Comparison of examination of thoracic radiographs and thoracic computed tomography in dogs with appendicular osteosarcoma

Appendicular osteosarcoma (OSA) is a highly metastatic tumour in dogs. The aim of the study was to compare thoracic radiographs with thoracic computed tomography (CT) in the staging of canine appendicular OSA. In all, 39 canine patients histologically diagnosed with OSA were reviewed in the retrospective study. All dogs underwent radiographic examination as well as CT examination of the thoracic cavity. Pulmonary nodules were detected radiographically in two cases (5%), whereas the CT imaging showed that pulmonary nodules were evident in 11 cases (28%, P = 0.024). There was an improved detection of small pulmonary nodules in the lung parenchyma with CT (P = 0.021). The number of nodules in CT examination had a significant negative influence on survival time (P = 0.005). However, whether nodules were present in CT or not did not influence overall survival (P = 0.368). CT examination was superior to thoracic radiography in the screening and detection of pulmonary nodules in dogs with OSA.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

Cutaneous metastasis of primary appendicular osteosarcoma in a dog

A 6-year-old, neutered male Rottweiler was presented to the University of Illinois Veterinary Teaching Hospital because of a lytic bone lesion involving the distal portion of the right radius and possible pulmonary metastases on thoracic radiographs. Results of serum biochemical analysis were unremarkable. Aspiration and cytologic examination of the bone lesion indicated likely sarcoma with reactive bone. Cutaneous masses were found on the left thigh, interscapular region, and dorsal lumbar region, 4 weeks after initial presentation. Neoplastic spindle cells were found in aspirates from 2 of the masses. The neoplastic cells stained positive for alkaline phosphatase activity using cytochemistry. Re-evaluation of serum biochemical values at this time revealed a marked increase in alkaline phosphatase activity (413 U/L, reference interval 12-110 U/L) compared with the initial value (26 U/L). Due to progressive disease, the dog was euthanized and a necropsy was performed. Histologic findings included primary osteosarcoma of the distal portion of the right radius, with metastases in the lungs, spleen, left fourth and fifth ribs, soft tissue of the right medial thigh, and T1-T3/interscapular region. Cutaneous metastasis of primary appendicular osteosarcoma has been reported rarely in animals and humans. Increased serum alkaline phosphatase activity may be a potential indicator of poor prognosis for this neoplasm.     

Feasibility of computed tomography in awake dogs with traumatic pelvic fracture

In veterinary medicine, general anesthesia or sedation is generally required to immobilize patients during computed tomography (CT) scanning. This may not be suitable in all patients because of risks of anesthesia. We evaluated the feasibility of pelvic CT examination in 14 awake animals with pelvic trauma. Physical restraint was applied by wrapping the patient in a towel and then taping to the CT table or by directly taping the patient to the CT table. The effect of patient positioning, cooperation on the CT table, preparation time for scanning, scanning time, frequency of repeat scans, image quality, and complications related to physical restraint were evaluated. Fractures were recorded and compared between radiography and CT. Ten of 14 dogs were scanned in lateral recumbency and four in sternal recumbency. All patients were cooperative with the exception of one that moved slightly during the scan. Both physical restraint methods were adequate for CT scanning. Patient preparation took less than 5 min while the scan time was typically less than 1 min. No repeat scans were required in any patient. The transverse CT image quality was good (10/14) or fair (4/14) for interpretation. When comparing the CT images to radiographs, more pelvic fractures were identified with CT than with radiography and a few patients were overdiagnosed based on radiographs. No complications or additional injuries associated with physical restraint were noticed.     

Evaluation of caudal vena cava size using computed tomography in dogs under general anesthesia

This study investigated the association between caudal vena cava (CVC) size and circulatory dynamics in dogs using computed tomography (CT) under general anesthesia. The subjects were 104 dogs who had undergone CT under general anesthesia in the past. The ratio of short diameter of the CVC to aortic diameter (CVC_S/Ao) and the ratio of long to short diameter of the CVC (CVC_L/CVC_S) in the thorax and abdomen, respectively, were calculated using factors such as mean blood pressure (MBP), shock index (SI), anemia, hypoproteinemia, presence of intra-abdominal mass, and cardiac disease. There was a significant but negligible negative correlation between CVC_S/Ao and MBP. In contrast, no significant correlation was found between CVC size and SI. The low MBP group had significantly higher CVC_S/Ao of the thorax than the normal MBP group. The group with intra-abdominal mass had significantly lower CVC_S/Ao of the abdomen than the group without intra-abdominal mass. The group with cardiac disease had significantly lower CVC_L/CVC_S of the thorax than the group without cardiac disease. In multiple regression analysis, low MBP, cardiac disease, intra-abdominal mass, and anemia were significant factors for CVC_S/Ao of the thorax, CVC_L/CVC_S of the thorax, CVC_S/Ao of the abdomen, and CVC_L/CVC_S of the abdomen, respectively. In conclusion, CVC size assessment using CT in dogs under general anesthesia is influenced by various factors.     

