CONTRAST‐ENHANCED PORTAL MAGNETIC RESONANCE ANGIOGRAPHY IN DOGS WITH SUSPECTED CONGENITAL PORTAL VASCULAR ANOMALIES

Contrast‐enhanced multiphase magnetic resonance angiography (CE‐MRA) was used in 17 dogs with a suspected congenital portal vascular anomaly. Portal vascular anomalies were identified in 16 of the 17 dogs. Eleven had a single intrahepatic portocaval shunt (two central divisional, three right divisional, and six left divisional), one dog had a double intrahepatic portocaval shunt, one dog had a hepatic arteriovenous malformation, one dog had a complex intrahepatic porto‐caval shunt. Two dogs had an extrahepatic portosystemic shunt and no shunt was identified in one dog. Total imaging time was <10 min and image quality was good to excellent in all dogs. Portal CE‐MRA is a feasible, fast and non invasive technique to diagnose portal vascular anomalies in dogs, with a large field‐of‐view and good anatomic depiction of the abnormal vessels. Based on these results, CE‐MRA is an efficient imaging technique for the diagnosis of portal vascular anomalies in dogs.     

Nonselective computed tomography angiography for detecting arterial blood flow to the distal limb following trauma in two small equids

Two equids weighing <250 kg were examined several days after suffering severe mid‐diaphyseal dorsal metatarsal lacerations. Distal limb vascular disruption was suspected in both cases. Nonselective computed tomography angiography with contrast medium injected peripherally via the jugular veins was used to evaluate the vascular supply to the distal limb. The use of this imaging technique demonstrated either intact or disrupted distal limb vasculature. The imaging results were verified with a positive long‐term outcome in the case with a diagnosis of an intact vasculature and with histological findings of avascular necrosis in the case with a diagnosis of disrupted vasculature.     

Diagnostic imaging for the assessment of acquired abdominal vascular diseases in small animals: A pictorial review

Advances in interventional radiology and surgical techniques now allow complex abdominal diseases to be more successfully treated in small animals. Abdominal vascular alterations, acquired as individual process or as complication of other lesions such as neoplasia, can be life‐threatening or at least greatly limit curative interventions of underlying diseases. Computed tomography (CT) and high‐definition ultrasonography are now readily available in veterinary referral centers. Yet, there is little information currently available on the use of these modalities for the diagnosis and characterization of these vascular alterations. The purpose of this article is to review the CT and ultrasonographic findings of acquired vascular diseases in the abdomen of dogs and cats, using both the veterinary and human medicine literature as references, and highlighting essential concepts through figures.     

COMPUTED TOMOGRAPHY OF NONANESTHETIZED CATS WITH UPPER AIRWAY OBSTRUCTION

Upper airway obstruction is a potentially life‐threatening problem in cats and for which a noninvasive, sensitive method rapid diagnosis is needed. The purposes of this prospective study were to describe a computed tomography (CT) technique for nonanesthetized cats with upper airway obstruction, CT characteristics of obstructive diseases, and comparisons between CT findings and findings from other diagnostic tests. Ten cats with clinical signs of upper airway obstruction were recruited for the study. Four cats with no clinical signs of upper airway obstruction were recruited as controls. All cats underwent computed tomography imaging without sedation or anesthesia, using a 16‐slice helical CT scanner and a previously described transparent positional device. Three‐dimensional (3D) internal volume rendering was performed on all CT image sets and 3D external volume rendering was also performed on cats with evidence of mass lesions. Confirmation of upper airway obstruction was based on visual laryngeal examination, endoscopy, fine‐needle aspirate, biopsy, or necropsy. Seven cats were diagnosed with intramural upper airway masses, two with laryngotracheitis, and one with laryngeal paralysis. The CT and 3D volume‐rendered images identified lesions consistent with upper airway disease in all cats. In cats with mass lesions, CT accurately identified the mass and location. Findings from this study supported the use of CT imaging as an effective technique for diagnosing upper airway obstruction in nonanesthetized cats.     

