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Mucocele formation in dogs is a unique and enigmatic muco-obstructive disease of the gallbladder caused by the amassment of abnormal mucus that bears striking pathological similarity to cystic fibrosis. We investigated the role of cystic fibrosis transmembrane conductance regulatory protein (CFTR) in the pathogenesis of this disease. The location and frequency of disease-associated variants in the coding region of CFTR were compared using whole genome sequence data from 2,642 dogs representing breeds at low-risk, high-risk, or with confirmed disease. Expression, localization, and ion transport activity of CFTR were quantified in control and mucocele gallbladders by NanoString, Western blotting, immunofluorescence imaging, and studies in Ussing chambers. Our results establish a significant loss of CFTR-dependent anion secretion by mucocele gallbladder mucosa. A significantly lower quantity of CFTR protein was demonstrated relative to E-cadherin in mucocele compared with control gallbladder mucosa. Immunofluorescence identified CFTR along the apical membrane of epithelial cells in control gallbladders but not in mucocele gallbladder epithelium. Decreases in mRNA copy number for CFTR were accompanied by decreases in mRNA for the Cl - /[Formula: see text] exchanger SLC26A3 , K + channels ( KCNQ1 , KCNN4 ), and vasoactive intestinal polypeptide receptor ( VIPR1 ), which suggest a driving force for change in secretory function of gallbladder epithelial cells in the pathogenesis of mucocele formation. There were no significant differences in CFTR gene variant frequency, type, or predicted impact comparing low-risk, high-risk, and definitively diagnosed groups of dogs. This study describes a unique, naturally occurring muco-obstructive disease of the canine gallbladder, with uncanny similarity to cystic fibrosis, and driven by the underlying failure of CFTR function. NEW & NOTEWORTHY Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.

Background: Gallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown., Methods: A prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium., Results: Gallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism., Conclusion: Our study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gookin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bacterial infection of bile is a common cause of hepatobiliary disease in cats. Whether bile harbors a core microbiota in health or in cases of suspected hepatobiliary disease in cats is unknown., Objectives: Establish if gallbladder bile in apparently healthy cats harbors a core microbiota composed of bacterial taxa common to many individuals. Compare results of bile cytology, bile culture, and 16S rRNA gene amplicon sequencing in apparently healthy cats and cats with suspected hepatobiliary disease., Animals: Forty-three client-owned cats with suspected hepatobiliary disease and 17 control cats., Methods: Bile was collected by ultrasound guided cholecystocentesis (cats with suspected hepatobiliary disease) or laparotomy after euthanasia (controls). Bile samples underwent cytologic examination, aerobic and anaerobic culture, and DNA was extracted for 16S rRNA gene amplification and sequencing., Results: Microbiome sequencing did not identify a core microbiota in control cats or cats having bile sampled because of clinical suspicion for hepatobiliary disease. Microbiome profiles from control cats were indistinguishable from profiles obtained from sampling instruments and reagents that were not exposed to bile (technical controls). Bacterial taxa that could not be explained by contamination or off-target amplification were identified only in samples from cats with bactibilia and positive bile culture results for Escherichia coli. In several E. coli positive samples, microbiome sequencing also identified a small number of potentially co-infecting bacterial genera not identified by culture., Conclusions and Clinical Importance: Cat bile does not harbor a core microbiota. Uncultured bacteria may contribute to pathogenesis of hepatobiliary disease in cats with bile E. coli infection., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Chronic kidney disease (CKD) is a major health condition in cats that can lead to poor quality of life and financial implications for therapy. Currently staging and identification of CKD is limited by diagnostic testing such as creatinine and urine-specific gravity, which do not change until late in the disease course. Other methods to evaluate CKD would be valuable in the clinical setting. Shear wave elastography is one novel ultrasound method, which has shown promise in identifying increases in tissue stiffness and identifying CKD in people. As CKD is often histologically characterized by tubulointerstitial fibrosis, shear wave elastography has the potential to identify CKD and differentiate between stages of CKD in cats. This prospective observational case-control study with 78 cats found no difference in shear wave velocities between groups (P = 0.33), a contradictory finding to one prior publication. There was no effect of weight (P = 0.65), nor the presence of mineralization (P = 0.31) or infarction (P = 0.52) on cortical shear wave velocities. There was a significant effect of age on shear wave velocity (P = 0.018) where velocities increased with age. The intraclass correlation coefficient was only moderate (0.62). Possible reasons for the difference in results between our work and that published prior, include differences in methodology and differences in instrumentation. Variability in measurements in our population may be due to the effects of respiratory motion or limitations in shear wave elastography software. As such, shear wave elastography is not currently recommended as a tool to evaluate CKD in cats and further work is necessary., (© 2022 American College of Veterinary Radiology.)

Progressive myelomalacia (PMM) is a fatal sequela of acute thoracolumbar intervertebral disc extrusion in dogs, with unpredictable onset in the days after the inciting injury. No single reliable diagnostic test is currently available. Magnetic resonance imaging (MRI) features such as T2-weighted spinal cord hyperintensity and loss of subarachnoid signal in a half-Fourier single-shot turbo spin echo (HASTE) sequence have been associated with PMM, but are sometimes present in other dogs with severe deficits. Magnetic resonance imaging findings in 22 dogs with a clinical or histopathologic diagnosis of PMM and 38 deep pain-negative paraplegic dogs were compared in a retrospective case-control study. Length of T2-weighted hyperintense spinal cord change and HASTE signal loss were significantly associated with clinically evident PMM (P = .0019 and P = .0085), however, there were no significant differences between groups when analysis was restricted to dogs not yet showing clinical signs of PMM. The PMM group also had significantly shorter compressive lesions than the control group (P = 0.026), suggesting a possible role of more severe focal pressure at the extrusion site. A segment of total loss of contrast enhancement in the venous sinuses and meninges, a feature not previously described, was more common in the PMM group and the difference approached significance (P = 0.054). Findings show that MRI features can support the diagnosis in dogs with clinical evidence of PMM, and absence of these features supports absence of PMM at time of imaging. However, their absence does not reliably differentiate dogs with imminent progressive myelomalacia from other dogs with severe deficits following intervertebral disc extrusion., (© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

