The development of an indirect computed tomography lymphography protocol for sentinel lymph node detection in head and neck cancer and comparison to other sentinel lymph node mapping techniques.

Identification of metastatic disease critically impacts the care and prognosis of patients with neoplasia. Multiple techniques exist for identifying the sentinel or first lymph node(s) that receive draining tumour lymph. Identification of the sentinel lymph node enables accurate tissue sampling for determination of lymphatic metastasis. The aims of this study were to develop a computed tomography (CT) protocol for identifying the sentinel lymph node in dogs with tumours of the head and neck. In addition, indirect CT lymphography was compared to lymphoscintigraphy and vital dye injection to determine which technique more reliably identified the sentinel lymph node. CT indirect lymphography using intratumoral injection of iodinated contrast identified draining lymphatic vessels in eight of 18 dogs and identified the sentinel lymph node in five of 18 dogs. CT indirect lymphography employing four-quadrant peritumoral injection of iodinated contrast identified draining lymphatic vessels in 18 of 20 dogs and identified the sentinel lymph node in 11 of 20 dogs. Vital dye injection and lymphoscintigraphy identified the sentinel lymph node in 17 of 18 and 20 of 20 dogs, respectively. Identified sentinel lymph nodes were either ipsilateral or bilateral to the primary tumour. Both CT techniques were found to be safe and simple. Peritumoral injection has the greatest promise for the detection of sentinel lymph nodes in various head and neck cancers using CT, while lymphoscintigraphy had the greatest success of the compared techniques.

Occupational Exposure to Veterinary Workers from the Positron Emission Tomography Imaging Agent 64Cu-ATSM.

Cu-ATSM is an emerging radiopharmaceutical for diagnostic use in positron emission tomography (PET), but to date there are no studies that assess the potential occupational doses to workers in either human or veterinary medicine. This study was aimed at determining the external radiation dose to veterinary workers from clinical PET/CT (PET combined with computed tomography) procedures using Cu-ATSM. To determine the dose to the workers, each worker was assigned two Electronic Personal Dosimeters (EPDs) to be worn on the chest and waist during the entirety of each procedure. The workers monitored during this study included a radiobiologist, a nuclear medicine technologist, an anesthesiologist, and a veterinary surgeon. Seven canine patients were imaged with an average mass of 33.7 kg (a range of 20.0-55.1 kg) with an average injected activity of 5 MBq kg. The dose range for the radiobiologist was 2-17 µSv (mean of 7.1 µSv), for the nuclear medicine technologist 0-14 µSv (mean of 5.6 µSv), for the anesthesiologist 0-12 µSv (mean of 4.0 µSv), and for the surgeon 0-10 µSv (mean of 3.6 µSv). In a comparison between the results of this study and published literature on occupational exposures from veterinary FDG PET/CT procedures, Cu-ATSM veterinary PET/CT procedures, on a per patient bias, exposed workers to less radiation.

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission.

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a (64)Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of (64)Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from (64)Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair-deficient xrs5 cells were exposed to (64)Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D(10) values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that (64)Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/µm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from (64)Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after (64)Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that (64)Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of (64)Cu-ATSM as a cancer treatment modality for hypoxic tumors.

Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction.

PURPOSE/OBJECTIVES: Erectile dysfunction is common after radiation therapy for prostate cancer; yet, the etiopathology of radiation-induced erectile dysfunction (RI-ED) remains poorly understood. A novel animal model was developed to study RI-ED, wherein stereotactic body radiation therapy (SBRT) was used to irradiate the prostate, neurovascular bundles (NVB), and penile bulb (PB) of dogs. The purpose was to describe vascular and neurogenic injuries after the irradiation of only the NVB or the PB, and after irradiation of all 3 sites (prostate, NVB, and PB) with varying doses of radiation. METHODS AND MATERIALS: Dogs were treated with 50, 40, or 30 Gy to the prostate, NVB, and PB, or 50 Gy to either the NVB or the PB, by 5-fraction SBRT. Electrophysiologic studies of the pudendal nerve and bulbospongiosus muscles and ultrasound studies of pelvic perfusion were performed before and after SBRT. The results of these bioassays were correlated with histopathologic changes. RESULTS: SBRT caused slowing of the systolic rise time, which corresponded to decreased arterial patency. Alterations in the response of the internal pudendal artery to vasoactive drugs were observed, wherein SBRT caused a paradoxical response to papaverine, slowing the systolic rise time after 40 and 50 Gy; these changes appeared to have some dose dependency. The neurofilament content of penile nerves was also decreased at high doses and was more profound when the PB was irradiated than when the NVB was irradiated. These findings are coincident with slowing of motor nerve conduction velocities in the pudendal nerve after SBRT. CONCLUSIONS: This is the first report in which prostatic irradiation was shown to cause morphologic arterial damage that was coincident with altered internal pudendal arterial tone, and in which decreased motor function in the pudendal nerve was attributed to axonal degeneration and loss. Further investigation of the role played by damage to these structures in RI-ED is warranted.

