Optimal injection rate and catheter size for brain perfusion computed tomography using non-ionic contrast medium in clinically normal Beagles.

OBJECTIVE: To evaluate the effects of contrast medium injection rates and intravenous injection catheter sizes on the time-density curve (TDC) of brain perfusion computed tomography (PCT) images in clinically normal Beagles and provide a reference range for the perfusion parameters for clinical application of PCT in veterinary medicine. ANIMALS: 5 healthy, sexually intact male Beagles. PROCEDURES: All dogs underwent general anesthesia for PCT. Contrast medium (350 mg I/kg) was injected at 3 different injection rates (2, 3, and 4 mL/second) and with 2 sizes of an intravenous catheter (20-gauge and 24-gauge). The rostral cerebral artery and dorsal sagittal sinus were selected as the regions of interest of the TDC. Initiation time of arterial inflow (ta), venous outflow (tv), peak time of arterial enhancement (Tap), and the peak time of venous enhancement (Tvp), were measured, and the difference between Tap and tv (Tap-tv) and between Tap and ta (Tap-ta) was calculated. RESULTS: Both Tap-tv and Tap-ta were significantly (P < .05) shorter at the rate of 3 mL/second than at 2 mL/second with the 24-gauge catheter. However, there was no significant difference according to catheter sizes. Particularly, a 4 mL/second injection rate using a 24-gauge catheter mostly resulted in contrast medium leakage and catheter rupture. CLINICAL RELEVANCE: CONTRAST MEDIUM INJECTION: At a rate of 3 mL/second and with a 24-gauge catheter ensures optimal image acquisition and stable contrast medium injection in brain PCT for small dogs. PCT may be useful for diagnosing cerebrovascular events and hemodynamic changes in small dogs.

Deep learning-based diagnosis of stifle joint diseases in dogs.

In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.

Clinical evaluation of toll-like receptor-5 agonist for radiation-induced oral mucositis in beagle dogs.

This study aimed to evaluate the clinical safety and validate the radiomitigative effect of KMRC011, against radiation-induced oral mucositis in beagle dogs. Clinical safety was evaluated by assessing tolerability, complete blood tests, and plasma biochemistry after drug administration. The radiomitigative effect of KMRC011 was evaluated macropathologically and histopathologically after inducing oral mucositis iatrogenically using 20 Gy irradiation. The plasma concentration of interleukin-6 was measured via enzyme-linked immunosorbent assay, as a biomarker of KMRC011 bioreactivity. Decreased tolerability, increased neutrophil count, hepatic enzyme concentration, C-reactive protein concentration, and interleukin-6 concentration after the administration was observed and ceased within 24 h without additional treatment. Although all animals included in the present study developed severe mucositis in the late course of the study, animals administered KMRC011 showed less erythema, ulcer, inflammatory infiltration. These results suggest that KMRC011 may be used as an adjuvant for radiotherapy without severe adverse effects, especially during short-term radiotherapy, such as hypofractionated radiotherapy or stereotactic radiotherapy.

Feasibility of ultrasonographic hepatic parenchymal attenuation imaging in healthy Beagles.

OBJECTIVE: To investigate the clinical feasibility of attenuation imaging of the hepatic parenchyma in healthy dogs, identify technical factors that influence measured attenuation coefficients, and determine intraobserver repeatability of measurements. ANIMALS: 10 healthy Beagles. PROCEDURES: Attenuation coefficients were calculated for various measurement sites (left vs central division of the liver), scanning planes (transverse vs sagittal plane), scanning depths (10 to 20 mm vs 20 to 30 mm), scanning approaches (intercostal vs subcostal approach), and breathing conditions (free breathing vs breath holding at end expiration). Intraoperator intraday and interday reliability was assessed by computing intraclass correlation coefficients. RESULTS: Attenuation coefficients were not influenced significantly by scanning plane (P = .120 to 1.000), measurement site (P = .292 to .848), or breathing condition (P = .166). However, coefficients were significantly (P < .01) less with deeper scanning depths and significantly (P < .05) more for the subcostal approach than the intercostal approach. The intraday and interday intraclass correlation coefficients showed good repeatability (0.799 and 0.771, respectively), regardless of the scanning plane and measurement site. Scanning the central division of the liver with the right intercostal approach at a depth of 10 to 20 mm from the liver capsule yielded good reliability. CLINICAL RELEVANCE: Attenuation imaging was a feasible technique for evaluating the hepatic parenchyma in healthy dogs with good repeatability. Measured attenuation coefficients were not affected by the scanning plane, measurement site, or breathing condition.

Effects of Confounding Factors on Liver Stiffness in Two-Dimensional Shear Wave Elastography in Beagle Dogs.

