pulmonary embolism. Acta Radiol 2002;43:48691.
27. Gottsater A, Berg A, Centergard J, et al. Clinically suspected pulmonary
embolism: is it safe to withhold anticoagulation after a negative spiral CT?
Eur Radiol 2001;11:6572.
28. Henry JW, Relyea B, Stein PD. Continuing risk of thromboemboli
among patients with normal pulmonary angiograms. Chest
1995;107:13758.
29. Ost D, Rozenshtein A, Saffran L, et al. The negative predictive value of
spiral computed tomography for the diagnosis of pulmonary embolism
in patients with non-diagnostic ventilation-perfusion scans. Am J Med
2001;110:1621.
30. Tillie-Leblond I, Mastora I, Radenne F, et al. Risk of pulmonary
embolism after a negative spiral CT angiogram in patients with pulmonary
disease: 1-year clinical follow-up study. Radiology 2002;223:4617.
31. de Monye W, van Strijen MJ, Huisman MV, et al. Suspected pulmonary
embolism: prevalence and anatomic distribution in 487 consecutive
patients. Advances in New Technologies Evaluating the Localisation of
Pulmonary Embolism (ANTELOPE) Group. Radiology. 2000;215:1848.
32. Remy-Jardin M, Tillie-Leblond I, Szapiro D, et al. CT angiography of
pulmonary embolism in patients with underlying respiratory disease:
impact of multislice CT on image quality and negative predictive value. Eur
Radiol 2002;12:19718.
33. Mόller C, Kopka L, Funke M, et al. Diagnosis of lung embolism and
underlying venous thrombosis in multi-slice spiral CT. Fortschr Rφntgenstr
2001;173:52835.
34. Ghaye B, Szapiro D, Mastora I, et al. Peripheral pulmonary arteries:
how far in the lung does the multi-detector row spiral CT allow analysis?
Radiology 2001;219:62936.
35. Schoepf UJ, Holzknecht N, Helmberger TK, et al. Subsegemental
pulmonary emboli: improved detection with thin collimation multidetector
row spiral CT. Radiology 2002;222:48390.
36. Diffin D, Leyendecker JR, Johnson SP, et al. Effect of anatomic
distribution of pulmonary emboli on interobserver agreement in
the interpretation of pulmonary angiography. AJR Am J Roentgenol
1998;171:10859.
37. Stein PD, Henry JW, Gottschalk A. Reassessment of pulmonary
angiography for the diagnosis of pulmonary embolism: relation of
interpreter agreement to the order of the involved pulmonary arterial
branch. Radiology 1999;210:68991.
38. Coche E, Pawlak S, Dechambre S, et al. Peripheral pulmonary arteries:
identification at multislice spiral CT with 3D reconstruction. Eur Radiol
2003;13:81522.
39. Goldhaber SZ, Elliott CG. Acute pulmonary embolism, Part 1:
epidemiology, pathophysiology, and diagnosis. Circulation 2003;108:
27269.
40. British Thoracic Society Standards of Care Committee Pulmonary
Embolism Guideline Development Group. British Thoracic Society
guidelines for the management of suspected acute pulmonary embolism.
Thorax 2003;58:47083.
41. Ginsberg MS, OH J, Welber A, et al. Clinical usefulness of imaging
performed after CT angiography that was negative for pulmonary embolus
ina high-risk oncologic population. AJR Am J Roentgenol 2002;179:12058.
42. Diederich S. Radiation dose in helical CT for detection of pulmonary
embolism. Eur Radiol 2003;13:14913.
43. Ghaye B, Dondelinger RF. Nontraumatic thoracic emergencies: CT
venography in an integrated diagnostic strategy of acute pulmonary
embolism and venous thrombosis. Eur Radiol 2002;12:190621.
44. Gottschalk A, Stein PD. Goodman LR, et al. Overview of prospective
investigation of pulmonary embolism diagnosis II. Semin Nucl Med
2002;32:17382. |
|
|
