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Acute Pulmonary

Embolism
Jean Kuriakose, MBBS, MRCP, FRCRa,
Smita Patel, MBBS, MRCP, FRCRb,*

KEYWORDS
 CT pulmonary angiography  Pulmonary embolism
 CT venography  Radiation exposure

Imaging plays a crucial role in the diagnosis of population, in order to minimize unnecessary
pulmonary embolism (PE) and deep venous medical radiation exposure.
thrombosis (DVT), a spectrum of the same disease Pretest risk stratification using Wells criteria,
entity. PE is the third most common cause of clinical probability scores, assessing premorbid
cardiovascular death in the United States, fol- conditions, past history, and a thorough clinical
lowing ischemic heart disease and stroke, with examination should precede an appropriate,
an annual incidence of 300,000 to 600,000 per timely ,and accurate diagnostic test.8,9 In some
year.1,2 Despite the high prevalence, PE is difficult common scenarios like pregnancy and in critically
to diagnose, with only 43 to 53 patients per ill patients, the diagnosis of PE still remains
100,000 being accurately diagnosed, and up to challenging.
70% of clinically unsuspected PE diagnosed at
autopsy.1,3 In the past few decades, the incidence
of PE has decreased by 45%, whereas that of DVT
DIAGNOSIS OF ACUTE PULMONARY
is unchanged.4,5 Death occurs in up to 90% of
EMBOLISM
patients with unrecognized PE, whereas in treated
Ventilation-Perfusion Scintigraphy
patients PE accounts for less than 10% of
deaths.6,7 Combined ventilation and perfusion (V/Q) scintig-
Rapid and timely diagnosis of this life-threat- raphy had been the imaging technique of choice
ening disease is important to improve patient for decades. A V/Q scan with normal findings
outcome as the signs and symptoms as well as essentially excludes pulmonary embolism with an
ancillary tests are nonspecific. The recent rapid NPV (Negative Predictive Value) close to 100%,
growth in CT technology over the past decade thereby precluding the use of anticoagulation,
has seen the emergence of CT pulmonary angiog- whereas a high-probability scan is highly specific
raphy (CTPA) as the single first line test in the diag- for the diagnosis of PE, allowing definitive treat-
nosis of PE because of its high diagnostic ment. In the original PIOPED (Prospective Investi-
accuracy and ability to provide alternate diagnosis gation of Pulmonary Embolism Diagnosis) study
for diseases of the lung parenchyma, pleura, peri- only 14% of patients had a normal V/Q scan and
cardium, aorta, heart, thoracic lymph nodes, and 13% a high-probability V/Q scan, rendering
mediastinum. a definitive diagnosis in only a small group of
The widespread availability and use of CTPA patients; most (73%) had an indeterminate (non-
has made the diagnosis of PE easier in most diagnostic) or low-probability test result.10 This
cases, but has raised the need for optimal use high degree of uncertainty makes initiation of
of this technique in the appropriate patient definitive anticoagulant therapy difficult because
radiologic.theclinics.com

a
Division of Cardiothoracic Radiology, Department of Radiology, University of Michigan Health System, 1500
East Medical Center Driver, Ann Arbor, MI, USA
b
Department of Radiology, University of Michigan Health System, Cardiovascular Center - Room 5338, 1500
East Medical Center Drive, Ann Arbor, MI 48109-5868, USA
* Corresponding author.
E-mail address: smitap@med.umich.edu (S. Patel).

Radiol Clin N Am 48 (2010) 31–50


doi:10.1016/j.rcl.2009.10.002
0033-8389/09/$ – see front matter ª 2010 Published by Elsevier Inc.
32 Kuriakose & Patel

