Grading of oligodendroglioma in dogs based on magnetic resonance imaging.

BACKGROUND Oligodendroglioma (OG) accounts for 22% of primary brain tumors in dogs. Oligodendroglioma in dogs is graded as low-grade (II) or high-grade (III), based on the presence of microvascular proliferation and necrosis. OBJECTIVE To investigate if magnetic resonance imaging (MRI) features differ between OG II and III in dogs. ANIMALS Thirty-two dogs with histological diagnosis of intracranial OG and MRI. METHODS Retrospective descriptive study. Histology was reviewed to grade OG according to the revised classification. Brain MRI results were reviewed following criteria including contrast enhancement (CE) pattern, presence of cystic structures, gradient-recalled-echo (GRE) signal voids, and necrosis based on signal intensity, as well as diffusion-weighted imaging characteristics. The MRI features were compared between OG II and III using Fisher's exact tests and logistic regression models. RESULTS Histology identified 8 dogs with OG II (25%) and 24 with OG III (75%). All OG III showed moderate-to-marked CE including 18/24 (75%) with a ring pattern. These features were not seen in OG II. Heterogeneity, cystic structures, GRE signal voids, and necrosis were associated with OG III. No difference in diffusion characteristics was detected between OG II and III. CONCLUSION AND CLINICAL IMPORTANCE Moderate-to-marked CE and ring pattern were present in dogs with OG III but not in OG II. The presence of cystic structures, GRE signal voids, and necrosis was strongly associated with OG III. Although the importance of brain tumor grading in dogs with regard to prognosis and treatment options remains unknown, the results indicate that MRI reflects the histological features used for grading OG in dogs

Feasability of a Frameless Brain Biopsy System for Companion Animals Using Cone-Beam CT-Based Automated Registration.

The aim of the present study was to evaluate the use of a novel intraoperative cone-beam computed tomography (CBCT)-based automated registration system for frameless stereotactic brain biopsy in companion animals. An experimental cadaveric study evaluated thalamic and piriform lobe target site needle placement error in three dogs and three cats without a history of intracranial disease. Diagnostic accuracy and diagnostic yield were prospectively evaluated in twenty-four client-owned dogs and four cats with intracranial disease. Twenty-one procedures were performed post mortem (eighteen dogs and three cats), and seven biopsy procedures were performed in alive patients (six dogs and one cat). Procedural duration was evaluated in ten post mortem and four living patients. Outcome was evaluated in six dogs and one cat. In dogs, the calculated median needle placement error was 1.8 mm (range 0.71-2.84 mm) and 1.53 mm (range 1.45-1.99 mm) for piriform lobe and thalamus target sites, respectively. In cats, the calculated median needle placement error was 0.79 mm (range 0.6-1.91 mm) for the piriform lobe target site and 1.29 mm (range 0.47-2.69 mm) for the thalamic target site. The diagnostic yield was 96.4% (95% CI 0.81-0.99), the diagnostic accuracy was 94.4% (95% CI 0.72-0.99). Median total procedural duration for post mortem biopsies was 57.5 min (range 41-69 min). Median total procedural duration for intra vitam biopsies was 122.5 min (range 103-136 min). Three dogs were discharged 1 day after biopsy and one dog after 6 days. Two dogs and one cat were euthanized 24 and 48 h after biopsy. Intraoperative CBCT-based automated image registration for frameless stereotactic biopsies in companion animals is capable of providing diagnostic brain biopsy specimens independent of skull size and morphology with diagnostic yield and accuracy comparable to published values for diverse frameless and frame-based stereotaxy systems used in veterinary medicine. Duration of the procedure is not negatively affected and within the published range with other systems. Mobile intraoperative CBCT-based registration combined with neuronavigation delivers diagnostic brain biopsies in companion animals

