Evaluation of 18F-FDG PET/CT as a diagnostic imaging and staging tool for feline oral squamous cell carcinoma.

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy-proven oral SCC were imaged with whole body 18FDG-PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG-PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9-24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG-PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG-PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.

Computed tomographic angiography under sedation in the diagnosis of suspected canine pancreatitis: a pilot study.

BACKGROUND: Computed tomography (CT) is highly accurate for diagnosing pancreatitis in humans. The diagnosis of pancreatitis in dogs is based on clinical signs, laboratory findings, and ultrasonographic (US) changes. There are, however, inherent limitations in relying on laboratory and ultrasound findings for the clinical diagnosis of pancreatitis in dogs. HYPOTHESIS/OBJECTIVES: We hypothesized that CT angiography would be a rapid and reliable method to confirm pancreatitis in dogs compared to ultrasonography. The aim was to describe the CT characteristics and compare them to ultrasound findings and correlate the CT appearance to the severity of the patients' clinical course. ANIMALS: A prospective pilot case series; 10 dogs with pancreatitis were enrolled if the history, clinical signs, laboratory, and ultrasonographic findings were indicative of pancreatitis. METHODS: A 3-phase angiographic CT was performed under sedation. Afterward, each dog had US-guided aspirates of the pancreas collected and blood drawn for cPLi assay. Images were evaluated for portion of visible pancreas, pancreatic size and margin, pancreatic parenchyma, presence of peripancreatic changes and contrast enhancement pattern. The results were compared with outcome. RESULTS: An enlarged, homogeneously to heterogeneously attenuating and contrast-enhancing pancreas with ill-defined borders was identified in all dogs. CT identified more features characterizing pancreatic abnormalities compared to US. Thrombi were found in 3/10 dogs. Three dogs with heterogeneous contrast enhancement had an overall poorer outcome than those with homogenous enhancement. CONCLUSIONS AND CLINICAL IMPORTANCE: CT angiography under sedation was used in dogs to confirm clinically suspected pancreatitis and identified clinically relevant and potentially prognostic features of pancreatitis in dogs.

Lung tumor development and spontaneous regression in lambs coinfected with Jaagsiekte sheep retrovirus and ovine lentivirus.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring and experimentally inducible lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The first aim of this study was to monitor the development of OPA with minimally invasive, real-time observations of animals experimentally infected with JSRV as well as ovine lentivirus (maedi-visna virus). Worldwide, simultaneous infection of sheep with these 2 retroviruses is a common occurrence, naturally and experimentally; consequently, the lung tumor homogenates used as inocula contained both viruses. Following inoculation, computed tomography was used to detect tumor nodules early, before the onset of clinical signs, and to monitor tumor advancement. However, not only was OPA disease progression observed, but the apparent spontaneous regression of OPA was witnessed. In fact, regression was more common than progression following JSRV inoculation of neonatal lambs. Immune responses were detected, particularly involving CD3(+) T cells and the production of antibodies against JSRV that may mediate the spontaneous regression of JSRV-induced OPA. The second aim of this study was to determine whether OPA tumors harbor genetic alterations similar to those found in human lung adenocarcinoma. No mutations were found in the tyrosine kinase domain of the epidermal growth factor receptor, KRAS codons 12 and 13, or the DNA-binding domain of p53 in tumor DNA from naturally occurring and experimentally-induced OPA cases. Overall, the genetic profile combined with the disease development data provides further important characterization of OPA and describes, for the first time, spontaneous regression of OPA tumors in experimentally infected sheep.

Determination of lesion volume by MRI and stereology in a macaque model of tuberculosis.

Sensitive and reproducible methods are needed to measure the impact on the host following experimental challenge with Mycobacterium tuberculosis, in order to determine the degree of protection conferred by new vaccines. Here we compare how well different clinical and post-mortem measures of disease burden predict the response by the host to increasing doses of M. tuberculosis in rhesus and cynomolgus macaques. The total lung and lesion volume was quantified from magnetic resonance imaging (MRI) digital stacks obtained from lungs of M. tuberculosis infected animals that were formalin fixed and scanned ex-vivo. The total lung lesion volume relative to the fixed whole lung volume was superior at indicating disease burden when compared to thoracic radiography, pathology scores, changes in body weight and temperature, as well as erythrocyte haemoglobin concentrations and sedimentation rate. The total lesion volume accurately reflected differences in challenge doses of M. tuberculosis that ranged from 30 to 500 CFU delivered by aerosol. The determination of total lesion volume from MR images demonstrated a species-dependent difference between rhesus and cynomolgus macaques in susceptibility to M. tuberculosis infection. MR stereology provides an accurate, quantifiable and relatively simple assessment, which can be easily standardized between laboratories and should form an essential component of the clinical assessment of disease progression, or vaccine efficacy.

