Contrast harmonic imaging characterization of canine splenic lesions

Background: Although B-mode ultrasound is very sensitive for the detection of splenic lesions, its specificity is low. Contrast harmonic imaging is used successfully to differentiate benign from malignant liver lesions in humans and dogs.
Hypothesis: Contrast harmonic imaging could be useful to differentiate benign and malignant splenic lesions in dogs.
Animals: Sixty dogs (clinical patients) with splenic abnormalities detected during abdominal ultrasonography.
Methods: A prospective study was performed with a Philips ATL 5000 unit for contrast pulse inversion harmonic imaging (mechanical index: 0.08, contrast medium: SonoVue). Perfusion was assessed subjectively and quantitatively.
Results: Cytology or histology identified 27 benign (hyperplasia, extramedullary hematopoiesis, hematoma) and 29 malignant (hemangiosarcoma, malignant lymphoma, malignant histiocytosis, mesenchymal tumors without classification, mast cell tumors, and others) lesions and 4 normal spleens. Except for 1 benign nodule, extensive to moderate hypoechogenicity was only seen in malignant lesions during wash-in, at peak enhancement, and during wash-out ( P = .0001, odds ratios: 37.9 [95% CI 4.5–316.5], 66.4 [95% CI 8.0–551.1], and 36.9 [95% CI 4.4–308.4]). Although all but 1 benign lesion enhanced well and were mildly hypo-, iso-, or hyperechoic in comparison with the normal spleen during all blood pool phases, marked enhancement occurred both in benign as well as in malignant splenic lesions. Quantitative perfusion values did not differ significantly between benign and malignant lesions.
Conclusions and Clinical Importance: Moderate to extensive hypoechogenicity clearly identifies canine splenic malignant lesions. In nodules with marked enhancement, contrast harmonic ultrasound is of limited value and histology is needed.     

CONTRAST-ENHANCED ULTRASONOGRAPHY FOR CHARACTERIZATION OF CANINE FOCAL LIVER LESIONS

In six normal beagles and 27 dogs with spontaneous focal or multifocal liver lesions, contrast-enhanced ultrasonography using Sonazoid^® was performed. Sonazoid^® is a newly developed second-generation contrast agent with the ability to be used for real-time contrast imaging along with parenchymal imaging. An appropriate protocol for the evaluation of all three phases (arterial, portal, and parenchymal) was established based on the results for normal beagles. By evaluation of the echogenicity of hepatic nodules during the arterial and parenchymal phases it was possible to differentiate malignant tumors from benign nodules with very high accuracy. In 15 of 16 dogs diagnosed as malignant tumors, nodules were clearly hypoechoic to the surrounding normal liver during the parenchymal phase. Additionally, malignant tumors had different echogenicity compared with the surrounding normal liver during the arterial phase in 14 of 15 dogs. In the portal phase, there were no characteristic findings. Contrast-enhanced ultrasonography with Sonazoid^® appears to improve the characterization of canine focal and multifocal hepatic lesions.     

CONTRAST ENHANCED SONOGRAPHIC ASSESSMENT OF FEEDING VESSELS AS A DISCRIMINATOR BETWEEN MALIGNANT VS. BENIGN FOCAL SPLENIC LESIONS

Contrast‐enhanced sonography was conducted in 17 confirmed focal splenic lesions (five malignant, 12 benign). Relative echogenicity changes were used for subjective interpretation of lesion perfusion. A rapid influx of contrast agent, resulting in an increased relative echogenicity of the lesion, followed by a rapid clearance of contrast agent was referred to as early washin/early washout. There were 6/12 benign, and 3/5 malignant lesions characterized by early washin/early washout. Therefore, sensitivity, specificity, and accuracy for this parameter in differentiating malignant from benign lesions was 60%, 50%, and 53%, respectively. There were 2/12 benign, and 2/5 malignant lesions with persistent hypoperfusion throughout all phases. Therefore, sensitivity, specificity, and accuracy for malignancy using this criterion were 40%, 83%, and 71%, respectively. However, none of the benign and all malignant lesions were characterized by tortuous and persistently visible feeding vessels. This suggests that interpretation of splenic lesions cannot be performed accurately on the basis of echogenicity or persistent hypoperfusion, but that assessment of vascular tortuosity may be helpful in discriminating between a malignant vs. benign focal splenic lesion.     

