ANGIOTOMO EMBOLISMO PULMONAR HEARTWORM

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COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR EVALUATION
OF PULMONARY EMBOLISM IN AN EXPERIMENTAL MODEL
AND HEARTWORM INFESTED DOGS
JOOHYUN JUNG, JINHWA CHANG, SUNKYOUNG OH, JUNGHEE YOON, MINCHEOL CHOI
This study was performed to characterize pulmonary embolism with computed tomography pulmonary an-
giography in experimental pulmonary embolism and heartworm infected dogs. In the experimental group, there
were pulmonary changes after pulmonary embolism induction as follows: hypoattenuating round filling defects
in pulmonary arteries, arterial dilations with straight and abrupt cut-off appearances in the pulmonary embolism
regions, pulmonary infarctions, a cavity formation and spontaneous pneumothorax, and emboli migration. In
the heartworm-infected group, three out of eight dogs developed pulmonary embolism, especially in the right
caudal arteries. Arterial dilations with typical tortuosity were also identified, mainly in the right caudal arteries
in five dogs. Computed tomography pulmonary angiography can be an important imaging modality in the
diagnosis of pulmonary embolism and the evaluation of pulmonary arterial and parenchymal changes in dogs.
r 2010 Veterinary Radiology & Ultrasound, Vol. 51, No. 3, 2010, pp 288–293.
Key words: computed tomography pulmonary angiography, dog, experimental pulmonary embolism,
heartworm, pulmonary embolism.
Introduction
PULMONARY EMBOLISM IS a life-threatening condition withsubstantial morbidity and mortality.1 Since clinical signs
are nonspecific, a prompt and accurate diagnostic tool for
detection of pulmonary embolism is important. With fast-
scanning and contrast injection techniques, computed to-
mography pulmonary angiography (CTPA) is more precise
and noninvasive than lung scintigraphy and pulmonary an-
giography in diagnosing pulmonary embolism.2–4 Both
CTPA and magnetic resonance angiography are highly spe-
cific for detection of pulmonary embolism, but CTPA is
more sensitive.5 The aims of this study were to determine the
value of CTPA for the assessment of pulmonary embolism
and pulmonary changes caused by pulmonary embolism in
an experimental model, and in dogs with heartworm disease.
Materials and Methods
The experimental group included 16 healthy beagles, 2–4
years old, with weights weighing between 8 and 10kg. All
experimental dogs were negative for the Dirofilaria immitis
immunodiagnostic antigen test.� The heartworm group
included eight beagles with naturally acquired heartworm
infection, 2–5 years old, weighing between 7.4 and 15.4 kg.
Heartworm dogs had a positive D. immitis antigen test but
had no abnormal radiographic changes.
In the experimental group, pulmonary embolism was
induced under general anesthesia as follows. Under flu-
oroscopy, a 5-F, 75 cm flow-directed Swan Ganz thermo-
dilution catheterw was advanced into the right or left
jugular vein using the Seldinger technique.6 The catheter
was selectively positioned in the right caudal (six dogs),
accessory (four dogs), or left caudal pulmonary artery (six
dogs). Pieces of gelatin spongez were injected into the se-
lected peripheral pulmonary artery with saline and Iohexol
300mgI/ml.y Complete obstruction of these arteries and
increased pulmonary capillary wedge pressure were con-
firmed using angiography and the anesthetic patient mon-
itoring system.z
CTPA scansk were acquired in both groups using the
following procedure. After an unenhanced scan, a single-
level scan was acquired under the following conditions:
1-mm thickness, 120kVp, 60mA, 50 serial transverse
images, and 1.5 s per rotation. Images were acquired
at the region of experimental pulmonary embolism in the
experimental dogs. Iohexol 300mgI/ml was injected at
Address correspondence and reprint requests to Prof Mincheol Choi,
Department of Veterinary Radiology, College of Veterinary Medicine,
Seoul National University, Seoul, Korea. E-mail: mcchoi@snu.ac.kr
Received 11 August 2008; accepted for publication 13 November 2009.
doi: 10.1111/j.1740-8261.2009.01659.x
From the Department of Veterinary Radiology, College of Veterinary
Medicine, Seoul National University, San 56-1, Shillim-dong, Kwanack-
gu, Seoul 151-741, Korea.