Radiotherapy isocenters verified by matching to bony landmarks of the canine and feline head differ when localized using volumetric versus planar imaging

The “gold standard” for verification of patient positioning before linear accelerator‐based stereotactic radiation therapy is kilovoltage cone‐beam computed tomography (kV‐CBCT), which is not uniformly available or utilized; planar imaging is sometimes used instead. The primary aim of this study was to determine if the position of the bony skull, when used as a surrogate for isocenter verification, is different when orthogonal megavoltage (MV) portal or kilovoltage (kV/kV) radiographs are used for image guidance, rather than kV‐CBCT. A secondary aim was to determine the influence of intra‐observer variability, body size and skull conformation on positioning, as determined using these three imaging modalities. Dogs and cats receiving radiotherapy of the head were recruited for this prospective analytical study. Planar (MV portal and kV/kV images) and volumetric (kV‐CBCT) images were acquired before treatment, and manually coregistered with reference images. Differences in skull position when matched based on MV portal, kV/kV images and kV‐CBCT were compared. A total of 65 subjects and 148 unique datasets were evaluated. The Wilcoxon rank‐sum test was used to evaluate effects of transitioning between imaging modalities. When comparing magnitude of shifts in MV to kV‐CBCT, MV to kV/kV and kV/kV to kV‐CBCT, there were statistically significant differences. Results were not measurably impacted by body size, skull conformation or interobserver differences. Based on shift magnitude and direction, an isotropic setup margin of at least 1 mm should be incorporated within the planning target volume when MV or kV planar imaging is used for position verification.     

TRIPLE‐PHASE HELICAL COMPUTED TOMOGRAPHY IN DOGS WITH HEPATIC MASSES

The purpose of this study was to determine the utility of triple‐phase helical computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs with hepatic masses underwent triple‐phase CT followed by surgical removal of the hepatic masses. Triple‐phase helical CT scans for each dog included precontrast, arterial phase, portal venous phase, and delayed phase studies. The removed hepatic masses were histopathologically classified as hepatocellular carcinoma (n = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a heterogeneous pattern with hyper‐, iso‐, and hypoenhancement in both the arterial and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most common CT findings were a homogeneous pattern with hyper‐ and isoenhancement in both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic metastatic tumors, the most common CT findings included a homogeneous hypoenhancement pattern in both the arterial and portal venous phases (8/9, 88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the delayed phase. Findings from our study indicated that triple‐phase CT is a useful tool for preoperative differentiation of hepatocellular carcinoma, nodular hyperplasia, and hepatic metastatic tumors in dogs.     

CONTRAST‐ENHANCED MAGNETIC RESONANCE ANGIOGRAPHY FOR DIAGNOSIS OF PORTOSYSTEMIC SHUNTS IN 10 DOGS

Computed tomography angiography, sonography, scintigraphy, and portography can be used to evaluate the portal vasculature to evaluate for a portosystemic shunt (PSS). Time‐of‐flight magnetic resonance angiography (TOF‐MRA) and contrast‐enhanced MRA (CE‐MRA) are other potentially useful techniques. The aim of this study was to evaluate CE‐MRA in 10 dogs suspected of having a PSS. Noncontrast MR images of the abdomen were obtained using a Siemens Symphony MR‐scanner (1.5 T) and a T1‐weighted FLASH‐3D sequence with a very short scan time (about 20 s). After injection of contrast medium, the initial sequence was repeated five times. The sequence with the best contrast medium filling of the portal vasculature was selected subjectively, subtracted from the initial survey image series, and a maximum intensity projection (MIP) of the subtraction data, in multiple views, was created. The cross‐sectional and MIP images were evaluated for abnormal portosystemic vasculature. A single PSS was identified and confirmed at surgery in all dogs. A portocaval shunt was found in five dogs, a portophrenic shunt in three dogs, a portoazygos shunt in one, and a central divisional intrahepatic shunt in one other dog. Based on our results, CE‐MRA is a useful tool for imaging abdominal and portal vasculature and for the diagnosis of a PSS.     