Dynamic computed tomography evaluation of the nasopharynx in normal Beagle dogs

Pharyngeal collapsibility has been used as diagnostic criteria in dogs, whereas the normal range and quantitative method have not been studied. Dynamic and static computed tomography (CT) was performed in 23 normal Beagle dogs to quantify the nasopharyngeal collapsibility at different locations. Using dynamic CT, maximum and minimum nasopharyngeal cross-sectional areas (CSAs) were measured at the level of the cranial end of the soft palate, pterygoid hamulus, foramen lacerum, bony labyrinth, and caudal end of the soft palate. The ratio of all maximum and minimum CSA to nasopharyngeal CSA at the level of the caudal hard palate (rCSAmax and rCSAmin) and the nasopharyngeal collapsibility were calculated. The differences of rCSAmax, rCSAmin, and nasopharyngeal collapsibility were analyzed at various locations. The nasopharyngeal collapsibility at the level of foramen lacerum, bony labyrinth, and caudal end of soft palate were higher than the others. At the level of the caudal end of the soft palate, rCSAmin was lower than that of the foramen lacerum and bony labyrinth, whereas rCSAmax at foramen lacerum was higher than that of the caudal end of the soft palate. These results indicated that the nasopharynx at the level of foramen lacerum and caudal end of the soft palate were considered notable locations for evaluating collapsibility. Dynamic CT could show the nasopharyngeal dynamic profile and will be an adequate modality for evaluating nasopharynx. Our results will be helpful for further comparative studies in dogs with and without nasopharyngeal collapse.     

Assessment of glomerular filtration rate with dynamic computed tomography in normal Beagle dogs

The objective of our study was to determine individual and global glomerular filtration rates (GFRs) using dynamic renal computed tomography (CT) in Beagle dogs. Twenty-four healthy Beagle dogs were included in the experiment. Anesthesia was induced in all dogs by using propofol and isoflurane prior to CT examination. A single slice of the kidney was sequentially scanned after a bolus intravenous injection of contrast material (iohexol, 1 mL/kg, 300 mgI/mL). Time attenuation curves were created and contrast clearance per unit volume was calculated using a Patlak plot analysis. The CT-GFR was then determined based on the conversion of contrast clearance per unit volume to contrast clearance per body weight. At the renal hilum, CT-GFR values per unit renal volume (mL/min/mL) of the right and left kidneys were 0.69 ± 0.04 and 0.57 ± 0.05, respectively. No significant differences were found between the weight-adjusted CT-GFRs in either kidney at the same renal hilum (p = 0.747). The average global GFR was 4.21 ± 0.25 mL/min/kg and the whole kidney GFR was 33.43 ± 9.20 mL/min. CT-GFR techniques could be a practical way to separately measure GFR in each kidney for clinical and research purposes.     

Accuracy of computerized tomographic evaluation of canine radio-ulnar incongruence in vitro

OBJECTIVE: To evaluate the accuracy of linear measurements obtained from computer tomography (CT) images of staged radio-ulnar incongruence in a canine cadaver forelimb model. STUDY DESIGN: CT evaluation of induced progressive radio-ulnar incongruence in canine cadaveric forelimbs. SAMPLE POPULATION: Eight cadaveric canine left forelimbs. PROCEDURE: A type 2 external skeletal fixator (ESF) with linear motors was attached to the radius in 8 cadaveric left canine forelimbs. Contiguous incremental and helical CT images of the proximal radio-ulnar articulation were acquired in the transverse, sagittal and dorsal planes. The radius was shortened by 1, 2, and 4 mm increments and scanning protocols were repeated at each increment. Digital caliper and CT image analysis measured the progressive change in distance between 2 marking spheres and the epiphyseal bone surfaces of the radio-ulnar articulation. Statistical analysis of measurements from incremental and helical CT acquisitions, and direct and reformatted images were compared with inter-sphere distance using Pearson product moment correlation coefficients. RESULTS: The reformatted incremental acquisition series at the mid-coronoid in the oblique plane had the highest correlation coefficient (r-value) at 0.908. The mid-coronoid in the dorsal plane had the second highest r-value (0.856). The coronoid incisure in the sagittal plane had an r-value of 0.826. The reformatted incremental acquisition series at the coronoid incisure in the oblique plane had the lowest r-value, 0.592. CONCLUSION: Measurement of radioulnar incongruence may be best performed using reformatted incremental acquisition CT in the mid-coronoid region in an oblique plane. CLINICAL RELEVANCE: Use of the technique reported in this study may enable determination of the association, if any, between radioulnar incongruence and developmental diseases of the canine elbow.     