�Snap; IDEXX Laboratories Co, Westbrook, ME.
wTD1504NX, a safety wedge TM thermodilution catheter with the
biotray; Biosensors International Co., Ltd., Singapore.
zGelfoam, Lot no. 100; Upjohn Inc., Kalamazoo, MI.
yOmnipaque300
s
; Amersham Health, Cork, Ireland.
zS-3; Datex-Ohmeda, Helsinki, Finland.
kA third generation single channel helical CT scanner, GE CT/es;
General Electric Medical System, Yokogawa, Japan.
288
5ml/s at a dose of 0.5ml/kg using a power injector.�� The
delay times for the pulmonary embolism regions were ob-
tained through analysis of time–attenuation curves; these
delay times were used to program an enhanced dynamic
scan, having parameters of 2mm thickness, 2mm intervals,
120kVp, 60mA, and a pitch of 1.3. Iohexol was injected at
5ml/s contrast injection flow rate and a dose of 3ml/kg
using a power injector.7 Respiratory motion artifacts were
minimized by inducing hyperventilation and breath-hold-
ing. All enhanced scan images were reconstructed to
0.5mm multiplanar retro-reconstructed images and 3D
images. In the experimental group, CTPA was repeated
before embolization and on the 1st, 2nd, 4th, 7th, 10th,
14th, 17th, and 21st days after pulmonary embolism in-
duction. In the heartworm group, CTPA under same pa-
rameters were repeated three times at 3- to 5-day intervals
to rule out a false positive diagnosis of pulmonary embo-
lism, due to technical artifacts including improper contrast
medium injection.
To verify the presence of pulmonary embolism and
evaluate the pulmonary changes, eight experimental dogs
were euthanized and examined at postmortem, and all
heartworm dogs had D-dimer tests.ww The eight experi-
mental dogs undergoing euthanasia included three dogs
with right caudal arterial pulmonary embolism, two dogs
with accessory arterial pulmonary embolism, and three
dogs with left caudal arterial pulmonary embolism. These
dogs were selected as representatives having pulmonary
edema, pulmonary infarction, emboli migration, or
pneumothorax.
Results
All experimental dogs developed mild postembolization
leukocytosis 1 or 2 days following the induction of pul-
monary embolism, but these resolved spontaneously with-
out further problems. Other serum biochemistry tests,
blood pressure, and echocardiography were normal during
all procedures. Four dogs had mild respiratory distress
with rapid and shallow tachypnea and three dogs had a
mild intermittent cough. Five of seven dogs with clinical
signs had a mild alveolar pattern in the territory of the
pulmonary embolism and these findings disappeared spon-
taneously after the 4th and 7th days. There were no ra-
diographic signs of arterial dilation. Clinical signs resolved
after the 2nd to 10th days.
In heartworm-infected dogs, the results of the hemato-
logic and blood chemistry tests, blood pressure, and echo-
cardiography were normal during all procedures. Three of
the eight dogs had an intermittent nonproductive cough.
Thoracic radiographs of two of these dogs were charac-
terized by an unstructured interstitial pattern in the ca-
udodorsal lung lobes. The remaining five dogs had no
clinical signs and normal thoracic radiographs.