PCYT1A Missense Variant in Vizslas with Disproportionate Dwarfism

Disproportionate dwarfism phenotypes represent a heterogeneous subset of skeletal dysplasias and have been described in many species including humans and dogs. In this study, we investigated Vizsla dogs that were affected by disproportionate dwarfism that we propose to designate as skeletal dysplasia 3 (SD3). The most striking skeletal changes comprised a marked shortening and deformation of the humerus and femur. An extended pedigree with six affected dogs suggested autosomal recessive inheritance. Combined linkage and homozygosity mapping localized a potential genetic defect to a ~4 Mb interval on chromosome 33. We sequenced the genome of an affected dog, and comparison with 926 control genomes revealed a single, private protein-changing variant in the critical interval, PCYT1A:XM_038583131.1:c.673T>C, predicted to cause an exchange of a highly conserved amino acid, XP_038439059.1:p.(Y225H). We observed perfect co-segregation of the genotypes with the phenotype in the studied family. When genotyping additional Vizslas, we encountered a single dog with disproportionate dwarfism that did not carry the mutant PCYT1A allele, which we hypothesize was due to heterogeneity. In the remaining 130 dogs, we observed perfect genotype–phenotype association, and none of the unaffected dogs were homozygous for the mutant PCYT1A allele. PCYT1A loss-of-function variants cause spondylometaphyseal dysplasia with cone–rod dystrophy (SMD-CRD) in humans. The skeletal changes in Vizslas were comparable to human patients. So far, no ocular phenotype has been recognized in dwarf Vizslas. We propose the PCYT1A missense variant as a candidate causative variant for SD3. Our data facilitate genetic testing of Vizslas to prevent the unintentional breeding of further affected puppies

Post-mortem computed tomographic angiography in equine distal forelimbs: A feasibility study

In-depth understanding of pathophysiological processes occurring in the vasculature of the equine distal limb is of great importance to improve both diagnostic and therapeutic approaches to diseases. To gain further insights, a model allowing high-resolution 3D-visualization of the vasculature is necessary. This pilot study evaluated the feasibility of restoring vascular perfusion in frozen-thawed distal equine cadaver limbs without prior preparation using computer tomographic imaging (CT). Five frozen-thawed, radiographically normal forelimbs were perfused with a lipophilic contrast agent through the median artery and radial vein in three phases (arterial, venous, and arterial-venous combined (AVC) dynamic). For comparison, one additional limb was perfused with a hydrosoluble contrast agent. The CT-studies (16-slice MDCT, 140 kV, 200 mA, 2 mm slice thickness, 1 mm increment, pitch 0.688) were evaluated at 11 specified regions for visualization of the vasculature and presence of artifacts or anatomic variations. The protocol used in this study proved to be feasible and provided good visualization (93.1%) of vasculature with low rates of artifacts. During the different phases, vascular visualization was similar, but while filling defects decreased in the later phases, extravasation worsened in the 2 limbs where it was observed. Subjectively, the best quality of angiographic images was achieved during the AVC dynamic phase. Perfusion with hydrosoluble contrast resulted in significantly lower vascular visualization (74.0%) and higher artifact rates. This study shows that reperfusion of frozen-thawed equine distal limbs with a lipophilic contrast agent allows for high-quality 3D-visualization of the vasculature and may serve as a model for in situ vascular evaluation in the future

Outcome of radioiodine therapy for feline hyperthyroidism: Fixed dose versus individualized dose based on a clinical scoring system.