of risk of bleeding and necessitates additional a single breath-hold, allowing diagnosis predomi-
tests to diagnose or exclude pulmonary embolism. nantly of central and segmental PE. With rapid
The criteria for reporting V/Q scans have evolvement of CT technology, the CT diagnosis
improved significantly.11 Recent use of V/Q scan- of PE has been a subject of much research in the
ning with SPECT allows 3-dimensional visualiza- past couple of decades, and has resulted in
tion of segments previously not identified on CTPA becoming a first-line imaging test at many
planar imaging, such as the medial basal segment centers.21 CTPA is a relatively safe, accurate,
of the right lower lobe. The lung segments are readily available and cost-effective noninvasive
more clearly defined and can be viewed in any test that not only diagnoses PE, but also provides
orthogonal plane, resulting in better detection diagnosis of alternative pathologies in the thorax
and characterization of defects.12 SPECT also accounting for patient symptoms, particularly in
improves image contrast, thus decreasing the the inpatient and emergency department settings.
rate of intermediate scan reports. Large-scale Faster multidetector scanners have set the way
trials are needed to fully assess this modality and for a potential new gold standard test. With newer
compare its performance with CTPA. Currently 128 and higher slice scanners, the sensitivity and
the definitive primary role of V/Q scanning is in specificity is likely to increase albeit at a cost of
patients where CTPA is contraindicated as in increased radiation.
severe renal impairment or history of iodine or
contrast allergy. Advances in MDCT
MDCT has several advantages over SDCT (single
Catheter Pulmonary Angiography detector CT) in the diagnosis of PE, which include
Catheter pulmonary angiography has been improved z-axis resolution, shorter scan times,
considered as the reference test for the diagnosis reduction in volume of contrast, and the ability to
of PE since the late 1960s. However, the invasive do a combined CTPA/CT venography (CTV) exam
nature and expense of the study along with a small at the same setting with a single bolus of contrast.
but definite risk in morbidity has contributed to its
underutilization. Two studies, done 12 years apart Z-Axis Resolution
in 1240 patients, showed that following an incon- Advances in MDCT technology with improved
clusive V/Q scan result, catheter pulmonary angi- gantry rotation speeds and increased detector
ography was performed in less than 15% of width allow rapid acquisition of large volumetric
patients.13,14 Many patients were treated with anti- datasets over a greater craniocaudal distance
coagulants without a definitive result. Accurate than with SDCT. While reduction in slice collima-
diagnosis is important, as anticoagulants them- tion with SDCT results in a longer breath hold
selves account for significant morbidity (up to and a likelihood of increased respiratory motion
6.5%), that increases with age and with comorbid artifact, with MDCT reduction in slice thickness
conditions.15,16 leads to better visualization of subsegmental
With the newer generation of MDCT (multidetec- pulmonary arteries, with 94% of fifth order and
tor CT) scanners, the role of catheter pulmonary 74% of sixth order pulmonary arteries being visu-
angiography as the gold standard test has been alized.22–24 Reducing the reconstruction thickness
questioned and is considered to be flawed, partic- decreases partial volume averaging and also
ularly at the subsegmental level.17–19 The interob- results in better visualization of the obliquely
server agreement at the subsegmental level on oriented middle lobe and lingular arteries, in which
the original PIOPED study was reported to be an estimated 20% of emboli occur.17 Reducing the
only 66%.10 In PIOPED II, in the 20 discordant slice thickness also improves the interobserver
cases, PE was missed at the lobar, segmental, agreement for diagnosis of PE.25
and subsegmental levels in 13 patients; 8 of 13
were at the subsegmental level.19 The current Shorter Scan Acquisition Time
role of catheter pulmonary angiography is when
A shorter breath hold translates into decreased
CTPA is inconclusive, or when the clinical findings
respiratory motion artifact which in turn results in
are discordant with CTPA results.
less indeterminate studies and allows better visu-
alization of the subsegmental pulmonary arteries.
CT Pulmonary Angiography
The scan range for SDCT typically ranges from
Incidental detection of PE was first documented 15 to 20 cm from the top of the aortic arch to the
by Sinner in 1978.20 The advent of single-detector dome of the diaphragm, with a breath hold of 30
helical CT in the early 1990s, made it possible to to 40 seconds or longer, whereas the entire chest
obtain volumetric datasets with good contrast in can be scanned with 16-slice or higher generation
Acute Pulmonary Embolism 33

MDCT scanners at a shorter breath hold of 3 to 10 pulmonary arteries. Incorrect timing is a common
seconds. cause of suboptimal studies. A fixed scan delay
of 20 to 25 seconds was used especially for
Decrease in Contrast Volume SDCT and early generation of MDCT scanners,
The shorter acquisition time enables a reduction in which leads to adequate opacification of the
volume and tighter bolus of contrast for optimal pulmonary arteries in at least 85% of patients
opacification of the pulmonary arteries. With with normal cardiac function. However, with the
SDCT and early generation MDCT, contrast current generation of scanners, a timing bolus or
volumes of 120 mL or higher were commonly bolus tracking method is more commonly used
used, whereas on the current generation of MDCT to optimize opacification of pulmonary arteries.
scanners, studies can be performed with doses of A timing bolus is usually performed by injecting
80 mL or less. A saline chase can also be used to 15 to 20 mL of intravenous contrast material and
further reduce the volume of contrast and to placing a region of interest in the pulmonary trunk
decrease beam hardening artifact from the SVC to obtain a time-density curve from which the
as is done for imaging of the coronary arteries. scan delay can be calculated. When comparing
empirical delay with test bolus, Hartmann and col-
CT Pulmonary Angiography Technique leagues reported that despite objective improve-
ment in pulmonary artery enhancement, there
With rapidly advancing MDCT technology, the was no significant difference in image quality.26
techniques and protocols are continually evolving. Additionally, 16% of the studies had to be excluded
Precise techniques vary between the different because of uninterpretable time density curves.
generation of scanners and between vendors. Alternatively, bolus tracking method can be
Table 1 suggests parameters for CTPA using used with a cursor in the main pulmonary artery
different generations of MDCT scanners. The that triggers scanning at a preset threshold. For
imaging acquisition on the current generation of the 16-slice scanner, the scan is triggered when
scanners includes the entire lungs with resolution a threshold of 120 HU is reached and for the 64-
of 1.25 mm or less. The aim is to perform the study slice scanner, at the first sight of contrast in the
at thinnest slice collimation with a single short pulmonary artery. A timing or bolus tracking
breath hold in full suspended respiration. With method should be used in patients with suspected
the 64-slice and higher generation scanners, it is or known cardiac dysfunction because the optimal
possible to obtain the entire study with a breath scan delay time can be 40 seconds or more.
hold of less than 5 seconds. In intubated patients, In larger patients, a larger volume of high-
because of the short acquisition time, respiration density contrast should be injected at a higher
can be suspended for the duration of the study. flow rate to improve the signal to noise, a higher
With such short breath holds, it does not matter kVP should be used, and images should be
whether the scan is acquired in a caudocranial or acquired at thicker collimation of 2.0 to 2.5 mm
craniocaudal direction. to decrease quantum mottle.
Power injectors are required for rapid contrast
delivery to obtain adequate enhancement of the
pulmonary arteries. An 18- to 20-gauge intrave- ECG Gating
nous cannula is placed in the antecubital vein. The benefit of ECG gating in diagnostic PE evalu-
The degree and quality of pulmonary arterial ation is controversial.27 Only 1% of subsegmental
enhancement depends on the amount and pulmonary arteries are inadequately visualized
concentration of contrast, injection rate, and the secondary to cardiac motion artifact using a 4-
scan delay. On the 64-slice scanner we use row scanner at 1-mm collimation.22 The higher
70 mL of contrast (Isovue 370, Bracco Diagnos- radiation dose secondary to ECG gating is there-
tics, New Jersey) for CTPA imaging of the chest fore not justified. ECG gating in patients with
alone, and for a combined CTPA/CTV study we high or irregular heart rates would lead to consid-
use 120 mL of contrast (Isovue 370 Bracco Diag- erable artifacts. With MDCT scanners, 16-slice
nostics) at 4 mL/s. A greater degree of arterial and higher, the addition of ECG gating to the
enhancement can be achieved by increasing the CTPA study can be helpful when there is a need
rate of contrast, independent of the concentration for a double/triple rule-out study to detect or
of iodine contrast medium. exclude pathology within the pulmonary arteries,
aorta, and/or the coronary arteries. Significant
Timing Bolus/Bolus Tracking
stenosis of coronary arteries or nonenhancement
The timing of contrast bolus administration is crit- of the myocardium in patients with acute myocar-
ical to obtain optimal opacification of the dial infarction may offer an alternative differential
34
Kuriakose & Patel
Table 1
CT pulmonary angiography protocols with evolution of MDCT technology at our institution