Radiographic interpretation of normal skeletal variations and pseudolesions in the equine foot.

Effective radiographic interpretation requires a veterinarian who is knowledgeable of equine limb anatomy and the various principles that affect the resulting image. The normal and its variations must be recognized and understood before the abnormal can be confidently identified as pathologic. Proper patient positioning and sound radiographic technique are mandatory if reliable diagnostic radiographs are to be produced. This review emphasizes equine foot radiographic variations of normal and pseudolesions that occur with commonly used radiographic views performed in equine practice.

Physical principles and technical considerations for equine computed tomography and magnetic resonance imaging.

This article discusses how cross-sectional imaging methods such as computed tomography and magnetic resonance imaging can provide unique and diagnostically important information in situations where radiography or diagnostic ultrasound have been unrewarding.

Mensuration of the normal pituitary gland from magnetic resonance images in 96 dogs.

The pituitary gland was measured from transverse magnetic resonance T1-weighted images after Gadolinium administration in 96 dogs weighing from 13 to 45 kg. The measurements were done by hand with calipers. The mean (+/- standard deviation) pituitary gland height was 5.1 mm (+/-0.9 mm). The mean width was 6.4 mm (+/- 1.1 mm). The correlation coefficient between pituitary and brain measurements, between pituitary measurement and body weight, and brain measurements and body weight was 0.0 to 0.3. A hyperintense region was present on T1-weighted images in the center of the pituitary gland in 64% of the dogs. At necropsy the pituitary glands were grossly and histologically normal. No pituitary gland measurements were performed at necropsy.

Primary hemangiosarcoma of the iliopsoas muscle eliciting a peripheral neuropathy.

An eight-year-old, male castrated bullmastiff presented to the Kansas State University Veterinary Medical Teaching Hospital with left hind-limb paralysis. A mass was identified in the left paralumbar soft tissue adjacent to the fourth (L4) to sixth (L6) lumbar vertebrae by magnetic resonance imaging. The iliopsoas muscle contained the mass which was identified as a hemangiosarcoma on histopathological examination. Hemangiosarcoma is rarely reported as a primary tumor arising from muscle vascular endothelium.

Plasma pharmacokinetics of warfarin enantiomers in cats.

The purpose of this study was to determine the dispositions of S-warfarin and R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin. Citrated blood samples were collected from 10 cats prior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72, 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemic warfarin. After a 21-day washout period, samples were then similarly collected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin were detected using a high-performance liquid chromatography assay validated for cat plasma. Drug concentration-time curves were subjected to non-compartmental analysis. Median pharmacokinetic parameters associated with the intravenous administration of 0.5 mg/kg racemic warfarin were as follows: t1/2 (S:28.2, R:18.3 h), area under the plasma concentration-time curve (AUC; S:33.0, R:24.6 h*microg/mL), area under the moment curve (AUMC; S:1889, R:527.8 h*h*microg/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each parameter, S-warfarin was significantly different from R-warfarin (P<0.05). Warfarin was absorbed rapidly after oral administration, and the dosage did not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dosage significantly influenced maximum plasma concentration (ng/mL, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0.1 mg/kg), AUC (h*microg/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*microg/mL, S:2135, R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t1/2 (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). Both warfarin enantiomers were highly (>96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an unequal distribution of the drug throughout the tablet.

Pharmacodynamics of warfarin in cats.

