DOI:10.2214/AJR.06.0640
AJR 2007; 189:171-176
© American Roentgen Ray Society
18F-FDG PET of Pulmonary Embolism
Conrad Wittram1 and
James A. Scott2
1 Division of Thoracic Radiology, Massachusetts General Hospital, Founders 202,
55 Fruit St., Boston, MA 02114.
2 Division of Nuclear Medicine, Massachusetts General Hospital, Boston,
MA.
Received May 13, 2006;
accepted after revision December 29, 2006.
Address correspondence to C. Wittram
(cwittram{at}partners.org).
Abstract
OBJECTIVE. The purpose of this study was to describe the
manifestations of pulmonary embolism on 18F-FDG PET scans in 13
patients.
CONCLUSION. The activity of acute pulmonary embolism on FDG PET
scans was significantly higher than the activity of vessels not containing
thrombi. The shape of the abnormal FDG uptake may be focal or curvilinear.
Keywords: CT • nuclear medicine • oncology • PET • pulmonary embolism
Introduction
Pulmonary embolism (PE) is the third most common acute cardiovascular
disease, after myocardial infarction and stroke, and it leads to thousands of
deaths each year because it often goes undetected
[1]. Patients with suspected PE
are almost exclusively imaged with dedicated CT pulmonary angiography. As
recent results [2] show, in
comparison with a composite reference standard, CT pulmonary angiography has a
sensitivity of 83% and specificity of 96% in the detection of PE, and combined
CT pulmonary angiography and CT venography has a sensitivity of 90% and
specificity of 95% in the detection of venous thromboembolic disease. The
finding of PE on contrast-enhanced CT for indications other than
thromboembolic disease ranges from 1.5% to 4%
[3,
4] in a mixed population. Among
oncology patients, the coincidence rate of PE on contrast-enhanced CT has been
cited as being as high as 6%
[5].
There is a sustained increase in utilization of 18F-FDG PET in
the evaluation of patients with known or suspected malignancy in the thorax
[6]. Integrated PET/CT scanners
have the added advantage of high anatomic resolution and the ability to show
tissue with increased glucose metabolism. In the literature, a series of three
pathologically proven pulmonary infarcts exhibited an increase in FDG uptake
[7], and there has been one
case report [8] of FDG uptake
by pulmonary emboli. The purpose of our study was to evaluate pulmonary emboli
on FDG PET scans in a large series of patients.
Materials and Methods
Patients
Our institutional review board approved this retrospective study and waived
informed consent. The study was compliant with the requirements of the Health
Insurance Portability and Accountability Act. The study period was January
2004 through February 2006. All 2,216 consecutive oncology patients who
underwent integrated contrast-enhanced PET/CT at our institution were found
with our radiology information database search program (Folio). From this
group, all cases of coincidental PE were identified. One of the investigators
reviewed the charts for corroborative imaging or clinical evidence that
confirmed the diagnosis of PE, which was assigned on CT. Other information
collected included tumor type and size and change in tumor size. Thirteen
patients with coincidental acute PE were identified: two women and 11 men with
an age range of 36-81 years (mean age, 59 years).
PET/CT Technique
An integrated PET/16-MDCT scanner (Sensation, Siemens Medical Solutions)
was used to acquire the images. The patients were given an injection of 15 mCi
of FDG. Forty-five minutes later, attenuation-correction unenhanced CT scans
were acquired from neck to pelvis at 2-mm slice thickness, 83 ± 31 (SD)
mA (range, 60-150 mA) at 120 kVp, and 0.5-second tube rotation time. The
imaging field of view was the widest rib-to-rib distance acquired during quiet
breathing. The PET images were acquired at 3.75-mm slice thickness and mean
full width at half maximum of 6 ± 0.7 (range, 5-7). For the final CT
scan, IV access was through an antecubital vein. An injection of 120 mL of
ioxilan 300 mg I/mL was given through a 20-gauge catheter at 2.5 mL/s. Images
were acquired with a collimation and reconstruction width of 2.00 mm,
0.5-second tube rotation time, and 195 ± 43 mA (range, 166-275 mA) at
140 kVp. Image acquisition was started 48 seconds after commencement of IV
administration of contrast medium, and patients were asked to take a small
breath in and hold it. CT images were acquired with a standard algorithm. For
this study, the chest component was analyzed.