Indication Suspected Thromboembolic Disease


Scan type Lightspeed QXi 4-row Lightspeed Ultra 8-row Lightspeed 16 16-row thin/ VCT 64-row
ultrathin collimation
Detector rows 4-row 8-row 16-rowa 64-rowa
Tube setting
kVp 140 140 120 120
mA 380 380 400 500
Gantry speed (s): 0.8 0.7 0.7 0.6
Table speed (mm/rotation): 7.5 13.5 27.5a/13.75a 55
Pitch 1.5 1.35:1 1.375:1 1.375:1
Slice collimation (mm): 1.25 1.25 1.25a/0.625a 1.25/0.625
Breath-hold: Suspended Respiration
Anatomic coverage: Mid diaphragm to lung apices (25 cm) Entire lungs
Acquisition time (s): 27.6 13.8 7.0a/13.5a 3–5
Recon kernel: Standard
Reconstruction thickness 1.25 1.25 1.25/0.625 0.625
(mm):
Effective slice thickness (mm): 2.5 1.6 1.6/0.8
Reconstruction interval (mm): 0.625 0.625 0.625 0.625

Note that protocols vary depending on types of scanners and with different vendors.
a
The 16-row and 64-row scanner allows for a choice of rapid acquisition using a 1.25-mm collimation, which is particularly useful in dyspneic patients, or thinner collimation for
greater spatial resolution.
Acute Pulmonary Embolism 35

diagnosis on these studies. In patients with large


central emboli or a large thrombus burden, right
ventricular function can be assessed on ECG-
gated studies, albeit at increased radiation expo-
sure. Poor right ventricular function has prognostic
implications in patients with significant pulmonary
embolic disease.28

Image Interpretation
Given the large volume datasets and the increased
number of images generated for these studies,
CTPA is now routinely read off a dedicated work
station or PACS system and not on hard copy
images. The window level and width are adjusted
on the fly while scrolling to optimally visualize the
opacified pulmonary arterial lumen. At some insti-
tutions, coronal and sagittal reformats are
routinely generated to aid fast review of the pulmo- Fig. 1. Contrast-enhanced paddle wheel view depicts
nary arterial tree. In an interobserver study evalu- pulmonary emboli in the bilateral main pulmonary
ating the utility of multiplanar reconstructions in arteries, with embolus extending into the right lower
CTPA, the authors report that generated sagittal lobe segmental and subsegmental arteries. Note that
the vessels can be followed in a continuous manner
and coronal reformats do not increase diagnostic
from the hilum.
accuracy, but do increase reader agreement and
reader confidence, and may decrease interpreta-
Indirect Findings
tion time (Espinosa et al, presented at Society of
Thoracic Radiology Annual Meeting, 2008). Pulmonary hemorrhage can occur as a result of PE
The paddle wheel technique helps delineate the and usually resolves within a week. Pulmonary
vessel and its branches in continuity as the artery infarction is seen more frequently in the lower
radiates from the hilum, allowing visualization of lobes as wedge-shaped peripheral areas of
the extent of thrombus burden on a single image consolidation with central low attenuation that do
(Fig. 1). There is no significant difference between not enhance and represent uninfarcted secondary
the paddle wheel technique and axial images for pulmonary lobules (see Figs. 4 and 5).32 Air bron-
detecting central PE.29,30 However, for the diag- chograms are typically not seen in the areas of
nosis of peripheral pulmonary emboli, there is infarcted lung.33,34 The vascular sign (Fig. 4A, B)
significantly lower sensitivity and specificity for increases the specificity for infarction and corre-
the paddle wheel method alone without the sponds to acute embolus in a dilated vessel
concurrent use of axial images.29 leading to the apex of the consolidation (see
Fig. 4).35,36 Other indirect signs of acute PE
include areas of linear parenchymal bands, focal
CT FINDINGS OF PULMONARY EMBOLISM
oligemia, atelectasis or small pleural effusions.33
Direct Findings
Although mosaic attenuation is more common
The diagnosis of PE is made on CT by direct visu- with chronic PE, it can sometimes be seen with
alization of a low attenuation filling defect that acute PE.
partially (Fig. 2) or completely occludes a contrast Acute large central pulmonary emboli can lead
filled artery. A vessel ‘‘cut-off’’ sign is seen when to right heart strain (Fig. 6). The effect of PE on
the distal artery is not opacified owing to the pres- the right heart can be assessed by dilatation of
ence of occlusive PE (Fig. 3). The involved artery the right ventricle (RV) when the short axis diam-
could be significantly larger than the well- eter of the RV to left ventricle (LV) ratio is greater
enhanced corresponding artery on the opposite than one, straightening or deviation of the inter-
side, particularly with occluded smaller-sized ventricular septum toward the LV and compres-
arteries (Fig. 4).31 When PE partially occludes an sion of the LV (Fig. 6) or acute enlargement of
artery, the ‘‘rim-sign’’ (Fig. 2A, C) is seen on short the central pulmonary arteries.28,37,38 Signs of
axis views of the vessel, when the low attenuation right heart strain need to be promptly communi-
embolus is surrounded by a rim of high attenuation cated to the referring physician so that appropriate
contrast, or the ‘‘railway-track’’/‘‘tram-track’’ sign, therapy can be implemented immediately to
on the long axis view of the vessel (Fig. 2B). prevent circulatory collapse.
36 Kuriakose & Patel