CONTRAST‐ENHANCED ULTRASONOGRAPHIC FINDINGS IN THREE DOGS WITH PANCREATIC INSULINOMA

Abdominal ultrasonography is one of the most common diagnostic imaging modalities used for dogs with suspected insulinoma; however, pancreatic masses are clearly identified in fewer than half of affected dogs and benign pancreatic nodules can be difficult to differentiate from malignant ones. The purpose of this prospective study was to describe contrast‐enhanced ultrasonography (CEUS) characteristics of confirmed pancreatic insulinoma in a group of dogs. Inclusion criteria were as follows: (1) repeated hypoglycemia (blood glucose levels <60 mg/dl, twice or more); (2) elevated blood insulin levels with hypoglycemia; (3) pancreatic nodules detected with conventional ultrasonography; and (4) histological confirmation of pancreatic islet cell carcinoma. Immediately following conventional ultrasonography of the entire abdomen, CEUS of the pancreatic nodule and adjacent parenchyma was performed using contrast‐specific technology pulse inversion imaging and perflubutane microbubble contrast agent. Three dogs met inclusion criteria. Pancreatic nodules in all the three dogs became more clearly demarcated after injection of the contrast agent. Each nodule showed different enhancement patterns: markedly hyperechoic for 5 s, slightly hyperechoic for 1 s, and clearly hypoechoic for over 30 s. These results were not in complete agreement with previously reported CEUS findings in human patients with insulinoma. All nodules were surgically resected and histopathologically confirmed as malignant insulinomas. Findings from the current study indicated that contrast‐enhanced ultrasound may help to increase conspicuity of pancreatic insulinomas in dogs and that enhancement characteristics may be more variable in dogs than in humans.     

Magnetic resonance imaging of focal splenic and hepatic lesions in the dog

Focal hepatic and splenic lesions in the dog are common, and approximately half of such lesions are malignant. Both incidentally discovered lesions and lesions in patients with known malignancies represent diagnostic dilemmas. Ultrasound often fails to characterize such lesions adequately. This uncertainty may result in unnecessary splenectomies and liver biopsies for benign lesions or noncurative surgery for advanced-stage malignancies. In humans, ultrasound largely has been supplanted by computed tomography and magnetic resonance imaging (MRI) for the characterization of focal hepatic and splenic lesions. The inherently high soft tissue contrast of MRI allows the differentiation of benign from malignant hepatic and splenic lesions in the human patients. In this prospective study, 35 focal lesions of either the spleen (n = 8) or the liver (n = 27) were characterized by MRI in 23 dogs. Lesions were presumptively classified as malignant or benign on the basis of MRI findings. Imaging results then were correlated with histopathologic (29) or cytologic (6) evaluation of the lesions. The overall accuracy in differentiating malignant from benign lesions was 94% (33 of 35 lesions). The overall sensitivity and specificity were 100% (95% CI, 78-100%) and 90% (95% CI, 68-99%), respectively. MRI classified malignant hepatic lesions as hepatocellular carcinoma (HCC) in all confirmed cases and correctly predicted the histologic grade of 5 HCC lesions. These results suggest that MRI is a useful modality for abdominal imaging in veterinary patients, and MRI accurately differentiated benign from malignant focal hepatic and splenic lesions in this sample of patients.     

Description of the use of contrast‐enhanced ultrasonography in four dogs with pancreatic tumours

Canine pancreatic tumours are rare compared to human medicine and the detection and differentiation of pancreatic neoplasia is challenging with B‐mode ultrasonography, which often leads to late clinical diagnosis and poor prognosis. This case report describes the findings of contrast‐enhanced ultrasonography in four dogs with pancreatic adenocarcinoma or insulinoma. B‐mode ultrasonography of the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue in one dog. Contrast‐enhanced ultrasonography was able to differentiate between two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions, whereas insulinomas showed uniformly hypervascular lesions. Contrast‐enhanced ultrasonography findings were confirmed by cytology and/or histopathology. The results demonstrated that contrast‐enhanced ultrasonography was able to establish different enhancement patterns between exocrine (adenocarcinoma) and endocrine (insulinoma) tumours in dogs .     