IMAGING DIAGNOSIS—CELIAC ARTERY PSEUDOANEURYSM ASSOCIATED WITH A MIGRATING GRASS AWN

The ultrasound and computed tomography findings of a retroperitoneal pseudoaneurysm associated with a grass awn are described in a 10‐month‐old dog. Ultrasound was used to localize the lesion and surrounding reaction as well as to determine its relationship with the celiac artery, but inadequate Doppler settings hindered the diagnosis of its vascular nature. Dual phase CT enabled further characterization, particularly its close relationship with the major retroperitoneal vessels. The imaging examination was fundamental in recommending nonsurgical therapy. The dog died as a consequence of the rupture of this pseudoaneurysm. A grass awn was confirmed.     

MULTIPHASE TIME-RESOLVED CONTRAST-ENHANCED PORTAL MRA IN NORMAL DOGS

Portal vein anomalies are common in dogs and cats. Diagnostic imaging is central in their diagnosis and fundamental with regard to choosing the best therapeutic option. Various imaging techniques are used in veterinary medicine to assess the portal vein. Each has individual advantages and disadvantages. Contrast-enhanced magnetic resonance angiography (CE-MRA) is used routinely in humans to image the portal system and has excellent spatial and temporal resolution and three-dimensional (3D) acquisition. Herein, we report the development of a CE-MRA protocol that resulted in fast 3D imaging of the arterial splanchnic and portal venous system in normal dogs. Multiphase acquisition strategy allowed acquiring the same volume several times during one single breath-hold, thereby capturing the portal venous phase with excellent signal. Excellent depiction of the vascular anatomy, especially the portal afferent vessels and branches, was observed. Elliptical centric view ordering of k-space was used to acquire the contrast-sensitive data faster. Parallel imaging was used to increase coverage in the dorsal to ventral direction while keeping imaging time short. It is anticipated that 3D CE-MRA is a fast and noninvasive imaging method that could be used to diagnose various portal vascular anomalies in small animals.     

IMAGING DIAGNOSIS—MULTICENTRIC LYMPHOMA OF GRANULAR LYMPHOCYTES IMAGED WITH FDG PET/CT IN A DOG

A 5‐year‐old female spayed bulldog was referred for mild dyspnea, decreased activity and appetite, occasional nonproductive cough, polydipsia, and polyuria. A 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed unexpected activity in the heart, lungs, and mild generalized lymphadenopathy that led to the diagnosis of lymphoma of granular lymphocytes after nonspecific findings on imaging with standard modalities of echocardiography, thoracic radiography, and abdominal ultrasound. PET/CT scanning is a useful whole body imaging modality with high sensitivity for changes associated with canine lymphoma.     

Tumour‐associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours

Tumour‐associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin‐fixed paraffin‐embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.     

Video‐Assisted Thoracoscopic Resection of Noninvasive Thymomas Using One‐Lung Ventilation in Two Dogs

Objective— To report the technique and outcome of video‐assisted thoracoscopic surgery (VATS) for resection of cranial mediastinal thymoma in 2 dogs. Study Design— Case report. Animals— Eleven‐year‐old Labrador Retrievers (n=2). Methods— Two dogs had VATS resection of thymoma. Preoperative computed tomography (CT) scans revealed well‐circumscribed cranial mediastinal masses with dimensions of 4.5 cm × 4.2 cm × 3.7 cm and 2.1 cm × 2.1 cm × 4.1 cm (at the time of resection) without CT evidence of vascular invasion. One‐lung ventilation (OLV) was achieved using a bronchoscopically placed double‐lumen endobronchial tube. A 3‐portal technique was used for VATS access to the thorax. Thymomas were dissected from the tissues of the cranial mediastinum with the aid of a harmonic scalpel and retrieved in specimen retrieval bags. Results— Two cranial mediastinal thymomas were resected successfully, with their capsules intact, using a VATS technique. One dog developed aspiration pneumonia postoperatively which resolved with treatment and remains healthy 18 months postoperatively with no radiographic evidence of tumor recurrence. The second dog was diagnosed with myasthenia gravis, megaesophagus, and aspiration pneumonia preoperatively and despite recovering well from the procedure had a second episode of aspiration pneumonia 5 days postoperatively and was euthanatized. Conclusions— VATS resection of modestly sized noninvasive thymoma is possible in dogs. Careful case selection and preoperative imaging are the keys. Clinical Relevance— Thoracoscopic resection of modestly sized mediastinal masses forms part of an increasingly expansive set of indications for minimally invasive surgery in select veterinary patients.     