Fig. 2. ‘‘Rim-sign’’ and ‘‘railway-track’’ sign. (A) A low attenuation filling defect from nonocclusive embolus is
completely surrounded by a rim of contrast on cross-sectional view of the left lower lobe pulmonary artery.
Note large central PE in the right upper lobe artery. (B) On the long axis view of a segmental pulmonary artery,
contrast is seen on either side of the nonocclusive embolus in the lateral segmental artery of the middle lobe.
Occlusive thrombus is seen in the middle lobe medial segmental artery and its branches. (C) The ‘‘rim-sign’’
(arrows) can be identified even in the presence of consolidation in the right lower lobe.

ARTIFACTS A common pitfall is poor contrast opacification


Technical of the pulmonary arteries. This may be because
of poor cardiac function and can be overcome
Respiratory motion artifact is a common cause for
by delaying the trigger point by using bolus
an indeterminate study. The use of 16-slice and
tracking or timing bolus. Improper coordination
higher generation scanners result in shorter breath
of the total contrast injection dose and injection
holds. Routine use of oxygen via a nasal cannula
flow rate may lead to a pseudo filling defect in
and practicing breath holding with the patient
the pulmonary artery that mimics pulmonary em-
before the acquisition can also help to reduce
bolism (Fig. 8).
this artifact. Motion artifact can cause doubling
A soft tissue reconstruction algorithm should be
of vessels creating a pseudo filling defect
used to avoid high attenuation around vessels that
(Fig. 7).39
Acute Pulmonary Embolism 37

Anatomical
Lymph nodes in the intersegmental region can be
confused for emboli. This is less of a problem with
thin collimation and active scrolling on the work-
station. Low-density mucus-filled bronchi and
pulmonary veins might also mimic filling defects.
This can be differentiated from the corresponding
artery by tracing the structure proximally to its
origin.

Accuracy of CT Pulmonary Angiography


In the first prospective study by Remy-Jardin and
colleagues21 in 1992, single detector CTPA at
5-mm collimation was compared with catheter
angiography, in an ideal group of patients with
optimal contrast, with reported sensitivity of
100% and specificity of 96%, demonstrating
promise for the use of this technique.41 This study
was followed by several studies that compared
single-detector CTPA with catheter angiography
Fig. 3. Vessel cutoff sign of PE. Multiplanar sagittal as the reference test, with sensitivity ranging
oblique reformat of the lower lobe an abrupt cutoff from 53% to 97% and specificity from 78% to
(long arrow) of the contrast column from embolus 97%.42 The wide variability in sensitivity and spec-
that completely occludes the lobar artery in the artery ificity partly reflects differences in technique and
and its distal branches (short arrows). selection bias, as many of these studies were per-
formed on selective patient groups rather than in
consecutive patients with suspected PE. In
mimics PE. Image noise because of large body a systematic literature review of accuracy for PE
habitus increases the quantum mottle and makes detection by Eng and coworkers, combined sensi-
it difficult to evaluate the subsegmental arteries. tivity for PE detection ranged from 66% to 93% and
Increasing the collimation, volume, concentration, combined specificities from 89% to 97%.43 Most of
and rate of contrast helps to increase the signal- these studies were performed on SDCT. With
to-noise ratio. continuously evolving technology, the true accu-
Streak artifacts from beam hardening can occur racy of the technique is difficult to know.
from dense contrast material in the superior vena With the advent and evolution of MDCT tech-
cava or of from a Swan Ganz balloon catheter in niques over the past decade, the higher spatial
the pulmonary artery. This may obscure emboli and temporal resolution of near isotropic data
or may mimic pulmonary embolism. Using a saline sets, with shorter breath holds at thinner collimation,
push immediately after the intravenous (IV) con- has increased the sensitivity and specificity of
trast injection and scanning in the caudal-to- MDCT for PE detection when compared with
cranial direction reduces the density of the SDCT, with reported sensitivity ranging from
contrast material in the SVC. A Swan-Ganz balloon 83% to 100%, and specificity from 89% to
catheter must ideally be pulled out of the pulmo- 97%.18,23,44–46 The recently published PIOPED II
nary artery and placed in the heart or superior study, which was mainly performed on four-slice
vena cava before CTPA acquisition in order to MDCT scanners, that compared CT with a com-
avoid this artifact. posite reference standard, a sensitivity of 83% and
A pulmonary arterial flow artifact called the specificity of 96% was reported for CTPA.18 When
stripe sign is caused by deep inspiration immedi- CTV was also performed, the sensitivity for the
ately before scanning that results in an inhomoge- combined CTPA/CTV exam increased to 90%.18
neous admixture of contrast material from the
superior vena cava and unopacified blood from
Comparison of CT Pulmonary Angiography
the inferior vena cava within the right atrium
with Ventilation and Perfusion Scan
that leads to transient interruption of the con-
trast column in the pulmonary arteries.40 This In a study of 179 patients by Blachere and
can be reduced by scanning in suspended colleagues a statistically significant greater accu-
inspiration. racy for CTPA was reported (sensitivity, 94.1%;
38 Kuriakose & Patel

