Multimodal Imaging Characteristics of a Migrating Oropharyngeal-Spinal Foreign Body in a Cat.

A 2.5 yr old female spayed domestic shorthair presented for acute tetraparesis, dull mentation, and fever. MRI and computed tomography identified a thin linear foreign body extending from the caudal nasopharynx through the atlanto-occipital joint and cervicomedullary junction. Signal changes within the musculature were consistent with myositis, edema, and abscessation. Inflammation and edema surrounded the foreign body, and a dorsal cervical myelopathy extended caudally to the level of C6. Computed tomography attenuation values of the foreign body were most consistent with plant material. Euthanasia was performed; postmortem dissection of the soft palate confirmed a plant stem with abscess.

Multimodality characteristics of multifocal choroid plexus carcinoma with bilateral calvarial defects in a dog.

An 8-year-old male intact miniature poodle presented for blindness, obtundation, tetraparesis, and vestibular signs. Magnetic resonance imaging, radiography, and ultrasound revealed a left piriform lobe lesion, right cerebellar and left brainstem lesions, and hydrocephalus and bilateral calvarial defects. Histopathology confirmed a choroid plexus carcinoma with meningeal and intraventricular metastases. The calvarial defect did not show evidence of necrosis, osteoclastic resorption, inflammation or neoplastic infiltration, reflecting a quiescent calvarial atrophy or dysplasia. These novel findings supported inclusion of bone atrophy secondary to chronic increased intracranial pressure as a differential diagnosis for large calvarial defects in dogs with choroid plexus carcinoma.

Multimodality imaging of an azygous continuation of the caudal vena cava in a dog with pulmonary thromboembolic disease.

A 5-year-old spayed female English Bulldog was evaluated for acute anorexia, lethargy, respiratory distress, and syncope. Contrast-enhanced computed tomography revealed the vascular malformation of azygous continuation of the caudal vena cava with extensive thrombus formation and pulmonary arterial thromboembolic disease. The patient was hospitalized for supportive treatment and was prescribed long-term clopidogrel therapy. The patient survived to discharge and at last follow-up remained clinically stable. While this vascular malformation has been reported in canines, to the authors' knowledge, this is the first reported case of pulmonary thromboembolic disease in a canine concurrent with this condition.

Multimodality imaging of primary ureteral hemangiosarcoma with thoracic metastasis in an adult dog.

A 12-year-old spayed female standard Poodle was presented for investigation of severe hematuria. Abdominal ultrasound and thoracic and abdominal computed tomography identified severe hydronephrosis due to an obstructive ureteral mass with no evidence of metastasis. Histological examination after nephrectomy and ureterectomy confirmed an obstructive ureteral hemangiosarcoma. Forty days after surgery, the dog was presented with severe dyspnea. Survey radiographs of the thorax revealed a severe diffuse nodular interstitial pattern. Postmortem histological examination revealed pulmonary metastasis of hemangiosarcoma.

Multimodality characterization of a noncommunicating congenital duodenal duplication cyst causing pyloric outflow obstruction in a young dog.

A 10-month-old German Shepherd Dog presented for evaluation of intermittent vomiting. Abdominal radiographs revealed a marked right cranial mass effect. Initial differentials included abscess/cyst or less likely neoplasia from undetermined origin. On abdominal ultrasound the mass appeared cystic and thin walled. Computed tomography revealed a large cystic lesion originating from the pyloroduodenal junction causing pyloric outflow obstruction. A noncommunicating duodenal duplication cyst was found on exploratory laparotomy and further confirmed with histopathology and immunohistochemistry. Enteric duplication cyst should be considered as a differential in young dogs with gastrointestinal signs and a cystic abdominal mass detected with different imaging modalities.

Multimodality imaging characteristics of tension pyopneumothorax secondary to pulmonary carcinoma in a cat.

A 3-year-old Himalayan cat was presented with respiratory distress. Radiography showed multiple gas opacity foci, with the locations dependent on patient positioning, and severe pleural effusion with a contralateral mediastinal shift. A large volume of fluid and air was aspirated, and the fluid components were consistent with a nonseptic exudate. A pulmonary mass, pleural nodules, and an air-fluid interface with air bubbles trapped in fibrous septations were identified using thoracic ultrasonography and CT. The cat died 2 days after imaging studies. Necropsy revealed tension pyopneumothorax caused by pulmonary carcinoma and multiple pleural metastases.

A combined positron emission tomography (PET)-electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner.