To date studies have not investigated the culture-independent microbiome of bile from dogs, a species where aseptic collection of bile under ultrasound guidance is somewhat routine. Despite frequent collection of bile for culture-based diagnosis of bacterial cholecystitis, it is unknown whether bile from healthy dogs harbors uncultivable bacteria or a core microbiota. The answer to this question is critical to understanding the pathogenesis of biliary infection and as a baseline to exploration of other biliary diseases in dogs where uncultivable bacteria could play a pathogenic role. A pressing example of such a disease would be gallbladder mucocele formation in dogs. This prevalent and deadly condition is characterized by excessive secretion of abnormal mucus by the gallbladder epithelium that can eventually lead to rupture of the gallbladder or obstruction of bile flow. The cause of mucocele formation is unknown as is whether uncultivable, and therefore unrecognized, bacteria play any systematic role in pathogenesis. In this study we applied next-generation 16S rRNA gene sequencing to identify the culture-negative bacterial community of gallbladder bile from healthy dogs and gallbladder mucus from dogs with mucocele formation. Integral to our study was the use of 2 separate DNA isolations on each sample using different extraction methods and sequencing of negative control samples enabling recognition and curation of contaminating sequences. Microbiota findings were validated by simultaneous culture-based identification, cytological examination of bile, and fluorescence in-situ hybridization (FISH) performed on gallbladder mucosa. Using culture-dependent, cytological, FISH, and 16S rRNA sequencing approaches, results of our study do not support existence of a core microbiome in the bile of healthy dogs or gallbladder mucus from dogs with mucocele formation. Our findings further document how contaminating sequences can significantly contribute to the results of sequencing analysis when performed on samples with low bacterial biomass., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gookin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This consensus statement is designed to provide a standard of care document and describes the ACVR and ECVDI definition for performing a standard abdominal ultrasound examination in dogs and cats. The ACVR and ECVDI define a standard abdominal ultrasonographic examination as a complete exam of the abdominal organs which is appropriately documented. The consensus statement intends to provide guidance to veterinary sonographers and veterinarians for the performance and documentation of high-quality diagnostic ultrasound examination. The document may also serve as a teaching aid for veterinary students, veterinarians, and residents in diagnostic imaging who seek proficiency in diagnostic ultrasound. Finally, it may serve an additional role in educating the public as to what a high-quality abdominal ultrasound examination should entail., (© 2022 American College of Veterinary Radiology.)

The leading cause of treatment failure in Staphylococcus aureus infections is the development of biofilms. Biofilms are highly tolerant to conventional antibiotics which were developed against planktonic cells. Consequently, there is a lack of antibiofilm agents in the antibiotic development pipeline. To address this problem, we developed a platelet-rich plasma (PRP)-derived biologic, termed BIO-PLY (for the BIOactive fraction of Platelet-rich plasma LYsate) which has potent in vitro bactericidal activity against S. aureus synovial fluid free-floating biofilm aggregates. Additional in vitro studies using equine synoviocytes and chondrocytes showed that BIO-PLY protected these cells of the joint from inflammation. The goal of this study was to test BIO-PLY for in vivo efficacy using an equine model of infectious arthritis. We found that horses experimentally infected with S. aureus and subsequently treated with BIO-PLY combined with the antibiotic amikacin (AMK) had decreased bacterial concentrations within both synovial fluid and synovial tissue and exhibited lower systemic and local inflammatory scores compared to horses treated with AMK alone. Most importantly, AMK+BIO-PLY treatment reduced the loss of infection-associated cartilage proteoglycan content in articular cartilage and decreased synovial tissue fibrosis and inflammation. Our results demonstrate the in vivo efficacy of AMK+BIO-PLY and represents a new approach to restore and potentiate antimicrobial activity against synovial fluid biofilms., Competing Interests: The contents of this manuscript are the subject of a patent filed by NC State University and the University of Pennsylvania by the authors (JG, TS, and LS). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gilbertie, Schaer, Engiles, Seiler, Deddens, Schubert, Jacob, Stefanovski, Ruthel, Hickok, Stowe, Frink and Schnabel.)

Objectives: The goal of this study was to document the outcomes and toxicity of a novel multimodality treatment protocol for feline gastrointestinal intermediate- or large-cell lymphoma (FGL) in which cats were treated at 21-day intervals., Methods: This was a prospective, single-arm study. Twelve client-owned cats with cytologically diagnosed FGL were treated with a combination of abdominal cavity radiation therapy (RT; 8 Gy total dose administered in two 4 Gy fractions, 21 days apart), lomustine chemotherapy (approximately 40 mg/m 2 , administered orally at 21-day intervals for four treatments), prednisolone (5 mg PO q24h) and cobalamin (250 µg/week SC)., Results: Three cats were euthanized prior to the second treatment and it was difficult to discern treatment-associated toxicity from progressive disease. Four of the remaining cats developed cytopenias, resulting in 7-14-day lomustine treatment delays and/or dose reductions. Six cats had a partial response to treatment and three had stable disease based on ultrasound at day 21 (50% overall response rate). Three of these six cats completed the study and lived >240 days; one died of refractory diabetes mellitus with no clinical evidence of FGL, and the other two died as a result of FGL. The median overall survival time was 101 days (95% confidence interval [CI] 9-240). The median progression-free survival time was 77 days (95% CI 8-212). Necropsies were performed in eight cats, which revealed multifocal lymphoma throughout the gastrointestinal tract and other organs., Conclusions and Relevance: Oncological outcomes reported herein are comparable to those achieved with multiagent injectable chemotherapy (eg, CHOP). Treatment was seemingly well tolerated in most cats and was relatively cost-effective. It is therefore plausible that improved disease control may be achievable through continued optimization and intensification of the combinatorial chemoradiotherapy protocol.

Objective: To investigate the use of microwave ablation (MWA) with cooling urethral perfusion and with no perfusion (MWA-UP and MWA-NP, respectively) for prostate gland ablation in canine cadavers., Animals: Cadavers of 18 sexually intact male dogs., Procedures: After technique refinement in 2 cadavers, laparotomy with ultrasound-guided MWA-UP (n = 8) or MWA-NP (8) of the prostate gland was performed in 16 cadavers. Normograde cystourethroscopy was performed before and after treatment; recorded images were reviewed in a blinded manner for scoring of urethral mucosal discoloration and loss of integrity. Difficulty with cystoscope insertion was recorded if present. Excised prostate glands were fixed for serial sectioning, gross measurements, and calculation of percentage ablation. Percentages of prostate tissue necrosis from MWA, denuded urethral mucosa, and depth of epithelial surface loss in an adjacent section of the colon were estimated histologically. Variables of interest were statistically analyzed., Results: Difficulty with cystoscope insertion after treatment was significantly more common and scores for urethral mucosal discoloration and loss of integrity were significantly higher (indicating more severe lesions) for the MWA-NP group than for the MWA-UP group. The histologically assessed percentage of denuded urethral mucosa was also greater for the MWA-NP group. Overall median percentage prostate gland ablation was 73%; this result was not associated with prostate gland volume or chronological order of treatment., Conclusions and Clinical Relevance: MWA-UP induced subtotal thermal necrosis of prostate glands in canine cadavers while limiting urethral mucosal injury. Further study is required to optimize the technique and evaluate its safety and efficacy in vivo as a future curative-intent treatment for prostatic tumors in dogs.