In both groups, CTPA findings of pulmonary embolism
were intraluminal hypoattenuating filling defects sur-
rounded by contrast medium.8 In the experimental group,
pulmonary embolism and arterial dilations were identified
in all dogs (Fig. 1) and these were confirmed histopatho-
logically (Fig. 2). The pattern of the arterial dilation was
with loss of tapering andabrupt cut-offs. Tortuosity was
not identified. The mean diameter of the pulmonary arter-
ies with pulmonary embolism was 7.9 � 2.0mm on the 1st
day and 4.5 � 0.9mm on the 21th day. Pulmonary embo-
lism, arterial dilation, and complete occlusion tended to
resolve gradually, especially on the 4th or 7th day. In the
heartworm-infected dogs, three had intraluminal filling de-
fects surrounded by contrast medium, consistent with pul-
monary embolism, in mildly dilated and tortuous right
caudal lobe pulmonary arteries (Fig. 3A). These dogs had
irregular hyperattenuating periarterial regions and positive
D-dimer results. One of these dogs also had pulmonary
embolism in the accessory pulmonary artery (Fig. 3B) and
had a more dilated and tortuous left caudal lobe artery
than the right caudal and accessory arteries (Fig. 3C and
D). However, there was no evidence of pulmonary embo-
lism in the left caudal artery. The mean hounsfield unit
(HU) value of pulmonary embolism was 52.9 � 12.2 on
postcontrast images. The mean diameter of the right cau-
dal arteries with pulmonary embolism was 7.0mm and the
mean diameter of the dilated right caudal arteries including
arteries without pulmonary embolism was 6.5mm. Two
more dogs had pulmonary embolism suspected due to di-
lated and irregular unopacified right caudal arteries, but
pulmonary embolism was ruled out because of a negative
D-dimer test.9
In the experimental group, one dog with complete oc-
clusion of the right caudal artery had emboli migration. An
embolus in the right main pulmonary artery identified the
day after embolization subsequently disappeared on the
2nd day. A new embolus in the left caudal artery was
identified on the 4th day (Fig. 1B) and resolved on the 7th
day, but the original pulmonary embolism in the right
caudal artery with pulmonary infarction was still identified
on the 21st day. Three of the four dogs with complete
occlusion of the accessory artery also had emboli migra-
tion. Two dogs had a small new embolus in the right cau-
dal artery whereas an original pulmonary embolism began
to resolve on the 7th day. One dog also had a new embolus
in the right caudal artery on the 10th day after the acces-
sory arterial pulmonary embolism had almost completely
disappeared on the 7th day. Similarly, two of the six dogs
with pulmonary embolism in the left caudal arteries had
pulmonary embolism in the right caudal arteries on the 7th
and 10th days, respectively. There were no arterial dilations
��LF CT9000
s
ADV; Liebel-Flarsheim, Cincinnati, OH.
wwAGEN Biomedical Ltd., Brisbane, Australia.
289EVALUATION OF PULMONARY EMBOLISMVol. 51, No. 3
and there was complete occlusion at the new pulmonary
embolism regions in all dogs.
All experimental dogs had periarterial ground-glass
hyperattenuation in the region of pulmonary embolism
on the 1st or 2nd day. The mean HU value was�434 � 52.
These periarterial opacities resolved spontaneously after
the 2nd or 4th day. These lesions were confirmed histo-
logically to be due to pulmonary edema and hemorrhage.
Three dogs had hyperattenuating pleural-based triangu-
lar opacities around the regions of pulmonary embolism
(Figs. 1B–D and 2). These pleural-based triangular opac-
ities did not resolve until the 21st day and were confirmed
histologically to pleural infarction. The mean HU value
was 41� 10 in the unenhanced scans.
One dog with complete occlusion of the left caudal ar-
tery developed a pleural-based cavity near the region of
Fig. 1. Computed tomography pulmonary angiography (CTPA) images from experimental dogs. (A) a small pulmonary embolus (arrow) is still identified in
the accessory artery on the 7th day. (B) Pulmonary infarction appearing as a triangular pleural-based hyperattenuation (arrow) and a new embolus in the left
caudal artery (arrowhead) near to the region of pulmonary embolism (circle) on the 4th day. (C and D) A dog with a cavity (arrow) around the region of
pulmonary embolism in the left caudal lung lobe on the 2nd day and spontaneous pneumothorax on the 7th day. (E and F) Arterial dilation with loss of
tapering and abrupt cut-off in the right caudal artery (arrow).
Fig. 2. Necropsy and histopathologic findings in experimental dogs. (A) A recent pulmonary embolus with arterial dilation. (B) A resolving pulmonary
embolus (arrow) with a compact appearance; such emboli can be movable. (C and D) Pleural-based triangular pulmonary infarcts (arrows) are visible.
290 JUNG ET AL. 2010
pulmonary embolism on the 2nd day and pneumothorax
on the 7th day (Fig. 1C and D). Thoracocentesis was per-
formed to relieve the respiratory distress. The gas volume
was 150 cm3 on the right side and 180 cm3 on the left side.
On the 17th day, the pneumothorax has resolved sponta-
neously, but a cavity remained.