A proposed simple model for estimating occupational radiation dose to staff from veterinary 18F-FDG pet procedures.

Several studies have been conducted concerning the radiation dose to hospital personnel from positron emission tomography (PET) radiopharmaceuticals, but to date only one parallel study has been conducted for veterinary staff. Veterinary patients present challenges not encountered with human patients, as they require anesthesia and therefore more intensive monitoring than human patients. This paper presents a simple model for estimating the effective radiation dose to veterinary staff using occupational dose data from PET studies at Colorado State University's (CSU) James L. Voss Veterinary Teaching Hospital. The model consists of three point sources within a soft tissue cylinder, and sample calculations are provided for estimating dose to nuclear medicine technologists and an anesthesia technologist based on four different sized dogs. The estimated doses are within the range of actual occupational doses published previously. There are different protocols for the sequence of events in veterinary PET, specifically the order of anesthesia induction and radiopharmaceutical injection. When F-FDG injection is performed prior to anesthesia induction, the estimated dose is between 1.5 and 3.6 times higher than the doses received if injection is done after anesthesia induction, although expected doses for both protocols are below occupational dose limits based on a case load of 100 veterinary patients per year. The model is based on the techniques used at CSU, but it can be modified for different hospitals as well as differently sized animals.

Physiologic variants, benign processes, and artifacts from 106 canine and feline FDG-PET/computed tomography scans.

18F-Fluoro-deoxyglucose positron emission computed tomography (FDG-PET/CT) is an emerging diagnostic imaging modality in veterinary medicine; however, little published information is available on physiologic variants, benign processes, and artifacts. The purpose of this retrospective study was to describe the number of occurrences of non-neoplastic disease-related FDG-PET/CT lesions in a group of dogs and cats. Archived FDG-PET/CT scans were retrieved and interpreted based on a consensus opinion of two board-certified veterinary radiologists. Non-neoplastic disease-related lesions were categorized as physiologic variant, benign activity, or equipment/technology related artifact. If the exact cause of hypermetabolic areas could not be determined, lesions were put into an indeterminate category. A total of 106 canine and feline FDG-PET/CT scans were included in the study. In 104 of the 106 scans, a total of 718 occurrences of physiologic variant, areas of incidental benign activity, and artifacts were identified. Twenty-two of 23 feline scans and 82 of 83 canine scans had at least one artifact. Previously unreported areas of increased radiopharmaceutical uptake included foci associated with the canine gall bladder, linear uptake along the canine mandible, and focal uptake in the gastrointestinal tract. Benign activity was often seen and related to healing, inflammation, and indwelling implants. Artifacts were most often related to injection or misregistration. Further experience in recognizing the common veterinary FDG physiologic variation, incidental radiopharmaceutical uptake, and artifacts is important to avoid misinterpretation and false-positive diagnoses.

Accuracy of CT and MRI for contouring the feline optic apparatus for radiation therapy planning.