Objective: To determine the efficacy of contrast peritoneography in delineating liver lobe fissures by using computed tomography (CT)., Study Design: Prospective cross-sectional study., Animals: Canine cadavers (n = 10)., Methods: An abdominal CT image of each cadaver was obtained under three conditions: without peritoneal contrast (precontrast), after insufflation of the peritoneal cavity with CO 2 (negative contrast), and after intraperitoneal administration of iohexol (positive contrast). Images were reconstructed in three planes. Three reviewers independently scored each plane/contrast combination. Observers measured the length of each fissure in each plane. The measurable length of fissures was compared between techniques but was not compared with the actual length on cadavers., Results: When assessment of all fissures was combined, measurements were obtained in 96 to 108 of 120 (80%-90%) positive contrast studies, 56 to 96 of 120 (47%-80%) negative contrast studies, and 12 to 32 of 120 (10%-27%) precontrast CT images. All observers measured fissures in all planes that were approximately two times longer on positive compared with negative contrast studies and two times longer on negative contrast studies compared with CT images without contrast. Measurable fissure lengths were greater on positive contrast CT images (P < .0001) than on other CT images., Conclusion: Positive contrast CT peritoneography improved the delineation of hepatic interlobar fissures in normal canine cadavers., Clinical Significance: These results justify further studies to determine the ability to locate large hepatic masses in dogs with positive CT. Positive contrast CT peritoneography may assist treatment planning in dogs with large hepatic tumors., (© 2019 The American College of Veterinary Surgeons.)

The lymphostins are a family of closely related pyrrolo[4,3,2- de ]quinoline natural products produced by Streptomyces and Salinispora actinobacteria. Neolymphostin A was recently shown to strongly inhibit phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) in a covalent manner via conjugation to a catalytic lysine residue in the ATP-binding pocket of the enzymes, making this metabolite the first reported covalent kinase inhibitor from a bacterium. A flexible and efficient synthetic route toward these alkaloids would allow for improvements in their solubility, stability, and selectivity and help to deliver a viable drug candidate. We have since established a short synthesis to methyl 8-bromo-1,3,4,5-tetrahydropyrrolo[4,3,2- de ]quinoline-4-carboxylate via a conjugate addition/intramolecular Ullman reaction sequence. However, attempts to oxidize this intermediate to the pyrrolo[4,3,2- de ]quinoline characteristic of the lymphostins resulted in formation of either a 2-oxo-1,2-dihydropyrrolo[4,3,2- de ]quinoline or an unusual N , C -linked tetrahydropyrroloquinoline-pyrroloquinoline heterodimer. We expect that key modifications to the tetrahydropyrroloquinoline intermediate prior to oxidation should prevent these side reactions and pave the way for the completion of the synthesis.

Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine:creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study., Competing Interests: The authors have declared that no competing interests exist.

Using a novel chemistry-based assay for identifying electrophilic natural products in unprocessed extracts, we identified the PI3-kinase/mTOR dual inhibitor neolymphostin A from Salinispora arenicola CNY-486. The method further showed that the vinylogous ester substituent on the neolymphostin core was the exact site for enzyme conjugation. Tandem MS/MS experiments on PI3Kα treated with the inhibitor revealed that neolymphostin covalently modified Lys802 with a shift in mass of +306 amu, corresponding to addition of the inhibitor and elimination of methanol. The binding pose of the inhibitor bound to PI3Kα was modeled, and hydrogen-deuterium exchange mass spectrometry experiments supported this model. Against a panel of kinases, neolymphostin showed good selectivity for PI3-kinase and mTOR. In addition, the natural product blocked AKT phosphorylation in live cells with an IC 50 of ∼3 nM. Taken together, neolymphostin is the first reported example of a covalent kinase inhibitor from the bacterial domain of life.

Lymph node evaluation is an important component of oncology staging in dogs and cats, however diagnosis of malignancy currently requires cytology or histopathology. Elastography is an ultrasound technique that allows estimation of tissue stiffness. In people, it has been shown to increase the sensitivity of sonography in detection of metastatic lymph nodes. The objective of this prospective, cross-sectional study was to determine if elastographic stiffness differs for malignant versus benign canine and feline lymph nodes that were considered abnormal in gray-scale ultrasound imaging. Animals scheduled for ultrasound-guided fine needle aspirates of a lymph node at a single center were prospectively enrolled. Elastography was performed by a board-certified veterinary radiologist (G.S.) prior to tissue sampling. Softness was scored qualitatively as 1-4 (1 = hard; 4 = soft) on an image depicted by a color scale (blue = hard, red = soft). Quantitative analysis was performed using custom-made software. Fifty-one lymph nodes were included in the evaluation, 21 had benign and 30 had neoplastic cytology. Benign lymph nodes were softer (median score of 2.5, range 1-4) than malignant lymph nodes (median = 2, range 1-3), and differences were significant in qualitative and quantitative analyses (P < 0.01). Of the lymph nodes with a score of 2 or below (hard), 19/25 (76%) were malignant, of the lymph nodes with a score over 2 (soft), 24/36 (67%) were benign. Findings indicated that elastographic stiffness scores differed between benign and malignant lymph node groups; however overlapping scores for the two groups limited the use of this technique for routine clinical diagnosis of malignancy., (© 2017 American College of Veterinary Radiology.)