INCIDENTAL AND NONINCIDENTAL CANINE THYROID TUMORS ASSESSED BY MULTIDETECTOR ROW COMPUTED TOMOGRAPHY: A SINGLE‐CENTRE CROSS SECTIONAL STUDY IN 4520 DOGS

Thyroid nodules are common in dogs and are increasingly likely to be detected with the increased use of advanced imaging modalities. An unsuspected, nonpalpable, asymptomatic lesion, defined as a thyroid incidentaloma, may be discovered on an imaging study unrelated to the thyroid gland. The objective of this single‐center cross‐sectional study was to assess the prevalence and computed tomography (CT) characteristics of incidental and nonincidental thyroid tumors in a large population of dogs, using prospective recruitment of patients undergoing CT examination for various reasons during the period of 2005–2015. Unilateral or bilateral thyroid masses were detected in 96/4520 dogs (prevalence, 2.12%; 95% confidence interval [CI], 1.70–2.54%). Seventy‐nine (82.3%) lesions were malignant and 17 (17.7%) were benign. Masses were discovered incidentally in 34/96 dogs (overall prevalence of incidentaloma, 0.76%; 95% CI, 0.51–1.02), and 24 (70.6%) of these 34 masses were thyroid carcinomas. Among the CT variables assessed, mineralization, vascular invasion, and tissue invasion were detected only in malignant tumors. Intratumoral vascularization was significantly associated with the presence of thyroid malignancy (P < 0.001). Although incidental thyroid nodules in dogs are relatively rare, they are often malignant. Findings indicated that the neck should be thoroughly assessed in middle‐aged and old patients undergoing body CT for various reasons. Thyroid nodules detected incidentally on CT should be sampled to avoid missing thyroid cancer.     

CELLULAR FEATURES OF SONOGRAPHIC TARGET LESIONS OF THE LIVER AND SPLEEN IN 21 DOGS AND A CAT

Target lesions are seen in ultrasound images of the liver or spleen as nodules or masses with a hypoechoic rim and a hyperechoic or isoechoic center. To assess the diagnostic significance of finding a target lesion, the cytologic and/or histopathologic findings were reviewed in a series of 21 dogs and a cat that had hepatic and/or splenic target lesions noted during abdominal ultrasonography. Twelve of 16 hepatic target lesions and 5 of 7 splenic target lesions were malignant. In this series, the finding of one or more target lesions in the liver or spleen had a positive predictive value for malignancy of 74%; for the finding of multiple target lesions in one organ, the positive predictive value for malignancy was 81%. Benign lesions associated with target lesions were nodular hyperplasia of the liver and spleen, pyogranulomatous hepatitis, cirrhosis, and chronic active hepatitis.     

Use of contrast-enhanced ultrasound for characterization of focal splenic lesions.

Contrast-enhanced ultrasound was used to study focal and multifocal lesions of the spleen in 26 dogs and two cats affected by 11 benign and 18 malignant splenic diseases. A second-generation microbubble contrast medium (Sonovue) was injected into the cephalic vein and enhancement patterns were subjectively described and time intensity curves calculated. Final diagnosis was obtained by histopathologic examination after splenectomy (n=19) or by needle aspiration and sonographic follow-up after 4 and 8 weeks (n=9). Contrast-enhanced ultrasound parameters, improving the characterization between benign and malignant lesions, were established. The most useful criterion was the hypoechogenicity of the lesion in the wash-out phase combined with the presence of tortuous feeding vessels, which was observed in association with malignancy. All malignant lesions were hypoechoic to the surrounding spleen 30s after starting the contrast medium injection. Lymphosarcoma and hemangiosarcoma had characteristic perfusion patterns. Lymphosarcoma had rapid time to peak and early wash-out phase with a honeycomb pattern during the wash-out. Hemangiosarcomas were large nonperfused masses in all phases surrounded by hypervascular splenic parenchyma. Benign lesions except one hematoma and a benign histiocytoma had the same perfusion pattern as the surrounding spleen. Ultrasonographic and contrast-enhanced ultrasound findings of an accessory spleen are reported. Contrast-enhanced ultrasound can improve the characterization of focal or multifocal lesions of the spleen.     

