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The Veterinary Journal 197 (2013) 541552
Review
a r t i c l e i n f o a b s t r a c t
Article history: Imaging technology is critical for adequate diagnosis and staging in human and veterinary oncology. Sen-
Accepted 6 May 2013 sitive detection of lesions is necessary to determine appropriate local or systemic therapy and to monitor
therapeutic results. New technology in digital radiography, ultrasound, and computed tomography (CT)
scanning are now widely available in veterinary medicine. Advanced imaging with high-detail CT scans,
Keywords: magnetic resonance imaging (MRI), and positron-emission tomography (PET) are now available in aca-
Cancer demic centers and some private specialty practices. This review describes the current and future appli-
Diagnostic imaging
cations of these new imaging systems and modalities in veterinary oncology and how advanced
Molecular imaging
Dog
imaging contributes to diagnosis, staging, and monitoring of cancers. The potential of molecular imaging
Cat for accurate, minimally invasive diagnosis and monitoring is discussed.
2013 Elsevier Ltd. All rights reserved.
1090-0233/$ - see front matter 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tvjl.2013.05.022
542 J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552
of the entire lesion (Fig. 2). This is a very useful feature, but cannot
provide accurate measurements and is a static image (vs. real-
time). Although ultrasound is used in practice to assess the extent
of cancer and its margins for surgical resection and radiation ther-
apy, it is of limited value in this application; CT and MRI provide
better information. Despite these inherent limitations, ultrasound
is used appropriately to screen for disease, assess for multi-organ
involvement in known disease, acquire guided samples, and re-
evaluate disease during or following therapy.
Computed tomography
Fig. 2. Older neutered male dog with carcinoma of the trigone (arrow) of the urinary bladder and prostate gland. Extended eld-of-view sagittal ultrasound image of urinary
bladder cancer (UB) and prostate cancer (P), with regional lymph node (ln) metastasis. The large eld view provides a panoramic perspective of large lesions or lesions
involving more than one organ, partially overcoming one of ultrasounds major limitations of small eld view. While precise measurements are not possible, size estimates
can be made using the depth (vertical) and length (horizontal) cm markers located along the right and bottom margins, respectively. We have found extended eld view
imaging to be valuable in subjective assessment pre- and post-cancer therapy. This image was obtained with a Biosound Esaote MyLab 70 ultrasound machine using a 4
13 MHz linear array transducer, operating in VPan mode. Cranial is to the left, caudal to the right. (Image courtesy of Washington State University).
Nuclear medicine in a radiation isolation facility until their radioactive emissions are
below a prescribed level.
Nuclear medicine generates images through tissue physiology
rather than anatomic abnormalities. Nuclear medicine uses in- Single photon emission computed tomography (SPECT)
jected radioactive substances to create a functional diagnostic im-
age. Radioactive substances are termed radionuclides, or SPECT uses collimated scintillation crystals moving around the
radiopharmaceuticals when combined with specic compounds. patient to generate a three-dimensional (3D) rendering of the
Radiopharmaceuticals can be selected which preferentially target structure of interest. The principal advantage of SPECT is a more
certain organs. A detector called a gamma camera records gamma accurate image of the distribution of the agent within the eld.
rays emitted from the patient. Lesions are identied by altered Identifying the target of interest within a tumor or organ could se-
radiopharmaceutical metabolism. Because nuclear medicine lect candidates for targeted treatment and guide therapy decisions
images provide poor anatomic detail, they can be combined with in the future. SPECT imaging has been used to evaluate tumor
CT or MRI to yield both functional and anatomic information. There metabolism in dogs with cancer (Ogilvie, 2000; Whittemore
are three fundamental forms of diagnostic nuclear medicine: (1) et al., 2004).
two-dimensional planar scintigraphy; (2) three-dimensional sin-
gle-photon emission computed tomography (SPECT), and (3) PET.