The advent of hybrid scanners, combining complementary modalities, has revolutionized the application of advanced imaging technology to clinical practice and biomedical research. In this project, we investigated the melding of two complementary, functional imaging methods: positron emission tomography (PET) and electron paramagnetic resonance imaging (EPRI). PET radiotracers can provide important information about cellular parameters, such as glucose metabolism. While EPR probes can provide assessment of tissue microenvironment, measuring oxygenation and pH, for example. Therefore, a combined PET/EPRI scanner promises to provide new insights not attainable with current imagers by simultaneous acquisition of multiple components of tissue microenvironments. To explore the simultaneous acquisition of PET and EPR images, a prototype system was created by combining two existing scanners. Specifically, a silicon photomultiplier (SiPM)-based PET scanner ring designed as a portable scanner was combined with an EPRI scanner designed for the imaging of small animals. The ability of the system to obtain simultaneous images was assessed with a small phantom consisting of four cylinders containing both a PET tracer and EPR spin probe. The resulting images demonstrated the ability to obtain contemporaneous PET and EPR images without cross-modality interference. Given the promising results from this initial investigation, the next step in this project is the construction of the next generation pre-clinical PET/EPRI scanner for multi-parametric assessment of physiologically-important parameters of tissue microenvironments.

Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic Resonance, and Positron Emission Tomography Imaging.

Gliomas are the most common type of primary, malignant brain tumor and significantly impact patients, who have a median survival of ~1 year depending on mutational background. Novel imaging modalities such as luciferase bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized tomography (micro-CT), and micro-positron emission tomography (micro-PET) have expanded the portfolio of tools available to study this disease. Hypoxia, a key oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by the concomitant use of noninvasive MRI and PET imaging. We present a protocol involving stereotactic injection of syngenic F98 luciferase-expressing glioma cells generated by our laboratory into Fischer 344 rat brains and imaging using luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F-fluorothymidine PET imaging are compared with quantified luciferase flux. These tools can potentially be used for assessing tumor growth characteristics, hypoxia, mutational effects, and treatment effects.

Measuring embryo metabolism to predict embryo quality.

Measuring the metabolism of early embryos has the potential to be used as a prospective marker for post-transfer development, either alone or in conjunction with other embryo quality assessment tools. This is necessary to maximise the opportunity of couples to have a healthy child from assisted reproduction technology (ART) and for livestock breeders to efficiently improve the genetics of their animals. Nevertheless, although many promising candidate substrates (e.g. glucose uptake) and methods (e.g. metabolomics using different spectroscopic techniques) have been promoted as viability markers, none has yet been widely used clinically or in livestock production. Herein we review the major techniques that have been reported; these are divided into indirect techniques, where measurements are made from the embryo's immediate microenvironment, or direct techniques that measure intracellular metabolic activity. Both have strengths and weaknesses, the latter ruling out some from contention for use in human ART, but not necessarily for use in livestock embryo assessment. We also introduce a new method, namely multi- (or hyper-) spectral analysis, which measures naturally occurring autofluorescence. Several metabolically important molecules have fluorescent properties, which we are pursuing in conjunction with improved image analysis as a viable embryo quality assessment methodology.

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging.

UNLABELLED: Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a small-animal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. METHODS: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm(3) (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. RESULTS: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. CONCLUSION: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.

IMAGING DIAGNOSIS-MULTIMODALITY FINDINGS IN AN ADULT DOG WITH PRIMARY SARCOMA OF THE PULMONARY ARTERY AND MYOCARDIAL METASTASES.

Intravascular pulmonary artery sarcomas in combination with myocardial metastasis are rare in dogs. We describe the radiographic, echocardiographic, and electrocardiographic-gated (ECG-gated) computed tomographic angiography (CTA) findings in a dog with pulmonary artery sarcoma. All imaging studies demonstrated severe main pulmonary artery enlargement. Echocardiography and ECG-gated CTA revealed a mass occluding the lumen of the right pulmonary artery. In addition, CTA revealed focal left ventricular myocardial contrast enhancement and parenchymal lung changes. Postmortem examination confirmed the presence of a large thrombus associated with arteriosclerosis and an intravascular sarcoma in the right pulmonary artery with metastases to the myocardium, lungs and brain.

A multimodality imaging approach for guiding a modified endovascular coil embolization of a single intrahepatic portosystemic shunt in dogs.

Intrahepatic portosystemic shunts (IHPSS) in dogs are aberrant vascular anomalies that connect the portal and the systemic venous vessels. In most of the patients, the surgical approach is unfavourable due to the difficulties in isolating the IHPSS, making the option of a percutaneous transvenous coil embolization (PTCE) one of the safer occlusive procedures. This study describes the treatment of eight dogs with a single IHPSS using a multimodality imaging approach to guide the modified PTCE procedure. This new technique results in a decrease of 71% of the time of the entire procedure with the reduction of 91% in the time required involved the IHPSS identification and in the fluoroscopy exposure time avoiding the need for iodinated contrast agents during the procedure. Moreover, the placement of the catheter before the caval stent ensures its greater stability, enhancing the procedural safety in the phase when the coils are released and avoiding the risk of their dislocation.