Diagnostic Criteria for PE and Pulmonary Infarction
One of the investigators identified acute PE as an intraluminal filling
defect that had a sharp interface with intravascular contrast enhancement that
manifested as follows: Complete arterial occlusion with failure to opacify the
entire lumen, sometimes with enlargement of the artery in comparison with
pulmonary arteries of the same order of branching
[9-11];
a central arterial filling defect surrounded by intravascular contrast
enhancement [9]; and a
peripheral intraluminal filling defect at an acute angle to the arterial wall
[10,
11]. In all three types of
manifestation, the anatomic levels of the pulmonary emboli were categorized
and recorded as main, right or left, interlobar, lobar, segmental, or
subsegmental pulmonary artery.
Because FDG can be taken up in both lymphadenopathy and PE, it was
important to differentiate these abnormalities on contrast-enhanced CT. Lymph
nodes were recognized as being in an extravascular location, and PE was
recognized as an intravascular filling defect that fulfilled the three
aforementioned diagnostic criteria for PE. The diagnosis of pulmonary
infarction was considered on CT when a region of ground-glass opacification or
consolidation was identified in lung parenchyma distal to a vessel occluded by
thrombus.
Evaluation of Systemic Veins in the Abdomen and Pelvis
The veins of the abdomen and pelvis were evaluated for adequacy of vascular
opacification on contrast-enhanced CT and for the presence of thrombus. If
thrombus was identified, the corresponding PET image was evaluated for the
presence or absence of increased FDG uptake.
Quantitative Evaluation
All images were viewed on a Reveal-MVS workstation (Mirada Solutions). The
program resampled the contrast-enhanced CT data to accord with PET slice
thickness. For each axial level of a study, three images were displayed: the
CT image viewed on mediastinal window (width, 350 H; level, 40 H), combined
PET/CT image, and PET image. Two radiologists, one with 10 years of experience
in thoracic radiology, and a nuclear medicine radiologist with 20 years of
experience in nuclear medicine interpretation reviewed the images at one
sitting. The largest thrombus in an individual lung was identified, and a
region of interest was drawn around the margin of the vessel. After input of
the patient's body weight, the maximum standard uptake value (SUV) from the
region of interest was recorded. A vessel of similar size, which did not
contain thrombus, also was identified. The process was repeated for this
vessel, and the data recorded. Region-of-interest measurements of vessels
containing and not containing thrombus were obtained from vessels that did not
have visually detectable lymphatic tissue or extravascular soft tissue around
the vessel. The cases with infarction were identified, an SUV region of
interest was drawn around the margin of the opacity, and the maximum SUV was
recorded. A normal region of lung on the opposite side with a similarly sized
region of interest was used as a control.
Qualitative Evaluation
All cases were reviewed by consensus to evaluate the shape of the abnormal
FDG uptake by pulmonary emboli. Six patients had undergone prior
contrast-enhanced CT and PET that did not show PE. In these six cases, the
study images and previous PET images were viewed side by side to evaluate for
interval change.
Statistical Analysis
The two-tailed paired Student's t test was used. Statistical
significance was considered when p < 0.05.
Results
Review of the charts and previous images showed that six patients had lung
cancer; two, lymphoma; two, colon cancer; one, melanoma; one, rectal
carcinoma; and one, carcinoma of the pancreas. Combined PET/CT was used for
initial tumor staging in two cases. In the other 11 cases, PET/CT showed an
increase in tumor burden in four patients, a decrease in two, stable disease
in two, and no tumor in three cases.
All patients had evidence of acute PE on contrast-enhanced CT. No cases of
chronic embolism were identified. The site of the largest pulmonary embolus
was the right pulmonary artery in two cases, lobar artery in nine cases, and
segmental artery in two cases. In two cases, no previous contrast-enhanced CT
scans were available. In 11 cases, previous contrast-enhanced CT scans showed
evidence of PE in four cases, less thrombus than visualized with PET/CT in
three of the four cases, and a larger thrombus in one case. In the other seven
cases, previous CT showed no evidence of PE. The mean time between previous CT
and PET/CT was 11 ± 9 weeks (range, 2-28 weeks). Follow-up CT scans
were available for eight of the study patients, and all scans showed the
thrombus had cleared. The time period between the study CT and follow-up
contrast-enhanced CT was a mean of 19 ± 12 weeks (range, 7-34
weeks).