Immortalization and characterization of a new canine mammary tumour cell line FR37‐CMT

Here we describe the establishment of a new canine mammary tumour (CMT) cell line, FR37‐CMT that does not show dependence on female hormonal signaling to induce tumour xenografts in NOD‐SCID mice. FR37‐CMT cell line has a stellate or fusiform shape, displays the ability to reorganize the collagen matrix, expresses vimentin, CD44 and shows the loss of E‐cadherin which is considered a fundamental event in epithelial to mesenchymal transition (EMT). The up‐regulation of ZEB1, the detection of phosphorylated ERK1/2 and the downregulation of DICER1 and miR‐200c are also in accordance with the mesenchymal characteristics of FR37‐CMT cell line. FR37‐CMT shows a higher resistance to cisplatin (IC₅₀>50 µM) and to doxorubicin (IC₅₀>5.3 µM) compared with other CMT cell lines. These results support the use of FR37‐CMT as a new CMT model that may assist the understanding of the molecular mechanisms underlying EMT, CMT drug resistance, fostering the development of novel therapies targeting CMT.     

PET/CT today and tomorrow in veterinary cancer diagnosis and monitoring: fundamentals,early results and future perspectives

Functional imaging using positron emission tomography (PET) plays an important role in the diagnosis, staging, image‐guided treatment planning and monitoring of malignant diseases. PET imaging complements conventional anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI). The strength of CT scanning lies in its high spatial resolution, allowing for anatomical characterization of disease. PET imaging, however, moves beyond anatomy and characterizes tissue based on functions such as metabolic rate. Combined PET/CT scanners were introduced commercially in 2001 and a number of technological advancements have since occurred. Radiolabelled tracers such as ¹⁸F‐fluorodeoxyglucose (FDG) and ¹⁸F‐fluorothymidine (FLT) allow visualization of various metabolic processes within cancer cells. Many studies in human oncology evaluating the utility of PET/CT have demonstrated clinical benefits. Few veterinary studies have been performed, but initial studies show promise for improved detection of malignancy, more thorough staging of canine cancer and determination of early response and disease recrudescence.     

IMAGING DIAGNOSIS—PORTAL VEIN APLASIA AND INTERRUPTION OF THE CAUDAL VENA CAVA IN THREE DOGS

Severe portal vascular anomalies have been reported previously accompanying azygos continuation of the caudal vena cava, polysplenia, and situs anomalies in dogs and people. Three dogs with portal vascular anomalies were identified by means of CT angiography as having portal vein aplasia with portal insertion into the caudal vena cava, azygos continuation of the caudal vena cava, and interruption of the pre‐hepatic caudal vena cava. This information confirms that complex embryological defects may occur in patients presenting for congenital portosystemic shunt, and that CT angiography is a non‐invasive method of completely evaluating these potentially non‐surgical portal vascular anomalies.     