Efficacy of levofloxacin, amoxicillin and a proton pump inhibitor in the eradication of Helicobacter pylori in Brazilian patients with peptic ulcers

OBJECTIVES: The eradication of Helicobacter (H.) pylori allows peptic ulcers in patients infected with the bacteria to be cured. Treatment with the classic triple regimen (proton pump inhibitor, amoxicillin and clarithromycin) has shown decreased efficacy due to increased bacterial resistance to clarithromycin. In our country, the eradication rate by intention to treat with this regimen is 83%. In Brazil, a commercially available regimen for bacterial eradication that uses levofloxacin and amoxicillin with lansoprazole is available; however, its efficacy is not known. Considering that such a treatment may be an alternative to the classic regimen, we aimed to verify its efficacy in H. pylori eradication. METHODS: Patients with peptic ulcer disease infected with H. pylori who had not received prior treatment were treated with the following regimen: 30 mg lansoprazole bid, 1,000 mg amoxicillin bid and 500 mg levofloxacin, once a day for 7 days. RESULTS: A total of 66 patients were evaluated. The patients’ mean age was 52 years, and women comprised 55% of the sample. Duodenal ulcers were present in 50% of cases, and gastric ulcers were present in 30%. The eradication rate was 74% per protocol and 73% by intention to treat. Adverse effects were reported by 49 patients (74%) and were mild to moderate, with a prevalence of diarrhea complaints. CONCLUSIONS: Triple therapy comprising lansoprazole, amoxicillin and levofloxacin for 7 days for the eradication of H. pylori in Brazilian peptic ulcer patients showed a lower efficacy than that of the classic triple regimen. .

Molecular imaging biomarkers of resistance to radiation therapy for spontaneous nasal tumors in canines.

PURPOSE: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. METHODS AND MATERIALS: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV(max); SUV(mean)) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R(2). RESULTS: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV(mean) (P=.018), and midtreatment FLT SUV(max) (P=.006). Large decreases in FLT SUV(mean) from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV(max) (P=.022) in combination with large FLT response from pretreatment to midtreatment (P=.041). CONCLUSIONS: In addition to tumor volume, pronounced tumor proliferative response quantified using FLT PET, especially when associated with high residual FLT PET at midtreatment, is a negative prognostic biomarker of outcome in canine tumors following radiation therapy. Neither FDG PET nor Cu-ATSM PET were predictive of outcome.

Imaging technologies and basic considerations for welfare of laboratory rodents.

Imaging technologies are regularly used in biomedical research to study processes in living animals in a noninvasive manner. But imaging procedures can affect animal physiology, and the need to anesthetize animals for imaging entails potential health risks. In addition, certain imaging modalities require the use of ionizing radiation or the administration of contrast agents or imaging biomarkers, which also have consequences for animal physiology. Finally, procedures associated with imaging, such as animal preparation (e.g., fasting, premedication) and blood sampling, can also affect physiology and animal welfare. Here, the authors review the imaging modalities commonly used for rodents in biomedical research and their associated considerations for animal welfare.

Spatiotemporal stability of Cu-ATSM and FLT positron emission tomography distributions during radiation therapy.

PURPOSE: In dose painting, in which functional imaging is used to define biological targets for radiation therapy dose escalation, changes in spatial distributions of biological properties during treatment can compromise the quality of therapy. The goal of this study was to assess the spatiotemporal stability of 2 potential dose painting targets--hypoxia and proliferation--in canine tumors during radiation therapy. METHODS AND MATERIALS: Twenty-two canine patients with sinonasal tumors (14 carcinoma and 8 sarcoma) were imaged before hypofractionated radiation therapy with copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed tomography (PET/CT) for hypoxia and 3'-deoxy-3'-(18)F-fluorothymidine (FLT) PET/CT for proliferation. The FLT scans were repeated after 2 fractions and the Cu-ATSM scans after 3 fractions. Midtreatment PET/CT images were deformably registered to pretreatment PET/CT images. Voxel-based Spearman correlation coefficients quantified the spatial stability of Cu-ATSM and FLT uptake distributions between pretreatment and midtreatment scans. Paired t tests determined significant differences between the patients' respective Cu-ATSM and FLT correlations coefficients. Standardized uptake value measures were also compared between pretreatment and midtreatment scans by use of paired t tests. RESULTS: Spatial distributions of Cu-ATSM and FLT uptake were stable through midtreatment for both sarcomas and carcinomas: the population mean ± standard deviation in Spearman correlation coefficient was 0.88 ± 0.07 for Cu-ATSM and 0.79 ± 0.13 for FLT. The patients' Cu-ATSM correlation coefficients were significantly higher than their respective FLT correlation coefficients (P=.001). Changes in Cu-ATSM SUV measures from pretreatment to midtreatment were histology dependent: carcinomas experienced significant decreases in Cu-ATSM uptake (P<.05), whereas sarcomas did not (P>.20). Both histologies experienced significant decreases in FLT uptake (P<.05). CONCLUSIONS: Spatial distributions of Cu-ATSM were very stable after a few fractions of radiation therapy. FLT spatial distributions were generally stable early in therapy, although they were significantly less stable than Cu-ATSM distributions. Canine tumors had significantly lower proliferative activity at midtreatment than at pretreatment, and they experienced histology-dependent changes in Cu-ATSM uptake.