Positron emission tomography imaging (PET)
Fig. 3. A 9-year-old, spayed female mixed breed dog was presented for evaluation of a subcutaneous mast cell tumor over the left dorsal thorax. The mass appeared mobile
relative to underlying tissue on examination. Thoracic radiographs were normal for a dog of this age (A, left lateral; B, dorsoventral). (C and D) CT scan revealed a markedly
enlarged contrast enhancing left axillary lymph node (black arrow) (C) and intrathoracic invasion of the mast cell tumor (white arrow) (D). The original treatment plan of
surgery was abandoned in favor of medical therapy in light of a more extensive and metastatic tumor than identied on clinical examination and thoracic radiography. The CT
images are displayed in a soft tissue window and level setting. A, aorta; T, trachea; E, esophagus; GB, gallbladder. (Images courtesy of Washington State University).
not unique to cancer cells as metabolically active tissue, including et al., 2011). Some human tumors, such as prostate cancer, cannot
inammation, can concentrate the molecule, yielding a false-posi- be imaged well with 18F-FDG (Sharkey et al., 2007).
tive scan (Ballegeer et al., 2006). In human oncology, 18F-FDG The utility of 18F-FDG in veterinary patients has been only min-
imaging is indicated for staging a variety of tumors including imally explored to date (Lawrence et al., 2010; Hansen et al., 2011;
breast cancer, hepatocellular carcinoma, lung tumors, head and LeBlanc et al., 2012). Imaging results with 18F-FDG in dogs are very
neck carcinoma, brain tumors, and many sarcomas (Alberini similar to those in humans. The most commonly used PET
J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552 545
Molecular imaging is the creation of a diagnostic image by tar- Selected disease entities
geting a molecule or a tissue property for imaging using the tech-
nologies described above. Most commonly, the images derived are Hemangiosarcoma
nuclear medicine images, but contrast agents for MRI can also tar-
get tumor-associated molecules or processes (Makowski et al., Hemangiosarcoma is a highly metastatic form of cancer that
2009). The target could be a metabolic pathway unique to the tis- arises from a malignant endothelial cell precursor of myeloid der-
sue of origin of the cancer, such as iodine trapping in thyroid can- ivation (Lamerato-Kozicki et al., 2006). It arises most commonly in
cer, or a specic antigen that is overexpressed in the type of cancer, the spleen, skin/subcutis, right atrium, and liver, but may occur in
such as prostate specic membrane antigen (PSMA) in prostate almost any tissue in dogs. The disease may spread from any pri-
cancer. Molecular imaging is evolving towards specic diagnostic mary site to the lung, liver, right atrium, omentum, mesentery, kid-
assays that might identify the exact type of cancer in vivo, giving ney, skeleton, adrenal glands, and cerebrum (Snyder et al., 2008).
546 J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552
Fig. 5. Dog with extensive soft-tissue sarcoma of the left ventral neck. (A) Axial post-contrast computed tomography (CT) image at the level of the occipital bone and ears
shows extensive and complex tumor (T). (B) Sagittal reconstruction post-contrast CT image to the left of midline through the tumor (T). The head is to the left (HR). B, brain; C,
cervical spine. (C) Dorsal plane reconstruction post-contrast CT image through the tumor (T). The head is pointed upward (HR). ET, endotracheal tube. (D) Three-dimensional
reconstruction of the head and neck showing the extensive nature of the tumor (T) and complex blood supply. The head is pointed toward the top of the image, the patients
left is to the right (LH). C, common carotid arteries; M, mandible; ET, endotracheal tube. (Images courtesy of Washington State University).
Hemangiosarcoma is similar to the relatively rare disease, angi- splenic lesions (Fife et al., 2004). However, in our practice, CT dif-
osarcoma, in people. The imaging appearance of angiosarcoma in ferentiation has not been reliable. Doppler ultrasound examination
human beings is very similar to that of hemangiosarcoma in dogs. of splenic masses can identify vascular tumors.
In humans, ultrasound examination reveals angiosarcoma as a Recently, contrast harmonic ultrasonography has been sug-
complex mass with heterogeneous echotexture containing cystic gested as useful for differentiating metastatic HSA from benign le-
regions (Abbott et al., 2004). On CT angiosarcoma will appear ill- sions in liver parenchyma (Ivancic et al., 2009). The enhanced
dened with heterogeneous contrast uptake and areas of necrosis. imaging was not, however, benecial in distinguishing hemangio-
MRI examination tends to be enhanced by hemorrhage within and sarcoma and splenic hematoma. In another study, contrast har-
around the angiosarcoma in the spleen (Abbott et al., 2004). Heter- monic ultrasonography was highly predictive of malignancy for
ogeneity on T1 and T2 weighted images suggest bleeding from the lesions that were moderately or markedly hypoechoic (Ohlerth
mass into splenic parenchyma (Abbott et al., 2004). Gadolinium et al., 2008). Even so, there are no pathognomonic signs of heman-
contrast enhancement causes heterogeneic enhancement of the le- giosarcoma on ultrasound examination. Ultrasound examination of
sions and can be used to distinguish them from benign lesions (Ab- the heart base should be performed to identify lesions in that loca-
bott et al., 2004). Radiographic images of the thorax are used to tion. Use of an echocardiogram to detect right atrial masses has
stage angiosarcoma patients for pulmonary metastasis. been associated with a 92% positive predictive value and a 64%
Dogs and cats with hemangiosarcoma should be staged with negative predictive value (Fruchter et al., 1992).
