Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Glucagon infusion alters the circulating metabolome and urine amino acid excretion in dogs.

Glucagon plays a central role in amino acid (AA) homeostasis. The dog is an established model of glucagon biology, and recently, metabolomic changes in people associated with glucagon infusions have been reported. Glucagon also has effects on the kidney; however, changes in urinary AA concentrations associated with glucagon remain under investigation. Therefore, we aimed to fill these gaps in the canine model by determining the effects of glucagon on the canine plasma metabolome and measuring urine AA concentrations. Employing two constant rate glucagon infusions (CRI) - low-dose (CRI-LO: 3 ng/kg/min) and high-dose (CRI-HI: 50 ng/kg/min) on five research beagles, we monitored interstitial glucose and conducted untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) on plasma samples and urine AA concentrations collected pre- and post-infusion. The CRI-HI induced a transient glucose peak (90-120 min), returning near baseline by infusion end, while only the CRI-LO resulted in 372 significantly altered plasma metabolites, primarily reductions (333). Similarly, CRI-HI affected 414 metabolites, with 369 reductions, evidenced by distinct clustering post-infusion via data reduction (PCA and sPLS-DA). CRI-HI notably decreased circulating AA levels, impacting various AA-related and energy-generating metabolic pathways. Urine analysis revealed increased 3-methyl-l-histidine and glutamine, and decreased alanine concentrations post-infusion. These findings demonstrate glucagon's glucose-independent modulation of the canine plasma metabolome and highlight the dog's relevance as a translational model for glucagon biology. Understanding these effects contributes to managing dysregulated glucagon conditions and informs treatments impacting glucagon homeostasis.

Serum vitamin D metabolite and acute-phase protein concentrations are frequently abnormal in a cohort of hospitalized dogs and cats.

OBJECTIVE: To determine whether serum 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH]2D) concentrations are associated with survival and negatively correlate with acute-phase protein (APP) concentrations in ill dogs and cats admitted to nursing care units. ANIMALS: Client-owned dogs (n = 79) and cats (16) admitted to 2 academic veterinary hospital nursing care units. METHODS: A prospective cohort study was conducted between August 12, 2019, and October 26, 2021. A diagnostic laboratory measured 25(OH)D, 1,25(OH)2D, and haptoglobin (HPT) in dogs and cats; C-reactive protein (CRP) in dogs; and serum amyloid A (SAA) in cats. Serum was collected within 12 hours of admission. Illness severity (acute patient physiologic and laboratory evaluation [APPLEfast]) scores and survival data were recorded. RESULTS: Serum 25(OH)D concentrations were in the deficient range for 22 of 79 dogs and 2 of 16 cats. There were no associations between serum analyte concentrations (25[OH]D, 1,25[OH]2D, and APP) or APPLEfast score and survival in dogs or cats. In dogs, HPT was negatively correlated with 25(OH)D (P = .002; r = -0.34) and 1,25(OH)2D (P = .012; r = -0.28), while CRP was positively correlated with HPT (P = .001; r = 0.32) and APPLEfast score (P = .014; r = 0.16). In cats, 1,25(OH)2D was negatively correlated with APPLEfast scores (P = .055; r = -0.49) and SAA was positively correlated with HPT (P = .002; r = 0.73). CLINICAL RELEVANCE: Serum 25(OH)D or 1,25(OH)2D was not associated with survival in our hospitalized patient population. Relationships between APP and serum vitamin D metabolites with APPLEfast scores in cats warrant further investigation as illness severity biomarkers.

Short-term parenteral infusions with high-osmolality amino acid solutions can be safely administered through peripheral catheters in dogs treated for hypoaminoacidemia-related conditions.