Fig. 4. Pulmonary infarct and the ‘‘vascular-sign’’. (A) Axial CT shows an occluded and dilated (white arrow) right
lower lobe (RLL) pulmonary artery owing to the presence of PE. The vessel is enlarged (vascular sign) courses to
the apex of a subpleural nonenhancing triangular opacity, which is an infarct (arrowheads). The asterisk indicates
a small right pleural effusion. (B) Coronal reformatted image along the long axis of the vessel shows embolus
(white arrow) occluding the RLL segmental pulmonary artery. Note the nonenhancing infarct along the lateral
pleura (arrowheads), and enhancing atetectasis adjacent to the diaphragm (black arrow). (C) On lung window
images the infarct is triangular in shape and has a broad base with the pleura (arrowheads).

specificity, 93.6%; positive predictive value [PPV], are sufficient justification for CT pulmonary angi-
95.5%; NPV, 96.2%) than for planar V/Q scans ography to replace V/Q scintigraphy in the diag-
(sensitivity, 80.8%; specificity, 73.8%; PPV, nostic algorithm for suspected acute pulmonary
95.5%; NPV, 75.9%).47 Similar results were re- embolism. PIOPED II is the largest and most signif-
ported by Grenier: sensitivities, specificities, and icant study that has assessed the use of MDCT in
kappa values with helical CT and scintigraphy the diagnosis of PE in outpatients and inpatients,
were 87%, 95%, and 0.85 and 65%, 94%, and with reported sensitivity of 83% for CTPA, which
0.61, respectively.48 Many believe these results is comparable to V/Q scanning.
Acute Pulmonary Embolism 39

did not show 100% sensitivity, but only 87%. In


the PIOPED II study, in the 20 cases with discor-
dant CTPA and catheter angiography results, an
expert panel concluded that CTPA was accurate
in 14 of 20 cases, with 13 cases false-negative
and one false-positive on conventional catheter
angiography and CT results were false-negative
in 2/20 cases. In the remaining 4/20 cases, the
panel thought that the CTPA was initially truly
negative, however the subsequent pulmonary
angiogram showed the presence of PE.19 This
resulted in the sensitivity for detection of PE of
87% with CT, and 32% with conventional angiog-
raphy (P 5 0.007). With better visualization of sub-
Fig. 5. Pulmonary infarction. Bilateral lower lobe segmental pulmonary arteries on CT and greater
infarction with wedge-shaped areas of peripheral interobserver agreement, investigators have ques-
consolidation (arrows) showing central lucencies, tioned whether catheter pulmonary angiography
a reliable finding of infarction in the presence of PE. should still be considered the gold standard test
Air bronchograms are absent. The patient had exten- by which MDCT is judged.
sive bilateral central and peripheral PE.

Interobserver Agreement
Comparison of CT Pulmonary Angiography
and Catheter Angiography For CTPA, interobserver agreement for the detec-
tion of acute PE is moderate to almost excellent,
28
Baile and coworkers evaluated the accuracy of with kappa values ranging from 0.59 to
CTPA with catheter pulmonary angiography for 0.94.39,45,50–54 Remy-Jardin and colleagues41
the detection of subsegmental PE using post- report that using thinner collimation of 2 mm
mortem methacrylate casts of the pulmonary versus 3 mm, the kappa values improve, 0.98
arteries in a porcine model. CT and pulmonary versus 0.94 (P<.05).53
angiography were both performed. The sensitivity For subsegmental PE, interobserver agreement
for 1-mm collimation helical CT of 87% (95% is significantly better with MDCT (k 5 0.56–0.85)
confidence interval [CI] 79%–93%) was the same than with SDCT (k 5 0.21–0.54), with worse agree-
as catheter angiography, 87% (95% CI 79%– ment in the obliquely oriented arteries of the
93%) (P 5 .42).49 Note that catheter angiography middle lobe and lingula.55–57

Fig. 6. Right ventricular strain. (A) The interventricular septum (arrowheads) is bowed toward the left ventricle
(LV) and the LV is compressed. Note central PE in the RLL pulmonary artery (arrow). (B) In another patient with
central and peripheral PE (arrow), the right atrium and right ventricle are dilated. The short axis diameter of the
RV is greater than that of the LV.
40 Kuriakose & Patel

Fig. 7. Technical and interpretative pitfall. (A) Axial CT shows a filling defect (arrow) in a segmental RLL pulmo-
nary artery suggestive of PE, discordant with clinical findings. (B) Coronal reformat at soft tissue window shows
a horizontal linear filling defect (arrows) in the corresponding pulmonary artery, which was an artifact corre-
sponding to the pseudofilling defect. Note step artifacts in the ribs from respiratory motion. (C) Lung window
settings also show respiratory motion artifact.

For catheter angiography the interobserver Society for Computed Body Tomography and
agreement is moderate to poor at the subsegmen- Magnetic Resonance annual meeting). There is
tal level. The interobserver agreement for central not only improved visualization of the subsegmen-
arteries is reported as 89%, whereas that for sub- tal pulmonary arteries using 1-mm collimation, but
segmental pulmonary arteries is only 13% to also improved interobserver agreement regarding
66%.58–60 the presence or absence of emboli.25
The prevalence of isolated subsegmental PE
(ISSPE) varies from 3% to 36% at pulmonary angi-
Isolated Subsegmental Pulmonary Embolism
ography or CT (Fig. 9).10,22,44,59,61,62 With better
Ninety-four percent of segmental and 88% of subsegmental artery visualization at MDCT, and
subsegmental pulmonary arteries are well visual- the increased diagnosis of subsegmental PE, the
ized using 16-MDCT (Patel and colleagues, 2003 question arises as to clinical significance of these
Acute Pulmonary Embolism 41