Consistency and accuracy in normal tissue contouring in radiotherapy planning is important for comparison of dosimetry and toxicity data between studies. The purpose of this study was to determine whether magnetic resonance imaging (MRI) improves the accuracy of optic apparatus contouring as compared with computed tomography (CT) in both normal and acromegalic cats, and to construct a reference contour of the feline optic apparatus. Both CT and MRI were performed on cadavers of four healthy cats, as well as on five radiotherapy patients with feline acromegaly. Contours of the optic apparatus were drawn for each imaging study. The volume, center of mass, and the degree of concordance and mismatch were determined for each, and compared with a reference standard. Precontrast CT was found to overestimate volume as compared with MRI in acromegalic cats; no other statistically significant differences were identified in the volume, concordance index or mismatch index values of normal or acromegalic cats. Contours derived from T2-wieghted MRI were subjectively considered to best match the reference standard. The caudal margin of the optic chiasm and the optic tracts were difficult to confidently contour regardless of which imaging modality and/or sequence was used. In conclusion, findings from the current study supported the use of a combination of CT and MR images and a priori knowledge of the shape of the optic apparatus to guide accurate contouring, especially where image contrast is not sufficient to clearly delineate the margins. Guidelines for feline optic apparatus contouring developed in this study can be used for future studies.

Interobserver agreement and diagnostic accuracy of brain magnetic resonance imaging in dogs.

OBJECTIVE: To evaluate interobserver agreement and diagnostic accuracy of brain MRI in dogs. DESIGN: Evaluation study. ANIMALS: 44 dogs. PROCEDURES: 5 board-certified veterinary radiologists with variable MRI experience interpreted transverse T2-weighted (T2w), T2w fluid-attenuated inversion recovery (FLAIR), and T1-weighted-FLAIR; transverse, sagittal, and dorsal T2w; and T1-weighted-FLAIR postcontrast brain sequences (1.5 T). Several imaging parameters were scored, including the following: lesion (present or absent), lesion characteristics (axial localization, mass effect, edema, hemorrhage, and cavitation), contrast enhancement characteristics, and most likely diagnosis (normal, neoplastic, inflammatory, vascular, metabolic or toxic, or other). Magnetic resonance imaging diagnoses were determined initially without patient information and then repeated, providing history and signalment. For all cases and readers, MRI diagnoses were compared with final diagnoses established with results from histologic examination (when available) or with other pertinent clinical data (CSF analysis, clinical response to treatment, or MRI follow-up). Magnetic resonance scores were compared between examiners with κ statistics. RESULTS: Reading agreement was substantial to almost perfect (0.64 < κ < 0.86) when identifying a brain lesion on MRI; fair to moderate (0.14 < κ < 0.60) when interpreting hemorrhage, edema, and pattern of contrast enhancement; fair to substantial (0.22 < κ < 0.74) for dural tail sign and categorization of margins of enhancement; and moderate to substantial (0.40 < κ < 0.78) for axial localization, presence of mass effect, cavitation, intensity, and distribution of enhancement. Interobserver agreement was moderate to substantial for categories of diagnosis (0.56 < κ < 0.69), and agreement with the final diagnosis was substantial regardless of whether patient information was (0.65 < κ < 0.76) or was not (0.65 < κ < 0.68) provided. CONCLUSIONS AND CLINICAL RELEVANCE: The present study found that whereas some MRI features such as edema and hemorrhage were interpreted less consistently, radiologists were reasonably constant and accurate when providing diagnoses.

Comparison between 2-(18) F-fluoro-2-deoxy-d-glucose positron emission tomography and contrast-enhanced computed tomography for measuring gross tumor volume in cats with oral squamous cell carcinoma.

Feline oral squamous cell carcinoma is one of the most refractory feline malignancies. Most patients succumb due to failure in local tumor control. 2-(18) F-fluoro-2-deoxy-D-glucose positron emission tomography ((18) F-FDG PET) is increasingly being used for veterinary oncology staging as it highlights areas with higher glucose metabolism. The goal of the current prospective study was to compare gross tumor volume measurements using (18) F-FDG PET vs. those using computed tomography (CT) for stereotactic radiation therapy planning in cats with oral squamous cell carcinoma. Twelve cats with confirmed oral squamous cell carcinoma underwent pretreatment (18) F-FDG PET/CT. Gross tumor volumes based on contrast-enhanced CT and (18) F-FDG PET were measured and compared among cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary squamous cell carcinoma group (n = 8, P = 0.002) and for the total number of patients (n = 12, P = 0.006), but not in the lingual/laryngeal group (n = 4, P = 0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high-(18) F-FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group (P = 0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that (18) F-FDG PET warrants further investigation as a supplemental imaging modality in cats with oral squamous cell carcinoma because it detected regions of possible primary tumor that were not detected on CT images.

