Comparison of high-resolution magnetic resonance imaging and micro-computed tomography arthrography for in-vivo assessment of cartilage in non-human primate models.

BACKGROUND: Non-human primate (NHP) could be an interesting model for osteoarthritis (OA) longitudinal studies but standard medical imaging protocols are not able to acquire sufficiently high-resolution images to depict the thinner cartilage (compared to human) in an in vivo context. The aim of this study was thus to develop and validate the acquisition protocols for knee joint examination of NHP using magnetic resonance imaging (MRI) at 1.5 T and X-ray micro-computed tomography arthrography (µCTA). METHODS: The first phase of the study focused on developing dedicated in vivo HR-MRI and µCTA protocols for simultaneous acquisitions of both knee joints on NHP. For MR, a dedicated two-channel receiver array coil and acquisition sequence were developed on a 1.5 T Siemens Sonata system and tuned to respect safety issues and reasonable examination time. For µCTA, an experimental setup was devised so as to fulfill similar requirements. The two imaging protocols were used during a longitudinal study so as to confirm that repeated injections of loxaglic acid (contrast agent used for µCTA) didn't induce any bias in cartilage assessment and to compare segmentation results from the two modalities. Lateral and medial cartilage tibial plateaus were assessed using a common image processing protocol leading to a 3D estimation of the cartilage thickness. RESULTS: From HR-MRI and µCTA images, thickness distributions were extracted allowing for proper evaluation of knee cartilage thickness of the primates. Results obtained in vivo indicated that the µCTA protocol did not induce any bias in the measured cartilage parameters and moreover, segmentation results obtained from the two imaging modalities were consistent. CONCLUSIONS: MR and µCTA are valuable imaging tools for the morphological evaluation of cartilage in NHP models which in turn can be used for OA studies.

Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model.

BACKGROUND: Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. NEW METHOD: A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. RESULTS: Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. COMPARISON WITH EXISTING METHOD: Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic METHODS: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. CONCLUSION: This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset.

Impact of Anesthesia Protocols on In Vivo Bioluminescent Bacteria Imaging Results.

Infectious murine models greatly benefit from optical imaging using bioluminescent bacteria to non-invasively and repeatedly follow in vivo bacterial infection. In this context, one of the most critical parameters is the bioluminescence sensitivity to reliably detect the smallest number of bacteria. Another critical point is the anesthetic approaches that have been demonstrated to impact the bioluminescence flux emission in studies with luciferase-transfected tumor cells. However, this impact has never been assessed on bacteria bioluminescent models. To this end, we investigated the effects of four anesthesia protocols on the bioluminescence flux in a central venous catheter murine model (SKH1-hr(hr) mice) infected by a bioluminescent S. aureus Xen36 strain. Bioluminescence imaging was performed on mice anesthetized by either ketamine/xylazine (with or without oxygen supplementation), or isoflurane carried with air or oxygen. Total flux emission was determined in vivo daily for 3 days and ex vivo at the end of the study together with a CFU counting of the biofilm in the catheter. Bioluminescence flux differences appear between the different anesthetic protocols. Using a ketamine/xylazine anesthesia (with air), bacteria detection was impossible since the bioluminescence signal remains in the background signal. Mice anesthetized with isoflurane and oxygen led to a signal significantly higher to the background all along the kinetics. The use of isoflurane in air presents a bioluminescence signal similar to the use of ketamine/xylazine with oxygen. These data highlight the importance of oxygen to improve bioluminescence flux by bacteria with isoflurane as well as with ketamine/xylazine anesthetics. As a conclusion, we recommend the use of isoflurane anesthetic with oxygen to increase the bioluminescence sensitivity in this kind of study.

Computed tomography or rhinoscopy as the first-line procedure for suspected nasal tumor: a pilot study.

