Impact of long-term rapamycin treatment on age-related osteoarthritis in common marmoset.

Objective: Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) can attenuate experimental osteoarthritis (OA) in young, male preclinical models. However, the potential of mTOR inhibition as a therapeutic mechanism for OA remains unknown. The goal of this study was to determine if mTOR-inhibition by oral rapamycin can modify OA pathology in the common marmoset, a translational model of age-associated OA. Methods: microCT and histopathologic assessments of the knee were performed on formalin-fixed hindlimbs obtained from common marmosets treated with oral rapamycin (n=24; 1mg/kg/day) or parallel control group (n=41). Rapamycin started at 9.2±3.0 years old and lasted until death (2.1±1.5 years). In a subset of marmosets, contralateral hind limbs were collected to determine mTOR signaling in several joint tissues. Results: Rapamycin decreased P-RPS6Ser235/36 and increased P-Akt2Ser473 in cartilage, meniscus, and infrapatellar fat pad, suggesting inhibition of mTORC1 but not mTORC2 signaling. Rapamycin-treated marmosets had lower lateral synovium score versus control but there was no difference in the age-related increase in microCT or cartilage OA scores. Subchondral bone thickness and thickness variability were not different with age but were lower in rapamycin-treated geriatric marmosets, which was largely driven by females. Rapamycin also tended to worsen age-related meniscus calcification in female marmosets. Conclusion: Oral rapamycin attenuated mTORC1 signaling and may have caused feedback activation of mTORC2 signaling in joint tissues. Despite modifying site-specific aspects of synovitis, rapamycin did not modify the age-associated increase in OA in geriatric marmosets. Conversely, rapamycin may have had deleterious effects on meniscus calcification and lateral tibia subchondral bone, primarily in geriatric female marmosets.

The common marmoset as a translational model of age-related osteoarthritis.

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression. The purpose of this study was to determine whether the common marmoset is a faithful model of human age-related knee OA. Semi-quantitative microCT scoring revealed greater radiographic OA in geriatric versus adult marmosets, and the age-related increase in OA prevalence was similar between marmosets and humans. Quantitative assessments indicate greater medial tibial cortical and trabecular bone thickness and heterogeneity in geriatric versus adult marmosets which is consistent with an age-related increase in focal subchondral bone sclerosis. Additionally, marmosets displayed an age-associated increase in synovitis and calcification of the meniscus and patella. Histological OA pathology in the medial tibial plateau was greater in geriatric versus adult marmosets driven by articular cartilage damage, proteoglycan loss, and altered chondrocyte cellularity. The age-associated increase in medial tibial cartilage OA pathology and meniscal calcification was greater in female versus male geriatric marmosets. Overall, marmosets largely replicate human OA as evident by similar 1) cartilage and skeletal morphology, 2) age-related progression in OA pathology, and 3) sex differences in OA pathology with increasing age. Collectively, these data suggest that the common marmoset is a highly translatable model of the naturally occurring, age-related OA seen in humans.

Computed tomographic evaluation of pancreatic perfusion in 10 dogs with acute pancreatitis.

Severe canine acute pancreatitis can be fatal; imaging features that can predict the clinical course of disease are useful for clinicians. On computed tomography (CT), both pancreatic heterogeneous contrast enhancement and portal vein thrombosis have been correlated with poorer outcome. Perfusion CT is used in human medicine to evaluate pancreatic microcirculation to predict the future development of severe sequela to pancreatitis; this technology has yet to be explored in dogs with acute pancreatitis. The objective of this prospective, case-control study is to evaluate pancreatic perfusion using contrast-enhanced CT in dogs with acute pancreatitis and compare it with previously established values obtained in healthy dogs. Ten client-owned dogs preliminarily diagnosed with acute pancreatitis received a full abdominal ultrasound, specific canine pancreatic lipase (Spec cPL), and perfusion CT. Computer software calculated pancreatic perfusion, peak enhancement index, time to peak enhancement, and blood volume for 3-mm and reformatted 6-mm slices. The data was analyzed using Shapiro-Wilk test, linear mixed model, and Spearman's rho. Values for 3-mm slices were similar to 6-mm slices (all P < 0.05). Dogs with acute pancreatitis had a faster time to peak enhancement than healthy dogs (P = 0.04-0.06). Dogs with acute pancreatitis and homogeneous pancreatic enhancement had higher perfusion, faster time to peak enhancement, and greater blood volume compared to healthy dogs and dogs with acute pancreatitis and heterogeneous pancreatic enhancement (all P = / < 0.05). Pancreatic perfusion decreased with increased pancreatitis severity. No correlation was identified between Spec cPL and pancreatic perfusion (all P > 0.05). These findings preliminarily support perfusion CT in dogs with acute pancreatitis.