Magnetic resonance (MR) imaging and MR cholangiopancreatography findings in cats with cholangitis and pancreatitis.

Cholangiohepatitis/cholangitis is second only to hepatic lipidosis as the most common liver disease in cats and is often associated with concurrent pancreatitis. Magnetic resonance imaging (MRI) and MR cholangiopancreatography (MRCP) have developed into an accurate, highly sensitive and specific imaging tool for the diagnosis of biliary and pancreatic duct disorders in humans. In this prospective case series, 10 cats with suspected cholangitis and/or pancreatitis were enrolled based on clinical history, physical examination and appropriate diagnostic test results. MRI and MRCP sequences with secretin stimulation of the cranial abdomen were performed, and sonography and laparoscopic biopsies for histologic diagnosis were obtained for comparison. MRI detected pancreatic abnormalities in cats suspected of pancreatitis, including T1 pre-contrast hypointense and T2 hyperintense pancreatic parenchyma and a dilated pancreatic duct. The MRI findings of the liver were non-specific. Nine of 10 cats had biliary abnormalities, including gall bladder wall thickening, gall bladder wall moderate contrast enhancement and/or gall bladder debris. Eight of 10 cats had histologic evidence of pancreatitis, as well as hepatitis or cholangitis, with one cat diagnosed with hepatic lymphoma. The advantages of MRI/MRCP over sonography of these cats included the striking pancreatic signal changes associated with pancreatitis and the ability to comprehensibly assess and measure the pancreas and hepatobiliary structures without operator dependence or interference from bowel gas. MRI/MRCP imaging of the feline abdomen may be beneficial in cases with equivocal ultrasound imaging findings.

Susceptibility of domestic cats to chronic wasting disease.

Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated intracerebrally (i.c.) or orally (p.o.) with CWD-infected deer brain. At 40 and 42 months postinoculation, two i.c.-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and the cats progressed to terminal disease within 5 months. Brains from these two cats were pooled and inoculated into cohorts of cats by the i.c., p.o., and intraperitoneal and subcutaneous (i.p./s.c.) routes. Upon subpassage, feline CWD was transmitted to all i.c.-inoculated cats with a decreased incubation period of 23 to 27 months. Feline-adapted CWD (Fel(CWD)) was demonstrated in the brains of all of the affected cats by Western blotting and immunohistochemical analysis. Magnetic resonance imaging revealed abnormalities in clinically ill cats, which included multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyperintensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 i.p./s.c.- and 2 of 4 p.o. secondary passage-inoculated cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to-feline transmission in nature.

Assessment of blood pool, soft tissue, and skeletal uptake of sodium fluoride F 18 with positron emission tomography-computed tomography in four clinically normal dogs.

OBJECTIVE: To determine the ideal interval to image acquisition after IV injection of sodium fluoride F 18 ((18)F-NaF) and evaluate biodistribution of the radiopharmaceutical in clinically normal skeletally immature dogs. ANIMALS: 4 female dogs. PROCEDURES: Each dog was anesthetized for evaluation with a commercial hybrid positron emission tomography (PET)-CT instrument. A low-radiation dose, whole-body CT scan was acquired first. An IV injection of (18)F-NaF (0.14 mCi/kg) was administered, and a dynamic PET scan centered over the heart and liver was acquired during a period of 120 minutes. Uptake of (18)F-NaF in the blood pool, soft tissues, and skeletal structures was evaluated via region of interest analysis to derive standardized uptake values and time-activity curves, which were used to determine the optimal postinjection time for skeletal image acquisition. Biodistribution was also assessed from a final whole-body PET-CT scan acquired after the dynamic scan. RESULTS: Time-activity curves revealed a rapid decrease in the amount of radiopharmaceutical in the blood pool and soft tissues and a rapid increase in the amount of radiopharmaceutical in bones soon after injection. At 50 minutes after injection, the greatest difference in uptake between soft tissues and bones was detected, with continued subtle increase in uptake in the bones. Uptake of (18)F-NaF was slightly increased at growth plates and open ossification centers, compared with that at other parts of the bone. CONCLUSIONS AND CLINICAL RELEVANCE: At 50 minutes after IV injection of (18)F-NaF at the dose evaluated, PET-CT yielded excellent bone-to-background ratio images for evaluation of the skeletal system in dogs.