All but one patient received anticoagulation therapy as a result of the
diagnosis of coincidental PE. The other underwent placement of an inferior
vena caval filter. The mean SUV of acute PE was 1.65 ± 0.61 (range,
0.45-3.03). Vessels without thrombus had a mean SUV of 1.15 ± 0.38
(range, 0.42-1.64) (p = 0.009). The average SUV per vessel size was
the main pulmonary artery, 1.5 ± 0.27 (range, 1.3-1.69); lobar
pulmonary artery, 1.75 ± 0.60 (range, 1.24-3.03); and segmental
pulmonary artery, 1.57 ± 0.75 (range, 0.45-2.62). In three cases, CT
showed lung opacification peripheral to the acute thrombus: consolidation in
two of the cases and ground-glass opacification in one case. These lesions
were consistent with infarction and had a mean SUV of 1.84 ± 0.96
(range, 0.8-2.69). The normal region of lung had a mean SUV of 0.80 ±
0.29 (range, 0.56-1.13) (p = 0.129).
In all six cases in which previous PET/CT had not shown PE, direct
comparison of the study PET scans with the previous images showed evidence of
an increase in FDG uptake in the hila. This increased uptake represented a new
focal or curvilinear abnormality corresponding to the contrast-enhanced CT
abnormality that represented PE (Figs.
1A,
1B,
1C,
1D,
2A,
2B,
2C,
2D,
2E, and
2F).
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Fig. 1A —55-year-old man with history of colon cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Contrast-enhanced CT scan shows acute pulmonary embolism
(arrow) in lobar artery of left lower lobe.
|
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Fig. 1B —55-year-old man with history of colon cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Obtained at same time as A,18F-FDG PET scan shows
focal increased uptake of FDG at site of acute pulmonary embolism
(arrow).
|
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Fig. 1C —55-year-old man with history of colon cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. FDG PET scan obtained 11 weeks before A and B shows
normal left hilar FDG PET activity.
|
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Fig. 1D —55-year-old man with history of colon cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Integrated PET/CT scan shows focal increase in FDG uptake over acute
pulmonary embolism (arrow) in A. Normal mediastinal uptake
over heart (arrowheads) is evident.
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Fig. 2A —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Contrast-enhanced CT scan shows acute pulmonary embolism
(arrow) in lobar artery of right lower lobe.
|
|
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Fig. 2B —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Obtained at same level as A, 18F-FDG PET scan shows
curvilinear increase in FDG uptake at site of acute pulmonary embolism
(arrow).
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Fig. 2C —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. FDG PET scan obtained 26 weeks before B shows normal right hilar
FDG PET activity.
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Fig. 2D —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Integrated PET/CT image of A and B shows curvilinear
increase in FDG uptake over acute pulmonary embolism (arrow) within
lobar artery of right lower lobe. Normal left ventricular uptake
(arrowhead) is evident.
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Fig. 2E —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. Contrast-enhanced CT scan obtained at level more caudal than A
shows acute pulmonary embolism (arrow) in posterior basal segment
artery of right lower lobe.
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Fig. 2F —62-year-old man with history of lung cancer and incidental
finding of acute pulmonary embolism. Previous scan had shown no residual
tumor. FDG PET scan obtained at same level as E shows focal increase in
FDG uptake at site of acute segmental pulmonary embolism (arrow).
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On review of the images of the abdomen and pelvis, we found that in four
cases images had poor opacification of the veins, making them indeterminate
for identification of deep venous thrombosis. In five cases there was no
evidence of deep venous thrombosis. Deep venous thrombosis was found in four
patients: one with thrombus in the right internal iliac vein, one with
thrombus in the left common femoral vein, one with thrombus in the left and
right common femoral veins (Figs.
3A and
3B), and one with thrombus in
the right common iliac vein. In all of these cases, PET/CT showed an increase
in FDG uptake (Figs. 3A and
3B).