OBJECTIVE: To compare complications between central and peripheral administration of high-osmolarity (approx 700 to 1,000 mOsm/L) amino acid (± lipid) infusions. ANIMALS: 18 client-owned dogs diagnosed with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome or superficial necrolytic dermatitis receiving parenteral amino acid ± lipid infusions. METHODS: In this retrospective case series, medical records were reviewed for administration route (central vs peripheral), catheter details and infusion characteristics (product osmolarity, concurrent lipid administration, infusion volume, duration, and rate), and complications for each infusion. RESULTS: 18 dogs received 277 infusions (median, 8.5; range, 1 to 84). Effective infusion osmolarities were 683 mOsm/L in 22% of infusions, 791 mOsm/L in 8%, 802 mOsm/L in 2%, 837 mOsm/L in 45%, and 998 mOsm/L in 23% (65% peripheral, 35% central). Most (n = 230 [83%]) infusions were given peripherally. The osmolarities of solutions administered by each route (P = .53), the infusion rate indexed to body weight (P = .17), or the lipid infusion rates indexed to body weight (P = .89) did not differ. One dog suffered 2 complications in 63 infusions-1 mild, 1 severe-both occurring with peripheral infusions. Thus, the overall complication rate was 2 of 277 (0.9%) infusions. CLINICAL RELEVANCE: Short-term peripherally administered amino acid ± lipid infusions < 1,000 mOsm/L confer little risk compared to centrally administered infusions. Additional studies are needed to determine the safety of infusions with longer durations. Due to the relative ease of peripheral catheterization, clinicians should consider this route for medically managing aminoaciduric canine hypoaminoacidemic hepatopathy syndrome and superficial necrolytic dermatitis in dogs.

A prospective cohort study to identify clinical diagnostic and prognostic markers of primary immune thrombocytopenia in dogs.

BACKGROUND: Primary immune thrombocytopenia (pITP) in dogs presents a diagnostic challenge, and clinical markers of severity are lacking. OBJECTIVES: Identify clinicopathologic features that differentiate pITP from secondary ITP (sITP) and markers related to bleeding severity, transfusion, and survival of dogs with pITP. ANIMALS: Ninety-eight thrombocytopenic dogs (58 pITP and 40 sITP). METHODS: Client-owned dogs with platelet counts <50 000/µL were enrolled in a prospective, multi-institution cohort study. History and treatment information, through a maximum of 7 days, was recorded on standard data forms. Bleeding severity was scored daily using a bleeding assessment tool (DOGiBAT). At-admission blood samples were collected for CBC, biochemistry, C-reactive protein concentration, and coagulation panels, and to measure platelet surface-associated immunoglobulin G (PSAIg) and expression of platelet membrane proteins and phospholipids. Dogs with evidence of coincident disease were classified as sITP. RESULTS: No definitive pITP diagnostic test was found. However, pITP cases were characterized by lower platelet counts, D dimer concentrations, and platelet membrane protein expression than sITP cases. Differentiation between pITP and sITP was further enhanced using logistic regression modeling combining patient sex, coagulation profile, platelet count, D dimer, and PSAIg. A second model of pITP severity indicated that low hematocrit and high BUN concentration were associated with non-survival. Low hematocrit at admission, but not platelet count or DOGiBAT score, was associated with transfusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Pending validation studies, models constructed from at-admission clinicopathologic findings may improve differentiation of pITP from sITP and identify the most severe pITP cases at the time of presentation.

Untargeted metabolomic profiles reveal widespread metabolic perturbations and identify candidate biomarkers in aminoaciduric canine hypoaminoacidemic hepatopathy syndrome.