CHARACTERIZATION OF CANINE FOCAL LIVER LESIONS WITH CONTRAST-ENHANCED ULTRASOUND USING A NOVEL CONTRAST AGENT—SONAZOID

Contrast-enhanced ultrasound using Sonazoid, a novel contrast medium with a liver-specific Kupffer phase, was evaluated in canine focal liver lesions Twenty-five dogs with a liver mass were given intravenous Sonazoid, and the enhancement pattern in the arterial, portal, and parenchymal phase was characterized. An enhancement defect in the lesion in the parenchymal phase was observed in all malignant lesions, whereas only one of nine benign lesions had a filling defect. The diagnostic value of the presence of a filling defect for malignancy was statistically significant (100% sensitivity, 88.9% specificity, 94.1% positive predictive value, 100% negative predictive value), and was equal to that of hypoenhancement in the portal or delayed phase. The defect pattern (clear or irregular defect) was dependent ( P <0.05) on the types of malignancy (i.e., hepatocellular carcinoma and other types of malignancies). In the arterial phase, five of the six hepatocellular carcinomas had hypervascularity, whereas no other lesion was characterized by hypervascularity. In some dogs, additional lesions that could not be observed with conventional B-mode ultrasonography were detected in the parenchymal phase. The enhancement pattern of Sonazoid, especially in the parenchymal phase, has potential as a diagnostic tool for canine focal liver lesions.     

Magnetic resonance imaging characterization of canine splenic lesions

Introduction:  Splenic lesions are a common finding in veterinary medicine and typically 1/2 to 2/3 of these lesions are malignant. Due to the limited accuracy of ultrasound, unnecessary exploratory surgeries/biopsies may be performed for benign lesions and treatment may be delayed for malignant ones. Splenic lesions are rare in people. MR imaging, with its inherently high soft tissue contrast, is efficacious in imaging the human spleen. We have previously demonstrated the efficacy of MRI to differentiate canine hepatic lesions. In that study 8 splenic lesions were all accurately characterized. This current study represents a further evaluation of splenic lesions.
Methods:  In this prospective study, 27 dogs with splenic lesions were accrued. Histopathological/cytological confirmation of lesions occurred either before or shortly after imaging. MRI clinicians were blinded to histopathology results. MR (General Electric, 1.5 Tesla) images using a variety of sequences were obtained before and after intravenous administration of gadolinium.
Results:  32 lesions (9 malignant, 23 benign) were evaluated in 27 dogs. Lesions were confirmed via histopathology (n = 20) or cytology (n = 12). Benign lesions included, EMH (n = 7), hematoma/hemorrhage (n = 5), lymphoid hyperplasia (n = 9), and hemangioma (n = 2). Malignant lesions included anaplastic sarcoma (n = 3), malignant histiocytosis (n = 2), hemangiosarcoma (n = 2), plasma cell tumor (n = 1) and adenocarcinoma (n = 1). The overall accuracy in differentiating benign from malignant lesions was 88%(29/32 lesions). The overall sensitivity and specificity were 100%(95% CI, 66–100) and 87%(95% CI 66–97).
Conclusions:  Based upon these results, MRI is both sensitive and specific in distinguishing between malignant and benign splenic lesions.     

B-MODE AND DOPPLER ULTRASOUND IMAGING OF THE SPLEEN WITH CANINE SPLENIC TORSION: A RETROSPECTIVE EVALUATION

The ultrasonographic appearance of splenic torsion has been described; the splenic parenchyma can be normal, hypoechoic or anechoic with interspersed linear echoes (coarse/"lacy" appearance). The ultrasonographic parenchymal appearance of 15 dogs in this report with splenic torsion varied: mottled hypoechoic regions (n=2), diffusely hypoechoic (n=11) and normal (n=2). Because splenic torsion causes vascular congestion due to splenic vein compression and eventual thrombosis, visible splenic vein intraluminal echogenicities compatible with thrombi were seen in 13 dogs using B-mode. Using spectral Doppler and color Doppler imaging of the splenic veins, no measurable flow velocities were detected in any of the 15 dogs. The varied B-mode ultrasonographic appearance of the splenic veins for intraluminal echoes and spectral or color Doppler evaluation for absent velocity flow.     