Early removal of the infrapatellar fat pad/synovium complex beneficially alters the pathogenesis of moderate stage idiopathic knee osteoarthritis in male Dunkin Hartley guinea pigs.

BACKGROUND: The infrapatellar fat pad (IFP) is the largest adipose deposit in the knee; however, its contributions to the homeostasis of this organ remain undefined. To determine the influence of the IFP and its associated synovium (IFP/synovium complex or IFP/SC) on joint health, this study evaluated the progression of osteoarthritis (OA) following excision of this unit in a rodent model of naturally-occurring disease. METHODS: Male Dunkin-Hartley guinea pigs (n=18) received surgical removal of the IFP in one knee at 3 months of age; contralateral knees received sham surgery as matched internal controls. Mobility and gait assessments were performed prior to IFP/SC removal and monthly thereafter. Animals were harvested at 7 months of age. Ten set of these knees were processed for microcomputed tomography (microCT), histopathology, transcript expression analyses, and immunohistochemistry (IHC); 8 sets of knees were dedicated to microCT and biomechanical testing (material properties of knee joints tissues and anterior drawer laxity). RESULTS: Fibrous connective tissue (FCT) developed in place of the native adipose depot. Gait demonstrated no significant differences between IFP/SC removal and contralateral hindlimbs. MicroCT OA scores were improved in knees containing the FCT. Quantitatively, IFP/SC-containing knees had more osteophyte development and increased trabecular volume bone mineral density (vBMD) in femora and tibiae. Histopathology confirmed maintenance of articular cartilage structure, proteoglycan content, and chondrocyte cellularity in FCT-containing knees. Transcript analyses revealed decreased expression of adipose-related molecules and select inflammatory mediators in FCTs compared to IFP/SCs. This was verified via IHC for two key inflammatory agents. The medial articular cartilage in knees with native IFP/SCs showed an increase in equilibrium modulus, which correlated with increased amounts of magnesium and phosphorus. DISCUSSION/CONCLUSION: Formation of the FCT resulted in reduced OA-associated changes in both bone and cartilage. This benefit may be associated with: a decrease in inflammatory mediators at transcript and protein levels; and/or improved biomechanical properties. Thus, the IFP/SC may play a role in the pathogenesis of knee OA in this strain, with removal prior to disease onset appearing to have short-term benefits.

Association between feline hyperthyroidism and thoracic radiographic evaluation of cardiomegaly and pulmonary hyperinflation.

OBJECTIVES: Hyperthyroidism frequently affects middle-to-older-aged cats that can present with cardiorespiratory signs. The effects of hyperthyroidism on cardiac size and function have been previously documented. Anecdotally, pulmonary hyperinflation identified on thoracic radiographs may also be associated with hyperthyroidism; however, there is no literature to support this claim. The goal of this study was to determine any association between hyperthyroidism, pulmonary hyperinflation and cardiomegaly with the following hypotheses: (1) hyperthyroid cats would not have evidence of radiographic pulmonary hyperinflation compared with control cats; and (2) hyperthyroid cats were more likely to have evidence of radiographic cardiomegaly than control cats. METHODS: In this retrospective case-control study, the thoracic radiographs of 52 hyperthyroid cats and 46 non-hyperthyroid cats were evaluated for subjective and objective measurements of pulmonary hyperinflation and cardiomegaly. RESULTS: There were no statistically significant differences between hyperthyroid and non-hyperthyroid cats for any variable indicative of pulmonary hyperinflation. The mean ± SD vertebral heart score on lateral views for hyperthyroid cats was 7.75 ± 0.53 and for control cats was 7.55 ± 0.54, which was significantly different (P = 0.05). Among all cats, a more severe total elevation in thyroxine (T4) was correlated with a larger vertebral heart score on lateral views (Spearman's correlation coefficient = 0.23, P = 0.02). CONCLUSIONS AND RELEVANCE: While the results of this study suggest that hyperthyroid cats are more likely to have a larger vertebral heart score on lateral views than control cats, the clinical relevance of this finding is unclear given the large degree of overlap between hyperthyroid and non-hyperthyroid cats. In addition, among all cats, a greater total T4 elevation was weakly correlated with a larger vertebral heart score. Hyperthyroidism is not associated with radiographic pulmonary hyperinflation and is an unlikely differential for this radiographic finding.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Reprogramming the Canine Glioma Microenvironment with Tumor Vaccination plus Oral Losartan and Propranolol Induces Objective Responses.

