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Radiology Federica Morandi, DVM, MS, DACVR, DECVDI Associate Professor, University of Tennessee, Knoxville Comparative Imaging Of The Thorax - Neoplastic Processes Introduction - The thorax is composed of a skeletal base, formed by the 13 thoracic vertebrae and respective ribs, costal cartilages, sternebrae, sternal cartilages, and by the scapulae. The soft tissues that provide coverage to the thorax include the cutis, fascial planes, superficial and deep muscle planes, intercostal musculature and parietal pleura. The diaphragm represents the caudal border of the thorax; the cranial border is made up of loose connective tissue that seals the cranial mediastinum. Within the thorax, the mediastinum is the space between the lungs and is bounded on each side by a layer of mediastinal pleura, which is a component of the plural sac (each pleural sac is made up of mediastinal, diaphragmatic, costal and pulmonary pleurae). The mediastinum is divided into cranial, middle and caudal components. The mediastinum contains the esophagus, the trachea, the heart, the great vessels (aorta with its bifurcations, cranial and caudal vena cava, and azygos vein), lymph nodes (cranial mediastinal, tracheobronchial and sternal), the thoracic duct, nerve trunks and the thymus. The mediastinum can contain a variable amount of fat, especially in the dog. The lungs and pulmonary vessels complete the list of structures contained within the thorax. In light of the number and complexity of the thoracic structures, it is not a surprise that the evaluation of these structures is often difficult, and that various diagnostic imaging modalities are complementary to each other. This is especially true in the assessment of neoplastic processes, which can originate from each one of the structures and organs that make up the thorax. Such neoplasias include primary and metastatic lung tumors, tumors associated with the chest wall (such as vaccine-associated sarcoma and other soft tissue sarcomas), primary or metastatic bone tumors (osteosarcoma, chondrosarcoma, fibrosarcoma), tracheal neoplasia (such as osteocartilaginous tumors, carcinoma), esophageal neoplasia (such as squamous cell carcinoma); lastly one must remember lymphomas, thymomas, heart base tumors (hemangiosarcoma, chemodectoma, ectopic thyroid tumors) and mesothelioma. This list is by no mean inclusive of all possible neoplastic processes that can be encountered in the thorax, but gives an idea of the variety of pathologies one can encounter. While a tissue sample (in the form of fine needle aspirate or biopsy) is necessary for a definitive diagnosis, diagnostic imaging modalities are essential to narrow the differential list, for tumor staging, and for surgical planning. Radiology - Survey radiographs are still the first imaging modality for evaluation of thoracic pathology, including neoplastic processes. One of the most commonly performed radiographic studies is the so-called 'met-check' - that is, opposite lateral and VD / DV views of the thorax - which is an integral part of diagnostic screening in dogs and cats presented for cancer staging. The presence of soft tissue pulmonary nodules is typically interpreted as metastatic disease; the other, much less likely, differential diagnosis is granulomatous disease, either fungal or non-fungal. A solitary pulmonary nodule, on the other hand, may represent metastasis, a primary lung tumor, or less likely a granuloma or abscess. In human medicine, up to 50% of solitary pulmonary nodules represent benign, inactive granulomas; while in small animals it is usually assumed that benign granulomas are rare, their true incidence is unknown. Survey radiographs have well-know limitations in the ability to identify pulmonary nodules: generally speaking, a soft tissue nodular lesion must be at least 5 mm before it can be reliably detected on radiographs. Larger nodules can be difficult to identify if they are located in the paravertebral recesses, in the accessory lung lobe, or in the apical portion of the lungs adjacent to the cranial mediastinum. Another common use of radiography is to determine the origin of a larger thoracic mass. Depending on the mass size and location, it may be difficult to decide if a lesion if of pulmonary, extrapleural (for instance, a rib mass) or mediastinal (lymph nodes, esophagus) origin. In equivocal cases, additional projections, such as tangential views that can demonstrate an extrapleural sign, can be used; fluoroscopy is also helpful, as it can determine if a nodular lesion moves with the lung parenchyma; oral