three view thoracic radiographs, abdominal ultrasound, and echo-
cardiogram. Thoracic radiographs should be assessed extremely Thyroid carcinoma
carefully for subtle signs of metastatic disease (Fig. 1). CT of the
thorax is even more sensitive than radiography for metastatic Nuclear imaging of the thyroid gland and thyroid tumors relies
events (Fig. 4) (Nemanic et al., 2006). Contrast CT has also been re- on the unique metabolic property of iodine trapping and organi-
ported to facilitate the differentiation of malignant from benign cation of thyroid tissue. The most common imaging agent is
J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552 547
Fig. 6. Cat with an injection site brosarcoma (arrows) of the shoulder. (A) Axial T1 post-contrast magnetic resonance imaging (MRI). (B) Sagittal T1 post-contrast MRI. (C)
Post-contrast axial computed tomography (CT). (D) Post-contrast sagittal CT. This comparison illustrates the exquisite resolution of the tumor and surrounding soft tissues by
MRI. (E) Three-dimensional CT reconstruction shows excellent anatomic detail of the complex vascular nature of the tumor (arrows). CT images (C and D) are displayed in a
soft tissue window and level setting maximizes the relatively small differences in soft tissue contrast. This setting renders the lung almost entirely black. R, right; L, left. White
arrowhead indicates trachea. l, cranial lung; m, cranial mediastinum; c, cranial vena cava; H, heart. (Images courtesy of Washington State University).
548 J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552
Fig. 7. Positron emission tomography (PET; A and B) and PET/computed tomography (PET/CT; CE) images of a 9-year-old spayed female Labrador retriever with thyroid
carcinoma and a small pulmonary nodule. The images were acquired following the administration of 18FDG. (A) Ventral PET image. The thyroid mass (T) is easily identied
with lobulated uptake of FDG-18. A small focus of uptake is seen in the right caudal thorax overlying the cranial margin of the liver (black arrow). (B) Lateral PET image. The
thyroid mass (T) is seen as an area of inhomogeneous increase in FDG-18 uptake. (C) Ventral PET/CT image shows the tumor (T). The ventral PET image (A) has been fused
with a CT scan. (D) Lateral PET/CT image shows the thyroid tumor (T). The lateral PET image (B) has been fused with a CT scan. (E) Axial PET/CT image showing the right caudal
pulmonary nodule (white arrow), presumed to be metastatic disease. (Images courtesy of Colorado State University).
Fig. 8. Pretarget planar images of a dog with prostate cancer. In the 4.5 h image (a) the kidneys (white arrows) and a small shadow (dark arrow) of the bladder are visible. In
the 49 h image, the dark accumulation of activity (dark arrow) is not the bladder, but a metastatic lymph node that was not identied on earlier ultrasound imaging. (Image
courtesy of Drs. Michael R. Lewis and Jeffrey N. Bryan).
Fig. 10. In a study of 399 dogs presenting with osteosarcoma, 7.8% had a second
skeletal lesion consistent with an osteosarcoma metastasis detected on 99mTc-HDP
nuclear scintigraphy (Jankowski et al., 2003). Presented is a representative bone
scintigraphic scan with two apparent rib lesions (arrows) that were conrmed as
osteosarcoma metastases. The dog head is to the right, dorsal is at the top of the
image. (Image courtesy of Washington State University).
Scintigraphy has also been used to assess tumor margin prior to The proliferation of high quality diagnostic imaging in human
resection for limb-spare surgery. While plain radiographs tend to and veterinary medicine has resulted in the discovery of an
550 J.S. Mattoon, J.N. Bryan / The Veterinary Journal 197 (2013) 541552
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