COMPARISON BETWEEN SHOULDER COMPUTED TOMOGRAPHY AND CLINICAL FINDINGS IN 89 DOGS PRESENTED FOR THORACIC LIMB LAMENESS

Computed tomography (CT) is an established technique for detecting shoulder lesions in dogs, however the clinical significance of shoulder CT lesions often remains uncertain. The purposes of this retrospective study were to describe the prevalence of CT lesions in both shoulder joints for 89 dogs presenting with thoracic limb lameness and to compare CT lesions with clinical characteristics. For all included dogs, results of a full orthopedic examination, other diagnostic tests, and signalment data were available in medical records. Multilevel, multivariable logistic regression was used to test clinical significance of the most prevalent CT lesions and determine factors associated with their presence. Computed tomographic lesions were detected in one or both shoulder joints for 51/89 dogs (57.3%). Mineralization of one or more surrounding peri‐articular soft‐tissue structures was identified in 31.5% of dogs, with supraspinatus muscle/tendon mineralization being the most frequently identified (24.7%). The prevalence of humeral head osteochondrosis was 9 and 21.3% of dogs had shoulder osteoarthritis. Border collies (odds ratio [OR] 9.3; 95% CI 1.39–62.1, P = 0.02) and dogs with shoulder pain (OR 4.3; 95% CI 1.08–17.1, P = 0.04) had increased risk of osteochondrosis lesions. Border collies (OR 8.4; 95% CI 1.27–55.6; P = 0.03) and older animals (OR 1.04; 95% CI 1.02–1.1, P < 0.001) had increased risk of osteoarthritis lesions. Female entire dogs had an increased risk of supraspinatus mineralization lesions (OR 6.8; 95% CI 1.55–29.5, P = 0.01). Findings indicated that shoulder CT lesions are common in dogs with thoracic limb lameness, and that some CT lesions are not associated with shoulder pain.     

ULTRASONIC DETECTION OF SPLENIC NECROSIS IN THE DOG

Ultrasonographic findings of splenic infarction and necrosis in three dogs are presented. Two previously unreported ultrasonographic patterns are identified: (1) Focal, hypoechoic or isoechoic, circular, wellmarginated nodular masses with peripheral lesions causing deformation of the splenic margin. (2) Diffuse hypoechoic or heteroechoic coarse/"lacy" parenchymal pattern with no deformation of margin. The presence of gas within the splenic parenchyma of one dog was detected by both radiography and ultrasonography. Ultrasonographic patterns of splenic infarction in both man and the dog are discussed     

Color and power Doppler ultrasonography for characterization of splenic masses in dogs

Benign and malignant splenic masses can appear similar on B-mode imaging, making ultrasound sensitive but not specific in their diagnosis. Our goal was to characterize color and/or power Doppler characteristics of vasculature within and adjacent to a splenic mass, which would distinguish benign vs. malignant lesions. The hypothesis was that malignant splenic masses will have altered vascular patterns compared with benign masses. Color and power Doppler cineloops evaluating the vasculature within the mass and normal splenic parenchyma were obtained in sagittal and transverse planes using a standardized protocol. Categories of evaluation included presence of peritoneal effusion, a large aberrant or tortuous vessel within the mass, relative blood flow within the mass compared with normal parenchyma, and path of vessels in the adjacent parenchyma entering into the mass. All patients had histopathologic or definitive cytologic diagnosis. Thirty-one dogs were included. There were 13 malignant masses and 18 were benign. Peritoneal effusion was significantly associated with malignancy (P = 0.0007). Presence of an aberrant or tortuous vessel within the mass was nearly significant (P = 0.059). There was no significant difference in any of the color or power Doppler blood flow evaluations. Ultrasonographic findings of a splenic mass and peritoneal effusion may indicate malignancy. The presence of an aberrant vessel within a splenic mass could suggest malignancy; however more data are needed.     