OBJECTIVE: To identify metabolites and metabolic pathways affected in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared to healthy control (CON) dogs of similar ages and breeds. To improve our understanding of ACHES pathophysiology and identify novel candidate biomarkers associated with ACHES. ANIMALS: A prospective case-control study. Privately owned dogs with ACHES (n = 19) and healthy (CON) dogs (n = 9) were recruited between February 18, 2015, and April 18, 2018. METHODS: A prospective case-control study. Plasma and urine were collected from ACHES and CON dogs. The Cornell University Proteomics and Metabolomics Core Facility conducted an untargeted metabolomic analysis. RESULTS: After controlling for age, sex, and weight, 111 plasma and 207 urine metabolites significantly differed between ACHES and CON dogs. Data reduction and cluster analysis revealed robust segregation between ACHES and CON dogs. Enrichment analysis of significant compounds in plasma or urine identified altered metabolic pathways, including those related to AA metabolism, cellular energetics, and lipid metabolism. Biomarker analysis identified metabolites that best-distinguished ACHES from CON dogs, including pyruvic acid isomer and glycerol-3-phosphate in the plasma and an alanine isomer and choline in the urine. CLINICAL RELEVANCE: Our findings provide an in-depth analysis of metabolic perturbations associated with ACHES. Several affected metabolic pathways (eg, lipid metabolism) offer a new understanding of ACHES pathophysiology. Novel candidate biomarkers warrant further evaluation to determine their potential to aid in ACHES diagnosis, prognosis, and treatment monitoring.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy.

BACKGROUND: Alanine aminotransferase (ALT) is commonly used as a marker of hepatocellular injury. Increased serum ALT activity due to hepatocyte injury occurs in copper-associated hepatopathy (CuCH) and other necroinflammatory liver conditions. Blood ALT concentrations are frequently used to monitor therapy in cases of CuCH. Low serum ALT activities have been associated with an allele at a CFA13 locus. CASE PRESENTATION: A 9-year-old female spayed Siberian Husky was diagnosed with CuCH (hepatic copper dry weight 2680 µg/g [normal, 120-400 µg/g; toxic, > 1500 µg/g]) and a normal ALT (78 U/L; reference range, 10-125 U/L). Mild hepatocellular necrosis was evident histologically. Genetic testing (Embark) revealed that the dog was heterozygous for the low ALT activity gene allele. CONCLUSIONS: This case report illustrates the clinical implications for diagnosing and managing necroinflammatory liver disease such as CuCH in dogs with a low ALT activity genotype.

Plasma concentrations of glucagon and glucagon-like peptide-1 are reduced in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome versus healthy dogs: a preliminary study.

OBJECTIVE: To compare plasma concentrations of glucagon and glucagon-like peptide-1 (GLP-1) between healthy dogs and dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) dogs. ANIMALS: Privately owned healthy (n = 5) control (CON) and ACHES (8; including 3 with diabetes mellitus) dogs enrolled between October 2, 2019, and March 4, 2020. PROCEDURES: This was a prospective case-control study. Fasting and 15-minute postprandial plasma glucagon total GLP-1 concentrations were measured with commercial immunoassays. RESULTS: Dogs with ACHES had lower fasting (median, 0.5; mean difference, 3.8; 95% CI, 0.52 to 7.0 pmol/L; P = .021) and postprandial (median, 0.35; mean difference, 5.0; 95% CI, 1.8 to 8.3 pmol/L; P = .002) plasma glucagon concentrations than CON (fasting and postprandial medians, 3.5 and 4.6 pmol/L, respectively). ACHES dogs had significantly (median, 4.15; mean difference, 12.65; 95% CI, 2.0 to 16.3 pg/ml; P = .011) lower postprandial plasma GLP-1 concentrations than CON (median, 16.8 pg/ml). There was no significant difference between fasting GLP-1 levels between the 2 groups. CLINICAL RELEVANCE: Lower postprandial plasma GLP-1 concentrations may contribute to the propensity of diabetes mellitus in ACHES. Lower glucagon concentrations may reflect an appropriate physiologic response to hypoaminoacidemia.

Laparoscopic twist technique has the best overall artifact profile when comparing three laparoscopic hepatic cup biopsy techniques for dogs.