Occupational per-patient radiation dose from a conservative protocol for veterinary (18) F-fluorodeoxyglucose positron emission tomography.

The occupational external radiation dose to human medical personnel from positron emission tomography (PET) radiopharmaceuticals has been documented, but to date no corresponding veterinary staff dose data are available. Electronic personal dosimeters (EPDs) were used in this study to measure the per-patient external radiation doses to veterinary staff using a PET/CT (PET combined with computed tomography) protocol in which the patient radiopharmaceutical dose was injected after anesthetic induction. Radiation doses were recorded for the nuclear medicine technologists, the on-duty anesthesiology technologist, and an occasional observer from 19 veterinary (18) F-fluorodeoxyglucose PET/CT studies. Patient mass range was 2.8 to 61.0 kg (22.3 kg mean) and injected activity averaged 6 MBq kg(-1) . The dose range received by nuclear medicine technologists per procedure was 0-30 µSv (9.1 µSv mean), by anesthetists 1-22 µSv (8.2 µSv mean), and by the observer 0-2 µSv (0.5 µSv mean). In both feline and canine studies, placement of the EPD on staff was a significant predictor of radiation dose. Additional significant predictors of staff radiation dose from canine studies included job position and injected activity. The per-patient occupational radiation doses to veterinary PET/CT technologists were slightly greater than those reported for human nuclear medicine PET/CT technologists, but were comparable to estimated radiation doses for nurses caring for nonambulatory human PET/CT patients. Efforts toward maintaining staff radiation doses as low as reasonably achievable (ALARA) will be important as veterinary PET/CT caseload increases.

Indirect magnetic resonance lymphography of the head and neck of dogs using Gadofluorine M and a conventional gadolinium contrast agent: a pilot study.

The purpose of this pilot study was to evaluate lymph node enhancement with an indirect magnetic resonance (MR) lymphography technique using 2 different contrast agents in the head and neck region of healthy dogs. Five dogs were imaged at various times after intradermal injection of gadoversetamide and Gadofluorine M (minimum of 1 week apart) in the right and left mandibular, temporal, and lateral neck regions. We observed consistent progressive enhancement with time in the mandibular, retropharyngeal, and superficial cervical lymph nodes. The node enhancement was comparable for both contrast agents. Contrast enhancement of the parotid lymph nodes was not seen. We conclude that this technique of indirect MR lymphography using either agent could be used to identify those lymph nodes at highest risk of metastatic disease in dogs with cancer, and to guide staging and treatment.

Lymphographie par résonance magnétique indirecte de la tête et du cou des chiens en utilisant Gadofluorine M et un agent de contraste conventionnel au gadolinium : étude pilote. Le but de cette étude pilote était d'évaluer le contraste des ganglions lymphatiques à l'aide d'une technique de lymphographie par résonance magnétique (RM) indirecte en utilisant 2 agents de contraste différents dans la région de la tête et du cou des chiens en santé. L'imagerie de 5 chiens a été réalisée à divers moments après l'injection intradermique de gadoversétamide et de Gadofluorine M (avec un intervalle minimum de 1 semaine) dans les régions mandibulaires droite et gauche, temporale et du cou. Nous avons observé une augmentation progressive constante dans le temps dans les ganglions mandibulaires, rétropharyngiens et cervicaux superficiels. Le contraste des ganglions était comparable pour les deux agents. L'augmentation de contraste des ganglions lymphatiques parotidiens n'a pas été vue. Nous concluons que cette technique de lymphographie par RM indirecte, en utilisant l'un ou l'autre des agents, pourrait être utilisée pour identifier les ganglions lymphatiques les plus à risque de maladie métastasique chez les chiens atteints de cancer et pour guider la détermination des stades et le traitement.(Traduit par Isabelle Vallières).

Early detection of neuropathophysiology using diffusion-weighted magnetic resonance imaging in asymptomatic cats with feline immunodeficiency viral infection.