Multidetector row computed tomography evaluation of the micropig kidney as a potential renal donor

Multidetector row computed tomography (MDCT) provides anatomical information about the kidney and other internal organs. Presently, the suitability of 64-channel MDCT to assess the kidney of healthy micropigs was evaluated. Morphological evaluations of the kidney and the major renal vessels of six healthy micropigs were carried out using MDCT, recording kidney volume and the diameter and length of renal arteries and veins. The mean diameters and lengths of the renal artery were 0.44 ± 0.05 and 4.51 ± 0.55 cm on the right side and 0.46 ± 0.06 and 3.36 ± 0.27 cm on the left side, respectively. The mean diameters and lengths of the renal vein were 1.44 ± 0.52 and 4.22 ± 1.29 cm on the right side and 1.38 ± 0.17 and 5.15 ± 0.87 cm on the left side, respectively. The mean volume of the right kidney was 79.3 ± 14.5 mL and of the left kidney was 78.0 ± 13.9 mL. The data presented in this study suggest that the MDCT offers a noninvasive, rapid, and accurate method for the evaluation of the renal anatomy in living kidney donors. It also provides sufficient information about extra-renal anatomy important for donor surgery and determination of organ suitability.     

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma

Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T‐cell (Treg) percentage. Twenty‐two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression‐free survival time for all patients was 57 days (range 7‐176 days) with a median overall survival time of 89 days (range 7‐574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.     

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m^?2 (median dose 375 mg m^?2), with a median of two doses administered per dog (range 1–7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti‐tumour activity was observed.     

Effect of contrast media formulation on computed tomography angiographic contrast enhancement.

The characteristics of contrast media formulation (mgI/ml, osmolarity, and viscosity) are generally not considered important in computed tomography (CT) angiography in animals. The purpose of this study was to assess the contrast effect in CT angiography as a function of contrast media formulation, with a constant iodine dose. The contrast effects of three contrast media with different iodine concentrations were compared by administering identical iodine dosages (mgI/kg). The contrast effects of the three contrast media differed, and the area under the time-attenuation curve of iohexol 350 mgI/ml, which had the highest iodine concentration, was the lowest. It was hypothesized that the contrast effect of a contrast medium decreases with higher iodine concentration because of the high amount of residual iodine present in the circulatory system from the injection site to the portion immediately before the great vessels. In addition, the influence of osmotic dilution on contrast media with high osmolarity was also considered. In conclusion, the contrast effect varies with different contrast media formulations, even when the same iodine dosage is administered.     

Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells

The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.     

Development of a new canine osteosarcoma cell line

Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in vivo and in vitro models of OSA. The goal of this study was to develop, characterize and authenticate a new canine OSA cell line and a clone. A cell line and a clone were developed with standard cell culture techniques from a naturally occurring OSA in a dog. The clonal cell line induced a tumour after injection in RAG 1‐deficient mouse. Histology was consistent with OSA. The original tumour from the dog and the tumour induced in the mouse were both reactive with vimentin and osteonectin (ON). The parent cell line and clonal cell line were reactive with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found in the same three microsatellite markers in the parent and clonal cell lines, and the tumour tissue grown in the mouse.     

Anatomical evaluation of hepatic vascular system in healthy beagles using X-ray contrast computed tomography

Liver contrast X-ray computed tomography (CT) has been used for evaluation of hepatic vessels for liver transplantation, liver lobectomy, interventional radiology and diagnosis of hepatocellular carcinoma in humans. However, there remains scant available anatomical information on normal hepatic vessels in the veterinary field. In this study, visualization of hepatic vessels was evaluated in 32 normal beagle dogs by X-ray contrast CT using triple phase images. The following hepatic vessels were clearly visualized: arterial, portal and hepatic veins. With regards to the running patterns of the portal vein and hepatic vein, there were no significant differences between the dogs. However, the hepatic artery exhibited some differences in each dog. In particular, the hepatic artery of the quadrate lobe and the right lateral lobe had many running patterns. The results of the present study could be useful for veterinary diagnosis, surgery and interventional radiology.     

Establishment of optimal scan delay for multi-phase computed tomography using bolus-tracking technique in canine pancreas

To establish a protocol for a multi-phase computed tomography (CT) of the canine pancreas using the bolus-tracking technique, dynamic scan and multi-phase CT were performed in six normal beagle dogs. The dynamic scan was performed for 60 sec at 1-sec intervals after the injection (4 ml/sec) of a contrast medium, and intervals from aortic enhancement appearance to aortic, pancreatic parenchymal and portal vein peaks were measured. The multi-phase CT with 3 phases was performed three times using a bolus-tracking technique. Scan delays were 0, 15 and 30 in first multi-phase scan; 5, 20 and 35 in second multi-phase scan; and 10, 25 and 40 sec in third multi-phase scan, respectively. Attenuation values and contrast enhancement pattern were analyzed from the aorta, pancreas and portal vein. The intervals from aortic enhancement appearance to aortic, pancreatic parenchymal and portal vein peaks were 3.8 ± 0.7, 8.7 ± 0.9 and 13.3 ± 1.5 sec, respectively. The maximum attenuation values of the aorta, pancreatic parenchyma and portal vein were present at scan sections with no scan delay, a 5-sec delay and a 10-sec delay, respectively. When a multi-phase CT of the canine pancreas is triggered at aortic enhancement appearance using a bolus-tracking technique, the recommended optimal delay times of the arterial and pancreatic parenchymal phases are no scan delay and 5 sec, respectively.