A positron emission tomography (PET) scanner, with an openable ring of detectors, was specifically designed to image the distal limb of standing horses. The goals of this prospective, preclinical, experimental, methods comparison study were to validate the safety of the scanner, assess image quality, and optimize scanning protocols.Six research horses were imaged three times (twice standing, once anesthetized) and six horses in active race training were imaged once under standing sedation. Multiple scans of both front fetlocks were obtained with different scan durations and axial fields of view. A total of 94 fetlock scans were attempted and 90 provided images of diagnostic value. Radiotracer uptake was the main factor affecting image quality, while motion did not represent a major issue. Scan duration and field of view also affected image quality. Eight specific lesions were identified on PET images from anesthetized horses and were all also independently recognized on the PET images obtained on standing horses. Maximal standardized uptake values (SUVmax) had good repeatability for the assessment of specific lesions among different scans. Three feet and six carpi were also successfully imaged. This study validated the safety and practicality of a PET scanner specifically designed to image the distal limb in standing horses. Proper preparation of horses, similar to bone scintigraphy, is important for image quality. A 4-min scan with 12 cm field of view was considered optimal for clinical fetlock imaging. Evaluation of a larger clinical population is the next step for further assessment of the clinical utility of PET imaging in horses.

Vascular disruption that occurs as a consequence of bone fracture, leads to hypoxia at the site of damage. Hypoxia regulates the expression of a number of genes that can modulate energy conservation, cell survival, tissue regeneration and angiogenesis. In this study we investigated the expression of Angiopoietin-like 4, an adipocytokine that has additional roles in angiogenesis, at the fracture site. We demonstrate that Angptl4 mRNA expression increased early during fracture healing (day 3) returning close to baseline at day14. In the callus, Angptl4 mRNA was visualized in areas of condensing mesenchymal cells, callus cartilage and was especially high in mineralizing osteoblasts located in areas of new bone formation. In vitro, Angptl4 mRNA expression in osteoblasts increased under hypoxic conditions and in cells treated with the hypoxia mimetic desferrioxamine. Angptl4 levels were strongly induced at day 14 in differentiating MC3T3-E1 osteoblastic cells. Exogenous ANGPTL4 increased expression of Runx2, Spp1, vegfa, and Alp mRNA in differentiating osteoblasts. We suggest that the distribution of Angptl4 in the callus may be driven by hypoxia and that Angptl4 may play a role in osteoblastic differentiation, and possibly angiogenesis via regulation of VEGF. Keywords: osteoblast; hypoxia; fracture; angiopoietin-like 4; osteogenesis Subsequent to fracture, bone's vascular supply is disrupted, leading to a hypoxic environment within the developing callus. [1][2][3][4] Hypoxia is known to upregulate a subset of genes mediated by the hypoxiainducible factor (HIF) transcription pathway.5 Such genes are known to play key roles in energy conservation, cell survival and angiogenesis among others. 5,6 HIF is a heterodimer whose alpha subunit is directly regulated by oxygen tension. Under normoxic conditions HIFa is hydroxylated by prolyl hydroxylasedomain proteins (PHDs) and degraded by von HippelLindau tumor suppressor protein.7-9 However, under hypoxic conditions the activity of PHDs is reduced and HIFa levels stabilize leading to heterodimer formation with HIFb. Nuclear translocation of HIF allows binding to hypoxia responsive elements and induces transcription of target genes.10 VEGFa, a HIF1 target gene, has been extensively studied and is thought to play a role in angiogenesis and revascularization of the fracture site.3 However, there is limited data regarding a role for other angiogenic factors.Angiopoietin-like protein 4 (Angptl4) is a member of the angiopoietin/ angiopoietin-like family of proteins. While Angptl4 is commonly described as an adipocytokine involved in energy homeostasis and food intake regulation, via inhibition of lipoprotein lipase, 11-14 it has also been shown to have a role in angiogenesis. [15][16][17][18] Its effect on angiogenesis and vascular permeability seems to be dependent on the method and form of the protein used, with both proangiogenic and antiangiogenic effects shown. [15][16][17][18] Angptl4 has been shown to be upregulated during hypoxia in articular chondrocytes, osteoc...