HIV infection results in a highly prevalent syndrome of cognitive and motor disorders designated as HIV-associated dementia (HAD). Neurologic dysfunction resembling HAD has been documented in cats infected with strain PPR of the feline immunodeficiency virus (FIV), whereas another highly pathogenic strain (C36) has not been known to cause neurologic signs. Animals experimentally infected with equivalent doses of FIV-C36 or FIV-PPR, and uninfected controls were evaluated by magnetic resonance diffusion-weighted imaging (DW-MRI) and spectroscopy (MRS) at 17.5-18 weeks post-infection, as part of a study of viral clade pathogenesis in FIV-infected cats. The goals of the MR imaging portion of the project were to determine whether this methodology was capable of detecting early neuropathophysiology in the absence of outward manifestation of neurological signs and to compare the MR imaging results for the two viral strains expected to have differing degrees of neurologic effects. We hypothesized that there would be increased diffusion, evidenced by the apparent diffusion coefficient as measured by DW-MRI, and altered metabolite ratios measured by MRS, in the brains of FIV-PPR-infected cats relative to C36-infected cats and uninfected controls. Increased apparent diffusion coefficients were seen in the white matter, gray matter, and basal ganglia of both the PPR and C36-infected (asymptomatic) cats. Thalamic MRS metabolite ratios did not differ between groups. The equivalently increased diffusion by DW-MRI suggests similar indirect neurotoxicity mechanisms for the two viral genotypes. DW-MRI is a sensitive tool to detect neuropathophysiological changes in vivo that could be useful during longitudinal studies of FIV.

Imaging diagnosis--magnetic resonance imaging findings of primary cerebral hemangioma.

Intracranial hemangioma is a rare intraaxial hemorrhagic neoplasm with imaging characteristics similar to other intracranial hemorrhagic lesions. We describe two canine cerebral hemangiomas that appeared as poorly circumscribed intraaxial compressive lesions that were predominantly hypointense on T2 sequences and heterogeneously contrast enhancing. Both lesions had perilesional edema and were hypointense on T2(*) -gradient recalled echo sequences, consistent with hemorrhage. In one tumor a short partial peripheral rim was present, which was suggestive of hemosiderin deposition. Cerebral hemangioma should be included as a differential for hemorrhagic intracranial lesions.

Hepatic and pancreaticobiliary MRI and mr cholangiopancreatography with and without secretin stimulation in normal cats.

Magnetic resonance (MR) cholangiopancreatography is useful in humans to diagnose biliary and pancreatic diseases. Some of these protocols incorporate the use of secretin, which stimulates the exocrine pancreas to release bicarbonate with secondary dilation of the pancreatic duct. We compared the utility and quality of multiple hepatic-pancreaticobiliary MR imaging sequences before and after secretin stimulation of the pancreatic duct in five healthy cats. Multiple MR sequences were evaluated, including fast Spoiled Gradient Recalled in- and out-of-phase, Single Shot Fast Spin Echo (SSFSE), T2 Fast Spin Echo, MR cholangiopancreatography (pre- and postsecretin administration), and Fast Acquisition with Multiphase Efgre (FAME) (postsecretin and before and after gadolinium administration). The MR cholangiopancreatography protocol with secretin stimulation was feasible and yielded high-contrast maps of the biliary ductal anatomy but the pancreactic duct was seen inconsistently. The FAME series most consistently provided visualization of biliary and postsecretin pancreatic ductal anatomy, combined with very good depiction of the liver and pancreas. The remaining sequences each had satisfactory utility and diagnostic quality, with the exception of the SSFSE sequences. Secretin improved the conspicuity of the pancreatic duct.

Evaluation of standard chemotherapy in the guinea pig model of tuberculosis.

