Structural ‘brain age’ is a valuable but complex biomarker for several brain disorders. The dog is an unrivalled comparator for neurological disease modeling, however canine brain morphometric diversity creates computational and statistical challenges. Using a data-driven approach, we explored complex interactions between patient metadata, brain morphometry, and neurological disease. Twenty-four morphometric parameters measured from 286 canine brain magnetic resonance imaging scans were combined with clinical parameters to generate 9,438 data points. Network analysis was used to cluster patients according to their brain morphometry profiles. An ‘aged-brain’ profile, defined by a small brain width and volume combined with ventriculomegaly, was revealed in the Boxer breed. Key features of this profile were paralleled in neutered female dogs which, relative to un-neutered females, had an 11-fold greater risk of developing brain tumours. Boxer dog and geriatric dog groups were both enriched for brain tumour diagnoses, despite a lack of geriatric Boxers within the cohort. Our findings suggest that advanced brain ageing enhances brain tumour risk in dogs and may be influenced by oestrogen deficiency—a risk factor for dementia and brain tumours in humans. Morphometric features of brain ageing in dogs, like humans, might better predict neurological disease risk than patient chronological age.

/pdf/network-analysis-of-canine-brain-morphometry-links-tumour-4xhp1wk2yu.pdf

Network analysis of canine brain morphometry links tumour risk to oestrogen deficiency and accelerated brain ageing.

Voxel-based morphometry (VBM) based on high resolution three-dimensional data of magnetic resonance imaging has been developed as a statistical morphometric imaging analysis method to locate brain abnormalities in humans. Recently, VBM has been used for human patients with psychological or neurological disorders such as Alzheimer's disease, Parkinson's disease, and epilepsy. Traditional volumetry using region of interest (ROI) is performed manually and the observer needs detailed knowledge of the neuroanatomy having to trace objects of interest on many slices which can cause artificial errors. In contrast, VBM is an automatic technique that has less observer biases compared to the ROI method. In humans, VBM analysis is performed in patients with epilepsy to detect accurately structural abnormalities. Familial spontaneous epileptic cats (FSECs) have been developed as an animal model of mesial temporal lobe epilepsy. In FSECs, hippocampal asymmetry had been detected using three-dimensional magnetic resonance (MR) volumetry based on the ROI method. In this study, we produced a standard template of the feline brain and compared FSECs and healthy cats using standard VBM analysis. The feline standard template and tissue probability maps were created using 38 scans from 14 healthy cats. Subsequently, the gray matter was compared between FSECs (n = 25) and healthy controls (n = 12) as group analysis and between each FSEC and controls as individual analysis. The feline standard template and tissue probability maps could be created using the VBM tools for humans. There was no significant reduction of GM in the FSEC group compared to the control group. However, 5/25 (20%) FSECs showed significant decreases in the hippocampal and/or amygdaloid regions in individual analysis. Here, we established the feline standard templates of the brain that can be used to determine accurately abnormal zones. Furthermore, like MR volumetry, VBM identified morphometric changes in the hippocampus and/or amygdala in some FSECs.

/pdf/statistical-structural-analysis-of-familial-spontaneous-308jaigasa.pdf

Statistical Structural Analysis of Familial Spontaneous Epileptic Cats Using Voxel-Based Morphometry.

Background: Structural 9brain age9 is a valuable but complex biomarker for several brain disorders The dog is an unrivalled comparator for neurological disease modeling, however brain phenotypic diversity among pedigrees creates computational and statistical challenges 
Methods: We applied unbiased network correlation analysis in dogs to explore complex interactions between brain morphometrics, patient metadata, and neurological disease Twenty-four parameters measured from each of 286 brain magnetic resonance imaging scans generated 9,438 data points that were used to cluster canine patients according to their brain morphometry profiles The network was then explored for statistically significant enrichments within breed, sex, age, and diagnostic categories
Findings: Morphometric comparisons revealed an advanced 9aged-brain9 profile in the Boxer breed, consisting of a small brain length, width, and volume, combined with ventriculomegaly Key features of this profile were paralleled in neutered female dogs which, relative to un-neutered females, had an 11-fold greater risk of developing primary brain tumours Enrichment analysis confirmed that Boxers and geriatric individuals were enriched for brain tumour diagnoses, despite a lack of geriatric Boxers within the cohort 
Interpretation: These findings suggest that accelerated brain ageing might contribute to tumour risk in Boxers and may be influenced by oestrogen deficiency -- a risk factor for dementia and brain tumours in humans We propose that morphometric features of brain ageing in dogs, like humans, might better predict neurological disease risk than a patient9s chronological age 
Funding: Wellcome Trust Integrated Training Fellowship for Veterinarians (096409/Z/11/Z to NMR) and an MSD Animal Health Connect Bursary (to OMS)