OBJECTIVE: To determine the difference in histologic artifacts and morphologic diagnosis among 3 laparoscopic cup biopsy forceps techniques and wedge hepatic samples. ANIMALS: Cadavers of 20 client-owned dogs following euthanasia for unrelated reasons between January 3 and July 29, 2021. PROCEDURES: Four biopsy techniques were performed from the margin of 3 liver lobes/dog. Laparoscopic techniques used 5-mm cup biopsy forceps to obtain biopsy samples by pulling the forceps forcefully caudally to free a sample (the PULL technique), rotating the forceps 360° in 1 direction until freed (the TWST technique), or pulling the forceps through a 5-mm cannula to remove the sample (the CAN technique); wedge biopsy samples served as the control (CON). Data collected included sample weight, histologic features, diagnosis, and artifact characterization. Gwet AC1 or intraclass correlation coefficients (ICCs) were calculated to detect agreement among techniques. RESULTS: Sample weights for CON and TWST were significantly larger (P < .001 and P = .035, respectively) than for PULL and CAN. There was excellent agreement among all techniques for most diagnostic features (Gwet AC1, 0.93 to 1). The TWST technique resulted in the best overall artifact profile for laparoscopic techniques, with 90% of samples (54/60) having crisp edges and 65% of samples (39/60) having no or mild tearing. The agreement was moderate to good (ICC, 0.73 for edges and 0.76 for tearing) among all cup biopsy forceps techniques. CLINICAL RELEVANCE: The TWST technique resulted in the largest sample and had the fewest artifacts, supporting its continued use during laparoscopic procedures.

Elimination of probable praziquantel-resistant Dipylidium caninum with nitroscanate in a mixed-breed dog: a case report.

BACKGROUND: Praziquantel is the drug of choice for treating the tapeworm Dipylidium caninum in dogs; however, resistance is possible, and regular, non-targeted administration of praziquantel may select for anthelminthic-resistant populations. METHODS: The zinc sulfate fecal floatation procedure was conducted. Gross visualization was used to identify Dipylidium spp. segments, and capsule endoscopy was used to visualize adult tapeworms within the intestinal tract. RESULTS: An 18-month-old spayed female terrier mix was presented due to diarrhea, hematochezia and weight loss. The dog received appropriate anthelmintic therapy for Giardia spp., Ancylostoma spp. and Dipylidium spp. The dog's clinical signs resolved, and elimination of Ancylostoma spp. was confirmed by subsequent fecal analysis. However, Dipylidium spp. segments were repeatedly present in the stool. Observation of the segments confirmed the presence of adult Dipylidium spp in feces. Treatment with praziquantel and epsiprantel were unsuccessful in eliminating the organism but was apparently successful in flea prevention. A single dose of nitrosconate was administered and eliminated Dipylidium spp. infection in the dog. CONCLUSIONS: Nitrosconate can be an effective treatment for praziquantel-resistant dipylidiasis in dogs. The novel application of capsule endoscopy confirmed the anthelmintic efficacy of this treatment.

Complex Feline Disease Mapping Using a Dense Genotyping Array.

The current feline genotyping array of 63 k single nucleotide polymorphisms has proven its utility for mapping within breeds, and its use has led to the identification of variants associated with Mendelian traits in purebred cats. However, compared to single gene disorders, association studies of complex diseases, especially with the inclusion of random bred cats with relatively low linkage disequilibrium, require a denser genotyping array and an increased sample size to provide statistically significant associations. Here, we undertook a multi-breed study of 1,122 cats, most of which were admitted and phenotyped for nine common complex feline diseases at the Cornell University Hospital for Animals. Using a proprietary 340 k single nucleotide polymorphism mapping array, we identified significant genome-wide associations with hyperthyroidism, diabetes mellitus, and eosinophilic keratoconjunctivitis. These results provide genomic locations for variant discovery and candidate gene screening for these important complex feline diseases, which are relevant not only to feline health, but also to the development of disease models for comparative studies.