administration of barium sulfate can assist in differentiating a pulmonary from an esophageal mass; finally, horizontal-beam radiographs obtained with animal standing on all four, or with the front limbs elevated, are useful to differentiate between pleural effusion and/or a mass. In cases of pleural effusion, it also useful to repeat the radiographs after thoracocentesis; removal of pleural fluid allows better inflation of the lungs, and allows evaluation of the mediastinum, cardiac silhouette and pulmonary vessels. Ultrasound - Due to its relatively low cost, ease of use and non-invasive nature, ultrasound has become more widespread in recent years, and is often used to characterize thoracic pathology. Ultrasound is most useful when used in conjunction with radiography: these two imaging modalities are not alternative to each other, but rather complementary. The main limitation of ultrasonography is that sound waves cannot penetrate the normal lung: the interface between soft tissue and gas results in virtually 100% reflection of the sound waves. Pleural effusion, on the other hand, provides an 'acoustic window' that improves the examiner's ability to evaluate the cranial mediastinum, pleurae, diaphragm and lungs, especially when they are partially collapsed (atelectatic) due to compression from surrounding fluid. In the absence of plural fluid, ultrasonographic evaluation of a pulmonary mass or nodule is only possible when the lesion is peripherally located and in contact with the thoracic wall. Masses in the accessory lung lobe can sometimes be identified using a trans-abdominal approach, scanning through the liver and diaphragm. Once a lesion is identified, ultrasound is extremely useful to guide fine needle aspiration or biopsy, reducing the risk of damage to neighbouring structures and allowing precise sampling of the targeted lesion. Computed Tomography (CT) - Compared to convention radiology, CT has the great advantage to generate cross-sectional images of the body, thereby eliminating the superimposition of structures, which is inevitable in conventional radiography. Additionally, CT is superior to radiography in discriminating between tissues of similar density. Lastly, CT image display can be optimized by varying the window width and widow level, and permits evaluation of osseus, soft tissue structures and pulmonary parenchyma, using a single acquisition. These characteristics have made CT the most accurate imaging modality for characterization of some pulmonary pathologies (such as pulmonary nodules and interstitial lung disease) in human medicine. In veterinary medicine, CT is usually a secondary study that takes place after survey radiographs. Limitations of CT in veterinary medicine include the need for general anesthesia, high cost and limited availability of scanners compared to traditional radiographic equipment and ultrasound. CT is however irreplaceable when it is necessary to accurately determine the origin and extension of a neoplastic process arising from the lung, mediastinum or chest wall, the invasion of surrounding structures, and the presence/absence of metastatic pulmonary nodules. CT is superior to radiography in the identification of pulmonary nodular metastasis (both in human and veterinary medicine), and due to the high contrast between soft tissue nodules and surrounding aerated lung, can identify smaller lesions (1-2 mm) compared to survey radiography. Technical aspects of thoracic CT - While it is possible to perform a thoracic CT with an axial scanner, a helical (spiral) scanner is ideal to evaluate the lungs. Helical acquisition mode using a single slice scanner shortens the study time considerably (30-60 seconds to acquire the entire chest in medium-large size dog), eliminates or significantly reduces artefacts due to respiratory motion, and allows improved multiplanar and three-dimensional (3D) reconstruction. It is important to remember that, once the animal is under anesthesia, lateral recumbency will result in rapid collapse of the dependent lung (hypostasis), which is very difficult to clear even after prolonged positive pressure ventilation; this may result in a non-diagnostic study, especially when the CT is performed to look for pulmonary metastases, which, being small soft tissue nodules, can 'disappear' in a collapsed lung. It is therefore mandatory to maintain the animal in sternal recumbency from the moment of sedation, through induction, until the end of the study. Sternal recumbency is preferred over dorsal recumbency, as dorsal recumbency results is some degree of atelectasis of the