Diagnosis and ultrasonographic appearance of hepatic metastasis in six cases of canine appendicular osteosarcoma (2005-2013).

OBJECTIVES: The aims of this retrospective study were to identify clinical cases of dogs with appendicular osteosarcoma (OSA) in which hepatic metastasis was confirmed, to highlight the use of cytology for its diagnosis and to describe the radiographic and ultrasonographic appearances of the lesion. METHODS: Medical records were retrospectively reviewed for dogs with appendicular OSA and hepatic metastases between January 2005 and January 2013. Reviews of radiographs, ultrasounds and cytology were performed. RESULTS: Six dogs with appendicular OSA and hepatic metastases were identified. The ultrasonographic appearance of metastatic lesions varied, including hyperechoic with shadowing, hyperechoic without shadowing, hypoechoic and mixed echogenicity. In two cases, the hepatic metastases were also evident on thoracic radiographs. The mean survival time from diagnosis of appendicular OSA was 188 days (range 69-363 days) and from diagnosis of hepatic metastases was 35 days (range 2-69 days). Death was tumour-related in all cases. CONCLUSIONS: Hepatic metastasis varies widely in its ultrasonographic appearance. In three of six cases, hepatic metastasis was identified without concurrent pulmonary metastasis; therefore, abdominal ultrasound may be useful at regular intervals for patient evaluation, especially in clinical trials where accurate identification of the disease-free interval is crucial. Once hepatic metastasis is confirmed, survival times appear limited.

Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters.

Quality assurance for the clinical implementation of kilovoltage intrafraction monitoring for prostate cancer VMAT.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor monitoring system for cancer radiotherapy. KIM uses the commonly available gantry-mounted x-ray imager as input, making this method potentially more widely available than dedicated real-time 3D tumor monitoring systems. KIM is being piloted in a clinical trial for prostate cancer patients treated with VMAT (NCT01742403). The purpose of this work was to develop clinical process and quality assurance (QA) practices for the clinical implementation of KIM. METHODS: Informed by and adapting existing guideline documents from other real-time monitoring systems, KIM-specific QA practices were developed. The following five KIM-specific QA tests were included: (1) static localization accuracy, (2) dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency measurement, and (5) clinical conditions accuracy. Tests (1)-(4) were performed using KIM to measure static and representative patient-derived prostate motion trajectories using a 3D programmable motion stage supporting an anthropomorphic phantom with implanted gold markers to represent the clinical treatment scenario. The threshold for system tolerable latency is <1 s. The tolerances for all other tests are that both the mean and standard deviation of the difference between the programmed trajectory and the measured data are <1 mm. The (5) clinical conditions accuracy test compared the KIM measured positions with those measured by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a previous pilot study. RESULTS: For the (1) static localization, (2) dynamic localization, and (3) treatment interruption accuracy tests, the mean and standard deviation of the difference are <1.0 mm. (4) The measured latency is 350 ms. (5) For the tests with previously acquired patient data, the mean and standard deviation of the difference between KIM and kV/MV triangulation are <1.0 mm. CONCLUSIONS: Clinical process and QA practices for the safe clinical implementation of KIM, a novel real-time monitoring system using commonly available equipment, have been developed and implemented for prostate cancer VMAT.

DMLC tracking and gating can improve dose coverage for prostate VMAT.

PURPOSE: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. METHODS: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. RESULTS: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD99% and PTV D95% values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D99% for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V65% for the individual fractions from planned ranged from -44% to 101% and for the bladder V65% the range was -61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V65% difference to 6% and 4%, respectively. CONCLUSIONS: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion.

Association between absolute tumor burden and serum bone-specific alkaline phosphatase in canine appendicular osteosarcoma.

BACKGROUND: In dogs with appendicular osteosarcoma (OSA), increased pretreatment serum bone-specific alkaline phosphatase (BALP) activity is a negative prognostic factor, associated with shorter disease-free intervals and survival times, but a biologic basis for observed differential serum BALP activities in canine OSA patients remains incompletely defined. OBJECTIVE: Serum BALP activity will correlate with absolute tumor burden in dogs with OSA. ANIMALS: This study included 96 client-owned dogs with appendicular OSA. METHODS: In canine OSA cell lines, the expression and membranous release of BALP was evaluated in vitro. The correlation between serum BALP activity and radiographic primary tumor size was evaluated in OSA-bearing dogs. In dogs developing visceral OSA metastases, serial changes in serum BALP activities were evaluated in relation to progression of macroscopic metastases, and visceral metastatic OSA cells were evaluated for BALP expression. RESULTS: In vitro, BALP expression was not associated with either tumorigenic or metastatic phenotype, rather the quantity of membranous BALP released was proportional with cell density. In dogs devoid of macroscopic metastases, there was a positive correlation between serum BALP activity and absolute primary tumor size. In dogs with progressive OSA metastases, serum BALP activity increased and coincided with the development of macroscopic metastases. OSA cells derived from visceral metastatic lesions retained BALP expression. CONCLUSIONS AND CLINICAL IMPORTANCE: Tumor burden is a determinant of serum BALP activity in dogs with appendicular OSA. The association between increased pretreatment BALP activity and negative clinical prognosis may simply be attributed to greater initial tumor burden, and consequently more advanced tumor stage.

Ultrasonographic evaluation of the thickness of the small intestinal wall in dogs with inflammatory bowel disease.

OBJECTIVES: To establish whether the intestinal wall thickness, as measured ultrasonographically, is significantly increased in dogs with inflammatory bowel disease (IBD). The results would provide the information necessary to decide whether measurement of ultrasonographic wall thickness can predict IBD in dogs. METHODS: The intestinal wall thickness of 75 dogs with idiopathic IBD, as measured by ultrasonography, was compared with recently published normal values. IBD was either confirmed histologically (n = 54) or suspected (n = 21). In all cases there was a positive response to immunosuppressive treatment. RESULTS: A positive association between intestinal wall thickness in dogs and either the histological diagnosis or the response to treatment was not found. Ultrasonographic intestinal wall measurements do not appear to be able to establish a diagnosis of intestinal inflammation and may result in a false negative diagnosis in cases of IBD. CLINICAL SIGNIFICANCE: The same 'grey zone' of between 4 and 6 mm used in humans can be used in the canine duodenum to distinguish the normal range, reserving the term 'abnormal' for an intestinal measurement greater than 6 mm in the duodenum and greater than 4.7 mm in the jejunum.

Contrast harmonic ultrasound of spontaneous liver nodules in 32 dogs.

Thirty-two dogs with spontaneous hepatic nodules were given intravenous ultrasound contrast medium (Definity or Sonovue) and imaged with contrast harmonic software on a conventional ultrasound machine system. Digital video images were initially reviewed to describe the perfusion pattern of malignant nodules. The images were reviewed again to test this pattern against all individual nodules. Subjectively, there was improved conspicuity of malignant nodules after contrast enhancement compared with conventional imaging and increased numbers of malignant nodules were often noted. There was decreased conspicuity of benign nodules and no additional nodules were seen after contrast enhancement. There was a highly significant (P < 0.0001) association of malignancy with a hypoechoic nodule at surrounding normal liver peak contrast enhancement. Benign nodules were isoechoic to the surrounding normal liver at peak contrast enhancement. Only one benign nodule (hepatoma) had regions of hypoechogenicity compared with the surrounding normal liver at peak liver contrast enhancement. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were highly significant (P < 0.0001) (100%, 94.1%, 93.8%, 100%, and 96.9%, respectively). No complications or morbidity was noted throughout the course of the study. Contrast harmonic ultrasound appears to be accurate at discriminating between naturally occurring benign and malignant nodules in the liver of dogs.

Ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (Mustela putorius furo).

The large mesenteric lymph node of 28 normal ferrets was imaged with ultrasound. The large node, located in the mid-abdomen at the root of the mesentery, was round to ovoid and uniformly hyperechoic. Mean ultrasonographic dimensions of the lymph node were 12.6 +/- 2.6 mm by 7.6 +/- 2.0 mm. Fine needle aspirates of 20 lymph nodes were obtained either using ultrasound guided free-hand techniques or at necropsy. The cytological descriptions were compared to histological descriptions of 13 lymph node core biopsies obtained during laparotomy or necropsy as well as 10 peripheral blood smear differentials. The large mesenteric lymph node of ferrets could be easily imaged and measured by ultrasound and evaluated by fine needle aspirate cytology. Normal lymph node cytology may include an eosinophilic infiltrate.

Ultrasonographic appearance of exogenous isobutane gas in the mammary glands of dairy cows.

OBJECTIVE: To determine whether exogenous isobutane gas infused into the udders of dairy cattle could be detected ultrasonographically, and if so, what effects volume of gas infused and infusion pressure had on how long after infusion exogenous isobutane gas could be detected. DESIGN: Randomized block design. ANIMALS: 8 Holstein cows 28 to 32 days after parturition. PROCEDURE: In each cow, 1 mammary gland was not treated and the other 3 received 1 of 3 treatments by means of intramammary infusion: low volume-high pressure, low volume-low pressure, and high volume-high pressure infusion of isobutane gas. Mammary glands were examined ultrasonographically 1 hour before and 1, 3, 12, 24, 36, 48, 72, and 96 hours after treatment. RESULTS: After intramammary infusion of isobutane gas, bright echoes and associated acoustic shadows were seen ultrasonographically; echoes were no longer seen 72 hours after gas infusion. Percentages of mammary glands in which bright echoes were detected were not significantly different among the 3 treatment groups at any time during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exogenous isobutane gas infused into the mammary glands to enhance the appearance of the udder of show dairy cattle can be readily detected by ultrasonography.

Pancreatic pseudocysts in 4 dogs and 2 cats: ultrasonographic and clinicopathologic findings.

Pancreatic pseudocysts were diagnosed in 4 dogs and 2 cats based on ultrasonographic and clinicopathologic findings. All 6 animals had a clinical diagnosis of pancreatitis. Five of 6 pseudocysts were in the left pancreatic limb, and in 1 cat the pseudocyst was in the pancreatic body region. Cyst size ranged from 2 x 2 cm to 7 x 6 cm. All pseudocysts had anechoic regions that were aspirated using ultrasound guidance for diagnostic and therapeutic purposes. No morbidity was associated with the aspiration procedures. Cytologically the pseudocyst fluid was aseptic in all patients and had low numbers of inflammatory cells in 5 of 6 patients. All animals had high lipase activity in the pseudocyst fluid and in 2 dogs and 1 cat the lipase activity in the fluid was greater than in serum. Three of the 4 dogs were managed medically. In the 1 dog that had long-term follow-up ultrasound examination, the pseudocyst persisted for several days following aspiration and had disappeared 8 months after diagnosis. All 3 of these dogs were clinically normal 1.5-4 years after presentation. The 4th dog underwent surgical exploration and was euthanized shortly thereafter because of bronchopneumonia and chronic pancreatitis. The 2 cats died 10 days and 2 months, respectively, following initial diagnosis of the pseudocyst, but necropsies were not performed in either case. Ultrasound-guided fine-needle aspiration of pancreatic pseudocysts and clinicopathologic evaluation of cystic fluid are useful for diagnosis of pancreatic pseudocysts.

Treatment outcome and prognostic factors for infants with acute lymphoblastic leukemia treated on two consecutive trials of the Children's Cancer Group.

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

Ultrasound-guided fine-needle aspiration of focal parenchymal lesions of the lung in dogs and cats.

Ultrasound-guided fine-needle aspiration (FNA) of the lung was performed on 16 dogs and 3 cats with consolidated pulmonary lesions or masses identified on thoracic radiographs. The cytologic results from the FNA were confirmed by histopathology, response to treatment, or microscopic identification of Blastomyces organisms. Neoplasia was identified correctly by FNA cytology in 10 of 11 animals, and no false positive results occurred, yielding a positive predictive value of 100%. Of 8 animals with infectious disease, 5 of 6 had blastomycosis and 1 had a bacterial infection, based on cytologic evaluation. Eight animals required sedation for the procedure, and none had clinical complications. We conclude that ultrasound-guided FNA of pulmonary mass lesions is an inexpensive, safe, and accurate method for diagnosing blastomycosis or neoplasia, especially carcinomas, in dogs and cats.

Dental imaging.

Radiography continues to be the initial test of choice in equine dental imaging for reasons of availability and ability to detect bone and tooth changes. Contrast radiography may be useful to characterize dental involvement in cases with draining tracts. For radiographically occult lesions, other modalities are useful. CT is better than plain radiography due to the inherent avoidance of superimposition of the opposite dental arcade, excellent bone density characterization, and good spatial resolution. Nuclear medicine may be useful to verify bone involvement in the dental region in cases in which the signs are particularly vague or not readily localized. Ultrasonography is an excellent test for soft tissue characterization and may assist with the characterization of suspected bone lysis, pathologic fractures, and abscesses.

