Magnetic resonance imaging features of canine gliomatosis cerebri.

A retrospective, case series study was undertaken to identify magnetic resonance imaging (MRI) characteristics of gliomatosis cerebri in dogs. Fourteen dogs were included by review of histopathological records and contemporaneous MRI. On MRI, all lesions presented as ill-defined, intraaxial lesions within the left and right forebrain hemispheres with involvement of white and gray matter. Lesions presented as hyperintense areas on T2-weighted and FLAIR sequences and as hypointense or isointense areas on T1-weighted images, with mild parenchymal contrast enhancement in three dogs. Signal changes were noted in three to 10 cerebral lobes. Other most commonly affected structures were the thalamus (13), caudate nucleus (13), interthalamic adhesion (11), hypothalamus (11), callosal commissure (10), hippocampus (9), and quadrigeminal plate (8). Abnormalities within the caudal fossa were noted in 10 dogs. Solid tumor portions were identified in five dogs. The histopathological examination demonstrated in all dogs a widespread diffuse infiltration with neoplastic glial cells in white and gray matter with meningeal infiltration. Comparison between MRI and histopathology showed that all areas with signal changes on MRI corresponded to diffuse and dense infiltration with neoplastic cells. The signal intensity on T2-weighted and FLAIR images reflected the density of neoplastic cells. In all dogs, MRI underestimated lesion extent and meningeal infiltration. Involvement of the caudal fossa was not seen on MRI in three dogs. Despite this, MRI allowed identification of lesions extending into at least three cerebral lobes and therefore satisfying the criteria used for diagnosis of diffuse glioma with gliomatosis cerebri growth pattern in humans.

Canine Brachycephaly Is Associated with a Retrotransposon-Mediated Missplicing of SMOC2.

In morphological terms, "form" is used to describe an object's shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2. An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine.

Magnetic resonance features of the feline hippocampus in epileptic and non-epileptic cats: a blinded, retrospective, multi-observer study.

BACKGROUND: Hippocampal necrosis in cats has been reported to be associated with epileptic seizures. Magnetic resonance imaging (MRI) features of temporal lobe (TL) abnormalities in epileptic cats have been described but MR images from epileptic and non-epileptic individuals have not yet been systematically compared. TL abnormalities are highly variable in shape, size and signal, and therefore may lead to varying evaluations by different specialists. The aim of this study was to investigate whether there were differences in the appearance of the TL between epileptic and non-epileptic cats, and whether there were any relationships between TL abnormalities and seizure semiologies or other clinical findings. We also investigated interobserver agreement among three specialists. METHODS: The MR images of 46 cats were reviewed independently by three observers, who were blinded to patient data, examination findings and the review of the other observers. Images were evaluated using a multiparametric scoring system developed for this study. Mann-Whitney U-tests and chi-square were used to analyse the differences between observers' evaluations. The kappa coefficient (k) and Fleiss' kappa coefficient were used to quantify interobserver agreement. RESULTS: The overall interobserver agreement was moderate to good (k =0.405 to 0.615). The MR scores between epileptic and non-epileptic cats did not differ significantly. However, there was a significant difference between the MR scores of epileptic cats with and without orofacial involvement according to all three observers. Likewise, MR scores of cats with cluster seizures were higher than those of cats without clusters. CONCLUSION: Cats presenting with recurrent epileptic seizures with orofacial involvement are more likely to have hippocampal pathologies, which suggests that TL abnormalities are not merely unspecific epileptic findings, but are associated with a certain type of epilepsy. TL signal alterations are more likely to be detected on FLAIR sequences. In contrast to severe changes in the TL which were described similarly among specialists, mild TL abnormalities may be difficult to interpret, thus leading to different assessments among observers.

A missense change in the ATG4D gene links aberrant autophagy to a neurodegenerative vacuolar storage disease.

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10-136) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to the macroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.

Maine Coon renal screening: ultrasonographical characterisation and preliminary genetic analysis for common genes in cats with renal cysts.