Assessment of Sex, Age, and Metabolism Relationships to Serum Thyroid Concentrations in Retired Alaskan Husky Sled Dogs.

Sled dogs are purpose-bred dogs selected for endurance work. Prior studies in racing dogs showed that serum thyroid parameters (total T4, free T4, and T3) are lower than the reference range in approximately 25% of dogs. Whether this is related to training, breeding, or body condition remains unclear. We hypothesized that retired sled dogs of normal body condition (9-13 years old) would have predominantly normal serum thyroid parameters and that serum thyroid status would be correlated to energy consumption based on metabolic body weight. Eighty-six sled dogs who were deemed healthy on physical exam, not on confounding medications, and without a prior diagnosis of hypothyroidism were included. All dogs' mean body condition scores were 5.1 ± 0.4 and body weight 24.5 ± 4.2 kg at fasting blood collection with stable dietary intake for 3 months before sampling. The total T4, free T4, and T3 serum concentrations were 23.4 ± 9.1 nmol/L, 9.53 ± 4.3 pmol/L, and 0.93 ± 0.39 nmol/L, respectively, with 38% lower than the reference range for total T4, 45% for free T4, and 37% for T3. All dogs were negative for thyroglobulin antibody, and TSH results were within normal ranges. Pearson's correlates based on kilocalories consumed on a metabolic body weight basis for total T4 (R = 0.14), free T4 (R = 0.01) and T3 (R = 0.23) showed poor correlation. No differences were observed between thyroid hormones and age, breed, or sex. Inactive, retired sled dogs can be misdiagnosed with hypothyroidism; therefore, our data suggests that misdiagnosis of hypothyroidism can occur and that the racing Alaskan sled dog has a unique reference range that should be considered when assessing serum thyroid status.

Clinical features and amino acid profiles of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy.

BACKGROUND: Superficial necrolytic dermatitis (SND), hepatocutaneous-associated hepatopathy (HCH), aminoaciduria, and hypoaminoacidemia define hepatocutaneous syndrome (HCS) in dogs. Dogs without SND but that possess all other syndrome components are not well described. HYPOTHESIS/OBJECTIVES: To define an inclusive syndrome, aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) for dogs with HCH or HCS. Compare clinical features, salient clinicopathologic variables, and plasma and urine amino acid (AA) profiles among ACHES cases by skin lesion status. ANIMALS: Dogs of various breeds and ages diagnosed with ACHES (n = 41). A control (CON) cohort (n = 12) provided AA profile data. METHODS: Retrospective case series. Available medical records of previously identified cases were reviewed for salient clinical features and clinical pathology data. Plasma and urine AA profiles were performed. Cutaneous lesion status was classified as none, mild, or fulminant. RESULTS: Thirty cases (73%) developed SND at some time. Dogs with fulminant skin lesions at diagnosis (n = 22/41, 54%) had significantly lower hematocrit (P = .05) and mean corpuscular volume (P = .01) than dogs without SND. Principal component analysis of plasma AA profiles identified distinct clustering of CON from ACHES dogs, but not by skin lesion status. Plasma 1-methylhistidine (<7 nmol/mL) and cystathionine (<7.5 nmol/mL) were robust ACHES biomarkers. Urine lysine (>344 nmol/mg creatinine) and methionine (>68 nmol/mg creatinine) also were useful ACHES biomarkers. CONCLUSIONS AND CLINICAL IMPORTANCE: Specific AA biomarkers provide additional diagnostic utility in ACHES. Data suggests that HCH is an early stage, and SND a later stage manifestation of ACHES.

Treatment and outcomes of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy.