Fig. 8. Technical pitfall because of poor enhancement. (A) Axial CT shows low attenuation in the lower lobe
pulmonary arteries mimicking PE. (B) Sagittal reformats show poor enhancement of the lower lobe pulmonary
arteries because of poor bolus. This can be differentiated from vessel cut-off sign by the gradual and not abrupt
margin of the contrast column. Respiratory motion artifact is also seen.

small emboli. Should we treat ISSPE? Subseg- treatment is withheld because of risks associated
mental PE are common at autopsy, and when with anticoagulation, a lower extremity study is
the pulmonary arteries are carefully examined, warranted to exclude a DVT.
can be seen in 50% to 90% of patients, suggesting
that these small emboli are usually asymptomatic EVIDENCE FOR MDCT IN THE DIAGNOSIS
and many resolve naturally.1,63 OF ACUTE PULMONARY EMBOLISM
Currently there is no clear recommendation for
treatment of ISSPE. Small PE can be clinically A meta-analysis published in 2005 by Quiroz and
important and may benefit from anticoagulant colleagues found the overall negative likelihood
therapy in patients with poor cardiopulmonary ratio after a negative CTPA for PE was 0.07 (95%
reserve, in those with coexistent DVT or a pro- CI, 0.05–0.11); and the NPV was 99.1% (95% CI,
thrombotic stage, in those with chronic pulmonary 98.7%–99.5%).66 The clinical validity of using
hypertension, and in cases of ISSPE with right a CT scan to rule out PE is similar to that reported
ventricular dilatation, as the risk of death is for conventional pulmonary angiography, namely
increased in these patients.21,38,64,65 When 1.0% to 2.8% for CT (including single-section,
42 Kuriakose & Patel

after negative CTPA. The PIOPED II study


suggests that in patients with high clinical proba-
bility and negative CTPA, further testing should
be considered to exclude PE.18

Advantages
A significant advantage of CTPA is that it identifies
additional findings like pneumothorax, pneumonia,
lung cancer, pleural effusions, aortic dissection,
pericardial effusion, mediastinitis, and so forth to
account for patient symptoms. Alternative diag-
nosis rates can be seen in 25% to 67% of
cases.72,73 Of the negative CTPA studies in the
emergency department, 7% had an alternative
diagnosis that required specific and immediate
action.74 Aortic dissection and undiagnosed lung
cancer were detected in about 7% of these cases.
The incidental finding of clinically relevant disease
is a powerful benefit of this modality.75 There is
Fig. 9. Isolated subsegmental PE. An isolated nonoc- improved visualization of the segmental and
clusive filling defect is seen in a subsegmental branch subsegmental pulmonary arteries using MDCT in
of the right lower lobe posterior basal segmental patients with underlying pulmonary disease
artery compatible with PE.
(Fig. 2C).76 Cost analysis of different imaging algo-
rithms show that per life saved, CT is the least
multidetector, and electron-beam CT) versus
expensive imaging modality.77
1.1% to 2.9% for conventional pulmonary angiog-
raphy.67,68 There have been a number of outcome
Disadvantages
studies following a negative CTPA with SDCT that
report an average recurrence of VTE (venous CTPA is commonly used as a first-line imaging test
thromboembolic disease) in 1.3% and that of fatal for suspected acute PE. An increasing number of
PE in 0.3%. Similar results are reported for scans are performed especially in the ED setting,
outcome studies with MDCT. In the Christopher with a lower yield of positive PE test results. The
study, patients were classified as having a PE by high radiation dose is of concern particularly in
using an algorithm of a dichotomized decision the younger female patients, as it results in signif-
rule, D-dimer and CT (both SDCT and MDCT).69 icant radiation dose to the female breast. The
At 3-month follow-up in the 1505 untreated average whole-body doses for CTPA range from
patients following a negative CTPA, a 1.1% risk 2 to 10 mSv and that for V/Q, 0.6 to 1.5 mSv.
of thromboembolic disease was reported. In CTPA causes significant breast radiation of at least
a prospective management study in 756 ED (emer- 20 mGy (range 10 mGy–70 mGy).78,79 This is
gency department) patients with suspected PE, all equivalent to 10 to 25 two view mammograms or
patients with high clinical probability or non-high 100 to 400 chest radiographs. The Biological
clinical probability and positive D-dimer, under- Effects of Ionizing Radiation, seventh report
went both CTPA with MDCT and lower limb ultra- (BEIR VII) estimates that the lifetime attributable
sonography. Proximal DVT was found in only 3 of risk for breast cancer from a dose of 20 mGy is
318 patients (0.9%).70 Righini and colleagues approximately 1 in 1200 for a woman aged 20, 1
compared two diagnostic strategies that did or in 2000 for a woman age 30, and 1 in 3500 for
did not include lower extremity ultrasound along a woman aged 40. That is, if a woman aged 30
with D-dimer and MDCT. In the arm that did not has a CTPA with a breast dose of 20 mGy, there
use lower extremity ultrasound, the untreated would be an additional 1/2000 chance of her
patients with negative D-dimer and MDCT had developing breast cancer.78 Studies using
a 3-month risk of VTE of only 0.3%.71 These bismuth breast shields have shown radiation
studies demonstrate that a negative MDCT in dose reductions of 34% to 57% to the breast,
patients without a high clinical probability is without significant decrease in image quality or
adequate to exclude PE. Therefore, in most diagnostic accuracy.80
patients with suspected acute PE and no symp- Other dose-reduction strategies include
toms of DVT, especially in an outpatient setting, increasing pitch, dose modulation of tube current,
anticoagulation therapy can be safely withheld and lowering tube current–time product
Acute Pulmonary Embolism 43