Seven of eight heartworm dogs had mild hyperattenu-
ating periarterial and pulmonary parenchymal changes of
various degrees. The pulmonary arterial margins were ir-
regular and ill-defined. Irregular hyperattenuating ground
glass infiltrations were present in the caudal lung paren-
chyma, bilaterally in four dogs and in the right caudal lobe
in three. The mean HU value of infiltrated pulmonary pa-
renchyma was 24� 12 on precontrast images. There were
no changes in the pulmonary arteries and parenchyma of
the cranial lung lobes in any heartworm dog.
Discussion
Two major causes of indeterminate CTPA and misdi-
agnosis of pulmonary embolism are motion artifacts and
poor contrast enhancement.10 During the CTPA scan, all
dogs were in dorsal recumbency and hyperventilation and
breath-holding were induced. These techniques were useful
to control ventilation, to minimize positional atelectasis
and respiratory motion artifacts, and to consistently allow
detection of the region of pulmonary embolism.
The time-delayed contrast medium injection technique
based on analysis of time–attenuation curves allowed op-
timization of enhancement of pulmonary arteries and pro-
vided better characterization of the normal anatomy and
pathologic changes. During and after the CTPA scan, both
groups of dogs had normal laboratory tests and blood
pressure. There were no contrast medium related side
effects. The CTPA protocol used in this study was reliable
to identify pulmonary embolism and to evaluate pulmo-
nary changes.
The thoracic radiographic findings in human patients
with pulmonary embolism are conspicuous pulmonary ar-
teries, parenchymal areas of increased opacity, pleural-
based areas of increased opacity, atelectasis, oligemia,
pleural effusion, and an enlarged hilum. However, these
findings were not significantly different from patients with-
out pulmonary embolism.11,12 The most important and
specific finding of pulmonary embolism on CTPA is an
intraluminal filling defect surrounded by contrast me-
dium.11 Ancillary findings suggestive of pulmonary embo-
lism on CTPA include eccentric filling defects, expanded
and unopacified vessels, peripheral and wedge-shaped
consolidations, oligemia, and pleural effusion.8,13 In the
experimental dogs, only five dogs had a mild alveolar pat-
tern in the region of pulmonary embolism in thoracic ra-
diographs on the 1st and 2nd day after pulmonary
embolism induction. There were no other radiographic
changes related to pulmonary embolism, because most
pulmonary embolism and periarterial changes in this study
were present in the peripheral pulmonary arteries of the
caudal lung lobes. However, CTPA allowed accurate de-
tection of pulmonary embolism with regions of intralumi-
nal filling defects surrounded by contrast medium, arterial
dilation, and mild periarterial ground-glass hyperattenua-
tion in all dogs. In addition, pulmonary infarctionsdistal
to pulmonary embolism regions were detected with typical
pleural-based triangular hyperattenuating appearances.
Pulmonary infarction caused by pulmonary embolism
was uncommon because of the dual blood supply system
of the lungs originating from the bronchial and pulmonary
arteries, as well as the rich capillary anastomoses in the
lungs.5 In this study, pulmonary infarctions were found in
three out of 16 experimental dogs. In the heartworm group,
two dogs had a mild interstitial pattern in the caudodorsal
lung lobes in thoracic radiographs. There were no other
radiographic findings related to pulmonary embolism or
heartworm disease.
CTPA was characterized by a mildly irregular and
ill-defined margin of arteries and hyperattenuating pulmo-
nary infiltration in the caudal lungs in seven dogs. And
three dogs had intraluminal filling defects surrounded by
Fig. 3. Computed tomography pulmonary angiography (CTPA) images in heartworm dogs. (A) An embolus (circle) in the right caudal artery. (B) Two
emboli (circles) are present in the right caudal and accessory arteries, and there is left caudal arterial dilation (arrows) without intraluminal filling defects. (C and
D) 3D images from the dog in (B). Note the mild pruning of the right caudal arteries (arrow in C) and the tortuous and saccular dilated left caudal arteries
(arrows in D).
291EVALUATION OF PULMONARY EMBOLISMVol. 51, No. 3
contrast medium, consistent with pulmonary embolism.