Background Hyperthyroidism is the most frequent endocrinopathy in older cats. To date, there is no consensus on how to best calculate the dose of radioiodine to administer to hyperthyroid cats. Aim The goals of this study were to compare thyroid function, renal function, and survival time between hyperthyroid cats receiving a fixed dose of radioiodine and those receiving an individualized dose calculated using a clinical scoring system. Methods Medical records of 110 cats treated with radioiodine therapy at the University of Bern between 2010 and 2020 were reviewed. Thyroid function, renal function, and survival of cats treated with a fixed dose of radioiodine (2010-2015; n = 50) were compared to those of cats treated with an individualized dose (2015-2020; n = 60) at different time points after therapy. Results Treatment with a fixed dose of radioiodine (mean = 168 ± 26 MBq) was associated with 69% of euthyroidism, 19% persistent hyperthyroidism, and 12% hypothyroidism, whereas treatment with an individualized dose (mean = 120 ± 30 MBq) led to 54% euthyroidism, 23% hyperthyroidism, and 23% hypothyroidism (p = 0.73). More than 12 months after treatment, the incidence of azotemia was comparable between cats treated with a fixed dose (37%) and those treated with an individualized dose (31%) (p = 0.77). No factors were found to be predictive of treatment failure (hypothyroidism or hyperthyroidism) after therapy. Median survival time after radioiodine therapy was 44 months. In a multivariate analysis, persistent hyperthyroidism was the only variable independently associated with a shorter survival time (HR = 6.24, p = 0.002). Conclusion The method of calculating the dose of radioiodine (fixed vs. individualized) to treat feline hyperthyroidism does not appear to be decisive for posttreatment thyroid function, renal function, or survival

Random forest classification as a tool in epidemiological modelling: Identification of farm-specific characteristics relevant for the occurrence of Fasciola hepatica on German dairy farms

Fasciola hepatica is an internal parasite of both human and veterinary relevance. In order to control fasciolosis, a multitude of attempts to predict the risk of infection such as risk maps or forecasting models have been developed. These attempts mainly focused on the influence of geo-climatic and meteorological features. Predicting bovine fasciolosis on farm level taking into account farm-specific settings yet remains challenging. In the present study, a new methodology for this purpose, a data-driven machine learning approach using a random forest classification algorithm was applied to a cross-sectional data set of farm characteristics, management regimes, and farmer aspects within two structurally different dairying regions in Germany in order to identify factors relevant for the occurrence of F. hepatica that could predict farm-level bulk tank milk positivity. The resulting models identified farm-specific key aspects in regard to the presence of F. hepatica. In study region North, farm-level production parameters (farm-level milk yield, farm-level milk fat, farm-level milk protein), leg hygiene, body condition (prevalence of overconditioned and underconditioned cows, respectively) and pasture access were identified as features relevant in regard to farm-level F. hepatica positivity. In study region South, pasture access together with farm-level lameness prevalence, farm-level prevalence of hock lesions, herd size, parity, and farm-level milk fat appeared to be important covariates. The stratification of the analysis by study region allows for the extrapolation of the results to similar settings of dairy husbandry. The local, region-specific modelling of F. hepatica presence in this work contributes to the understanding of on-farm aspects of F. hepatica appearance. The applied technique represents a novel approach in this context to model epidemiological data on fasciolosis which allows for the identification of farms at risk and together with additional findings in regard to the epidemiology of fasciolosis, can facilitate risk assessment and deepen our understanding of on-farm drivers of the occurrence of F. hepatica

A machine learning approach using partitioning around medoids clustering and random forest classification to model groups of farms in regard to production parameters and bulk tank milk antibody status of two major internal parasites in dairy cows

Fasciola hepatica and Ostertagia ostertagi are internal parasites of cattle compromising physiology, productivity, and well-being. Parasites are complex in their effect on hosts, sometimes making it difficult to identify clear directions of associations between infection and production parameters. Therefore, unsupervised approaches not assuming a structure reduce the risk of introducing bias to the analysis. They may provide insights which cannot be obtained with conventional, supervised methodology. An unsupervised, exploratory cluster analysis approach using the k–mode algorithm and partitioning around medoids detected two distinct clusters in a cross-sectional data set of milk yield, milk fat content, milk protein content as well as F. hepatica or O. ostertagi bulk tank milk antibody status from 606 dairy farms in three structurally different dairying regions in Germany. Parasite–positive farms grouped together with their respective production parameters to form separate clusters. A random forests algorithm characterised clusters with regard to external variables. Across all study regions, co–infections with F. hepatica or O. ostertagi, respectively, farming type, and pasture access appeared to be the most important factors discriminating clusters (i.e. farms). Furthermore, farm level lameness prevalence, herd size, BCS, stage of lactation, and somatic cell count were relevant criteria distinguishing clusters. This study is among the first to apply a cluster analysis approach in this context and potentially the first to implement a k–medoids algorithm and partitioning around medoids in the veterinary field. The results demonstrated that biologically relevant patterns of parasite status and milk parameters exist between farms positive for F. hepatica or O. ostertagi, respectively, and negative farms. Moreover, the machine learning approach confirmed results of previous work and shed further light on the complex setting of associations a between parasitic diseases, milk yield and milk constituents, and management practices