There are no evidence-based guidelines as to whether computed tomography (CT) or endoscopy should be selected as the first-line procedure when a nasal tumor is suspected in a dog or a cat and only one examination can be performed. Computed tomography and rhinoscopic features of 17 dogs and 5 cats with a histopathologically or cytologically confirmed nasal tumor were retrospectively reviewed. The level of suspicion for nasal neoplasia after CT and/or rhinoscopy was compared to the definitive diagnosis. Twelve animals underwent CT, 14 underwent rhinoscopy, and 4 both examinations. Of the 12 CT examinations performed, 11 (92%) resulted in the conclusion that a nasal tumor was the most likely diagnosis compared with 9/14 (64%) for rhinoscopies. Computed tomography appeared to be more reliable than rhinoscopy for detecting nasal tumors and should therefore be considered as the first-line procedure.

Examen de première intention lors de suspicion de tumeur nasale: scanner où rhinoscopie? Une étude pilote. Lors de suspicion de tumeur nasale chez le chien et le chat, il n'existe à ce jour aucun consensus quant à l'examen de première intention à privilégier entre la tomodensitométrie et l'endoscopie lorsqu'un seul examen peut être réalisé. Les caractéristiques tomodensitométriques et endoscopiques de 17 chiens et 5 chats avec un diagnostic de tumeur nasale confirmé histologiquement ou cytologiquement ont été analysées rétrospectivement. Le degré de suspicion de tumeur nasale permis par l'endoscopie et/ou le scanner a été comparé au diagnostic final. Un examen tomodensitométrique a été réalisé chez 12 animaux, une rhinoscopie chez 14 et les deux examens ont été couplés dans quatre cas. L'examen scanner a conclu qu'une tumeur nasale était le diagnostic le plus probable dans 11 cas sur 12 (92 %), et la rhinoscopie dans 9 cas sur 14 (64 %). L'examen scanner apparait plus fiable que la rhinoscopie pour détecter les tumeurs nasales, et de ce fait devrait être considéré comme le meilleur examen de première intention.(Traduit par les auteurs).

Shunting between the CVC and both the azygos vein and thoracic duct in a dog with CTD.

A 5 mo old female rottweiler was referred for evaluation of a suspected congenital heart disease. Clinical signs included anorexia, exercise intolerance, and severe loss of body condition. Clinical examination revealed dyspnea, pale mucous membranes, and weak femoral pulses. Pleural and abdominal effusions and iron deficiency anemia were identified. A distended intrathoracic caudal vena cava (CVC) visible on thoracic radiographs suggested that the modified transudate abdominal effusion was the result of improper venous return to the right side of the heart. Cor triatriatum dexter (CTD) was diagnosed via echocardiography but did not explain all the anomalies detected during a contrast echocardiography. Abnormal communications between the CVC and azygos vein and the CVC and thoracic duct were subsequently identified by abdominal ultrasonography and angiography. Medical management with diuretics, iron supplements, and surgical treatment of CTD resulted in normalization of the respiratory rate, the exercise intolerance, and the anemia. To the authors' knowledge, this is the first reported case of CTD associated with shunts between the CTV and both the azygos vein and thoracic duct in dogs. This report emphasizes the importance of presurgical assessment of concurrent thoracic and abdominal congenital vascular abnormalities.

Persistent truncus arteriosus in a cat.

A 5-month-old male domestic cat presented with a history of rapid, heavy breathing and cyanosis after exercise. Physical examination showed an abnormal respiratory pattern with an increased rate and stress-induced cyanosis. Auscultation revealed tachycardia and a grade 5/6 systolic murmur best heard over the left base. Radiographs showed evidence of right atrial and ventricular enlargement with distended pulmonary vessels and an enlarged ascending aorta. An echocardiographic examination revealed a dilated right atrium, eccentric right ventricular hypertrophy and an overriding aorta associated with a large ventricular septal defect (VSD). The pulmonary trunk could not be identified by echocardiography. Doppler and saline contrast studies showed large right-to-left shunting through the VSD. These findings were compatible with persistent truncus arteriosus, which was confirmed at necropsy.

Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life.

Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TRalpha and TRbeta. In the absence of triiodothyronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TRalpha aporeceptors repress heart rate as well as the expression of TRbeta and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TRalpha (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TRalpha from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.