Background: Bacterial cholecystitis often is diagnosed by combination of gallbladder ultrasound (US) findings and positive results of bile culture. The value of gallbladder US in determining the likelihood of bile bacterial infection in cats and dogs with suspected biliary disease is unknown., Hypothesis/objectives: To determine the value of gallbladder US in predicting bile bacterial culture results, identify most common bacterial isolates from bile, and describe complications after cholecystocentesis in cats and dogs with suspected hepatobiliary disease., Animals: Cats (70) and dogs (202) that underwent an abdominal US and submission of bile for culture were included in the study., Methods: A cross-sectional study design was used to determine the association of gallbladder US abnormalities and the results of bile cultures, and complications of cholecystocentesis., Results: Abnormal gallbladder US had high sensitivity (96%) but low specificity (49%) in cats with positive and negative results of bile bacterial culture, respectively. Cats with normal gallbladder US findings were unlikely to have positive bile bacterial culture (negative predictive value of 96%). Gallbladder US had lower sensitivity (81%), specificity (31%), positive predictive value (20%), and negative predictive value (88%) in dogs. The most common bacterial isolates were of enteric origin, the prevalence being higher in cats. Incidence of complications after cholecystocentesis was 3.4%., Conclusions and Clinical Importance: Gallbladder US has a high negative predictive value for bile culture results in cats. This modality is less predictive of infection in dogs. Percutaneous US-guided cholecystocentesis has a low complication rate., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: The objective was to quantitatively evaluate the validity of ultrasonographic (US) muscle measurements as compared to the gold standard of computed tomography (CT) in the canine., Design: This was a prospective study., Population: Twenty-five, client-owned dogs scheduled for CT as part of a diagnostic work-up for the management of their primary disease process were included., Materials and Methods: Specific appendicular ( cubital flexors and extensors, coxofemoral flexors and extensors ) and axial ( temporalis, supraspinatus, infraspinatus, lumbar epaxials ) muscle groups were selected for quantitative measure based on CT planning and patient position. Prior to CT scan, the skin over the muscle sites was shaved and marked with a permanent marker. Patient body position was determined based on the patient's CT plan; positioning was consistent between CT and US imaging. To ensure identical imaging position for both CT and US measurements, radio-opaque fiducial markers were placed directly over the skin marks once the dog was positioned. Quantitative measurements (cm) for both lean muscle mass (LMM) and subcutaneous adipose (SQA) were recorded. Statistical comparisons between CT and US values were done separately for each site and type., Results: Muscle groups and associated SQA measured by US and CT were not statistically different based on an adjusted p -value using Bonferroni's correction ( p  < 0.0031). In addition, all LMM and SQA sites had good reliability and agreement (Cronbach's α  = 0.8 - 1.0) between the two metrics, excluding the coxofemoral extensor muscle group (Cronbach's α  = 0.73232). Linear regression analysis of muscle measures indicated close agreement (slope range 0.93-1.09) and minimal bias of variation (intercept range 0.05-0.11) between CT versus US modalities, with the exception of the coxofemoral extensor muscle. Similarly, SQA CT and US measures indicated close agreement with the slope range of 0.88-1.02 and minimal bias of variation with an intercept range of 0.021-0.098, excluding the cubital flexor and extensor groups. Additionally, the R 2 values for these remaining LMM and SQA sites are reported as >0.897 for LLM and >0.8289 for SQA., Conclusions: Ultrasound imaging of selected appendicular and axial muscle groups in dogs can provide comparable assessment of muscle thickness to the current gold standard, CT. In consideration of both statistical reliability to CT and cage-side accessibility, the temporalis, supraspinatus, infraspinatus, and lumbar epaxial LMM sites are considered the most useful targets for US LMM assessment in the canine. Our findings support the potential utility of US as a clinical tool in veterinary medicine to assess LMM status in patients. Additional studies are indicated to develop standardized protocols of its use in a cage-side setting and to elucidate the benefit of this modality, in conjunction with nutritional interventions, to manage body LLM stores in compromised patients., Competing Interests: The authors declare there are no competing interests.

Background: Quantification of brain herniation on MRI and its immediate clinical implications are poorly described., Objectives: Define the normal position of caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry, compare this to dogs and cats with caudal transtentorial herniation (CTH), foramen magnum herniation (FMH) or both identified on MRI, and investigate associations between herniation severity, clinical signs, and 24-hour outcome., Animals: Ninety-two controls (66 dogs, 26 cats), 119 cases with herniation (88 dogs, 31 cats)., Methods: Retrospective case series. The MRI database was searched for controls with normal brain anatomy and cases with brain herniation. Morphometry in controls established TTX (transtentorial to rostroventral cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum) to quantify FMH. Measurements were compared between cases and controls. Correlations with specific clinical variables and outcome were investigated., Results: Measurements in medium/large control dogs versus small dog and cat controls were significantly different (P < .001, TTX: -0.46, -0.305, -0.3, FMX: 0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain imaging had brain herniation. TTX and FMX were significantly different between controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with supratentorial lesions had no signs directly attributable to herniation. 71/119 (60%) had a normal anesthetic recovery. TTX was significantly associated with 24-hour survival (P < .001)., Conclusions and Clinical Importance: Brain herniation can be quantified on MRI. Clinical signs directly attributable to brain herniation commonly are absent, and more severe CTH based on TTX is associated with a worse short-term outcome., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases., (© 2016 American College of Veterinary Radiology.)

Reasons for Performing Study: Navigational ultrasound imaging, also known as fusion imaging, is a novel technology that allows real-time ultrasound imaging to be correlated with a previously acquired computed tomography (CT) or magnetic resonance imaging (MRI) study. It has been used in man to aid interventional therapies and has been shown to be valuable for sampling and assessing lesions diagnosed with MRI or CT that are equivocal on ultrasonography. To date, there are no reports of the use of this modality in veterinary medicine., Objectives: To assess whether navigational ultrasound imaging can be used to assist commonly performed interventional therapies for the treatment of equine musculoskeletal injuries diagnosed with MRI and determine the appropriateness of regional anatomical landmarks as registration sites., Study Design: Retrospective, descriptive clinical study., Methods: Horses with musculoskeletal injuries of the distal limb diagnosed with MRI scheduled for ultrasound-guided interventional therapies were evaluated (n = 17 horses with a total of 29 lesions). Anatomical landmarks used for image registration for the navigational procedure were documented. Accuracy of lesion location and success of the procedure were assessed subjectively and described using a grading scale., Results: All procedures were accurately registered using regional anatomical landmarks and considered successful based on our criteria. Anatomical landmarks were described for each lesion type. The addition of navigational imaging was considered to greatly aid the procedures in 59% of cases and added information to the remainder of the procedures. The technique was considered to improve the precision of these interventional procedures., Conclusions: Navigational ultrasound imaging is a complementary imaging modality that can be used for the treatment of equine soft tissue musculoskeletal injuries diagnosed with MRI., (© 2015 EVJ Ltd.)