The purpose of this study was 2-fold. First, we evaluated standard chemotherapy in the guinea pig model of tuberculosis to determine if this animal species could productively be used for this purpose. Second, given the similarities of the pathology of disease in guinea pigs and humans, we wished to evaluate additional parameters, including magnetic resonance imaging, microscopy, and cytokine expression and lymphocyte phenotypes, in response to an infection treated with drug therapy. This study shows that conventional rifampin-isoniazid-pyrazinamide chemotherapy significantly decreased the numbers of the highly virulent Erdman K01 strain of Mycobacterium tuberculosis, with most of the bacilli being eliminated in a month. Despite this result, bacteria could still be detected in the lungs and other tissues for at least another 3 to 4 months. Resolution of the nonnecrotic granulomas in the lungs and lymph nodes could be clearly visualized by magnetic resonance imaging at the macroscopic level. Microscopically, the majority of the pulmonary and extrapulmonary inflammation resolved spontaneously, leaving residual lesions composed of dystrophic calcification and fibrosis marking the site of necrosis of the primary lesion. Residual calcified lesions, which were also associated with pulmonary lymphangitis, contained acid-fast bacilli even following aggressive chemotherapy. The presence of intact extracellular bacilli within these lesions suggests that these could serve as the primary sites of disease reactivation. The chemotherapy reduced the level of T-cell influx into infected tissues and was accompanied by a large and sustained increase in TH1 cytokine expression. Chemotherapy also prevented the emergence in lung tissues of high levels of interleukin-10 and Foxp3-positive cells, known markers of regulatory T cells.

Preclinical investigation of PEGylated tumor necrosis factor alpha in dogs with spontaneous tumors: phase I evaluation.

PURPOSE: Tumor necrosis factor-alpha (TNF) is a cytokine with potent antitumor activity; however, toxicity and short half-life have limited its utility. Polyethylene glycol (PEG) conjugation of biotherapeutics can decrease immunogenicity while improving bioactivity and half-life. PEGylation of TNF (PEG-TNF) significantly improved half-life and toxicity in mice, resulting in enhanced antitumor activity. This study characterized toxicity, biological effect, and antitumor activity of PEG-TNF in pet dogs with spontaneous cancer. EXPERIMENTAL DESIGN: A phase I clinical trial enrolled dogs with measurable tumors in which standard therapy had failed or been declined. Physiologic, hematologic, and biochemical parameters were evaluated and tumor biopsies obtained serially. A subset of patients underwent serial dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Fifteen dogs were enrolled at doses from 20.0 to 30.0 microg/kg. Dose-limiting toxicity at 30.0 microg/kg consisted of vascular leak in one and hypotension/coagulopathy in one, establishing 26.7 microg/kg as the maximum tolerated dose. Mean elimination half-life was 15.3 +/- 4.9 hours. Biological activity (transient fever and leukopenia, increased tumor inflammation, and necrosis) was observed at all dosages. A significant increase in tumor blood flow was observed with dynamic contrast-enhanced magnetic resonance imaging. Minor/transient antitumor responses were observed in dogs with melanoma, squamous cell carcinoma, and mammary carcinoma, and a partial response was observed in a dog with angiosarcoma. CONCLUSIONS: Using a clinically relevant, spontaneous large animal model of neoplasia, we have shown that biologically effective doses of PEG-TNF can be administered safely, and that PEG-TNF administration is associated with encouraging biological activity. These results justify the clinical evaluation of PEG-TNF in human cancer.

Reduction in postlaminectomy epidural adhesions in sheep using a fibrin sealant-based medicated adhesion barrier.

Epidural adhesion formation is believed to be a central governing factor in the prevalence of pain after spinal surgery and is regarded as being the primary instigator of neural tethering, leading to complications during revision surgery. In this study, we assess the effectiveness and safety of fibrin sealant supplemented with tributyrin, termed Medicated Adhesion Barrier (MAB), as an alternative means of reducing the incidence of posterior spinal epidural adhesion formation. Laminectomy defects in sheep were treated with MAB, fibrin sealant alone, ADCONGel, or remained untreated. At 12 weeks postoperatively, the extent of fibrosis and epidural adhesion formation was evaluated using magnetic resonance imaging (MRI), peel-off testing, and histological examination. Initial invitro analysis revealed that tributyrin was retained in fibrin gel in a time-dependent manner and was an effective inhibitor of fibroblast proliferation. Treatment of sheep with MAB significantly reduced both the prevalence (p < 0.05) and tenacity (p < 0.05) of epidural adhesions. The effectiveness of MAB in preventing epidural adhesions was found to be comparable with that of ADCONGel. No adverse events were reported after the use of MAB. The MAB preparation seems to be an effective resorbable barrier for the prevention of epidural adhesions.