/pdf/network-analysis-of-canine-brain-morphometry-links-tumour-4iwshg4wli.pdf

Network analysis of canine brain morphometry links tumour risk to oestrogen deficiency and accelerated brain ageing

Simple Summary Although many dogs with blindness diagnosis can reach a similar age compared to those not affected, often the owners require euthanasia of their animals. This choice leads to conflicting moral principles relating to what is better for the animal and the owner. This article discusses the suitability of euthanasia in blind dogs. To better assess factors influencing the choice of euthanasia, four different scenarios were constructed that described various situations regarding the animal’s aptitude, pet owner, and veterinarian relations. Abstract In dogs, several primary or secondary diseases affecting the ocular structures may cause blindness. In cases where the visual impairment is not associated with severe systemic involvement and the animal can still have, predictably, a good “long-term” quality of life, the veterinarian should inform the owner about the differences between humans and animals, concerning the type of visual perception. In the light of the daily findings in veterinary clinic practice, the Authors report four different scenarios with conflicting views between veterinarians and owners about the euthanasia request for a blind dog. They underline how the diagnosis of incipient or already established blindness in dogs can sometimes lead to an inappropriate request for euthanasia.

/pdf/animal-welfare-considerations-and-ethical-dilemmas-inherent-c245ik79.pdf

Animal Welfare Considerations and Ethical Dilemmas Inherent in the Euthanasia of Blind Canine Patients

Canine idiopathic epilepsy (IE) is the most common chronic neurological brain disease in dogs, yet it can only be diagnosed by exclusion of all other potential causes. In people, epilepsy has been associated with a reduction in brain volume. The objective was to estimate the volume of the forebrain (FB), subarachnoid space (SAS) and lateral ventricles (LV) in dogs with IE compared to controls using Cavalieri’s principle. MRI scans of case and control dogs were identified from two neurology referral hospital databases. Eight breeds with increased odds of having IE were included: Golden Retriever, Labrador Retriever, Cocker Spaniel, Border terrier, German Shepherd dog, Parson Jack Russell terrier, Boxer, and Border Collie. Five dogs of each breed with IE and up to five controls were systematically and uniformly randomly sampled (SURS). The volume of the FB, SAS and LV were estimated from MRI scans by one blinded observer using Cavalieri’s principle. One hundred-two dogs were identified; 56 were diagnosed with IE and 46 were controls. There was no statistically significant difference in FB, SAS and LV volume between dogs with IE and controls. Dogs with a history of status epilepticus had significantly larger FB than those without (p = 0.05). There was a border-line trend for LV volume to increase with increasing length of seizure history in the IE group (p = 0.055). The volumes of the FB, SAS and LV are not different between dogs with IE and controls, so IE remains a diagnosis of exclusion with no specific neuroanatomical biomarkers identified. This is the first time FB and SAS volume has been compared in dogs with IE. Unfortunately, we have shown that the results reporting significantly larger FBs in dogs with status epilepticus and LV volume increase with length of seizure history were likely confounded by breed and should be interpreted cautiously. Whilst these associations are interesting and clinically relevant, further investigation with breed-specific or larger, breed-diverse populations are required to permit strong conclusions. The Cavalieri principle provided an effective estimation of FB, SAS and LV volumes on MRI, but may be too time-intensive for use in clinical practice.