Compression elastography is an ultrasonographic technique that estimates tissue strain and may have utility in diagnosing and monitoring soft tissue injuries in the equine athlete. Recently, elastography has been proven to be a feasible and repeatable imaging modality for evaluating normal tendons and ligaments of the equine distal forelimb. The purposes of this prospective study were to investigate the ability of elastography to detect spontaneously occurring lesions of equine tendons and ligaments diagnosed with magnetic resonance imaging (MRI) and gray-scale ultrasound (US) and to characterize the differences in the elastographic appearance of acute vs. chronic injuries. Fifty seven horses with a total of 65 lesions were evaluated. Images were assessed quantitatively and qualitatively. Acute lesions were found to be significantly softer (P < 0.0001) than chronic lesions (P < 0.0001) and the stiffness of lesions increased with progression of healing (P = 0.0138). A negative correlation between lesion hypoechogenicity and softness was appreciated with more hypoechoic lesions appearing softer (P = 0.0087) and more hyperechoic regions harder (P = 0.0002). A similar finding occurred with increased signal intensity on short tau inversion recovery (STIR) and proton density (PD) MRI sequences correlating with increased softness on elastography (P = 0.0164). Using US and MRI as references, commonly encountered soft tissue injuries of the equine distal limb could be detected with elastography. However, elastography was limited for detecting small, proximal injuries of the hindlimb proximal suspensory ligament. Elastographic evaluation of equine tendons and ligaments may allow better characterization of lesion chronicity and severity, and sequential examinations may optimize lesion management, rehabilitation, and return to training., (© 2015 American College of Veterinary Radiology.)

Carotid body tumors (paragangliomas) arise from chemoreceptors located at the carotid bifurcation. In imaging studies, this neoplasm may be confused with other neck neoplasms such as thyroid carcinoma. The purpose of this retrospective, cross-sectional study was to describe computed tomographic (CT) and magnetic resonance imaging (MRI) characteristics of confirmed carotid body tumors in a multi-institutional sample of dogs. A total of 16 dogs met inclusion criteria (14 examined using CT and two with MRI). The most common reason for imaging was a palpable cervical mass or respiratory signs (i.e., dyspnea or increased respiratory noises). The most commonly affected breed was Boston terrier (n = 5). Dogs were predominantly male castrated (n = 10) and the median age was 9 years [range 3-14.5]. Most tumors appeared as a large mass centered at the carotid bifurcation, with poor margination in six dogs and discrete margins in ten dogs. Masses were iso- to hypoattenuating to adjacent muscles in CT images and hyperintense to muscles in T1- and T2-weighted MRI. For both CT and MRI, masses typically showed strong and heterogeneous contrast enhancement. There was invasion into the adjacent structures in 9/16 dogs. In six of these nine dogs, the basilar portion of the skull was affected. The external carotid artery was entrapped in seven dogs. There was invasion into the internal jugular vein in three dogs, and into the external jugular, maxillary, and linguo-facial veins in one dog. Imaging characteristics helped explain some clinical presentations such as breathing difficulties, Horner's syndrome, head tilt, or facial nerve paralysis., (© 2015 American College of Veterinary Radiology.)

Background: Reports of histiocytic sarcoma (HS) involving the central nervous system (CNS) are sparse and consist mainly of case reports describing 1-3 animals., Objective: The objective of this study was to report the signalments, clinical signs, clinicopathologic and diagnostic imaging findings, treatment, and outcome of a series of dogs with HS and CNS involvement., Animals: Nineteen dogs with HS examined at veterinary referral hospitals., Methods: Retrospective case series. Medical records were reviewed and cases with a histopathological diagnosis of CNS HS were included in the study. Diagnostic imaging studies of the CNS were evaluated and histopathologic samples were reviewed to confirm the diagnosis., Results: Retrievers and Pembroke Welsh Corgis were overrepresented in this cohort of dogs. Tumors involved the brain in 14 dogs and the spinal cord in 5. In 4 dogs, HS was part of a disseminated, multiorgan process whereas it appeared confined to the CNS in 15 dogs. Diagnostic imaging had variable appearances although extraaxial masses predominated in the brain. There was meningeal enhancement in all dogs that was often profound and remote from the primary mass lesion. Pleocytosis was present in all dogs with CSF evaluation. Median survival was 3 days., Conclusions and Clinical Importance: Breed predispositions appear to vary from reports of HS in other organ systems. Some unique imaging and clinicopathologic characteristics, particularly brain herniation, profound meningeal enhancement, and pleocytosis in combination with 1 or more mass lesions, might help to differentiate this neoplasm from others involving the CNS, although this requires further study., (© 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Tendon and ligament injuries are common causes of impaired performance in equine athletes. Gray-scale ultrasonography is the current standard method for diagnosing and monitoring these injuries, however this modality only provides morphologic information. Elastography is an ultrasound technique that allows detection and measurement of tissue strain, and may provide valuable mechanical information about equine tendon and ligament injuries. The purpose of this study was to determine the feasibility, reproducibility, and repeatability of elastography; and to describe elastographic characteristics of metacarpal tendons in sound horses. Nineteen legs for 17 clinically sound horses without evidence of musculoskeletal pathology were included. Elastographic images of the superficial and deep digital flexor tendons and the branches of the suspensory ligament (tendon of the interosseous muscle) were described quantitatively and qualitatively. There was no statistically significant difference between operators (P = 0.86) nor within operators (P = 0.93). For qualitative assessments, reproducibility (0.46) was moderate and repeatability (0.78) was good. Similar to human Achilles tendons, equine tendons were classified as predominantly hard using elastography. There was no statistically significant difference in stiffness of the flexor tendons (P = 0.96). No significant difference in stiffness was found with altered leg position during standing (P = 0.84) and while nonweight bearing (P = 0.61). The flexor tendons were softer when imaged in longitudinal versus transverse planes (P < 0.01) however, the suspensory branches were not (P = 0.67). Findings supported future clinical application of elastography as a noninvasive "stall-side" imaging modality for evaluation of the tendons and ligaments of the distal forelimb in horses., (© 2013 American College of Veterinary Radiology.)