Lesions of the deep digital flexor tendon (DDFT) are a cause for foot lameness in horses.Positron emission tomography (PET) could provide valuable information regarding the metabolic activity of these lesions. The aims of this exploratory, prospective, methods comparison study were to assess the ability of 18 fluorine-fluorodeoxyglucose ( 18 F-FDG) PET to detect DDFT lesions and to compare the PET findings with CT and MRI findings. Eight horses with lameness due to pain localized to the front feet were included. Both front limbs of all horses were imaged with 18 F-FDG PET, noncontrast CT, and arterial contrast-enhanced CT; 11 limbs were also assessed using MRI. Two observers graded independently 18 F-FDG PET, noncontrast CT, arterial contrast CT, T1-weighted (T1-w) MRI, and T2-weighted (T2-w)/STIR MRI. Maximal standardized uptake values were measured. Lesions were found in seven of 16 DDFT on PET, 12 of 16 DDFT on noncontrast CT, six of 15 DDFT on arterial contrast CT, eight of 11 DDFT on T1-w MRI, and six of 11 DDFT on T2-w/STIR MRI. Positron emission tomography was in better agreement with arterial contrast CT (Kappa-weighted 0.40) and T2-w/STIR MRI (0.35) than with noncontrast CT (0.28) and T1-w MRI (0.20). Maximal standardized uptake values of lesions ranged from 1.9 to 4.6 with a median of 3.1.Chronic lesions with scar tissues identified on noncontrast CT or T1-w MRI did not have increased 18 F-FDG uptake. These results demonstrated that 18 F-FDG PET agreed more closely with modalities previously used to detect active tendon lesions, i.e. arterial contrast CT and T2-w/STIR MRI. 18 Fluorine-fluorodeoxyglucose PET can be used to identify metabolically active DDFT lesions in horses.

Computed tomography angiography (CTA) is currently the gold standard imaging modality for anatomically characterizing canine hepatic vascular anomalies; with conventional, gadolinium‐enhanced MR angiography being less frequently utilized. However, both imaging modalities are limited by a brief, first pass peak of contrast medium in the vasculature that necessitates precisely timed image acquisition. A long‐acting purely intravascular magnetic resonance imaging (MRI) contrast agent, ferumoxytol, offers the potential to reduce complexity of magnetic resonance angiography (MRA) protocol planning by ensuring diagnostic contrast medium concentration in all the vessels that are targeted for imaging. Aims of this prospective, pilot, methods comparison study were to develop an optimized MRA protocol using ferumoxytol in dogs with hepatic vascular anomalies, perform a dose escalation trial to compare image quality with four‐dose regimens of ferumoxytol, and compare accuracy of vascular anatomic depiction based on the gold standard of CTA. Six dogs (10.7–36.1 kg) with portosystemic shunts (four intrahepatic left divisional shunts and two intrahepatic right divisional shunts) were recruited for inclusion in the study. A dose‐escalation trial was performed to compare image quality at four incremental dose levels of ferumoxytol (1, 2, 3, and 4 mg/kg) and to compare the accuracy of vascular anatomic detection to CTA. Ferumoxytol contrast‐enhanced MRA (CE‐MRA) at 4 mg/kg provided similar conspicuity of normal and abnormal vasculature compared to CTA with a minimal decrease in spatial resolution. Findings indicated that ferumoxytol holds promise for comprehensive, single breath hold CE‐MRA of all abdominal vessels in dogs with portosystemic shunts. Background information provided in this study can be used to support development of other future applications such as intracranial and cardiac MRA, real‐time imaging, flow quantification, and potentially sedated MRI imaging.

Skeletal metastasis is a common finding in dogs with prostatic carcinoma and most frequently involves the lumbar vertebrae and pelvis. In the present report, we describe the case of a prostatic carcinoma in a 6‐year‐old Labrador retriever, who developed apparent oral sensitivity and pain within a week of initial diagnosis. Computed tomography of the skull revealed a mixed osteoproductive and osteolytic mass of the condylar process of the left mandible, and cytologic evaluation of the mass was consistent with metastatic prostatic carcinoma. To our knowledge, this is the first published report of mandibular metastasis of a prostatic carcinoma in a dog.

Background: Metaphyseal sclerosis secondary to canine distemper virus has been described histopathologically, but its radiographic appearance has not been described.Objectives: Describe the radiographic appearance of metaphyseal sclerosis secondary to canine distemper virus in juvenile dogs as distinct from metaphyseal osteopathy (formerly called hypertrophic osteodystrophy). Animals: Four dogs (2 intact females and 2 intact males) between 2.5 and 4 months of age presented to 2 different veterinary teaching hospitals. Methods: Retrospective case series in which definitive diagnosis of canine distemper virus based on antemortem positive reverse transcription-polymerase chain reaction (RT-PCR) result or necropsy was required. Results: All 4 dogs were presented for evaluation of neurologic abnormalities, respiratory signs, and lethargy; 2 dogs had gastrointestinal signs and ocular abnormalities. Radiographs on all patients featured multifocal, symmetric, metaphyseal sclerosis, with no evidence of lysis or changes to the adjacent growth plate. The metaphyseal sclerosis was most apparent at the proximal humeral diaphyses and other included long bones. Diagnosis of distemper was confirmed by necropsy (2 of 4 dogs) or positive RT-PCR results (2 of 4 dogs). Three dogs were euthanized because of progressive illness, and 1 dog was lost to follow-up. Conclusion and Clinical Importance: Identification of metaphyseal sclerosis on radiographs during diagnostic evaluation of young dogs should lead to a clinical suspicion of canine distemper virus infection. Sclerosis identified secondary to canine distemper virus is distinct from the necrosis and inflammation of metaphyseal osteopathy.

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