BACKGROUND: Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long-term remissions might be more common than previously believed and linked to treatment regimens. HYPOTHESIS/OBJECTIVES: Evaluate treatments and associated outcomes in dogs with hepatocutaneous-associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). ANIMALS: Forty-one dogs of various breeds and ages diagnosed with ACHES. METHODS: Retrospective study. Electronic surveys, medical records (2014-2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV-AA) infusions (≥2 vs <2), supplements including S-adenosylmethionine (SAMe), arginine with ornithine, glutathione, lysine, proline, omega-3 fatty acids, or zinc (≥3 vs <3), and diet type (home-cooked vs commercial). Optimal treatment was defined as receiving ≥2 IV-AA treatments, ≥3 nutritional supplements, and a home-cooked diet. RESULTS: Most dogs (29/41, 71%) received IV-AA infusions (23/29, ≥2 infusions). Twenty-one dogs (51%) were fed commercial diets; 17/41 (41%) were fed home-cooked diets. Most dogs received SAMe (32/41, 78%) and a median of 3 supplements. In 4 dogs, HCH remission occurred. Overall all-cause median survival time (MST) was 359 days, and disease-specific MST was 557 days (range, 1-1783 days). Optimally treated dogs (n = 9) lived significantly longer (MST, >1783 days, P = .02) than variably treated dogs (MST, 214 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Optimized ACHES management can resolve SND and HCH and confer long-term survival.

Development of infrastructure for a systemic multidisciplinary approach to study aging in retired sled dogs.

Canines represent a valuable model for mammalian aging studies as large animals with short lifespans, allowing longitudinal analyses within a reasonable time frame. Moreover, they develop a spectrum of aging-related diseases resembling that of humans, are exposed to similar environments, and have been reasonably well studied in terms of physiology and genetics. To overcome substantial variables that complicate studies of privately-owned household dogs, we have focused on a more uniform population composed of retired Alaskan sled dogs that shared similar lifestyles, including exposure to natural stresses, and are less prone to breed-specific biases than a pure breed population. To reduce variability even further, we have collected a population of 103 retired (8-11 years-old) sled dogs from multiple North American kennels in a specialized research facility named Vaika. Vaika dogs are maintained under standardized conditions with professional veterinary care and participate in a multidisciplinary program to assess the longitudinal dynamics of aging. The established Vaika infrastructure enables periodic gathering of quantitative data reflecting physical, physiological, immunological, neurological, and cognitive decline, as well as monitoring of aging-associated genetic and epigenetic alterations occurring in somatic cells. In addition, we assess the development of age-related diseases such as arthritis and cancer. In-depth data analysis, including artificial intelligence-based approaches, will build a comprehensive, integrated model of canine aging and potentially identify aging biomarkers that will allow use of this model for future testing of antiaging therapies.

Diffusion tensor-based analysis of white matter in the healthy aging canine brain.

White matter dysfunction and degeneration have been a topic of great interest in healthy and pathological aging. While ex vivo studies have investigated age-related changes in canines, little in vivo canine aging research exists. Quantitative diffusion MRI such as diffusion tensor imaging (DTI) has demonstrated aging and neurodegenerative white matter changes in humans. However, this method has not been applied and adapted in vivo to canine populations. This study aimed to test the hypothesis that white matter diffusion changes frequently reported in human aging are also found in aged canines. The study used Tract Based Spatial Statistics (TBSS) and a region of interest (ROI) approach to investigate age related changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). The results show that, compared to younger animals, aged canines have significant decreases in FA in parietal and temporal regions as well as the corpus callosum and fornix. Additionally, AxD decreases were observed in parietal, frontal, and midbrain regions. Similarly, an age- related increase in RD was observed in the right parietal lobe while MD decreases were found in the midbrain. These findings suggest that canine samples show commonalities with human brain aging as both exhibit similar white matter diffusion tensor changes with increasing age.

In vivo detection of microstructural spinal cord lesions in dogs with degenerative myelopathy using diffusion tensor imaging.

BACKGROUND: Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. OBJECTIVE: Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. ANIMALS: Thirteen dogs with DM and 13 aged-matched controls. METHODS: All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. RESULTS: Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition.