Simultaneous measurements of myocardial glucose metabolism and extracellular volumes with hybrid PET/MRI using concurrent injections of Gd-DTPA and [18F]FDG.

BACKGROUND: The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impact of glucose suppression using heparin on ECV. METHODS: Five healthy canine subjects were imaged to compare three different protocols for injecting Gd-DTPA and FDG: bolus alone, CI alone, bolus followed by CI. Suppression of myocardial glucose uptake was induced using a continuous infusion of 20% lipid at a rate of 0.25 mL·min-1·kg-1 as well as 2000 units of intravenous heparin injected 20 minutes prior to FDG/Gd-DTPA injection. RESULTS: There was no significant effect on ECV measurement when heparin was used for glucose suppression at equilibrium irrespective of infusion protocol). Measurements of ECV in myocardium, regardless of infusion protocol showed no significant difference at all time points (P = 0.21) prior to washout. CONCLUSIONS: The suppression of myocardial uptake of [18F]FDG with heparin did not alter the determination of myocardial ECV though a larger sample size may show differences. Further, the infusion protocol (bolus or constant infusion) had no effect on the calculated ECV.

Tracking the progress of inflammation with PET/MRI in a canine model of myocardial infarction.

BACKGROUND: Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined constant infusion of 18F-FDG and Gd-DTPA to quantitate inflammation and extracellular volume (ECV) from 3 to 40 days after myocardial infarction. METHODS: Eight canine subjects were imaged at multiple time points following induction of an MI with a 60-minute concurrent constant infusion of Gd-DTPA and 18F-FDG using a hybrid PET/MRI scanner. RESULTS: There was a significant increase in ECV in remote myocardium on day 14 post-MI (P = .034) and day 21 (P = .021) compared to the baseline. ECV was significantly elevated in the infarcted myocardium compared to remote myocardium at all time points post-MI (days 3, 7, 14, 21, and 40) (P < .001) while glucose uptake was also increased within the infarct on days 3, 7, 14, and 21 but not 40. CONCLUSIONS: The significant increase in ECV in remote tissue may be due to an ongoing inflammatory process in the early weeks post-infarct.

Coccidioidomycosis in llamas and alpacas diagnosed at the University of California, Davis (1990-2016).

Given the predisposition of South American camelids to coccidioidomycosis, we sought to describe the disease presentation in alpacas and llamas and identify potential risk factors for these species. The records of 224 llamas and alpacas that were tested for Coccidioides infection using immunodiffusion serology at the Coccidioidomycosis Serology Laboratory of the University of California, Davis, between 1990 and 2016 were examined; of those, 46 alpacas and 42 llamas had positive test results. The remaining 99 alpacas and 37 llamas were used as control groups. We found that male llamas were at increased risk for Coccidioides infection when compared with female llamas and when compared with male alpacas. South American camelids living within California were at higher risk for infection than camelids living in other states. Alpacas were more likely than llamas to have subclinical infections. We documented five cases of abortion or neonatal mortality attributable to coccidioidomycosis in alpacas. Our study demonstrates that South American camelids are susceptible to Coccidioides infection in areas where the disease is endemic, lending support to the importance of vigilance for this disease in alpacas and llamas and suggesting a possible role for these animals as sentinel species. LAY SUMMARY: We examined cases of Valley Fever and described the disease and risk factors for llamas and alpacas. Male llamas were at increased risk for infection as were animals living within California. Five alpacas had miscarriages or neonatal deaths as a result of Valley Fever infections.

Impact of human platelet lysate on the expansion and chondrogenic capacity of cultured human chondrocytes for cartilage cell therapy.

High hopes have been pinned on regenerative medicine strategies in order to prevent the progression of cartilage damage to osteoarthritis, particularly by autologous chondrocyte implantation (ACI). The loss of chondrocyte phenotype during in vitro monolayer expansion, a necessary step to obtain sufficient cell numbers, may be a key limitation in ACI. In this study, it was determined whether a shorter monolayer expansion approach could improve chondrogenic differentiation. The effects of two supplement types, foetal bovine serum (FBS) and Stemulate™ (a commercial source of human platelet lysate), on the expansion and re-differentiation potential of human chondrocytes, isolated from five individuals, were compared. Chondrocytes were expanded with 10 % FBS or 10 % Stemulate™. Pellets were cultured for 28 d in chondrogenic differentiation medium and assessed for the presence of cartilage matrix molecules and genes associated with chondrogenicity. Stemulate™ significantly enhanced the proliferation rate [average population doubling times: FBS, 25.07 ± 6.98 d (standard error of the mean, SEM) vs. Stemulate™, 13.10 ± 2.57 d (SEM)]. Sulphated glycosaminoglycans (sGAG), total collagen and qRT-PCR analyses of cartilage genes showed that FBS-expanded chondrocytes demonstrated significantly better chondrogenic capacity than Stemulate™-expanded chondrocytes. Histologically, FBS-expanded chondrocyte pellets appeared to be more stable, with a more intense staining for toluidine blue, indicating a greater chondrogenic capacity. Although Stemulate™ positively influenced chondrocyte proliferation, it had a negative effect on chondrogenic differentiation potential. This suggested that, in the treatment of cartilage defects, Stemulate™ might not be the ideal supplement for expanding chondrocytes (which maintained a chondrocyte phenotype) and, hence, for cell therapies (including ACI).

Federated Learning Survival Model and Potential Radiotherapy Decision Support Impact Assessment for Non-small Cell Lung Cancer Using Real-World Data.

AIMS: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy. METHODS: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups. RESULTS: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01). CONCLUSION: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care.

Ibuprofen blood plasma levels and onset of analgesia.

BACKGROUND: Ibuprofen is widely available as an over-the-counter treatment for pain and fever. New formulations are now available, with varying pharmacokinetic profiles. However, few studies have been specifically designed to examine the relationship between ibuprofen plasma levels and onset of analgesia. This study aimed to determine a value, or range of values, for the blood plasma level of ibuprofen at which onset of analgesia could be expected. METHODS: Placebo-controlled clinical trials, investigating the efficacy and pharmacokinetics of ibuprofen 200 mg and 400 mg, were identified. A retrospective posthoc analysis was performed on data from trials that incorporated time to perceived pain relief as an endpoint and the incidence of confirmed/unconfirmed perceptible pain relief was assessed. Mean ibuprofen blood plasma levels were computed at various time points using data from pharmacokinetic trials. RESULTS: Two trials were identified with sufficient data to analyse time to onset of analgesia (Current Controlled Trials ISRCTN73768226, ISRCTN86009231). For 400 mg ibuprofen, the incidence of confirmed perceptible pain relief was significantly greater vs. placebo at 20 min post dosing (both studies). For 200 mg ibuprofen, significance was reached at 20 min (one study). In the 17 trials, with data on plasma concentrations for patients receiving 400 mg ibuprofen, the weighted mean value at 20 min post dosing was 8.4 µg/ml (95% confidence interval, 6.8-10.1). CONCLUSIONS: RESULTS of this study provide useful information for the development of new ibuprofen formulations. Further prospective studies and studies using other endpoints to define efficacy and onset would be of interest.

Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia.

BACKGROUND: Vascular malformations in hereditary hemorrhagic telangiectasia (HHT) lead to chronic recurrent bleeding, hemorrhage, stroke, heart failure, and liver disease. There is great interest in identifying novel therapies for epistaxis in HHT given its associated morbidity and impact on quality of life. We aimed to measure the effectiveness of oral doxycycline for the treatment of epistaxis and explore mechanisms of action on angiogenic, inflammatory and pathway markers in HHT using a randomized controlled trial. METHODS: 13 HHT patients with epistaxis were recruited from the Toronto HHT Center at St. Michael's Hospital. Recruitment was stopped early due to COVID-19-related limitations. The study duration was 24 months. Patients were randomly assigned to the treatment-first or placebo-first study arm. We compared the change in weekly epistaxis duration and frequency, biomarkers, blood measurements, and intravenous iron infusion and blood transfusion requirements between treatment and placebo. RESULTS: There was no significant difference in the change in weekly epistaxis duration (p = 0.136) or frequency (p = 0.261) between treatment and placebo. There was no significant difference in the levels of MMP-9, VEGF, ANG-2, IL-6 or ENG with treatment. Hemoglobin levels were significantly higher (p = 0.0499) during treatment. Ferritin levels were not significantly different between treatment and placebo. There was no significant difference in RBC transfusions between treatment periods (p = 0.299). CONCLUSION: Overall, our study did not demonstrate effectiveness of doxycycline as a treatment for epistaxis in patients with HHT, though the study was underpowered. Secondary analyses provided new observations which may help guide future trials in HHT. Trial Registration ClinicalTrials.gov, NCT03397004. Registered 11 January 2018 - Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03397004.

A comparison of in-house and shared RapidPlan models for prostate radiation therapy planning.

Knowledge-based planning (KBP) can increase plan quality, consistency and efficiency. In this study, we assess the success of a using a publicly available KBP model compared with developing an in-house model for prostate cancer radiotherapy using a single, commercially available treatment planning system based on the ability of the model to achieve the centre's planning goals. Two radiation oncology centres each created a prostate cancer KBP model using the Eclipse RapidPlan software. These two models and a third publicly-available, shared model were tested at three centres in a retrospective planning study. The publicly-available model achieved lower rectum doses than the other two models. However, the planning-target-volume (PTV) doses did not meet the local planning goals and the model could not be adjusted to correct this. As a result, the plans most likely to satisfy local planning goals and requirements were created using an in-house model. For centres without an existing in-house model, a model created by another centre with similar planning goals was found to be preferred. Variations in local planning practices including contouring, treatment technique and planning goals can influence the relative performance of KBP. The value of publicly available KBP models could be enhanced through standardisation of planning goals and contouring guidelines, providing information related to the planning goals used to create the model and increased flexibility to allow local adaptation of the KBP model.

Meeting report of the International Consortium of Stem Cell Networks' Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis/Motor Neuron Disease.

The International Consortium of Stem Cell Networks' (ICSCN) Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND) was held on 24-25 January 2011. Twenty scientific talks addressed aspects of cell derivation and characterization; preclinical research and phased clinical trials involving stem cells; latest developments in induced pluripotent (iPS) cell technology; industry involvement and investment. Three moderated panel discussions focused on unregulated ALS/MND treatments, and the state of the art and barriers to future progress in using stem cells for ALS/MND. This review highlights the major insights that emanated from the workshop around the lessons learned and barriers to progress for using stem cells for understanding disease mechanism, drug discovery, and as therapy for ALS/MND. The full meeting report is only available in the online version of the journal. Please find this material with the following direct link to the article: http://www.informahealthcare.com/als/doi/10.3109/17482968.2011.590992 .

A potential pathway for managing diabetic patients with arterial emboli detected by retinal screening.

OBJECTIVE: The aim was to review a pathway of care for diabetic patients found to have retinal artery emboli detected by retinal screening. DESIGN: This was a retrospective review of a pathway agreed in 2001 by a multidisciplinary team. MATERIALS AND METHODS: The prospectively collected Gloucestershire Diabetic Retinal Screening Programme database was reviewed; patients sent for carotid duplex imaging underwent review of their scan results and their casenotes. RESULTS: The prevalence of retinal emboli was 214 out of 25,299 diabetic patients who had retinal screening (0.85%). Some 200 diabetic patients underwent carotid duplex imaging; 23 had ipsilateral and 2 had contralateral carotid stenosis > 70%. Of these, ten patients underwent carotid endarterectomy without any major morbidity. CONCLUSIONS: [corrected] A pathway was established for the small number of patients with retinal emboli, and could be tested in other populations.

Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California.

BACKGROUND: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). OBJECTIVES: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. ANIMALS: Twenty-six cats and 21 dogs with CNS cryptococcosis. METHODS: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. RESULTS: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long-term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.

Salmon poisoning disease in dogs: 29 cases.

BACKGROUND: Salmon poisoning disease (SPD) is a trematode-borne disease of dogs caused by Neorickettsia helminthoeca. OBJECTIVES: To determine risk factors and spatial epidemiology of SPD in dogs from northern California; to describe the clinicopathologic, microbiologic, and imaging findings of SPD in these dogs; and to evaluate treatments and outcomes for SPD. ANIMALS: Twenty-nine dogs with SPD based on the finding of trematode ova in the feces, or organisms consistent with N. helminthoeca in specimens submitted for microscopic examination. METHODS: Information regarding signalment, fish exposure, clinical signs, diagnostic evaluation, treatments, and outcomes was obtained for each dog. Archived lymph node aspirates and histopathology specimens were subjected to polymerase chain reaction (PCR) testing for Neorickettsia spp. RESULTS: Labrador Retrievers and intact male dogs were overrepresented. Exposure locations were often distant from the dogs' residence. Some dogs had neurologic signs, including twitching and seizures. Dogs lacking peripheral lymphadenomegaly had abdominal lymphadenomegaly on ultrasound examination. A combination of centrifugation fecal flotation and sedimentation had greatest sensitivity for finding fluke ova. N. helminthoeca DNA was amplified by PCR from 4/10 dogs. Penicillins, cephalosporins, and chloramphenicol did not appear to be effective treatments. Mortality rate was 4/29 (14%). CONCLUSIONS AND CLINICAL IMPORTANCE: SPD should be suspected in dogs with inappetence, gastrointestinal, or neurologic signs, with or without fever or peripheral lymphadenomegaly in the appropriate geographical setting. Diagnosis is facilitated by a combination of fecal sedimentation and centrifugal flotation, abdominal ultrasonography, and PCR-based assays on lymphoid tissue. The treatment of choice is tetracycline antimicrobials.

A Randomized, controlled, crossover trial to investigate times to onset of the perception of soothing and cooling by over-the-counter heartburn treatments.

This was a randomized, controlled, four-way crossover study in 45 subjects with a tendency to suffer from moderate heartburn following some meals. The study was designed to assess the time to onset of the perceived soothing and cooling effects of the alginate raft-forming products, Gaviscon Liquid (peppermint), Gaviscon Double Action Liquid (peppermint) and Gaviscon Powder Formulation (fresh tropical), compared with a non-active sublingual control. All three Gaviscon products provided significantly faster soothing and cooling effects compared with the control. Based on the upper 95% confidence limits for the median, time to onset of soothing was perceived within 3.15 min, 3.08 min and 4.05 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. Similarly, time to onset of cooling was perceived within 1.95 min, 1.23 min and 11.22 min for Gaviscon Liquid, Double Action Liquid and Powder Formulation, respectively. The results show that Gaviscon Liquid and Gaviscon Double Action soothe within 3.15 min and cool within 1.95 min.

Effect of an oral probiotic nutraceutical containing Aspergillus-derived ingredients on a serum and urine galactomannan antigen assay in dogs.

A commercial Aspergillus galactomannan antigen (GMA) enzyme linked immunosorbent assay (ELISA) is used to support a diagnosis of systemic aspergillosis in dogs. In human patients, false positive results have been associated with administration of medications derived from molds. We sought to determine the effect of administration of a commercially available oral probiotic nutraceutical that contained Aspergillus-derived ingredients on serum and urine Aspergillus GMA levels in dogs by conducting a prospective, cross-over study. Galactomannan index (GMI) was measured on the solubilized probiotic nutraceutical and was positive (GMI ≥ 0.5) with a mean of 7.91. Serum and urine galactomannan indices were measured in 10 healthy dogs before (day 0) and after 1 week (day 7) of probiotic nutraceutical administration, then again 2 weeks after the probiotic nutraceutical was discontinued (day 21). Median (range) serum GMI were 0.19 (0.08-0.62), 0.22 (0.07-1.15) and 0.17 (0.14-0.63) at day 0, 7 and 21, respectively. Two of 10 dogs developed positive GMI (≥0.5) results after probiotic nutraceutical administration; however, no significant changes were noted over the study period. Median (range) urine GMI results were 0.06 (0.04-0.22), 0.07 (0.05-0.41) and 0.06 (0.03-0.16) at day 0, 7 and 21, respectively. A trend towards an increase urine GMI was noted between day 0 and 7 (P = 0.18), and decrease was noted between day 7 and 21 (P = 0.09). Administration of probiotics containing Aspergillus-derived ingredients to dogs did not reliably result in elevated Aspergillus GMA levels.

Canine granulocytic anaplasmosis: a review.

Anaplasma phagocytophilum is an emerging pathogen of humans, horses, and dogs worldwide that is transmitted by Ixodid ticks and maintained in a variety of small wild mammal species. Recent studies suggest that multiple strains of A. phagocytophilum may be circulating in wild and domestic animal populations, and these strains may have differential host tropisms and pathogenicity. The organism infects and survives within neutrophils by disabling key neutrophil functions, including neutrophil motility, phagocytosis, the oxidative burst mechanism, and neutrophil-endothelial cell interactions, as well as interfering with neutrophil apoptosis. Coinfections with other tick-borne pathogens may occur, especially Borrelia burgdorferi. A. phagocytophilum causes an acute febrile illness in dogs with lethargy and inappetence. Less frequent signs include lameness, coughing, polydipsia, intermittent vomiting, and hemorrhages. Diagnosis is based on finding morulae within granulocytes in the peripheral blood, the combination of acute and convalescent serology using immunofluorescent antibody techniques, and detection of the DNA of A. phagocytophilum using specific polymerase chain reaction assays. Whether persistent infection or reinfection with A. phagocytophilum occurs after natural infection requires additional study, with most reports suggesting that anaplasmosis is a self-limiting disease in dogs that responds well to a 2-week course of doxycycline therapy.

Effect of repeated arthrocentesis on cytologic analysis of synovial fluid in dogs.

BACKGROUND: Serial arthrocentesis and synovial fluid examination can be used to monitor treatment efficacy in immune-mediated polyarthritis (IMPA), but whether this procedure induces inflammation that interferes with test result interpretation is unknown. OBJECTIVES: The aim of this study was to determine the effect of repeated arthrocentesis on synovial fluid cytology in healthy dogs. ANIMALS: Nine healthy client-owned dogs. METHODS: Prospective study. Arthrocentesis was performed under sedation on 4 joints (both carpi, 1 tarsus, 1 stifle) on each dog every 3 weeks, a total of 4 times. Automated cell counts were done on stifle fluid, smears were made, and differential cell counts done on smears from all joints. Slides were evaluated microscopically for erythrocyte numbers, total nucleated cell count, differential cell count, and cell morphology. Data were analyzed by 2-way analysis of variance. RESULTS: A total of 144 synovial fluid samples were examined. Repeated arthrocentesis was not associated with increases in synovial fluid neutrophil numbers. Mild mononuclear inflammation was detected in 13 samples from 6 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serial arthrocentesis at 3-week intervals can rarely be associated with mild mononuclear joint inflammation, but does not appear to induce neutrophilic inflammation, at least in healthy dogs, and can be useful to monitor treatment response in canine IMPA.

Evaluation of dual energy CT and iterative metal artefact reduction (iMAR) for artefact reduction in radiation therapy.

Metal artefacts pose a common problem in single energy computed tomography (SECT) images used for radiotherapy. Virtual monoenergetic (VME) images constructed with dual energy computed tomography (DECT) scans can be used to reduce beam hardening artefacts. Dual energy metal artefact reduction is compared and combined with iterative metal artefact reduction (iMAR) to determine optimal imaging strategies for patients with metal prostheses. SECT and DECT scans were performed on a Siemens Somatom AS-64 Slice CT scanner. Images were acquired of a modified CIRS pelvis phantom with 6, 12, 20 mm diameter stainless steel rods and VME images reconstructed at 100, 120, 140 and 190 keV. These were post-reconstructed with and without the iMAR algorithm. Artefact reduction was measured using: (1) the change in Hounsfield Unit (HU) with and without metal artefact reduction (MAR) for 4 regions of interest; (2) the total number of artefact pixels, defined as pixels with a difference (between images with metal rod and without) exceeding a threshold; (3) the difference in the mean pixel intensity of the artefact pixels. DECT, SECT + iMAR and DECT + iMAR were compared. Both SECT + iMAR and DECT + iMAR offer successful MAR for phantom simulating unilateral hip prosthesis. DECT gives minimal artefact reduction over iMAR alone. Quantitative metrics are advantageous for MAR analysis but have limitations that leave room for metric development.

Simulating Transplant Small-for-size Grafts Using Human Liver Monosegments: The Impact of Portal Perfusion Pressure.

Small-for-size-liver grafts (SFSG) in adult transplant recipients have elevated risk of graft failure, limiting its application in clinical liver transplantation. Relevant preclinical model of SFSG is lacking. Relevant to deceased-donor split liver transplant and living-donor liver transplant in adult recipients, in this study, we present our initial characterization of SFSG model using monosegments of a discarded human donor liver.

Measurement of cone beam CT coincidence with megavoltage isocentre and image sharpness using the QUASAR Penta-Guide phantom.

For image-guided radiotherapy (IGRT) systems based on cone beam CT (CBCT) integrated into a linear accelerator, the reproducible alignment of imager to x-ray source is critical to the registration of both the x-ray-volumetric image with the megavoltage (MV) beam isocentre and image sharpness. An enhanced method of determining the CBCT to MV isocentre alignment using the QUASAR Penta-Guide phantom was developed which improved both precision and accuracy. This was benchmarked against our existing method which used software and a ball-bearing (BB) phantom provided by Elekta. Additionally, a method of measuring an image sharpness metric (MTF(50)) from the edge response function of a spherical air cavity within the Penta-Guide phantom was developed and its sensitivity was tested by simulating misalignments of the kV imager. Reproducibility testing of the enhanced Penta-Guide method demonstrated a systematic error of <0.2 mm when compared to the BB method with near equivalent random error (s=0.15 mm). The mean MTF(50) for five measurements was 0.278+/-0.004 lp mm(-1) with no applied misalignment. Simulated misalignments exhibited a clear peak in the MTF(50) enabling misalignments greater than 0.4 mm to be detected. The Penta-Guide phantom can be used to precisely measure CBCT-MV coincidence and image sharpness on CBCT-IGRT systems.

Clinicopathologic and diagnostic imaging characteristics of systemic aspergillosis in 30 dogs.

BACKGROUND: Systemic aspergillosis is a serious disease of dogs for which the clinical characteristics are poorly described. OBJECTIVE: To describe the clinical and diagnostic imaging characteristics of dogs with systemic aspergillosis. ANIMALS: Thirty dogs with systemic aspergillosis. METHODS: Retrospective case review. Medical records were reviewed for signalment, clinical features, and results of clinicopathologic testing and diagnostic imaging. Diagnosis was confirmed by culture of Aspergillus terreus (n = 13), Aspergillus deflectus (n = 11), or other Aspergillus spp. (n = 6). RESULTS: Compared with the background hospital population, German Shepherd dogs and female dogs were overrepresented (odds ratio [OR] 43, 95% confidence interval [CI] 20-91, P < .0001, and OR 2.9, 95% CI 1.2-6.7, P= .02), respectively, with 20 of the 30 dogs being German Shepherd dogs and 77% (23 of 30) of the dogs being female. The median age was 4.5 years (range 2-8 years). Anemia, leukocytosis, hyperglobulinemia, azotemia, hypercalcemia, and hypoalbuminemia were present in 8, 21, 12, 9, 8, and 6 dogs, respectively. Diskospondylitis, osteomyelitis and thoracic lymphadenomegaly were present in 16, 10, and 5 dogs, respectively. Sonographic findings were enlarged hypoechoic lymph nodes (n = 12), mottled and irregular kidneys with or without masses (n = 12), pyelectasia, and an aggregate of echogenic material in the renal pelvis (n = 9). Thirteen dogs were treated with antifungal drugs, with survival times ranging from 0 to 25 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic aspergillosis typically involves young to middle-age female German Shepherd dogs, and there are characteristic abdominal ultrasound findings with the disease process. Infection with A. deflectus was as common as A. terreus, and in rare cases, long-term survival was associated with antifungal therapy.