Objective: To determine the incidence of adverse events within 24 hours after contrast-enhanced ultrasonography (CEUS) in dogs and cats and compare the risk of death within 24 hours after imaging for animals that underwent ultrasonography with and without injection of a contrast agent., Design: Retrospective case-control study., Animals: 750 animals (411 case dogs, 238 control dogs, 77 case cats, and 24 control cats)., Procedures: At 11 institutions, medical records were reviewed of dogs and cats that had CEUS performed (cases) as were medical records of dogs and cats with clinical signs similar to those of case animals that had ultrasonography performed without injection of a contrast agent (controls). Information regarding signalment; preexisting disease; type, dose, and administration route of contrast agent used; immediate (within 1 hour after CEUS) and delayed (> 1 and ≤ 24 hours after CEUS) adverse events; and occurrence and cause of death (when available) was extracted from each medical record. Risk of death within 24 hours after ultrasonography was compared between case and control animals., Results: Of the 411 case dogs, 3 had immediate adverse events (vomiting or syncope) and 1 had a delayed adverse event (vomiting). No adverse events were recorded for case cats. Twenty-three of 357 (6.4%) clinically ill case animals and 14 of 262 (5.3%) clinically ill control animals died within 24 hours after ultrasonography; risk of death did not differ between cases and controls., Conclusions and Clinical Relevance: Results indicated that CEUS was safe in dogs and cats.

Single-shot turbo spin-echo sequences are heavily T2-weighted sequences that are exceptionally well suited to evaluate the subarachnoid space. In the T2-weighted fast spin-echo sequences that are used routinely in spinal magnetic resonance (MR) imaging, the subarachnoid space is not well differentiated from the surrounding epidural fat, which could lead to decreased detection of lesions of the subarachnoid space such as arachnoid diverticula. Our purpose was to determine the added value of a single-shot turbo spin-echo sequence in identifying cystic lesions of the subarachnoid space in dogs. MR images of six dogs with a confirmed arachnoid diverticulum and 24 dogs with other spinal disease were included. Six observers were asked to interpret only T2-weighted images initially, and in a second session, T2-weighted and half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences. The MR images were anonymized, and no signalment, history, or clinical information was provided. Without the HASTE sequences, 25% of arachnoid diverticula were identified. Adding the HASTE sequence increased the diagnosis of arachnoid diverticulum to 52.8%. The resulting difference, after adding the HASTE sequence, of 27.8% was statistically significant (P = 0.002). No false-positive diagnoses of arachnoid diverticulum were made with either sequence. Although sensitivity in this study was likely artificially low, the significantly increased detection rate of arachnoid diverticula when using HASTE imaging indicates that this sequence is a valuable addition to MR imaging protocols for the canine spine.

Purpose: To determine the effects and posterior distribution of injections made into the anterior suprachoroidal space (SCS)., Methods: The anterior SCS of adult porcine and canine ex vivo eyes was cannulated. Latex injections and high frequency ultrasound (50 MHz) was used to image the effect and distension of the SCS. Flow characteristics and percentage maximal distribution of microbubble contrast injection into the SCS were assessed by 2D and 3D ultrasound., Results: Mean (SD) distension of the SCS with PBS increased from 1.57 (0.48) mm after injection of 250 μL to 3.28 (0.57) mm with 1000 μL PBS. Eyes injected at physiologic IOP had no significant difference in SCS distension. In real-time 2D ultrasound, the contrast agent flowed from the injection site to the opposite ventral anterior SCS and the posterior SCS. Contrast arrived at the opposite and posterior SCS 7.8 (4.6) and 7.7 (4.6) seconds after injection, respectively. In sagittal images, contrast was visible in 24.0%to 27.2% of the SCS; in 10 of 12 eyes, contrast reached the posterior pole of the eye. In 3D images, contrast medium occupied 39.0% to 52.1% of the entire SCS., Conclusions: These results suggest that the SCS can expand, in a dose-dependent manner, to accommodate various volumes of fluid and that it is possible to image the SCS with ultrasound contrast. The authors' hypothesis that a single anterior SCS injection can reach the ocular posterior segment was supported. Further development of SCS injections for treatment of the ocular posterior segment is warranted.

Pulsatile venous flow in the internal vertebral venous plexus of the cervical spine can lead to vertical, linear T2-hyperintensities in the spinal cord at the cranial aspect of C3 and C4 in transverse T2-weighted images in large breed dogs that are not accompanied by ghosting. The artifact is more conspicuous in pre- and postcontrast transverse T1-weighted images and is accompanied by ghosting in that sequence, typical of a pulsatility artifact. A flow-related artifact was confirmed as the cause for this appearance by noting its absence after either exchange of phase and frequency encoding direction or by flow compensation. Care should be exercised to avoid misdiagnosing this pulsatility artifact seen in transverse T2-weighted images of the midcervical spine in large dogs as an intramedullary lesion when T1-images or phase-swap images are not available to confirm its artifactual origin., (© 2010 Veterinary Radiology & Ultrasound.)

Cerebrovascular accidents, or strokes, and gliomas are common intraaxial brain lesions in dogs. An accurate differentiation of these two lesions is necessary for prognosis and treatment decisions. The magnetic resonance (MR) imaging characteristics of 21 dogs with a presumed cerebrovascular accident and 17 with a glioma were compared. MR imaging findings were reviewed retrospectively by three observers unaware of the final diagnosis. Statistically significant differences between the appearance of gliomas and cerebrovascular accidents were identified based on lesion location, size, mass effect, perilesional edema, and appearance of the apparent diffusion coefficient map. Gliomas were predominantly located in the cerebrum (76%) compared with presumed cerebrovascular accidents that were located mainly in the cerebellum, thalamus, caudate nucleus, midbrain, and brainstem (76%). Gliomas were significantly larger compared with presumed cerebrovascular accidents and more commonly associated with mass effect and perilesional edema. Wedge-shaped lesions were seen only in 19% of presumed cerebrovascular accidents. Between the three observers, 10-47% of the presumed cerebrovascular accidents were misdiagnosed as gliomas, and 0-12% of the gliomas were misdiagnosed as cerebrovascular accidents. Diffusion weighted imaging increased the accuracy of the diagnosis for both lesions. Agreement between observers was moderate (kappa = 0.48, P < 0.01).