caudodorsal aspect of the caudal lung lobes, especially in large dogs. To obtain a short period of apnea that lasts during the acquisition, one can hyperventilate the animal for about 1 minute prior to starting the acquisition; or maintain the lungs insufflated to about 15 cm H20 either using a ventilator, or manually (any personnel remaining in the room during the acquisition MUST wear protective lead clothing and wear a dosimeter). At our institution, we use a 4 mm collimation for animals weighing < 15 kg, and 8 mm collimation for animals weighing > 15 kg. A pitch of 1 is recommended; pitch is defined as the ratio between the table velocity to the rotational velocity of the X-ray tube. For example, if the slice thickness is set at 5 mm and the table moves at a speed that allows the gantry to rotate once every 5 mm of table travel, the pitch is 1. This is analogous to the acquisition of contiguous images with an axial scanner (however the helical acquisition mode is much faster). Lung evaluation necessitates the use of a high-resolution algorithm ('edge-enhancing' or 'sharp' - different manufacturers may have different names), while evaluation of soft tissues (mediastinum, chest wall) necessitates a low-contrast algorithm ('standard'). Depending on the scanner and on the amount of computer memory available, it may be possible to save the 'raw data' and reformat them in different algorithms without re-acquiring the images. When a small or equivocal lesion is detected, the helical scan can be followed by a limited high-resolution acquisition (HRCT or 'high-resolution computed tomography'). HRCT is performed by obtaining <2 mm (ideally 1 mm) collimated contiguous images; such thin sections minimize volume averaging effect and maximize the visibility of a small lesion. Obviously, it is impossible to acquire 1 mm thick slices through the whole lung; therefore HRCT must be limited to a small portion of the lungs. While the newest generation multislice CT scanners (up to 64 detector rings) allow acquisitions with a speed up to 18 cm/sec and isotropic resolution of 0.35 mm voxels, they are not routinely available in veterinary medicine. Intravenous contrast medium is not necessary for the identification of soft tissue metastatic nodules; it is however necessary to characterize origin and extension of primary pulmonary, mediastinal and chest wall tumors, and to evaluate compression/displacement/invasion of vascular structures, in order to determine resectability in preparation for definitive or debulking surgery.  
Two examples of helical pulmonary CT; both images are displayed in lung window (Window Width: 1300, Window Level: -700) and were obtained without iodinated contrast: SELECTED BIBLIOGRAPHY
Comparative Imaging Of The Thyroid Brief review of anatomy and physiology -In the dog and the cat, the thyroid gland is composed of two separate, fusiform lobes, located ventral and lateral to the first 5-8 tracheal rings. Two parathyroid glands are associated with each thyroid lobe: typically, one (external parathyroid) is located adjacent to the ventral surface of the cranial aspect of the gland, and one (internal parathyroid) is within thyroid parenchyma, in the caudal aspect of the gland. The thyroid gland is abundantly vascularized by vessels derived from the cranial thyroid artery (a branch of the common carotid artery), which runs together with the recurrent laryngeal nerve along the dorsal margin of each thyroid lobe, and enters the gland at the level of the cranial margin. The caudal thyroid artery (absent in the cat) is a branch of the brachiocephalic artery. Venous drainage is via the cranial and caudal thyroid veins (which drain in the internal jugular and brachiocephalic veins respectively). In both the dog and cat, ectopic thyroid tissue can be found along midline from the base of the tongue to level of the cranial mediastinum. Thyroid neoplasia can arise from either the thyroid gland or ectopic thyroid tissue in both species. The most common thyroid pathology in the cat is hyperthyroidism, resulting from excess production of thyroxine (T4) and triiodothyronine (T3). The most common cause of feline hyperthyroidism is nodular thyroid hyperplasia, or the presence of hyperfunctioning adenomas. Only about 3% of hyperthyroid cats have thyroid malignancies (carcinomas). Thyroid masses are rare in the dog; however, when present, they are likely to be malignant. While cats usually presented with clinical signs attributable to excessive secretion of thyroid hormones, dogs usually have signs attributable to the space-occupying effect of a cervical mass compressing