(milliampere–second) as well as using a lower kVP


of 80 to 100 mSV.81–83

CT VENOGRAPHY
Most PE originate as thrombi in the lower extremity
veins. These thrombi break off and propagate
cranially to lodge in the pulmonary arteries.
Sonography is the gold standard test for evalu-
ating lower extremity DVT. Loud and colleagues
first demonstrated the potential use for indirect
CTV in combination with CTPA as a single
exam.84 Multiple studies followed that compared
indirect CTV to sonography, with reported sensi-
tivity and specificity greater than 95% in symptom- Fig. 10. Indirect CTV with deep venous thrombosis. A
atic patients. The development of indirect CTV has low-attenuation filling defect completely occludes
enabled a rapid and accurate combined evaluation the right common iliac vein (arrow).
for both DVT and PE with one exam.
A variety of techniques ranging from incremental vascular calcification, and contrast pooling in the
to helical acquisition from the tibial plateaux to the urinary bladder can obscure portions of adjacent
iliac crests have been used, with similar accuracy vein.89
results. Controversy remains between the use of
helical versus incremental images with short skip Evidence for CT Venography
intervals of 2 to 4 cm.85 Helical scans minimize the
likelihood of missing small DVT, but result in a higher Multiple studies comparing indirect CTV to lower
radiation dose. Agreement with incremental discon- extremity ultrasound, the gold standard test,
tinuous imaging is good but not perfect; however, report sensitivities of 71% to 100%, specificity
the radiation dose is significantly reduced. 97% to 100%, PPV 67% to 100%, and NPV
97% to 100%. In a large retrospective study by
CT Venography Technique Loud and colleagues in 308 patients, the reported
sensitivity was 97% and specificity 100%.90 There
CT venography is performed after a 2.5- to 4.0- were only two false negative and no false positive
minute delay following start of injection bolus for results. Among other prospective studies, the
CTPA.86 Eighty-five percent of patients are within sensitivity ranges from 93% to 100% and
10% of their peak enhancement around this specificity, 97% to 100%.91–93 The interobserver
time, whereas in patients with peripheral vascular agreement is also moderate to excellent kappa
disease or poor cardiac output, the delays could (0.59–0.88).18,51,92
vary from 145 to 210 seconds.87,88 Scans are ob- The question arises whether the addition of CTV
tained from the tibial plateaus to the iliac crests at to the CTPA exam alters clinical management. In
5- to 10-mm collimation. a study by Richman and colleagues in 800 ED
DVT is seen as a low attenuation filling defect patients, CTPA was positive in 5% of patients,
partially or completely occluding the vein, with or combined CTPA/CTV in 4%, and CTV alone in
without vessel dilatation. Additional findings include 2%.94 Several studies report an increased detec-
dense rim enhancement owing to contrast straining tion rate of 2% to 5% of VTE when CTV is added
of the vasa vasorum (Fig. 10), perivenous soft tissue to the CTPA part of the exam. In PIOPED II, there
edema, and presence of collateral vessels. was 95% concordance between ultrasound and
CTV. Fourteen (8%) of 181 subjects had DVT alone
Technical Pitfalls and the addition of CTV to CTPA increased the
Venous return depends on cardiac function, arte- overall sensitivity for VTE to 90% versus 83% for
CTPA alone.18 CT is better for diagnosing pelvic
rial inflow, and venous integrity. Flow artifacts
owing to suboptimal contrast opacification and DVT and possibly nonobstructive DVT; however,
early scanning, can lead to streaming of contrast patients with pelvic DVT often have a thrombus
in the periphery of the vessel, mimicking DVT.89 load in the leg veins.
In patients with severe atherosclerotic disease,
Advantages
there are arterial inflow problems with delayed
venous return, and poor opacification of veins. CTV can be combined with CTPA without requiring
Streak artifacts from orthopedic hardware, any additional intravenous contrast material and
44 Kuriakose & Patel