Therefore, it is necessary to consider pulmonary embolism
in heartworm patients even if the patients have normal to
mild clinical signs or normal survey thoracic radiographs.
Two additional heartworm dogs had dilated and uno-
pacified pulmonary embolism regions in right caudal ar-
teries suspected to be pulmonary embolism, but these
findings were excluded as pulmonary embolism because of
the negative D-dimer results. The negative ELISA D-dimer
result is reliable to rule out pulmonary embolism with high
sensitivity.9 Therefore, these findings may have been due to
arterial intimal proliferation and heartworm arteritis.
In the experimental group, several interesting findings
after pulmonary embolism induction were noted, such as
the evidence of emboli migration and a rare complication
of a cavity formation and pneumothorax. One dog with a
right caudal arterial occlusion had an embolus in the right
main pulmonary artery and then an embolus in the left
caudal artery, simultaneously continuously. Three of the
four dogs with accessory arterial pulmonary embolism and
two of the six dogs with the left caudal arterial pulmonary
embolism had new emboli develop in the right caudal ar-
teries. On pathologic examination, a resolving pulmonary
embolus is compact and small and can be movable (Fig.
2B). This phenomenon may be explained by local pulmo-
nary hypertension and the anatomy of the pulmonary ar-
teries. Arterial orientation can be an important factor for
the pulmonary circulation. Based on the CTPA reformat-
ted images and 3D images, the right branch of the main
pulmonary artery was ventral to the left and coursed grad-
ually and slightly more ventrocaudally from the main pul-
monary artery than the left. The cranial pulmonary arteries
bent and curved slightly more acutely from the right or left
main pulmonary arterial branches than the caudal pulmo-
nary arteries. Therefore, resolving and movable small em-
boli may migrate easily to the right caudal arteries. These
emboli migrations were relatively common in the experi-
mental group, and migrated emboli did not cause arterial
dilation or complete occlusion. That the pulmonary em-
bolism in the experimental dogs was not the result of
pathologic pulmonary changes, such as arteritis, may have
contributed to the migration.
One dog with the left caudal arterial pulmonary embo-
lism developed a pleural-based cavitation on the 2nd day
and a spontaneous pneumothorax on the 7th day. Spon-
taneous pneumothorax following cavity infarct and pul-
monary embolism are rare in humans.11,14–18 This may
have been caused by rupture of the pleural surface of the
infarct followed by communication between airways and
the pleural cavity.15
In both the experimental and the heartworm group, ar-
terial dilations were identified in the region of the pulmo-
nary embolism. However, there were different patterns of
arterial dilation between the two groups. In the experi-
mental group, arterial dilations were straight with loss of
tapering and abrupt cut-off appearances. There was no
tortuosity. In the heartworm dogs, there were ill-defined
arterial margins, loss of tapering, tortuosity, or saccular
dilation of the caudal pulmonary arteries. These differences
are most likely due to pathologic arteritis in the tunica
intima and tunica media in the heartworm dogs.
One dog with pulmonary embolism in the right caudal
and accessory artery had a more tortuous and dilated left
caudal artery without pulmonary embolism. This is also
thought to be caused by the pathologic arteritis. In this
study, three heartworm dogs had pulmonary embolism and
arterial dilation in the right caudal arteries. This is similar
to one previous study where there was a tendency for more
right arterial dilation than the left.19 The right caudal ar-
teries and lobe were the most frequently affected even after
adulticide treatment.20 These seem to be most likely caused
by the anatomic orientation of pulmonary arteries as de-
scribed previously.
After considering the factors, pulmonary embolism and
arterial changes in clinical patients may be caused by com-
plex anatomic, pathophysiologic, or mechanical interaction
between the severity of arterial endothelial changes and the
amount of pulmonary embolism. Therefore, it may be
necessary to have an emphasis on the careful evaluation of
the pulmonary arterial changes as well as the identification
of pulmonary embolism on CTPA.
CTPA with optimal techniques was useful in the diag-
nosis and evaluation of both experimental pulmonary em-
bolism dogs and heartworm dogs.
REFERENCES
1. Carson JL, Kelley MA, Duff A, et al. The clinical course of pulmo-
nary embolism. N Engl J Med 1992;326:1240–1245.