The objective of this study was to assess the prevalence of renal cysts and other renal abnormalities in purebred Maine Coon cats, and to characterise these through genetic typing. Voluntary pre-breeding screening programmes for polycystic kidney disease (PKD) are offered for this breed throughout Switzerland, Germany and other northern European countries. We performed a retrospective evaluation of Maine Coon screening for renal disease at one institution over an 8-year period. Renal ultrasonography was performed in 187 healthy Maine Coon cats. Renal changes were observed in 27 of these cats. Renal cysts were found in seven cats, and were mostly single and unilateral (6/7, 85.7%), small (mean 3.6 mm) and located at the corticomedullary junction (4/6, 66.7%). Sonographical changes indicating chronic kidney disease (CKD) were observed in 10/187 (5.3%) cats and changes of unknown significance were documented in 11/187 (5.9%) cats. All six cats genetically tested for PKD1 were negative for the mutation, and gene sequencing of these cats did not demonstrate any common genetic sequences. Cystic renal disease occurs with a low prevalence in Maine Coons and is unrelated to the PKD observed in Persians and related breeds. Ultrasonographical findings compatible with CKD are not uncommon in juvenile Maine Coons.

A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

Ultrasonographic features of PMEL17 (Silver) mutant gene-associated multiple congenital ocular anomalies (MCOA) in Comtois and Rocky Mountain horses.

OBJECTIVE: (1) To describe the ultrasonographic appearance of multiple congenital ocular anomalies (MCOA) in the eyes of horses with the PMEL17 (Silver) mutant gene. (2) To compare the accuracy of B-mode ocular ultrasound to conventional direct ophthalmoscopy. ANIMALS STUDIED: Sixty-seven Comtois and 18 Rocky Mountain horses were included in the study. PROCEDURES: Horses were classified as being carriers or noncarriers of the PMEL17 mutant allele based on coat color or genetic testing. Direct ophthalmoscopy followed by standardized ultrasonographic examination was performed in all horses. RESULTS: Seventy-five of 85 horses (88.24%) carried at least one copy of the Silver mutant allele. Cornea globosa, severe iridal hypoplasia, uveal cysts, cataracts, and retinal detachment could be appreciated with ultrasound. Carrier horses had statistically significantly increased anterior chamber depth and decreased thickness of anterior uvea compared with noncarriers (P < 0.05). Uveal cysts had a wide range of location and ultrasonographic appearances. In 51/73 (69.86%) carrier horses, ultrasound detected ciliary cysts that were missed with direct ophthalmoscopy. CONCLUSIONS: In this study, ultrasonography was useful to identify uveal cysts in PMEL17 mutant carriers and to assess anterior chamber depth.

Magnetic resonance imaging findings in dogs with traumatic intervertebral disk extrusion with or without spinal cord compression: 31 cases (2006-2010).

OBJECTIVE: To determine the prevalence of spinal cord compression subsequent to traumatic intervertebral disk (IVD) extrusion in dogs, characterize factors associated with spinal cord compression in dogs with traumatic IVD extrusion, and evaluate the outcomes of dogs with traumatic IVD extrusion with or without spinal cord compression. DESIGN: Retrospective case series. ANIMALS: 31 dogs with traumatic IVD extrusion. PROCEDURES: Medical records and MRI findings were reviewed for dogs with a history of trauma to the spinal region. Dogs were included in the study if a neurologic examination and MRI were performed and there was a description of clinical signs and MRI findings including identification of the spinal cord segment affected by IVD extrusion, presence or absence of spinal cord compression, treatment, and outcome available for review. RESULTS: 31 of 50 (62%) dogs had traumatic IVD extrusions without any other detectable vertebral lesions; 9 (29%) and 22 (71%) of those 31 dogs did and did not have spinal cord compression, respectively. Dogs with spinal cord compression were significantly older and more likely to be chondrodystrophic and have evidence of generalized IVD degeneration, compared with dogs without spinal cord compression. The outcome for dogs with spinal cord compression was similar to that for dogs without spinal cord compression. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated traumatic IVD extrusion was common and should be considered as a differential diagnosis for dogs with trauma to the spinal region, and spinal cord compression should be evaluated, especially in older or chondrodystrophic dogs.