offers a one-stop comprehensive test in about increases at each trimester as the fetus enlarges
20 minutes. It is also superior for evaluating the and approaches the imaged area in the thorax.100
inferior vena cava and iliac veins especially in The worst estimated absorbed dose for the fetus in
obese patients and those with anomalous, dupli- the third trimester with CTPA is 130 mGy. The esti-
cated, and complex venous anatomy. mated fetal radiation dose for V/Q scanning is 100
Patients with recent surgery and with a cast in to 370 mGy, ie, the dose may be more than three
the lower extremity who are unable to undergo times greater than for CTPA. Based on the average
compression sonography can be assessed with background radiation to an adult, the equated
CTV. dose to the fetus in utero for 9 months is about
1000 mGy.101 So a third trimester CTPA delivers
Disadvantages only about seven times less than the natural back-
The main disadvantage is the additional radiation ground radiation. All radiation to the fetus carries
incurred to the thighs and pelvis. Calculated radia- a potential risk. The absorbed dose to the fetus
tion doses with helical CT range from 3.2 to (0.2 to 0.3 mSv) is well below the level that would
9.1 mSV, whereas with discontinuous axial images, increase the risk of congenital abnormality.
radiation is reduced to 0.6 to 2.3 mSv.85,95 Radiation Breast radiation dose from CTPA is an additional
dose can be minimized by the use of incremental consideration. The female breast is extremely
sections, tube current modulation, and scanning radiosensitive and a radiation dose of 100 cGy is
only up to the acetabuli as incidence of DVT is low associated with an increased risk of breast cancer
in the IVC (inferior vena cava) and pelvic veins, of 40% in young Western women. Epidemiological
reported in only 3% in the PIOPED II study.18 Given studies have not detected a significantly increased
the high radiation doses, combined CTPA/indirect risk of breast cancer below a dose of 20 cGy.
CTV should not be part of a routine test especially Female breast radiation exposure during CTPA
in the young female of childbearing years. The has been calculated at an effective minimum
Fleischner Society Guidelines recommend the use dose of 20 mGy (2 cGy)64 and that for ventilation/
of the combined test, when the emphasis is placed perfusion scanning 0.28 mGy. These estimates
on a complete vascular exam.79 are significantly below the level of 20 cGy, below
which no effect on the breast can be demon-
PULMONARY EMBOLISM IN PREGNANCY strated. This exposure should not be ignored and
the use of breast shields may reduce this dose
Venous thromboembolic disease is challenging to by up to 73%.102
diagnose, and is the second commonest cause of Although CTPA is advocated as the initial
mortality in pregnancy following hemorrhage.96 imaging test after ultrasound of the legs, the
Even though the risk of radiation is high, the risk quality of the scan may not be optimal in pregnant
of fetal death is much greater if the mother has patients. Two recently published articles report
untreated PE.97 The incidence of DVT is increasing a significantly lower enhancement of pulmonary
and is significantly higher than in the nonpregnant arteries on CTPA in pregnant women with non-
female, whereas the incidence in PE between the diagnostic rates of 7.5% or 27.5%.103,104 This is
two groups is not significantly different.98 Contro- thought to occur as a result of a combination
versy remains as to which is the best test to diag- of physiological factors: increased cardiac out-
nose VTE in the pregnant female. Initial evaluation put, increased plasma volume, increased body
should begin with venous ultrasound of the lower weight, hyperdynamic circulation, and increased
extremities. If this is negative, then the question effects of a Valsalva maneuver. Contrast injection
arises as to the preference for an imaging test protocols need to be modified to address this
that delivers the highest yield of a definitive test problem. In pregnant women, the contrast mate-
result, at the lowest radiation risk to the fetus. In rial arrives early within the pulmonary arteries
the pregnant female, the likelihood of a normal and the peak enhancement is lower. Therefore,
V/Q is high (74%) and a high probability scan low the scan should be performed on the highest
(2%), with a significantly fewer number of patients generation of scanners by using bolus tracking
(24%) having indeterminate scans compared and increased concentration of the contrast
with the general population with suspected VTE, material at higher rates of injection.105 Scarsbrook
probably because of young age and fewer and colleagues suggest radiation dose–reducing
comorbidities.99 methods with CTPA such as reduced mAs,
The Fleischner society advocates CT as the first reduced kVp, increased pitch, increased detector
line imaging test in pregnancy following leg ultra- and beam collimation, reducing z-axis range and
sound. The fetal radiation exposure for CTPA field of view, and the use of abdominal
varies from 3.3 mGy to 130.0 mGy; the dose shielding.96
Acute Pulmonary Embolism 45

Another consideration is the effect of contrast patient should undergo CTPA. If the CXR is
on a developing fetus, which has not been fully normal, either CTPA or V/Q scan can be done.
investigated. It is recommended that the infant The perfusion portion of the V/Q scan alone can
has thyroid function testing within a week of birth be performed initially if there is radiation concern.
because of the theoretical risk of contrast-induced The greatest drawback of the V/Q scan is the likeli-
hypothyroidism.106 hood of intermediate probability scans which in
Magnetic resonance angiography is another a setting of a raised D-dimer necessitates another
alternative to V/Q scanning and CTPA. MR is exam such as CTPA thereby increasing cost, radi-
advantageous because the fetus is not exposed ation, and a delay in diagnosis.
to ionizing radiation or to intravenous contrast
material.
High Pretest Probability
IMAGING ALGORITHM FOR DIAGNOSIS OF PE In high-risk cases and with strong pretest proba-
bility, D-dimer testing need not be performed
Imaging algorithms vary, depending on the clinical because a negative D-dimer result in a patient
probability (Fig. 11). with a high-probability clinical assessment may
not exclude VTE. Depending on local preference,
Low Pretest Probability
an early CTPA or V/Q scan can be performed if
In the low and intermediate probability population, the CXR is normal. If the test is negative, the leg
a cost-effective algorithm would be to perform veins should be evaluated with compression
a D-dimer. The value is in a negative test that sonography. If either CT angiography is positive
effectively rules out significant VTE. If the test is or DVT is diagnosed, definitive treatment is
positive, a diagnostic imaging study should be recommended.
performed depending on local availability, easy If the CTPA is nondiagnostic, the test can be
access, cost, radiation, and clinician preference. repeated. If repeat examination is unlikely to alter
The chest x-ray (CXR) may be helpful to strate- image quality owing to known patient parameters
gize management. If the CXR is abnormal, the (poor cardiac output, large patient habitus,

Fig. 11. Suggested diagnostic algorithm for suspected pulmonary embolism.


46 Kuriakose & Patel

extensive respiratory motion), then pulmonary refinements in technology, we will continue to opti-
angiography can be performed. If both CT angiog- mize imaging for PE detection. Ionizing radiation
raphy and leg vein studies are negative or CTPA/ remains a concern particularly in the young and
CTV results are negative, options include serial in pregnant patients, and methods to decrease
venous ultrasound examinations, pulmonary these are being advocated. SPECT V/Q may play
digital subtraction angiography, and pulmonary a bigger role in PE diagnosis in the future and the
scintigraphy. role of MR is yet to be determined in the PIOPED
In the critically ill patient, bedside echocardio- III study, with the potential of solving some of the
gram to assess the right ventricle and for right issues regarding radiation in a select group of
heart strain and ultrasound examination of the patients.
legs can be performed until the patient is stabilized
for further imaging tests. CTPA can be a chal-
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