The overall purpose of this study was to evaluate the pharmacodynamic response to warfarin in cats. The specific aim was to determine if a log-linear indirect response model (Nagashima et al., 1969) used to describe the in vivo effect of warfarin in humans could be applied to cats. The pharmacokinetics of racemic warfarin were described using a non-compartmental approach. The relationship between prothrombin complex activity (PCA) and normalized prothrombin time (PTR) was defined for feline plasma under our experimental conditions, and determined to be: %PCA=12.38+648 e-PTR/0.492. These data were then integrated and used to predict the warfarin dose associated with therapeutic anti-coagulation defined as an International Normalized Ratio (INR) of 2.0-3.0. The maximum prothrombinopenic response to warfarin in cats after a single intravenous dose of 0.5 mg/kg occurred at 24-48 h. Pharmacodynamic modeling suggested that each cat had a narrow therapeutic range of the steady-state concentration of total warfarin required to appropriately block prothrombin complex synthesis (median: 265.2-358.7 ng/mL). The median daily dose range predicted to yield therapeutic concentrations of warfarin was 0.061-0.088 mg/kg per day. Wide inter-individual variations in both pharmacokinetics and pharmacodynamic response suggest that a more optimal dosing of warfarin may be possible with the development of individual pharmacokinetic/pharmacodynamic algorithms, analogous to those currently employed in human patients.

Intracranial neoplasia.

A diagnosis of intracranial neoplasia in companion animals may be made by computed tomography (CT) or magnetic resonance imaging (MRI). MRI is the better method for detecting and characterizing intracranial tumors because of its superior depiction of soft tissues and relative lack of degrading artifacts, intracranial tumors may be characterized by distinct features; a systematic evaluation of these features on CT or MRI images may help to identify specific tumor types. In this article, guidelines for formulating differential diagnoses based on these imaging criteria will be discussed. Technical recommendations and protocols for CT and MR imaging will also be provided.

Magnetic resonance imaging of the brain of a dog with hereditary polioencephalomyelopathy.

Hereditary polioencephalomyelopathy was suspected in a young, female Australian Cattle Dog on the basis of clinical signs, including seizures, progressive ataxia, and weakness. Magnetic resonance imaging (MRI) of the brain revealed multiple ovoid, bilaterally symmetric signal abnormalities that were hypointense or isointense on T1-weighted images and hyperintense on T2-weighted images. On necropsy, these areas of signal abnormalities corresponded to areas of malacia in various brain and brain stem nuclei. In addition, poliomalacia was detected at the cervical intumescence of the spinal cord. Histologic examination revealed rarefaction of neuropil and vacuolation of glial cells in these areas, which are lesions consistent with hereditary polioencephalomyelopathy of Australian Cattle Dogs.

Development of interactive patient-based multimedia computer programs in veterinary orthopedic radiology.

Three computerized multimedia programs on large and small animal veterinary orthopedic radiology were developed and implemented for the radiology curriculum as an alternative to traditional film-based laboratory learning. Programs utilized "hot words" (colored text words that displayed an overlaid image label that highlighted lesions) and interactive quizzes which responded appropriately to selected answers. "Hot words" helped students develop confidence in accurate lesion detection and the interactive quizzes transformed learning from a passive to an active process. Multiple examples were provided for reinforcement and concepts were incorporated from other clinical disciplines for curriculum integration. Programs were written using a presentation software program, Toolbook for DOS based platform, and contained radiographic images made by laser-scanning digitization. Multiple students could simultaneously access the programs through a network server. These pilot programs were implemented successfully and computerized multimedia presentation proved to be well suited to teaching radiology. Development of the programs required attention to a number of hardware, software, time and cost factors.

An ovarian teratoma in a cat.

A 5-month-old, intact female, domestic shorthaired cat was presented for evaluation of abdominal distension. Abdominal radiographs revealed a midabdominal mass that contained multiple, irregular, mineralized opacities. The mass was surgically removed, and an ovariohysterectomy performed. The mass was located at the tip of the left uterine horn and was covered partially by haired skin. Histologically, the mass was diagnosed as a mature ovarian teratoma based on the presence of well-differentiated somatic structures derived from three primary embryonal germ-cell layers. Germ-cell tumor classification and feline ovarian teratomas are reviewed.

Magnetic resonance imaging of presumptive lumbosacral discospondylitis in a dog.