2. Remy-Jardin M, Remy J, Wattinne L, Giraud F. Central pulmonary
thromboembolism. Diagnosis with spiral volumetric CT with the single
breathhold technique: comparison with pulmonary angiography. Radiology
1992;185:381–387.
3. Teigen CL, Maus TP, Sheedy PF, Johnson CM, Stanson AW, Welch
TJ. Pulmonary embolism: diagnosis with electron-beam CT. Radiology
1993;188:839–845.
4. Teigen CL, Maus TP, Sheedy PF, et al. Pulmonary embolism: diag-
nosis with contrast-enhanced electron beam CT and comparison with
pulmonary angiography. Radiology 1995;194:313–319.
5. Hurst DR, Kazerooni EA, Stafford-Johnson D, et al. Diagnosis of
pulmonary embolism: comparison of CT angiography and MR angiography
in canines. J Vasc Interv Radiol 1999;10:309–318.
6. Seldinger SI. Catheter replacement of the needle in percu-
taneous arteriography; a new technique. Acta Radiol 1953;39:368–
376.
7. Tidwell AS, Welcome J, Kinney LM. Spiral CT Angiography of the
pulmonary artery tree in dogs: development and use of test bolus injection
protocol. Vet Rad US 2004;45:483.
8. Gotway MB, Edinburgh KJ, Feldstein VA, Lehman J, Reddy GP,
Webb WR. Imaging evaluation of suspected pulmonary embolism. Curr
Probl Diagn Radiol 1999;28:129–184.
292 JUNG ET AL. 2010
9. Eng CW, Wansaicheong G, Goh SK, Earnest A, Sum C. Exclusion of
acute pulmonary embolism: computed tomography pulmonary angiogram
or D-dimer? Singapore Med J 2009;50:403–406.
10. Jones SE, Wittram C. The indeterminate CT pulmonary angiogram:
imaging characteristics and patient clinical outcome.Radiology 2005;237:
329–337.
11. Vaideeswar P. Cavitary pulmonary infarction—a rare cause of
spontaneous pneumothorax. J Postgrad Med 1998;44:99–100.
12. Worsley DF, Alavi A, Aronchick JM, Chen JT, Greenspan RH, Ravin
CE. Chest radiographic findings in patients with acute pulmonary embolism:
observations from the PIOPED Study. Radiology 1993;189:133–136.
13. Coche EE, Muller NL, Kim KI, Wiggs BR, Mayo JR. Acute pulmo-
nary embolism: ancillary findings at spiral CT. Radiology 1998;207:753–758.
14. Goddard R, Scofield RH. Right pneumothorax with the S1Q3T3
electrocardiogram pattern usually associated with pulmonary embolus. Am J
Emerg Med 1997;15:310–312.
15. Lim KH, Tan LH, Liam CK, Wong CM. An unusual cause of
secondary spontaneous pneumothorax in a 27-year-old man. Chest 2001;
120:1728–1731.
16. Olazabal A, Bartrina J, Perez Andres R. Spontaneous pneumotho-
rax as a complication of septic pulmonary embolism in intravenous drug
addicts. Eur J Radiol 1990;10:56–58.
17. Pavlakis G, Siafakas K, Gorgogiannis D, Sakorafas GH. Pulmonary
embolism with cavity formation, spontaneous pneumothorax, and high-
output air leak in a patient with non-small-cell lung cancer. N Z Med J
2003;116:1177.
18. Stocker JT, McGill LC, Orsini EN. Post-infarction peripheral cysts
of the lung in pediatric patients: a possible cause of idiopathic spontaneous
pneumothorax. Pediatr Pulmonol 1985;1:7–18.
19. Tarish JH, Atwell RB. The development of pulmonary lesions
associated with dead adult D. immitis in naive dogs. Zentralbl Veterinarmed
B 1993;40:197–205.
20. Rawlings CA, Keith JC, Losonsky JM, Lewis RE, McCall JW.
Aspirin and prednisolone modification of postadulticide pulmonary arterial
disease in heartworm-infected dogs: arteriographic study. Am J Vet Res
1983;44:821–827.
293EVALUATION OF PULMONARY EMBOLISMVol. 51, No. 3