Purpose: Malignant gliomas have a highly immune suppressive tumor microenvironment (TME) which renders them largely unresponsive to conventional therapeutics. Therefore, the present study evaluated a therapeutic protocol designed overcome the immune barrier by combining myeloid cell targeted immunotherapy with tumor vaccination. Experimental Design: We utilized a spontaneously occurring canine glioma model to investigate an oral TME modifying immunotherapy in conjunction with cancer stem cell (CSC) vaccination. Dogs were treated daily with losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) plus anti-CSC vaccination on a bi-weekly then monthly schedule. Tumor volume was monitored by MRI and correlated with patient immune responses. Results: Ten dogs with histologically confirmed gliomas were enrolled into a prospective, open-label clinical trial to evaluate the immunotherapy protocol. Partial tumor regression was observed in 2 dogs, while 6 dogs experienced stable disease, for an overall clinical benefit rate of 80%. Overall survival times (median = 351 days) and progression-free intervals (median = 163 days) were comparable to prior studies evaluating surgical debulking followed by immunotherapy. Dogs with detectable anti-CSC antibody responses had an increased overall survival time relative to dogs that did not generate antibody responses (vaccine responder MST = 500 days; vaccine non-responder MST = 218 days; p = 0.02). Conclusions: These findings suggest that combining myeloid cell targeted oral immunotherapy with tumor vaccination can generate objective tumor responses, even in the absence of conventional therapy. Overall, this approach has promise as a readily implemented therapeutic strategy for use in brain cancer patients.

Advances in the diagnosis of acute pancreatitis in dogs.

In the last 20 years, the diagnosis of pancreatitis has become more frequent as a result of improved diagnostic modalities such as abdominal ultrasound examination, advanced imaging, and immunoassays for the measurement of pancreatic lipase. Our aim is to provide a state-of-the-art overview of the clinical diagnosis of acute pancreatitis (AP) in dogs with a particular focus on pancreatic lipase assay validation and clinical performance, in addition to advanced imaging modalities. We also discuss the potential indications for cytology and histopathology in dogs with suspected AP.

Computed tomographic evaluation of pancreatic perfusion in healthy dogs.

OBJECTIVE: To evaluate the feasibility of contrast-enhanced CT for assessment of pancreatic perfusion in healthy dogs. ANIMALS: 6 healthy purpose-bred female Treeing Walker Coonhounds. PROCEDURES: Contrast-enhanced CT of the cranial part of the abdomen was performed with 3-mm slice thickness. Postprocessing computer software designed for evaluation of human patients was used to calculate perfusion data for the pancreas and liver by use of 3-mm and reformatted 6-mm slices. Differences in perfusion variables between the pancreas and liver and differences in liver-specific data of interest were evaluated with the Friedman test. RESULTS: Multiple pancreatic perfusion variables were determined, including perfusion, peak enhancement index, time to peak enhancement, and blood volume. The same variables as well as arterial, portal, and total perfusion and hepatic perfusion index were determined for the liver. Values for 6-mm slices appeared similar to those for 3-mm slices. The liver had significantly greater median perfusion and peak enhancement index, compared with the pancreas. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of pancreatic perfusion with contrast-enhanced CT was feasible in this group of dogs. Hepatic arterial and pancreatic perfusion values were similar to previously published findings for dogs, but hepatic portal and hepatic total perfusion measurements were not. These discrepancies might have been attributable to physiologic differences between dogs and people and related limitations of the CT software intended for evaluation of human patients. Further research is warranted to assess reliability of perfusion variables and applicability of the method for assessment of canine patients with pancreatic abnormalities.

CT angiographic changes in dogs with acute pancreatitis: A prospective longitudinal study.