Cytologic–histologic concordance in the diagnosis of neoplasia in canine and feline lymph nodes: a retrospective study of 367 cases

Lymph nodes are frequently sampled in dogs and cats for the diagnosis of primary and metastatic neoplasia. We determined the accuracy of cytologic diagnosis in lymph nodes using histology as the gold standard. Lymph node reports (2001–2011) were retrospectively evaluated and diagnoses were categorized as neoplastic or non‐neoplastic. Lymph nodes from 296 dogs and 71 cats included 157 (42.7%) non‐neoplastic lesions, 62 (16.9%) lymphomas and 148 (40.3%) metastatic neoplasms. Cytology had a sensitivity of 66.6% [95% confidence interval (CI) 60.0–72.8%], specificity of 91.5% (CI 86.3–95.2%), and accuracy of 77.2% (CI 72.6–81.3%) for neoplasia. Likelihood of malignancy with a positive cytologic diagnosis of neoplasia was 93.0%. High proportions of false‐negative results were found in mesenteric T‐cell lymphoma (22/35, 63%, mainly cats), metastatic sarcoma (8/14, 57%) and metastatic mast cell tumour (15/48, 31%, mainly dogs). Factors contributing to discrepancies included well‐differentiated lymphocyte morphology, focal distribution of metastases and poorly defined criteria for metastatic mast cell tumours.     

Ultrasonographic features of splenic hemangiosarcoma in dogs: 18 cases (1980-1986)

The medical records of 18 dogs in which ultrasonography was useful in making a diagnosis of splenic hemangiosarcoma were reviewed. Splenic ultrasonography revealed masses with echo patterns that ranged from anechoic fluid to hyperechoic tissue. In 7 dogs, metastasis was detected ultrasonographically as anechoic to hypoechoic lesions in the liver.     

A randomized controlled study into the efficacy and toxicity of pegylated liposome encapsulated doxorubicin as an adjuvant therapy in dogs with splenic haemangiosarcoma

Safety and efficacy of pegylated liposome encapsulated doxorubicin (PL‐DOX) was compared with free doxorubicin as an adjuvant monotherapy in dogs with splenic haemangiosarcoma after splenectomy in a randomized prospective clinical trial. A total of 17 dogs in each group were treated. No significant difference in survival between the two treatments was found. The calculated median overall survival time for the 34 dogs was 166 days [95% confidence interval (CI) 148–184]. The ½ year and one‐year survival was 41.2% (95% CI 24.8–56.9) and 22.7% (95% CI 9.9–37.4), respectively. In dogs treated with PL‐DOX, a desquamating dermatitis like palmar‐plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions. Cardiotoxicity was not seen in either treatment groups.     

COMPARISON OF COMPUTED TOMOGRAPHIC AND PATHOLOGIC FINDINGS IN 17 DOGS WITH PRIMARY ADRENAL NEOPLASIA

The CT appearance of canine adrenal masses has been reported, but associations between imaging features and pathologic features of these lesions have not been investigated in detail. The purpose of this study was to test associations between different types of adrenal neoplasia and their CT and pathologic features. A retrospective cross‐sectional study was performed and inclusion criteria were histologic diagnosis of primary adrenal neoplasia, contrast‐enhanced CT examination of the abdomen and surgical resection of the mass or necropsy examination. For all included dogs, CT images and histopathologic specimens were reviewed independently by two veterinary radiologists and a veterinary pathologist, respectively. Seventeen dogs met inclusion criteria. Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%) dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3–18.3, P = 0.03) and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4–65.9, P = 0.02). There was excellent agreement between signs of vascular invasion in CT images and vascular invasion at surgery or necropsy (kappa = 0.86, P = 0.001). A peripheral contrast‐enhancing rim in delayed postcontrast CT images was associated with fibrous encapsulation of the tumor (kappa = 0.53, P = 0.05), and a heterogeneous pattern of contrast distribution in delayed postcontrast CT images was associated with adrenal hemorrhage or infarction on histological examination (kappa = 0.45, P = 0.05). Findings indicated that CT enabled assessment of adrenal neoplasia features that reflected their biological behavior and pathological findings, however overlapping characteristics between tumor types limited the potential for reliably distinguishing them based on CT alone.