/pdf/comparison-of-volume-of-the-forebrain-subarachnoid-space-and-2g1ia9nw8f.pdf

Comparison of volume of the forebrain, subarachnoid space and lateral ventricles between dogs with idiopathic epilepsy and controls using a stereological approach: Cavalieri’s principle

One of the most common chronic neurological disorders in dogs is idiopathic epilepsy (IE) diagnosed as epilepsy without structural changes in the brain. In the current study the hypothesis should be proven that subtle grey matter changes occur in epileptic dogs. Therefore, magnetic resonance (MR) images of one dog breed (Beagles) were used to obtain an approximately uniform brain shape. Local differences in grey matter volume (GMV) were compared between 5 healthy Beagles and 10 Beagles with spontaneously recurrent seizures (5 dogs with IE and 5 dogs with structural epilepsy (SE)), using voxel-based morphometry (VBM). T1W images of all dogs were prepared using Amira 6.3.0 for brain extraction, FSL 4.1.8 for registration and SPM12 for realignment. After creation of tissue probability maps of cerebrospinal fluid, grey and white matter from control images to segment all extracted brains, GM templates for each group were constructed to normalize brain images for parametric statistical analysis, which was achieved using SPM12. Epileptic Beagles (IE and SE Beagles) displayed statistically significant reduced GMV in olfactory bulb, cingulate gyrus, hippocampus and cortex, especially in temporal and occipital lobes. Beagles with IE showed statistically significant decreased GMV in olfactory bulb, cortex of parietal and temporal lobe, hippocampus and cingulate gyrus, Beagles with SE mild statistically significant GMV reduction in temporal lobe (p < 0.05; family- wise error correction). These results suggest that, as reported in epileptic humans, focal reduction in GMV also occurs in epileptic dogs. Furthermore, the current study shows that VBM analysis represents an excellent method to detect GMV differences of the brain between a healthy dog group and dogs with epileptic syndrome, when MR images of one breed are used.

/pdf/grey-matter-volume-in-healthy-and-epileptic-beagles-using-3sulrv45o4.pdf

Grey matter volume in healthy and epileptic beagles using voxel-based morphometry - a pilot study.

In dogs, meningiomas mostly cause chronic progressive clinical signs due to slow tumor growth. In contrast, three dogs were presented with the history of chronic generalized tonic-clonic seizures and peracute deterioration with sudden onset of neurological deficits in accordance with an extensive unilateral forebrain lesion. Magnetic resonance imaging examinations of the dogs revealed a well-delineated extraaxial T2W hyperintense mass in the rostral forebrain with homogeneous contrast enhancement. Additionally, an intraaxial, well-demarcated, unilateral lesion was apparent in the parenchyma supplied by the middle cerebral artery. In two cases, necropsy revealed meningothelial meningioma in the rostral fossa and marked eosinophilic neuronal necrosis, a sign of ischemia, focal malacia, edema and gliosis in the temporal lobe and hippocampus because of a focal thrombosis of the middle cerebral artery. In the third case symptomatic treatment resulted in improvement of clinical signs enabling a good quality of life for the patient. In dogs with structural epilepsy caused by meningioma, acute deterioration of clinical signs can be associated with ischemic infarctions as a potential complication.

/pdf/meningioma-and-associated-cerebral-infarction-in-three-dogs-28v9ojgpaj.pdf

Meningioma and associated cerebral infarction in three dogs.

Veterinary DermatologyEarly View Abstract Prevalence of Demodex gatoi in shelter and feral cats in the East Tennessee region S. BAIZ, S. BAIZ Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorL. FRANK, L. FRANK Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorE. DRAKE, E. DRAKE Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorS. KANIA, S. KANIA Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this author S. BAIZ, S. BAIZ Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorL. FRANK, L. FRANK Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorE. DRAKE, E. DRAKE Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this authorS. KANIA, S. KANIA Department of Biomedical and Diagnostic Sciences, University of Tennessee, Knoxville, TN, USASearch for more papers by this author First published: 06 June 2022 https://doi.org/10.1111/vde.13087Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Early ViewOnline Version of Record before inclusion in an issue RelatedInformation 

Prevalence of Demodex gatoi in shelter and feral cats in the East Tennessee region.

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Grey matter volume in healthy and epileptic beagles using voxel-based morphometry - a pilot study.

Meningioma and associated cerebral infarction in three dogs.

Prevalence of Demodex gatoi in shelter and feral cats in the East Tennessee region.