Computed tomographic angiography (CTA) has recently been shown to be a useful tool in the diagnosis of acute canine pancreatitis, the identification of pancreatic necrosis, and the detection of sequelae. Evidence of pancreatic necrosis on CTA has been shown to be correlated with a poorer outcome in both humans and dogs and early diagnosis and intervention may improve outcomes. In humans, pancreatic necrosis is typically evident on CTA within 48 h of clinical signs, thus, repeat CTA examinations are often performed to identify pancreatic necrosis that may not have been evident on CTA examinations performed early in the course of disease. Published information investigating the timing of CTA examinations and the use of serial CTA in dogs with acute pancreatitis is lacking. In this prospective, longitudinal study, CTA examinations were performed at the time of hospitalization and repeated 3-5 days later in 11 dogs suffering from acute canine pancreatitis to determine if pancreatic necrosis or sequelae are under diagnosed on examinations performed at the time of hospitalization. Computed tomographic angiography studies were evaluated for changes in pancreatic size, pancreatic contrast enhancement, and peri-pancreatic tissues and vessels. The only statistically significant difference between the initial and repeat CTA examinations was the improvement of fat stranding on the repeat CTA examinations (P < .045). Based on these results, CTA performed at the time of admission is likely adequate in the diagnosis and evaluation of dogs with acute pancreatitis. Repeat CTA examinations are unlikely to add additional information in the absence of worsening clinical signs.

CT imaging features of canine thymomas.

Canine thymomas have been evaluated based on clinical features, treatment options, surgical excision, and outcomes with limited information on specific CT features. The objective of this retrospective, descriptive, cross-sectional study was to describe the CT characteristics of confirmed thymomas and to compare these imaging features to outcome. A total of 22 dogs met the inclusion criteria of histologically confirmed thymomas with concurrent CT imaging. Tumor size varied widely ranging from small and well-circumscribed to large and invasive. Delayed-phase, contrast-enhanced CT studies were best for determining the degree of contrast enhancement in tumors. Of these, 19 of 22 masses had heterogeneous enhancement and three of 22 masses had homogeneous enhancement. Vascular invasion was present in seven of 22 cases. Larger tumors were associated with vascular invasion (height: P = .04; width and volume: P = .02). On precontrast CT, larger tumors (16/21) were heterogeneous and cystic, with smaller tumors (5/21) being more homogeneous (all values P < .05). A larger size was associated with recurrence in fully resected masses (height: P = .03), but not a shorter outcome (P > .3 for all size dimensions). Postoperative complications and incomplete tumor resection were associated with shorter outcome (both values P < .01). Metastasis was confirmed in four cases. There were six cases with lymphadenopathy noted on CT; five of the six cases did not have evidence of metastasis. Larger tumors were more likely to be cystic and associated with vascular invasion.

Calorie restriction with regular chow, but not a high-fat diet, delays onset of spontaneous osteoarthritis in the Hartley guinea pig model.

BACKGROUND: Obesity is a leading risk factor for osteoarthritis (OA). In contrast, calorie restriction (CR) may lessen OA due to improved systemic inflammatory status and reduced weight-bearing. The aim of this study was to determine how CR with regular chow versus a high-fat diet (HFD) alters OA progression using the Hartley guinea pig model of disease. METHODS: Twenty-four male guinea pigs were allocated to four groups at 2 months of age: (1) ad libitum regular chow (obese), (2) CR regular chow (lean), (3) ad libitum HFD, and (4) CR HFD. Animals in both HFD groups ate identical amounts and were combined into one HFD group for analyses. At 5 months, hind limbs were harvested for microcomputed tomography (microCT) and histopathologic evaluation of knee OA. Total body, gonad fat, and infrapatellar fat pad (IFP) masses were recorded. IFPs were collected for gene expression analysis. Immunohistochemistry for monocyte chemoattractant protein-1 (MCP-1) was performed on intact joints. Serum was utilized for protein C3 measurement. All data were compared using ordinary one-way ANOVA analyses with Tukey's post-hoc tests. RESULTS: Body mass in the lean and HFD groups were similar and lower than the obese group. Despite this, gonad fat pads in the HFD group were comparable to the obese group. MicroCT and histologic OA scores were similar in obese and HFD groups; both scores were significantly lower in the lean group. Obese and HFD groups displayed increased gene expression of pro-inflammatory and catabolic mediators in IFPs relative to lean animals. Consistent with this, immunohistochemistry for MCP-1 in knee joints demonstrated strong positive staining in obese and HFD groups but was minimally detected in lean animals. Serum protein C3 levels were also statistically higher. CONCLUSIONS: This study demonstrated that CR with a regular chow diet lessened knee OA in the Hartley guinea pig and was associated with decreased local and systemic inflammation compared to obese animals. HFD animals, although under CR conditions, had OA scores and inflammatory markers similar to obese animals. Thus, diet composition, and not solely body weight, may be a key factor in development of OA.