Discussion
Combined PET/CT is likely to become the standard of care for primary
staging and evaluation of treatment response in a large proportion of oncology
patients. However, a growing number of nonmalignant thoracic abnormalities,
including brown fat and benign tumors such as hamartoma, sclerosing
hemangioma, and leiomyoma, that take up FDG are being identified on PET scans.
Other causes of increased uptake are amyloid deposition, round atelectasis,
and inflammatory and infective lesions, such as organizing pneumonia,
actinomycosis, acute and chronic bacterial pneumonia, abscesses, mycobacterial
and fungal infections (e.g., coccidioidomycosis), sarcoidosis, parasitic
infestations (e.g., Paragonimus westermani), talc pleurodesis, and
pneumoconiosis [12,
13].
Pulmonary infarction causing increased uptake of FDG has been described in
three cases [7]. This study
demonstrates that PE can also cause an increase in FDG uptake on PET scans.
The differential diagnosis of vascular uptake of FDG in the thorax includes
atheromatous disease, which is common in the systemic arteries
[14], and Takayasu arteritis,
which can affect both systemic and pulmonary arteries
[15].
The pathologic mechanism of acute PE often involves impaction of thrombus
within a pulmonary artery by pulsatile flow. Distention of an affected artery
can lead to focal vessel wall inflammation and necrosis with aggregation of
leukocytes along the endothelial surface. These changes can occur within the
first few days of the onset of pulmonary thromboembolic disease. Vascular
uptake of FDG in atheroma and Takayasu arteritis is caused by inflammation
[14,
15]. It is assumed that a
similar process is the cause of acute PE.
Although they are not yet clarified, the exact mechanisms of FDG uptake by
PE are likely related to the chemical characteristics of the
radiopharmaceutical. This glucose analogue has a biodistribution determined in
large part by increased numbers of glucose transporter proteins and increased
intracellular levels of hexokinase and phosphofructokinase, among other
agents, which promote glycolysis. FDG is well known to be taken up by
inflammatory cells [16]. The
rationale is that activated macrophages and neutrophils in inflammatory tissue
use glucose as an energy source for chemotaxis and phagocytosis, whereas
fibroblasts use glucose for proliferation
[17]. We hypothesize that a
local increased influx of inflammatory cells causes a focal increase in uptake
of FDG at the embolic site. Further study of the exact mechanism is
required.
In a population of oncology patients, one concern for this study was how to
differentiate thrombotic and tumor emboli as a cause of the intravascular
filling defects. As a rule, large tumor emboli that affect vessels of
segmental size or larger arise from tumors that invade the inferior vena cava
or large feeding veins. Examples are hepatoma, renal cell carcinoma, and
choriocarcinoma [18]. In our
group of 13 patients, no patient fit this criterion. In addition, in cases in
which follow-up contrast-enhanced CT scans were available, eight patients had
complete resolution of PE after anticoagulation therapy.
One limitation of our study was the relatively small size of the
population. More subjects would have been included if the search had
incorporated cases in which FDG PET and contrast-enhanced CT were performed at
different times. Use of this criterion, however, would likely have produced
less accurate data because of a potential rapid change in size and position of
emboli as a result of fragmentation and lysis. We chose fewer subjects and
greater accuracy. Another limitation, as in all PET/CT studies, was that we
assumed accurate registration of the CT and PET images. Despite this
limitation, our results show the importance of temporal correlation, because
an increase in FDG hilar uptake can indicate PE. An additional limitation was
that only 13 (0.59%) of 2,216 patients with tumors were identified as having
PE. This number is much lower than in other series described
[3-5].
The explanation is that our cases were identified with a word-search system,
which can miss cases of coincidental PE not reported by radiologists. The
objective of this study was not to evaluate the rate of coincidental PE in a
group of oncology patients but to describe the manifestations of FDG uptake by
PE.
In conclusion, many patients undergo integrated PET/CT for tumor detection,
staging, and evaluation for response to therapy. The presence of coincidental
PE is likely in this population and should be recognized in the
contrast-enhanced CT component of PET/CT studies. In patients who do not
receive IV contrast material, a focal or curvilinear increase in FDG uptake
over a vessel should suggest the possibility of PE, and further imaging with
CT angiography should be considered.
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Abstract
Introduction