Sonographic renal findings in 20 dogs with leptospirosis.

Abdominal ultrasound examinations of 20 dogs with confirmed leptospirosis were reviewed retrospectively for renal abnormalities. Three dogs had a normal ultrasound examination. The remaining 17 dogs had sonographic abnormalities of the kidneys. These abnormalities, seen either alone or in combination, included renalmegaly (n=10), pyelectasia (n=9), increased cortical echogenicity (n=15), perinephric effusion (n=5), and a medullary band of increased echogenicity (n=6). At our institution, the medullary band of increased echogenicity has only been seen in dogs with leptospirosis and may therefore be a specific sonographic sign for this disease.

Urinary bladder mural hemorrhage associated with systemic bleeding disorders in three dogs.

The sonographic appearance of three dogs with diffuse bladder wall thickening due to mural hemorrhage is described. Two dogs were diagnosed with immune-mediated thrombocytopenia and the third dog with vitamin K antagonist toxicity. Urinary bladder wall thickening ranged from 5 to 12 mm on initial sonographic examination. In the two surviving dogs, the bladder wall returned to normal thickness. One dog, euthanatized for refractory hematuria, had submucosal hemorrhage in the urinary bladder at necropsy. Urinary wall thickening sonographically resolved at a rate of approximately 1 mm per day. Mural hemorrhage should be considered in patients with concurrent bleeding disorder and urinary bladder wall thickening.

Early detection of canine hip dysplasia: comparison of two palpation and five radiographic methods.

Hip joint laxity was evaluated in four breeds (i.e., greyhound, Labrador retriever, Irish setter, hound mixed-breed) of puppies (n=32) by Ortolani's and Bardens' maneuvers, by subjective assessment of radiographs (Orthopedic Foundation for Animals [OFA] method), and by four radiographic measurement indices. Puppies were studied at four, six-to-10, 16-to-18, and 52 weeks of age. The purpose of this study was to compare palpation and radiographic methods of hip laxity detection in puppies for predicting the development of degenerative joint disease (DJD) by one year of age. Twenty-seven (42%) hips developed DJD. Ortolani's method was not a reliable predictor of hip dysplasia at six-to-10 weeks; it was significantly predictive at 16-to-18 weeks but had a high incidence of false negatives. Bardens' and subjective (OFA) assessment methods were not reliable at six-to-10 or 16-to-18 weeks. Radiographic measurements taken with femurs in a neutral position and hips distracted (distraction index [DI] and Norberg angle) and measurements taken with femurs extended in OFA position (Norberg angle) of six- to 10-week-old puppies accurately predicted DJD occurrence by one year of age (p less than 0.01). Distraction index measurement (PennHIP method) was the most accurate in predicting the development of DJD (p less than 0.001). Distraction index radiography in puppies six-to-10 and 16-to-18 weeks of age was the most reliable predictor of hip dysplasia. Norberg angle measurement was more reliable during hip distraction than when hips were measured in the OFA position in 16- to 18-week-old puppies, but had similar reliability in six- to 10-week-old puppies.

Quantitative ultrasonography of the liver in cats during obesity induction and dietary restriction.

A study was designed to evaluate quantitative ultrasonographic characteristics of a diffuse parenchymal disease in an experimental model of subclinical fatty infiltration of the liver using diet-induced obesity and dietary restriction in the cat. Ultrasound images of livers were quantitatively analysed by a video signal analysis technique before, during and at the end of obesity induction, and then during and following dietary restriction. Attenuation and brightness (backscatter coefficient) were correlated with hepatic lipid content obtained from the livers by surgical and ultrasound-guided percutaneous biopsy. Attenuation and backscatter increased as hepatic lipid content increased. Both attenuation and backscatter significantly correlated with the hepatic lipid content (P=0.002 and P=0.02 respectively). This model of subclinical fatty infiltration of the liver in the cat demonstrates that hepatic lipid content increases as a consequence of obesity and of severe dietary restriction. Infiltration of the liver with fat may be evaluated non-invasively using quantitative ultrasonography by the video signal analysis technique. This method of image analysis may prove useful for the evaluation of diffuse parenchymal organ disease.