Computed tomographic angiography and ultrasonography in the diagnosis and evaluation of acute pancreatitis in dogs.

BACKGROUND: Acute pancreatitis in dogs is an under-diagnosed disease. Current diagnostic methods are insufficient at identifying sequelae and lack prognostic capability. Computed tomographic angiography (CTA) is accurate for diagnosis and prognostication of pancreatitis in humans. OBJECTIVES: In comparison to ultrasound (US), CTA will (1) better diagnose more severe pancreatitis and sequelae and (2) provide assessment of patient outcome by identification of pancreatic contrast enhancement patterns. ANIMALS: Twenty-six client-owned dogs suspected to have acute pancreatitis. METHODS: US and CTA examinations performed at time of admission were compared to determine the detection of pancreatic changes and sequelae. CTA findings also were compared to outcome indicators for prognosis of dogs with acute pancreatitis. Specific canine pancreatic lipase (cPL) samples were obtained and compared with CTA findings. RESULTS: Ten of 26 dogs had heterogeneous contrast enhancement of the pancreas. Compared to US, CTA better identified portal vein thrombosis (P = .003). Patients with heterogeneous contrast enhancement had longer hospitalization (P = .01), including hospital stays for >5 days (P = .02), had more relapses, and were more likely to have portal vein thrombosis (P = .002). Patients with heterogeneous contrast enhancement had increased spec cPL (P = .006). CONCLUSIONS AND CLINICAL IMPORTANCE: In comparison to US, CTA better identified dogs with more severe acute pancreatitis and those with portal vein thrombosis, factors that may predict longer hospitalization and increased risk of relapse. The presence of heterogeneous contrast enhancement and portal vein thrombosis may change therapy for patients with acute pancreatitis.

Determination of surgical exposure obtained with integrated endoscopic thoracolumbar hemilaminectomy in large-breed cadaveric dogs.

OBJECTIVE: To define boundaries of minimally invasive integrated endoscopic hemilaminectomy at 4 sites in the canine thoracolumbar spine. STUDY DESIGN: Experimental, randomized cadaveric study. ANIMALS: Six cadaver dogs that had been humanely euthanized for reasons unrelated to this study. METHODS: Hemilaminectomy was performed with an integrated endoscopic system at T11-12, T12-13, L1-2, and L2-3, 1 at each site, on the left or right side of each dog. Each site was randomly assigned either a 19-mm or a 23-mm cannula. The entire procedure, including soft tissue dissection, was performed through the cannula. Afterward, spines were imaged by computed tomography (CT) to measure the cranial and caudal extent of the hemilaminectomy from the center of the disc space. RESULTS: The mean ± SD cranial extent of the hemilaminectomy was 4.5 ± 1.4 mm for the 19-mm cannula and 5.6 ± 1.4 mm for the 23-mm cannulas (P = .0757). The caudal extent of the hemilaminectomy was 9.5 ± 2.2 mm for the 19-mm cannula and 10.3 ± 1.6 mm for the 23-mm cannula (P = .206). The mean length of the hemilaminectomy was 13.0 ± 1.5 mm for the 19-mm cannula and 15.0 ± 2.1 mm for the 23-mm cannula (P = .022). CONCLUSION: Integrated endoscopic systems were reliably used to access the spinal canal within the range of the above measurements relative to the disc space as identified by CT or magnetic resonance imaging. CLINICAL SIGNIFICANCE: Integrated endoscopy can be considered as an option in dogs with thoracolumbar disc extrusions or other pathology measuring within the parameters defined by this study. Access may be possible beyond the dimensions defined in this study with probing and repositioning.

Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis.