Quantitative positron emission tomography imaging of angiogenesis in rats with forelimb ischemia using (68)Ga-NOTA-c(RGDyK).

Gallium-68-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-cyclic Arg-Gly-Asp-D-Tyr-Lys (c(RGDyK)) was developed for αvß3 targeting, and is a promising agent for imaging of cancer and disorders related to angiogenesis. In this study, we performed kinetic analysis of (68)Ga-NOTA-c(RGDyK) in rats with surgically induced forelimb ischemia, and immunohistochemical analysis was also performed to assess αvß3 immuno-staining level. Animal models were created by excision of the left brachial vessels, and a sham operation was performed on the right brachial region under 2 % isoflurane anesthesia. Using an animal positron emission tomography/computed tomography (PET/CT) scanner, a list mode PET scan (120 min) was started with the injection of (68)Ga-NOTA-c(RGDyK) via the tail vein at 3, 5 and 7 days after ischemic surgery. Volumes of interest were drawn on the left ventricle, sham operation, control, and ischemic regions. Compartmental and two graphical analyses (Logan and RE plots) were performed for kinetic parameter estimation. The immunohistochemical analysis was also performed after the last PET scan, and cell components were scored on a six point scale for quantification of immuno-staining level (0-negative to 5-very high). A 3-compartment model with reversible binding best described the tissue time-activity curves. The distribution volume of the ischemic region was significantly higher than that of the sham operation (P < 10(-6)) and control region (P < 10(-9)). Both the Logan and RE plots showed high correlation with compartmental analysis (R(2) = 0.96 and 0.95 for Logan and RE, respectively). The temporal changes in distribution volume and binding potential were not significant. The immuno-staining level of the ischemic region was significantly higher than that of sham operation (P < 10(-4)) and control region (P < 10(-8)). Kinetic modeling studies with dynamic (68)Ga-NOTA-c(RGDyK) PET scan are feasible based on an image-derived input function in a rat ischemia model. The kinetic modeling analysis performed in this study will be useful for the quantitative evaluation of (68)Ga-NOTA-c(RGDyK) binding to αvß3 in angiogenic tissues.

Accuracy of a clinical PET/CT vs. a preclinical µPET system for monitoring treatment effects in tumour xenografts.

PURPOSE: Small animal imaging is of growing importance for preclinical research and drug development. Tumour xenografts implanted in mice can be visualized with a clinical PET/CT (cPET); however, it is unclear whether early treatment effects can be monitored. Thus, we investigated the accuracy of a cPET versus a preclinical µPET using (18)F-FDG for assessing early treatment effects. MATERIALS AND METHODS: The spatial resolution and the quantitative accuracy of a clinical and preclinical PET were evaluated in phantom experiments. To investigate the sensitivity for assessing treatment response, A431 tumour xenografts were implanted in nude mice. Glucose metabolism was measured in untreated controls and in two therapy groups (either one or four days of antiangiogenic treatment). Data was validated by γ-counting of explanted tissues. RESULTS: In phantom experiments, cPET enabled reliable separation of boreholes≥5mm whereas µPET visualized boreholes≥2mm. In animal studies, µPET provided significantly higher tumour-to-muscle ratios for untreated control tumours than cPET (3.41±0.87 vs. 1.60±.0.28, respectively; p<0.01). During treatment, cPET detected significant therapy effects at day 4 (p<0.05) whereas µPET revealed highly significant therapy effects even at day one (p<0.01). Correspondingly, γ-counting of explanted tumours indicated significant therapy effects at day one and highly significant treatment response at day 4. Correlation with γ-counting was good for cPET (r=0.74; p<0.01) and excellent for µPET (r=0.85; p<0.01). CONCLUSION: Clinical PET is suited to investigate tumour xenografts≥5mm at an advanced time-point of treatment. For imaging smaller tumours or for the sensitive assessment of very early therapy effects, µPET should be preferred.

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.