Magnetic resonance imaging features of sinonasal disorders in horses.

Diseases of paranasal sinuses and nasal passages in horses can be a diagnostic challenge because of the complex anatomy of the head and limitations of many diagnostic modalities. Our hypothesis was that magnetic resonance (MR) imaging would provide excellent anatomical detail and soft tissue resolution, and would be accurate in the diagnosis of diseases of the paranasal sinuses and nasal passages in horses. Fourteen horses were imaged. Inclusion criteria were lesions located to the sinuses or nasal passages that underwent MR imaging and subsequent surgical intervention and/or histopathologic examination. A low field, 0.3 tesla open magnet was used. Sequences in the standard protocol were fast spin echo T2 sagittal and transverse, spin echo T1 transverse, short-tau inversion recovery (STIR) dorsal, gradient echo 3D T1 MPR dorsal (plain and contrast enhanced), spin echo T1 fatsat (contrast enhanced). Mean scan time to complete the examination was 53 min (range 39-99 min). Lesions identified were primary or secondary sinusitis (six horses), paranasal sinus cyst (four horses), progressive ethmoid hematoma (two horses), and neoplasia (two horses). The most useful sequences were fast spin echo T2 transverse and sagittal, STIR dorsal and FE3D MPR (survey and contrast enhanced). Fluid accumulation, mucosal thickening, presence of encapsulated contents, bone deformation, and thickening were common findings observed in MR imaging. In selected horses, magnetic resonance imaging is a useful tool in diagnosing lesions of the paranasal sinuses and nasal passages.

Intervertebral disc cell- and hydrogel-supported and spontaneous intervertebral disc repair in nucleotomized sheep.

PURPOSE: Regenerative repair is a promising new approach in treating damaged intervertebral discs. An experimental scheme was established for autologous and/or allogenic repair after massive disc injury. METHODS: Disc healing was promoted in 11 animals by injecting in vitro expanded autologous/homologous disc cells 2 weeks after stab injury of lumbar discs L1-2. The following control discs were used in our sheep injury model: L2-3, vehicle only; L3-4, injury only; L4-5, undamaged; and lumbar discs from four non-experimental animals. Disc cells were suspended in a biologically supportive albumin/hyaluronan two-component hydrogel solution that polymerizes when inserted in order to anchor cells at the injection site. The parameters studied were MRI, DNA, glycosaminoglycan, collagen content, histology, immunohistology for collagens type I, II and aggrecan, and mRNA expression of GAPDH, ß-actin, collagen type I, II, X, aggrecan, lubricin, and IL-1ß. RESULTS: All parameters demonstrated almost complete healing of the injured discs after 6 months, when compared with data from both the endogenous non-injured controls as well as from the healthy animals. CONCLUSION: Sheep experience spontaneous recovery from disc injury. The process of endogenous repair can be enhanced by means of hydrogel-supported cells.

Usefulness of a half-fourier acquisition single-shot turbo spin-echo pulse sequence in identifying arachnoid diverticula in dogs.

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.

Magnetic resonance imaging characterization of vertebral endplate changes in the dog.

Spinal MR images acquired from canine patients over a 7-year period were reviewed for the presence of vertebral endplate changes. Seventy-five dogs with 76 distinct lesions were identified. Presumptive diagnoses fell into five categories: reactive endplate changes (10 dogs/13.2%), discospondylitis (29 dogs/38.2%), vertebral osteochondrosis (7 dogs/9.2%), intravertebral disc herniation (Schmorl's nodes) (4 dogs/5.3%), and fatty infiltration (26 dogs/34.2%). Fatty infiltration occurred significantly more often in small breed dogs (P < 0.001) and tended to be multifocal. The following features were observed in discospondylitis as well as in other nonfatty endplate pathologies: irregular endplates, endplate hyperintensity in T2w or STIR images, reduced endplate signal intensity in T1w SE, variable T1w GRE signal intensity, and endplate contrast enhancement. Overlap between MR characteristics of nonfatty endplate changes should prompt cautious evaluation of adjacent structures.