adjacent structures. The majority of dogs presenting with carcinomas have either normal or decreased thyroid hormones production; hyperthyroidism is rare. Radiology - Survey radiography is not very useful for evaluation of the thyroid. A normal sized thyroid, and even a mildly enlarged thyroid, is not radiographically visible, due to the silhouetting effect with surrounding cervical soft tissues. In the presence of a large thyroid mass, radiographs can reveal compression or displacement of the surrounding structures, such as the trachea, larynx or hyoid apparatus. Thyroid carcinomas can mineralize, and mineralizations have usually an irregular, amorphous or spiculated appearance. Administration of a barium sulfate bolus orally can be of assistance in excluding a mass of esophageal origin. Ultrasound - The thyroid is best examined using a high frequency probe (7.5 to 10 - 14 MHz). The thyroid lobes are most easily identified in the longitudinal plane, ventral and medial to the common carotid artery. Once a lobe is identified, a transverse image is obtained by rotating the probe by 90º. On the same transverse image, it is possible to identify the trachea, thyroid, carotid artery and jugular vein; on the left side of the trachea, the esophagus is also visible, dorsolateral to the gland. In the longitudinal plane, the thyroid lobes are fusiform, have homogeneous echogenicity and regular, smooth margins. In the transverse plane, the thyroid lobes have oval or triangular shape and are located just lateral to the trachea. Thyroid echogenicity is slightly higher than that of the surrounding muscle bellies. Ectopic thyroid tissue is extremely difficult to identify ultrasonographically. Color or Power Doppler can assist in identifying vascular structures, and in assessing vascularization of nodules or masses. It is important to remember that a normal ultrasound does not rule out thyroid pathology; furthermore, thyroid nodules can sometimes be seen in normal animals, and it can be difficult to determine if a thyroid nodule represents thyroid or parathyroid tissue. Diagnosing hypothyroidism on ultrasound is especially challenging. Differentiating adenoma and carcinomas can also be difficult based on ultrasound alone. Adenomas tend to have smooth margins, can be uni- or multi-focal, and are often hypoechoic compared to normal thryoid tissue. Some adenomatous lesion have also a cystic component. Thyroid cysts are anechoic structures, with distal enhancement, and can be multi-loculated. Thyroid carcinomas tend to be unilateral, large masses, and are often invasive. A large, irregularly marginated, heterogeneous mass, containing mineralizations and/or cystic components and abundant vascularization, and that invades the surrounding vessels and/or the esophagus is most likely a carcinoma. A definitive diagnosis requires a fine-needle aspirate or biopsy. Ultrasound has also the advantage of allowing simultaneous evaluation off the size, shape and ultrastructure of regional lymph nodes. Computed Tomography (CT) - The normal feline thyroid glands have high attenuation compared to the surrounding soft tissues (mean attenuation values: 123.2 Hounsfield Units [HU] pre-contrast; 168.5 HU immediately post-contrast; 132.1 HU at 4-13 minutes post-contrast). Similar values (107.5 HU pre-contrast and 169.0 HU post-contrast) have been reported in normal dogs. The thyroid's high density (due to its iodine content) makes it easy to identify even on the pre-contrast images. The main advantage of CT is that it permits assessment of the origin, size and extension of a cervical mass; this is especially useful in surgical planning. The use if intravenous iodinated contrast media allows differentiation between vascular tissue and necrotic or cystic areas, and permits assessment of surrounding vascular structures for tumor invasion or compression. Regional lymph nodes are evaluated based on dimension (normal or enlarged), but abnormal enhancement should also be noted. It is important to remember that contrast media are iodine compounds: a CT with contrast will result in saturation of the iodine receptors, therefore a scintigraphy performed immediately after CT will be negative. This must be kept in mind during the evaluation of cervical or cranial mediastinal masses, when both CT and scintigraphy are considered in the work-up. The time necessary to resolution of the effect of iodine contrast on the thyroid has not been determined in the dog and cat; based on human data, however, our institution recommends waiting 3 - 4 weeks after a contrast CT before performing thyroid scintigraphy. 