Associations of production characteristics with the on-farm presence of Fasciola hepatica in dairy cows vary across production levels and indicate differences between breeds

Fasciola hepatica is one of the economically most important endoparasites in cattle production. The aim of the present work was to evaluate the relevance of production level on the associations of on-farm presence of F. hepatica with farm-level milk yield, milk fat, and milk protein in Holstein cows, a specialised dairy breed, and in Simmental cows, a dual purpose breed. Furthermore, we investigated whether differential associations were present depending on breed. Data from 560 dairy farms across Germany housing 93,672 cows were analysed. The presence of F. hepatica antibodies was determined via ELISA on bulk tank milk samples. Quantile regression was applied to model the median difference in milk yield, milk fat, and milk protein depending on the interaction of breed and fluke occurrence. Whereas a reduction in milk yield (-1,206 kg, p < 0.001), milk fat (-22.9 kg, p = 0.001), and milk protein (-41.6 kg, p <0.001) was evident on F. hepatica positive German Holstein farms, only milk fat (-33.8 kg, p = 0.01) and milk protein (-22.6 kg, p = 0.03) were affected on F. hepatica positive German Simmental farms. Subsequently, production traits were modelled within each of the two breeds for low, medium, and high producing farms in the presence of F. hepatica antibodies and of confounders. On Holstein farms, the presence of F. hepatica seropositivity was associated with lower production, while on German Simmental farms such an association was less evident. This work demonstrates that production level is relevant when assessing the associations between the exposure to F. hepatica with production characteristics. Moreover, both models indicate a breed dependence. This could point towards a differential F. hepatica resilience of specialised dairy breeds in comparison with dual purpose breeds

Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs

Whole Genome Sequencing Indicates Heterogeneity of Hyperostotic Disorders in Dogs

Craniomandibular osteopathy (CMO) and calvarial hyperostotic syndrome (CHS) are proliferative, non-neoplastic disorders affecting the skull bones in young dogs. Different forms of these hyperostotic disorders have been described in many dog breeds. However, an incompletely dominant causative variant for CMO affecting splicing of SLC37A2 has been reported so far only in three Terrier breeds. The purpose of this study was to identify further possible causative genetic variants associated with CHS in an American Staffordshire Terrier, as well as CMO in seven affected dogs of different breeds. We investigated their whole-genome sequences (WGS) and filtered variants using 584 unrelated genomes, which revealed no variants shared across all affected dogs. However, filtering for private variants of each case separately yielded plausible dominantly inherited candidate variants in three of the eight cases. In an Australian Terrier, a heterozygous missense variant in the COL1A1 gene (c.1786G>A; p.(Val596Ile)) was discovered. A pathogenic missense variant in COL1A1 was previously reported in humans with infantile cortical hyperostosis, or Caffey disease, resembling canine CMO. Furthermore, in a Basset Hound, a heterozygous most likely pathogenic splice site variant was found in SLC37A2 (c.1446+1G>A), predicted to lead to exon skipping as shown before in SLC37A2-associated canine CMO of Terriers. Lastly, in a Weimaraner, a heterozygous frameshift variant in SLC35D1 (c.1021_1024delTCAG; p.(Ser341ArgfsTer22)) might cause CMO due to the critical role of SLC35D1 in chondrogenesis and skeletal development. Our study indicates allelic and locus heterogeneity for canine CMO and illustrates the current possibilities and limitations of WGS-based precision medicine in dogs