Influence of durotomy on laser-Doppler measurement of spinal cord blood flow in chondrodystrophic dogs with thoracolumbar disk extrusion.

OBJECTIVES: To assess influence of durotomy on spinal cord blood flow (SCBF) in chondrodystrophic dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Chondrodystrophic dogs with thoracolumbar disk extrusion (n = 11). METHODS: Diagnosis was based on neurologic signs, magnetic resonance imaging (MRI) findings, and surgical confirmation. Regional SCBF was measured 3 times intraoperatively by laser-Doppler flowmetry: (1) before surgical decompression; (2) immediately after decompression by hemilaminectomy-durotomy; and (3) after 15 minutes of lesion lavage. A standardized hemilaminectomy and durotomy performed by the same neurosurgeon, was used to minimize factors that could influence measurement readings. RESULTS: A significant increase in intraoperative SCBF was found immediately after spinal cord decompression and durotomy in dogs but SCBF returned to previous levels or lower after 15 minutes of lavage. Changes in SCBF were not associated with duration of clinical signs; neurologic status, degree of spinal cord compression, or signal intensity changes as assessed by MRI. CONCLUSION: Durotomy does not increase SCBF in dogs with disk extrusion associated spinal cord compression.

Contrast media enhancement of intracranial lesions in magnetic resonance imaging does not reflect histopathologic findings consistently.

Certain magnetic resonance (MR) enhancement patterns are often considered to be associated with a specific diagnosis but experience shows that this association is not always consistent. Therefore, it is not clear how reliably contrast enhancement patterns correlate with specific tissue changes. We investigated the detailed histomorphologic findings of intracranial lesions in relation to Gadodiamide contrast enhancement in 55 lesions from 55 patients, nine cats, and 46 dogs. Lesions were divided into areas according to their contrast enhancement; therefore 81 areas resulted from the 55 lesions which were directly compared with histopathology. In 40 of 55 lesions (73%), the histomorphologic features explained the contrast enhancement pattern. In particular, vascular proliferation and dilated vessels occurred significantly more often in areas with enhancement than in areas without enhancement (P = 0.044). In 15 lesions, there was no association between MR images and histologic findings. In particular, contrast enhancement was found within necrotic areas (10 areas) and ring enhancement was seen in lesions without central necrosis (five lesions). These findings imply that necrosis cannot be differentiated reliably from viable tissue based on postcontrast images. Diffusion of contrast medium within lesions and time delays after contrast medium administration probably play important roles in the presence and patterns of contrast enhancement. Thus, histologic features of lesions cannot be predicted solely by contrast enhancement patterns.

Pros and cons of low-field magnetic resonance imaging in veterinary practice.

Low-field (LF) (0.2-0.4T) magnetic resonance (MR) imaging predominates in veterinary practice. Advantages of LF MR include reduced costs, better patient access, and greater safety. High quality examinations can be achieved using appropriate protocols and investing more scanning time than with high-field (HF) systems. The main disadvantage of LF MR is the reduced signal to noise ratio compared with HF systems. LF MR protocols for small animal brain and spine imaging are described.

Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome.

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

MRI features of gastrocnemius musculotendinopathy in herding dogs.

Pelvic limb lameness that was localized clinically to the lateral gastrocnemius head was observed in dogs without history of trauma. The aim of this retrospective study was to describe magnetic resonance imaging (MRI) findings of this condition. Nine dogs were identified, eight Border Collies and one Australian Shepherd. They all had chronic pelvic limb lameness; no signs of joint effusion or instability were present. In MR images there was high signal intensity in the lateral head of the gastrocnemius muscle around the sesamoid bone in T2-weighted, T2*-weighted, and STIR images and an iso- to mildly hyperintense signal in T1-weighted images with marked contrast enhancement. The abnormal signal intensity most likely represents a myotendinous strain. The breed affiliation to Border Collies is striking, and a relation to biomechanical forces or motion pattern may be possible. Except for the dog with the most extensive lesion all dogs had an excellent outcome.