AIM: There is potential discrepancy between human and laboratory animal studies of osteoarthritis (OA), as radiographic assessment is the hallmark of the former and histopathology the standard for the latter. This suggests a need to evaluate OA in animal models in a manner similar to that utilized in people. Our study aimed to develop a whole joint grading scheme for microcomputed tomography (microCT) images in Hartley guinea pigs, a strain that recapitulates joint changes highlighted in human spontaneous OA. MATERIALS AND METHODS: Knees from animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and standard histologic scoring. Quantitative microCT parameters, such as bone volume/total volume were also collected. RESULTS: Both whole joint microCT and histologic scores increased with advancing age and showed strong correlation (r = 0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased progressively with age. Whole joint microCT scores, which characterize bony changes, followed a stepwise pattern: scores increased between 3 and 5 months of age, stayed consistent between 5 and 9 months, and worsened again between 9 and 15 months. CONCLUSIONS: This work provides data that advocates the use of a whole joint microCT scoring system in guinea pig studies of OA, as it provides important information regarding bony changes that occur at a different rate than articular cartilage changes. This grading scheme, in conjunction with histology and quantitative microCT measurements, may enhance the translational value of this animal model as it pertains to human work.

Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: A retrospective study.

Doppler echocardiography is a noninvasive method for estimating and grading pulmonary arterial hypertension. No current literature associates significance of radiographic findings with severity of pulmonary arterial hypertension. We hypothesized that the number and conspicuity of radiographic findings suggestive of pulmonary arterial hypertension would be greater based on the severity of pulmonary arterial hypertension. Dogs with pulmonary arterial hypertension and normal control dogs were included in this retrospective, case control study. Three radiologists blinded to echocardiographic results scored thoracic radiographs for right ventricular and main pulmonary artery enlargement and pulmonary lobar artery enlargement, tortuosity, and blunting by multiple methods. Presence or absence of each finding was scored in an additive fashion and averaged for each grade of pulmonary arterial hypertension severity. Seventy-one dogs (60 dogs with pulmonary arterial hypertension and 11 control dogs) of which some had multiple studies were included: 20 mild, 21 moderate, 25 severe, and 11 absent pulmonary arterial hypertension. The following radiographic findings were significantly associated with increasing pulmonary arterial hypertension severity: right ventricular enlargement by "reverse D" and "3/5-2/5 cardiac ratio" methods, main pulmonary artery enlargement, and caudal lobar artery enlargement by the "3rd rib" method. Mean scores for severe pulmonary arterial hypertension and normal dogs were significantly different (P-value < 0.0001). Mean scores between different pulmonary arterial hypertension grades increased with severity but were not statistically significant. Individually and in combination, radiographic findings performed poorly in differentiating severity of pulmonary arterial hypertension. Findings indicated that thoracic radiographs should be utilized in conjunction with Doppler echocardiography in a complete diagnostic work-up for dogs with suspected pulmonary arterial hypertension.

Diagnostic Imaging of the Hepatobiliary System: An Update.

Recent advances in diagnostic imaging of the hepatobiliary system include MRI, computed tomography (CT), contrast-enhanced ultrasound, and ultrasound elastography. With the advent of multislice CT scanners, sedated examinations in veterinary patients are feasible, increasing the utility of this imaging modality. CT and MRI provide additional information for dogs and cats with hepatobiliary diseases due to lack of superimposition of structures, operator dependence, and through intravenous contrast administration. Advanced ultrasound methods can offer complementary information to standard ultrasound imaging. These newer imaging modalities assist clinicians by aiding diagnosis, prognostication, and surgical planning.

REPEATABILITY AND RELIABILITY OF GLOMERULAR FILTRATION RATE DETERMINATION VIA GAMMA CAMERA UPTAKE OF TC-99M-DTPA IN CATS WITH CHRONIC KIDNEY DISEASE.

Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc-diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra- and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut-points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty-nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland-Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between -0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect.

Glioblastoma Multiforme with Hypodipsic Hypernatremia in a Seven-Month-Old Golden Retriever.

Primary hypodipsic hypernatremia is a rarely reported disease in dogs. Reported underlying causes associated with this disease in dogs include congenital malformations, encephalitis, intracranial neoplasia, and pressure atrophy of the hypothalamus secondary to hydrocephalus. The dog in this report had an infiltrative neoplastic disorder, likely causing damage to the hypothalamic osmoreceptors responsible for the thirst generation. The neoplastic process was identified histopathologically as glioblastoma multiforme, an unusual tumor to occur in a dog this young. A tumor of the central nervous system causing physical destruction of the osmoreceptors has rarely been reported in dogs and none of the previously reported cases involved a glial cell tumor.