Gadolinium-enhancement of compressive extradural material is detected occasionally with magnetic resonance (MR) imaging in dogs. Our goal was to characterize contrast enhancement of extradural compressive material associated with intervertebral disc herniation, and to evaluate the association between enhancement and histopathologic findings and the onset of clinical signs. Ninety-three dogs with a total of 99 lesions diagnosed as intervertebral disc herniation on MR imaging were assessed. Images were evaluated for lesion location, type of herniation, degree of compression, intramedullary T2-weighted (T2W) intensities, and contrast enhancement. In 23 dogs, surgically removed compressive material was evaluated histopathologically for hemorrhage, inflammation, neovascularization, fibroplasia, fibrosis, mineralization, necrosis, and chronicity. Contrast enhancement of extradural compressive material, meninges, and both the compressive materials and meninges was present in 51.5%, 39.4%, and 17.2% of lesions, respectively. Extradural enhancement occurred more frequently in extrusions than protrusions (P = 0.001). Meningeal enhancement and more severe neurologic deficits were significantly associated with a shorter duration of clinical signs (P = 0.04 and 0.01, respectively). Intramedullary T2W hyperintensities, present with 44.4% of lesions, were associated with more severe neurologic deficits (P = 0.001). Lesions with extradural enhancement were more often considered subacute to chronic in duration and more frequently associated with hemorrhage compared with nonenhancing material; however, no statistically significant association was established between contrast enhancement and histopathologic findings. Contrast enhancement of extradural compressive material and the meninges was found to be common with intervertebral disc herniation, and should not be interpreted as a specific sign of a mass lesion such as neoplasia.

Renal dysplasia is a hereditary disease characterized by abnormal differentiation of renal tissue. The ultrasonographic appearance of dysplastic canine kidneys has been reported in the late stage of the disease where inflammatory and degenerative changes are already present and the dogs are in chronic renal failure. In this study, we describe the ultrasonographic appearance of the kidneys of five related Cairn Terriers affected with renal dysplasia before the onset of clinical or laboratory evidence of renal failure. Common findings included poor corticomedullary definition and multifocal hyperechoic speckles in the renal medulla, or a diffusely hyperechoic medulla. Severity of ultrasonographic changes was related to the severity of histopathologic findings. The ability to detect dysplastic changes before clinical signs develop makes ultrasound a potentially useful screening method for canine renal dysplasia.

Evolution of pulmonary arterial and parenchymal changes as assessed with computed tomography (CT) is described in a dog experimentally infected with Dirofilaria immitis. The dog was imaged 125, 168, 216, and 402 days after infection. Initial changes during the prepatent phase of infection included enlargement of the peripheral caudal lobar pulmonary arteries and intermittent periarterial interstitial infiltrates. The changes were progressive, involving additional arteries over time, but remained mild. With the presence of adult filariae a filling defect was observed in the caudal lobar pulmonary artery using CT angiography. Recognizing thoracic CT findings associated with the prepatent phase of canine heartworm infection may be important in endemic areas.

Using cadaveric dogs, we established the ultrasonographic landmarks for performing paravertebral injections around the brachial plexus nerve roots in the dog, and assessed the accuracy and regional spread of the aliquots. A mixture of methylene blue dye and an iodinated contrast medium was used as the injectate. A 0.3 ml volume was used to assess accuracy and a 3.0 ml volume was used to assess regional spread. Accuracy and regional spread were assessed from computed tomography (CT) images acquired after injection by measuring the distance from each foramen to the nearest edge of contrast medium, and the dimensions of spread of contrast medium in each anatomic plane, respectively. The mean distance of small volume injections from each foramen was 0.9 cm (standard deviation [SD] 0.56 cm). The mean spread of contrast medium for the small volume injections measured 1.7 cm (SD 0.6 cm) cranial-to-caudal, 1.2 cm (SD 0.4 cm) dorsal-to-ventral and 7.4 cm (SD 0.4 cm) medial-to-lateral. The mean spread of contrast medium for the combined three large volume injections measured 7.4 cm (SD 1.7 cm) cranial-to-caudal, 3.1 cm (SD 0.8 cm) medial-to-lateral, and 2.8 cm (SD 0.5 cm) dorsal-to-ventral. After the CT studies, staining of each nerve root and any other regional structure was assessed grossly. Based on our results, ultrasound can be used to guide injections around the nerve roots of the brachial plexus in dogs.

Objective: To describe the computed tomographic and magnetic resonance imaging features of segmental caudal vena cava aplasia and associated vascular anomalies in dogs., Methods: A retrospective study was performed reviewing computed tomographic and magnetic resonance imaging archives of eight institutions for dogs with segmental caudal vena cava aplasia. Inclusion criteria included a computed tomographic or magnetic resonance imaging study and supportive diagnostic and follow-up information. Abdominal vessels were reviewed for size, shape, location and course (including tributaries and branches) and classified as normal, abnormal or shunt vessels., Results: Ten dogs with segmental caudal vena cava aplasia were identified. In all dogs, postrenal caval blood was shunted to either a right or a left azygos vein, with seven different angiographic patterns. Affected dogs were predominantly female (70 per cent) and young (mean 2.6 years). Additional portocaval and porto-azygos shunt vessels were identified in two cases each. Computed tomographic angiography and magnetic resonance angiography depicted details of abdominal vessels including thrombus formation in one dog., Clinical Significance: Segmental caudal vena cava aplasia is a vascular congenital anomaly in the dog that can be associated with thrombosis and portosystemic shunts. Computed tomographic angiography and magnetic resonance angiography are excellent tools to demonstrate the complex vascular anatomy and to guide treatment planning for portosystemic shunts and thrombolytic therapy.

Objective: To determine whether contrast harmonic ultrasonography (CHUS) can be used in dogs to distinguish splenic hemangiosarcoma from hematoma and to accurately detect and characterize liver nodules., Design: Cross-sectional study., Animals: 20 dogs with a splenic mass., Procedures: Routine abdominal ultrasonography was followed by CHUS of hepatic and splenic lesions. Qualitative evaluation included location, enhancement pattern, and vascularity of lesions. Quantitative evaluation included peak mean pixel intensity, interval to peak intensity, area under the curve (spleen), and liver-to-lesion intensity ratio (liver). Histologic findings were compared with CHUS lesion characteristics., Results: Histologic evaluation of the spleen was performed in 19 dogs, resulting in diagnoses of hemangiosarcoma (n=11), hematoma (7), and undifferentiated sarcoma (1). Benign and malignant processes in the spleen were indistinguishable via CHUS. Histologic evaluation of the liver was performed in 18 dogs, resulting in a diagnosis of hemangiosarcoma in 5 dogs. None of the dogs with splenic hematomas had evidence of hepatic lesions by means of conventional or contrast ultrasonography, and none had histologic evidence of liver metastases. In 3 of 18 dogs, isoenhancing liver nodules were detected and all were histologically benign. Five dogs had liver nodules that remained hypoechoic after contrast agent was injected; all had histologic evidence of metastatic hemangiosarcoma. Results of CHUS were used to characterize hepatic metastases with 100% sensitivity and specificity., Conclusions and Clinical Relevance: Contrast harmonic ultrasonography was a noninvasive and accurate means of differentiating metastatic versus benign hepatic disease in dogs with splenic hemangiosarcoma but was not useful in distinguishing splenic hemangiosarcoma from hematoma.