Transverse pre-contrast CT image of the neck of a 8 year-old female spayed Beagle evaluated for a left-sided cervical mass (asterisk). The image is displayed in a soft tissue window and was acquired with standard algorithm. The normal thyroid lobes are hyperattenuating compared to soft tissues (arrowheads) and the mass is clearly not of thyroid origin. Scintigraphy - Thyroid scintigraphy is performed using either technetium-99m in the form of pertechnetate (99mTc04-), or (less commonly) 123I, radioactive iodine-123. Pertechnetate has the advantages of emitting gamma rays with energy of 140 KeV, which is very favorable for image formation; and of having a short (6.01 hours) half-life. Iodine-123 emits gamma rays of slightly higher energy (159 KeV), has a longer half-life (13.3 hours), and has the further disadvantage of being more expensive. Iodine-123 behaves just like non-radioactive iodine, and is trapped by the follicular cells of the thyroid via active transport mechanism, regulated by TSH (thyroid stimulating hormone). Iodine is then bound to the aminoacid tyrosine to form monoiodotyrosine and diiodotyrosine, which then combine to form T3 and T4. Technetium is a transitional metal (group VIIB of the periodic table) which imitates the behavior of halogens (so-called 'pseudo-halogen'). In the form of pertechnetate, technetium is trapped and concentrated in the follicular cells of the thyroid. Pertechnetate, however, is not organified nor bound to the tyrosyl group in the formation of thyroglobulin. Therefore, pertechnetate is concentrated in the thyroid, but does not participate in the formation of thyroid hormones, nor is trapped within the colloid. Small lesions (such as small metastases or ectopic tissue) are therefore best seen using 123I than pertechnetate, because of the higher target-to-background ratio (in other words, the background is markedly suppressed on a 123I scan and any lesion becomes more visible). Thyroid Scintigraphy in the Cat - Thyroid scintigraphy is a very simple procedure: a dose of 1 to 4 mCi (37 to 148 MBq) of pertechnetate is injected intravenously, and 20 minutes later lateral and ventral images of the cervical area and of the thorax are acquired using a LEAP ('low-energy, all-purpose') collimator. At our institution, we also acquire a ventral view of the neck with a pinhole collimator, which results in a magnified view of the thyroid gland, with higher resolution. In a normal cat, the intensity of the two thyroid lobes is symmetric and slightly less that the intensity of the salivary glands. The ratio between the counts per pixel in the thyroid and those in the salivary (thyroid-to-salivary ratio, or T/S) 20 minutes post-injection is about 0.87:1 (variable from 0.6:1 to 1.03:1). The T/S ratio does not change significantly in the first hour post-injection. The intensity of the thyroid, however, keeps increasing between 1 and 4 hour: acquiring the images 4 hours post-injection, therefore, may result in the erroneous diagnosis of hyperthyroidisms in a normal cat. Pathologic findings in the cat: in cases of multifocal nodular hyperplasia (or adenomatous hyperplasia), one or both thyroid lobes exhibit increased uptake and intensity, due to the increased pertechnetate uptake. Typically, the thyroid lobes have smooth margins and homogenous pattern of uptake. The uptake may be symmetrical or asymmetrical; in cases if unilateral pathology (about 30% of cases), the contralateral lobe is completely suppressed through negative feedback mechanism via the pituitary gland. In cases in which one lobe shows increased uptake, and the contralateral normal or slightly decreased uptake, both lobes must be considered abnormal. In the cat, hyperthyroidism can also result from hyperfunctional thyroid adenomas. Adenomas can be single or multiple, uni- or bi-lateral or can originate from ectopic tissue. In the presence of a hyperfunctioning adenoma, the normal