A three-year-old male Boxer dog had hyperesthesia, symmetrical epaxial, gluteal and hind limb muscular atrophy and rear limb ataxia. Neurological deficits included decreased conscious proprioception of the left hind limb, decreased withdrawal and increased patellar reflexes of both hind limbs. The dog had a urinary tract infection with positive culture for Staphylococcus intermedius. On survey radiography of the lumbosacral spine there was active bone proliferation spanning the L7 S1 intervertebral disc space with an epidural filling defect at the ventral aspect of the vertebral canal on epidurography. On magnetic resonance imaging (MRI), findings were similar to those described for human diskospondylitis including altered signal intensity and nonuniform contrast enhancement of the L7-S1 intervertebral disc, adjacent vertebral end plates and epidural and sublumbar soft tissues. Although skeletal radiography is usually sufficient to reach a diagnosis of discospondylitis, MRI of this patient made it possible to reach a presumptive diagnosis of discospondylitis prior to development of definitive radiographic abnormalities.

Tricyclic pyrone analogs: a new class of microtubule-disrupting anticancer drugs effective against murine leukemia cells in vitro.

Novel 1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano [4,3-b][1]benzopyrans were synthesized in Hua's laboratory (code names H5, H10, H14 and H15) and tested for their ability to prevent L1210 leukemic cells from synthesizing macromolecules and growing in vitro. The aryl groups of these tricyclic pyrone (TP) analogs are either 3, 4-dimethoxyphenyl in H5 and H15 or 3-pyridyl in H10 and H14. Since 50 M H5 and H10 both inhibit DNA synthesis and tumor cell growth by 79-100%, concentrations 25 M were used in this study to assess the structure-activity relationships for this class of compounds. At 10-25 M, H5 and H14 are more potent inhibitors of DNA, RNA and protein synthesis than H10. In contrast, at 5-25 M, H10 is much more effective than H5 and H14 at inhibiting the growth of L1210 cells over a 4-day period. Interestingly, H15 inhibits DNA synthesis as much as H10 but fails to alter tumor cell growth. This discrepancy between the ability of TPs to inhibit macromolecule synthesis and leukemic cell growth suggests that other molecular targets may be involved in the antitumor action of these drugs. Their short-term inhibition of nucleic acid synthesis is reversible following drug removal but their long-term inhibition of tumor cell growth is not. Moreover, 25 M H5 and H10 are not cytotoxic at 2 days but equally decrease cell viability at 4 days, suggesting that the potent and irreversible inhibition of cell proliferation observed 1-4 days after H10 treatment is not solely caused by drug cytotoxicity. The effectiveness of H10 as inhibitor of L1210 cell growth is comparable to that of a spectrum of representative anticancer drugs. A critical finding is that 5 M H10 blocks the polymerization of purified tubulin by 90% and, therefore, may be a novel microtubule de-stabilizing drug. Indeed, H10 inhibits tubulin polymerization and L1210 cell growth as much as 5 M of vincristine (VCR). In contrast, 5 M H5 alters neither tubulin polymerization nor tumor cell growth. The ability of H10 to disrupt microtubule dynamics indirectly suggests that TPs may be novel cell cycle-specific anticancer drugs useful for arresting mammalian cells in mitosis.

Antitumor activity of tricyclic pyrone analogs, a new synthetic class of microtubule de-stabilizing agents, in the murine EMT-6 mammary tumor cell line in vitro.

Novel tricyclic pyrone (TP) analogs synthesized in Hua's laboratory (code names H10, H14 and H16) were tested against a spectrum of known antimitotic drugs for their ability to disrupt microtubule (MT) dynamics, alter the mitotic index, and prevent murine EMT-6 mammary sarcoma cells from synthesizing DNA and proliferating in vitro. At 2-10 microM, H10 inhibits DNA synthesis, tubulin polymerization and tumor cell growth to a greater degree than H14, whereas H16 has no effect. A linear skeleton with a pyridyl ring at C-3 of the A-ring, a pyran B-ring and no alkylation at C-7 of the C-ring is required for the antitumor activity of these TPs. Since H10 mimics the effect of vincristine (VCR), but not that of paclitaxel, on tubulin polymerization, TPs may represent a novel synthetic class of MT de-stabilizing anticancer drugs. H10 is less potent than VCR against tubulin polymerization (IC50: 1.5 microM versus 0.15 microM) and tumor cell proliferation (IC50: 1.5 microM versus 5 nM) but inhibits DNA synthesis (IC50: 10 microM) more effectively than all other MT-disrupting agents tested, except tubulozole-C. Although TPs disrupt DNA synthesis and might affect several phases of the cell cycle, the ability of H10 to increase the percentage of mitotic cells indicates that these novel compounds may be cell cycle-specific anticancer drugs useful for arresting mammalian cells in M-phase.