Cellular transplantation in the form of bone marrow has been one of the primary treatments of many lysosomal storage diseases (LSDs). Although bone marrow transplantation can help central nervous system manifestations in some cases, it has little impact in many LSD patients. Canine models of neurogenetic LSDs provide the opportunity for modeling central nervous system transplantation strategies in brains that more closely approximate the size and architectural complexity of the brains of children. Canine olfactory bulb-derived neural progenitor cells (NPCs) isolated from dog brains were expanded ex vivo and implanted into the caudate nucleus/thalamus or cortex of allogeneic dogs. Canine olfactory bulb-derived NPCs labeled with micron-sized superparamagnetic iron oxide particles were detected by magnetic resonance imaging both in vivo and postmortem. Grafts expressed markers of NPCs (i.e. nestin and glial fibrillary acidic protein), but not the neuronal markers Map2ab or beta-tubulin III. The NPCs were from dogs with the LSD mucopolysaccharidosis VII, which is caused by a deficiency of beta-glucuronidase. When mucopolysaccharidosis VII canine olfactory bulb-NPCs that were genetically corrected with a lentivirus vector ex vivo were transplanted into mucopolysaccharidosis VII recipient brains, they were detected histologically by beta-glucuronidase expression in areas identified by antemortem magnetic resonance imaging tracking. These results demonstrate the potential for ex vivo stem cell-based gene therapy and noninvasive tracking of therapeutic grafts in vivo.

Many factors affect the sensitivity and reliability of tumor vasculature assessment at the small doses of contrast agent necessary for imaging mice. In this study we investigate the dose-response relationship of ultrasound contrast agent for a minimal exposure power Doppler technique (minexPD) in a murine melanoma model. K1735 murine melanomas grown in 25 C3H/HeN mice were imaged by power Doppler ultrasound using different doses of contrast agents, Optison(R) and Definity(R). Six mice were treated with an antivascular agent, combretastatin A4-phosphate (CA4P), and imaged before and after treatment. The color-weighted fractional area (CWFA) of the peak-enhanced image was measured to assess tumor perfusion on a relative scale of 0 to 100. CWFA increased logarithmically with dose (R(2)=0.97). Treatment with CA4P resulted in pronounced reduction in tumor perfusion 2 h after contrast injection, but perfusion recovered in the tumor periphery after 2 days. CWFA was significantly different between pre- and post-treatment for all doses at 2 h and 2 days (p < 0.05, respectively). There was no significant difference detectable between the two contrast agents, Optison(R) and Definity(R) (p = 0.46). In vivo tumor enhancement in mice increases as logarithmic function with dose. Although the extent of enhancement is dose dependent, the difference between pre- and post-therapy enhancement is relatively unchanged and uniform at varying doses. The two contrast agents tested in this study performed equally well. These results suggest that quantitative contrast-enhanced power Doppler imaging is an effective method for monitoring therapy response of tumors in mice.

Objective: To determine the association between the 3-dimensional (3-D) motion pattern of the caudal lumbar and lumbosacral portions of the canine vertebral column and the morphology of vertebrae, facet joints, and intervertebral disks., Sample Population: Vertebral columns of 9 German Shepherd Dogs and 16 dogs of other breeds with similar body weights and body conditions., Procedure: Different morphometric parameters of the vertebral column were assessed by computed tomography (CT) and magnetic resonance imaging. Anatomic conformation and the 3-D motion pattern were compared, and correlation coefficients were calculated., Results: Total range of motion for flexion and extension was mainly associated with the facet joint angle, the facet joint angle difference between levels of the vertebral column in the transverse plane on CT images, disk height, and lever arm length., Conclusions and Clinical Relevance: Motion is a complex process that is influenced by the entire 3-D conformation of the lumbar portion of the vertebral column. In vivo dynamic measurements of the 3-D motion pattern of the lumbar and lumbosacral portions of the vertebral column will be necessary to further assess biomechanics that could lead to disk degeneration in dogs.

Objective: To evaluate the 3-dimensional motion pattern including main and coupled motions of the caudal lumbar and lumbosacral portions of the vertebral column of dogs., Animals: Vertebral columns of 9 German Shepherd Dogs (GSDs) and 16 dogs of other breeds with similar body weights and body conditions., Procedure: Main and coupled motions of the caudal lumbar and lumbosacral portions of the vertebral column (L4 to S1) were determined by use of a testing apparatus that permitted precise application of known pure moments to the vertebral column. Motion was compared between GSDs and dogs of other breeds., Results: All specimens had a similar motion pattern consisting of main motion and a certain amount of coupled motion including translation. Vertebral columns of GSDs had significantly less main motion in all directions than that of dogs of other breeds. Translation was similar in GSDs and dogs of other breeds and was smallest at the lumbosacral motion segment., Conclusions and Clinical Relevance: Results indicated that motion in the caudal lumbar and lumbosacral portions of the vertebral column of dogs is complex and provided a basis for further studies evaluating abnormal vertebral columns.

Objective: To evaluate the possible association between facet joint geometry and intervertebral disk degeneration in German Shepherd Dogs., Animals: 25 German Shepherd Dogs and 11 control dogs of similar body weight and condition., Procedure: Facet joint angles in the caudal portion of the lumbar region of the vertebral column (L5-S1) were measured by use of computed tomography, and the intervertebral discs were evaluated microscopically. The relationship between facet joint geometry and disk degeneration was evaluated by use of statistical methods., Results: German Shepherd Dogs had significantly more facet joint tropism than control dogs, but an association with disk degeneration was not found. However, German Shepherd Dogs had a different facet joint conformation, with more sagittally oriented facet joints at L5-L6 and L6-L7 and a larger angle difference between the lumbar and lumbosacral facet joints, compared with control dogs., Conclusions and Clinical Relevance: A large difference between facet joint angles at L6-L7 and L7-S1 in German Shepherd Dogs may be associated with the frequent occurrence of lumbosacral disk degeneration in this breed.