Diagnostic utility of computed tomography imaging in equine intracranial conditions

Reasons for performing study: The use of computer tomography (CT) and contrast‐enhanced CT (CCT) to image the head is common. However, the validity of CT as a neurodiagnostic indicator of intracranial diseases in horses is unknown. Objective: To define the validity of CT and CCT in horses with suspected intracranial disorders. Methods: The validity of CT imaging was estimated by comparing clinical, clinicopathological and histopathological findings to CT findings in 15 horses presented for intracranial disorders, for which pre‐ and post contrast CT images and post mortem examination of the brain and skull were reviewed. Post mortem examination (gross and histopathological examination) was considered as the gold standard; and sensitivity, specificity, predictive values, likelihood ratios, and pre‐ and post test probabilities were calculated. Results: All horses had abnormal neurological examinations on admission. Computer tomography imaging identified intracranial lesions in 8 horses, and included masses (oligodendroglioma, adenocarcinoma and cholesterinic granulomas), acute haemorrhage and skull fractures. Computer tomography imaging failed to identify intracranial lesions in 6 cases, which included meningitis, meningoencephalitis and nonacute haemorrhage. Lesions not recognised by CT were also not evident on gross examination but were identified by histopathological examination of the brain. Post mortem examination of the brain and skull was unremarkable in one horse, for which cranial CT imaging was normal (specificity, 100%). Therefore, the odds of having an intracranial lesion after an abnormal CT were very high. In contrast, there was a moderate sensitivity (57.1%, 95% confidence interval: 29.6–81.2). Conclusions and potential relevance: CT was an excellent neurodiagnostic tool in identifying skull fractures, intracranial space‐occupying lesions (e.g. neoplasia) and acute haemorrhage and allows to rule in intracranial disorders. However, CT showed limited sensitivity in identifying inflammatory disorders and small parenchymal lesions in the equine brain, which was not further detectable after contrast administration.     

In vitro study to assess the efficacy of CDK4/6 inhibitor Palbociclib (PD‐0332991) for treating canine mammary tumours

Therapy of canine mammary tumours (CMTs) with classical antitumour drugs is problematic, so better therapeutic options are needed. Palbociclib (PD‐0332991) is an innovative and effective anticancer drug for the treatment of breast cancer in women. Palbociclib is an inhibitor of cyclin‐dependent kinase 4 (CDK4) and CDK6, which are key regulators of the cell cycle machinery and thus cell proliferation. In the present in vitro study, we investigated whether Palbociclib also represents a candidate drug to combat CMT. For this purpose, the effect of Palbociclib was analysed in P114 and CF41 cells, two CMT cell lines with an endogenous CDK4/6 co‐expression. Incubation of P114 and CF41 cells with Palbociclib resulted in a dose‐ and time‐dependent loss of phosphorylated retinoblastoma protein (pRb), a classical CDK4/6 substrate within the cell cycle machinery. Moreover, treatment of CMT cells with Palbociclib‐induced cell cycle arrest affected cell viability, prevented colony formation and impaired cell migration activity. Palbociclib also inhibited the growth of P114 and CF41 cell spheroids. Immunohistochemical analysis of canine patient samples revealed a consistent expression of CDK6 in different canine mammary carcinoma types, but an individual and tumour‐specific expression pattern of phosphorylated pRb independent of the tumour grade. Together, our findings let us suggest that Palbociclib has antitumour effects on CMT cells and that canine patients may represent potential candidates for treatment with this CDK4/6 inhibitor.     

THREE-DIMENSIONAL MULTISLICE HELICAL COMPUTED TOMOGRAPHY TECHNIQUES FOR CANINE EXTRA-HEPATIC PORTOSYSTEMIC SHUNT ASSESSMENT

The purpose of the present study was to investigate the feasibility and usefulness of three-dimensional (3D) multislice computed tomography (CT) angiography with maximum intensity projection (MIP) and volume rendering (VR) in six dogs with clinical and sonographic findings suggestive of portosystemic shunt. Furthermore, we aimed to estimate the diameter of the portal vein and shunt vessels. MIP and VR reconstructions were performed for each patient and the origin and insertion of all shunt vessels were detected. In addition, 3D reconstructions allowed excellent depiction of vascular morphology and topography. All diagnoses and vessel measurements were confirmed by surgery. 3D multidetector CT angiography is a promising, noninvasive, and accurate method of evaluating dogs with suspected portosystemic shunts.