surrounding tissue is suppressed by the normal negative feedback mechanism. Adenomas are best seen using a pinhole collimator. Thyroid carcinomas are rare in the cat. Distinguishing between a benign adenomatous process and a malignancy is not always possible based on scintigraphy alone. In other words, thyroid carcinomas can have the same pattern of uptake as hyperplastic or adenomatous benign processes. Carcinomas, however, tend to have a more heterogeneous pattern of uptake, with irregular or spiculated margins. The scintigraphic findings more consistent with malignancy are extension of uptake outside the normal margins of the thyroid; and uptake in the regional lymph nodes, indicative of metastasis. Uptake at the base of the tongue, along midline in the cervical soft tissue, and in the cranial mediastinum can represent either metastatic or ectopic tissue, the latter in a benign process. Uptake in pulmonary nodules or masses is indicative of a neoplastic process, but is not pathognomonic of thyroid carcinoma; both primary pulmonary tumors or metastases from other neoplastic processes can uptake pertechnetate. Thyroid Scintigraphy in the Dog - Acquisition parameters are similar to those described for the cat; the dose is slightly higher (2-5 mCi, or 74-185 MBq). Pinhole images are often not acquired due to the larger size of the canine thyroid, but can be obtained in smaller dogs. The normal canine thyroid is more intense than the normal feline thyroid: the T/S ratio at 20 minutes post intravenous injection is about 1.21:1. Ectopic tissue in a sublingual location is much more common in the dog than in the cats, especially after thyroidectomy. Pathologic findings in the dog: most thyroid tumors in the dog are non-metabolically active carcinomas. The three most common patterns of uptake with canine thyroid carcinomas are: 1) increased, homogeneous uptake at the level of the entire thyroid lobe (follicular tumor); 2) mass of thyroidal origin, with decreased radionuclide uptake and loss of normal thyroid tissue (stromal tumor); 3) irregularly shaped, multifocal areas of both increased and decreased uptake (mixed-cell tumor). Scintigraphy is useful in tumor staging, mainly for the evaluation of the regional (retropharyngeal) lymph nodes, and to evaluate the cervical soft tissues, mediastinum and lungs. In such instances, scintigraphy is performed after removal of the primary tumor, and has the additional advantage to assess the tumor bed for presence of residual tumor tissue. Generally speaking, iodine-123 is superior to pertechnetate given its ability to be organified. 
Right and left lateral (top row) and ventral (bottom left) images obtained with a LEAP collimator after injection of 3 mCi (111 MBq) of 99mTc04- in a 12 year-old female spayed domestic shorthair cat presented for suspect hyperthyroidism; the bottom right image was acquired using a pinhole collimator. On the three LEAP images, the thyroid lobes have increased radioisotope uptake compared to the salivary glands, consistent with bilateral hyperthyroidism. On the pinhole view, multifocal hyperactive nodules are visible in both lobes, suggesting bilateral adenomatous hyperplasia or multifocal adenomas. 
Right lateral, ventral and right lateral (from left to right) images obtained with a LEAP collimator after injection of 4.7 mCi (174 MBq) of 99mTc04- in a middle-aged, mixed breed, male neutered dog presented for evaluation of a large cervical mass. The left thyroid lobe is normal. Only a small portion of thyroid tissue is present along the cranial pole of the right lobe of the gland; the majority of the right lobe has been replaced by a mass of blood pool intensity. This is consistent with a malignant thyroid tumor; the lack of suppression of the left lobe suggests that the tumor is not producing hormones - the dog's T4 concentration was normal. SELECTED BIBLIOGRAPHY
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