BACKGROUND: Two-dimensional shear wave elastography (2D-SWE) is a powerful technique that can non-invasively measure liver stiffness to assess hepatic fibrosis. PURPOSE: This study aimed to identify the effects of confounding factors, including anesthesia, breathing, and scanning approach, on liver stiffness when performing 2D-SWE in dogs. MATERIALS AND METHODS: Nine healthy Beagle dogs were included in this study. Hepatic 2D-SWE was performed, and liver stiffness was compared between conscious and anesthetized states, free-breathing and breath-holding conditions, and intercostal and subcostal approaches. For the anesthetized state, the breath-holding condition was subdivided into seven phases, which included forced-expiration (5 and 10 mL/kg), end-expiration (0 cm H2O), and forced-inspiration (5, 10, 15, and 20 cm H2O), and liver stiffness was compared among these phases. Changes in liver stiffness were compared between intercostal and subcostal approaches according to breathing phases. RESULTS: No significant difference was observed in liver stiffness between the conscious and anesthetized states or between the free-breathing and breath-holding conditions. No significant difference was noted in liver stiffness among the breathing phases, except for forced-inspiration with high airway pressure (15 and 20 cm H2O in the intercostal approach and 10, 15, and 20 cm H2O in the subcostal approach), which was associated with significantly higher liver stiffness (p < 0.05). Liver stiffness was significantly higher in the subcostal approach than in the intercostal approach (p < 0.05). Changes in liver stiffness were significantly higher in the subcostal approach than in the intercostal approach in all forced-inspiratory phases (p < 0.05). CONCLUSION: In conclusion, when performing 2D-SWE in dogs, liver stiffness is unaffected by anesthesia and free-breathing. To avoid inadvertent increases in liver stiffness, the deep inspiratory phase and subcostal approach are not recommended. Thus, liver stiffness should be interpreted considering these confounding factors.

Preoperative planning using computed tomography in tibial plateau levelling osteotomy: A comparison with conventional radiography.

BACKGROUND: Tibial plateau levelling osteotomy (TPLO) is currently one of the most common surgical procedures for the correction of the stifle joint with a ruptured cranial cruciate ligament. TPLO is based on the preoperative tibial plateau angle (TPA); therefore, it is essential to optimise the consistency and repeatability of TPA measurements. OBJECTIVES: This study aims to compare computed tomography (CT) with conventional radiography in the preoperative planning of TPLO. METHODS: This prospective study included six dogs (12 hindlimbs) and 13 canine cadaveric hindlimbs. In the six beagle dogs, TPAs were measured by three radiologists using digital radiographic and CT images to evaluate the intra- and inter-observer agreement. To evaluate the intra-observer agreement of the TPA before and after surgery, and the intended angle of the postoperative TPA according to the preoperative planning method, 13 cadaveric hindlimbs were evaluated thrice at random by a single radiologist. RESULTS: The intra- and inter-observer intraclass correlation coefficients (ICCs) of the CT method were higher than those of the radiographic method in normal beagle dogs. The intra-observer ICC of the CT method before and after TPLO was generally higher than that of the radiographic method in the cadaver. However, no significant difference was noted in the evaluation of the intended postoperative TPA according to the preoperative planning method. CONCLUSIONS: The intra- and inter-observer ICCs allowed for easy identification of landmarks required to consistently determine the TPA in the preoperative planning of TPLO based on CT images.

Efficacy of a Customized Three-Dimensional Printing Surgical Guide for Tibial Plateau Leveling Osteotomy: A Comparison With Conventional Tibial Plateau Leveling Osteotomy.

Objective: To prospectively evaluate the effect of a computed tomography (CT)-based three-dimensional (3D) printing surgical guide on surgical accuracy of tibial plateau leveling osteotomy (TPLO). Study Design: Cadaveric study. Animals: Canine cadaveric hindlimbs (n = 14). Methods: TPLO was performed on cadaver hindlimbs disarticulated at the coxofemoral joint to compare and evaluate the conventional TPLO method (n = 7) with one that used customized 3D printing surgical guides (n = 7). The operation time and postoperative tibial plateau angle (TPA) of the osteotomy were evaluated. Moreover, the osteotomy inclination, torsion, and distance and the direction of eccentricity were assessed using CT reconstruction. Results: Significant differences in the operation time (p < 0.001), postoperative TPA (p < 0.05), osteotomy inclination (p < 0.05), and osteotomy torsion (p < 0.05) were observed. Conclusion: The use of TPLO surgical guide reduced the operation time and inaccurate osteotomy. Clinical Significance: The surgical technique applied with a customized 3D printing surgical guide could be used to perform osteotomy and TPA adjustment more precisely than conventional TPLO.

Deep-Learning-Based Automatic Segmentation of Head and Neck Organs for Radiation Therapy in Dogs.

Purpose: This study was conducted to develop a deep learning-based automatic segmentation (DLBAS) model of head and neck organs for radiotherapy (RT) in dogs, and to evaluate the feasibility for delineating the RT planning. Materials and Methods: The segmentation indicated that there were potentially 15 organs at risk (OARs) in the head and neck of dogs. Post-contrast computed tomography (CT) was performed in 90 dogs. The training and validation sets comprised 80 CT data sets, including 20 test sets. The accuracy of the segmentation was assessed using both the Dice similarity coefficient (DSC) and the Hausdorff distance (HD), and by referencing the expert contours as the ground truth. An additional 10 clinical test sets with relatively large displacement or deformation of organs were selected for verification in cancer patients. To evaluate the applicability in cancer patients, and the impact of expert intervention, three methods-HA, DLBAS, and the readjustment of the predicted data obtained via the DLBAS of the clinical test sets (HA_DLBAS)-were compared. Results: The DLBAS model (in the 20 test sets) showed reliable DSC and HD values; it also had a short contouring time of ~3 s. The average (mean ± standard deviation) DSC (0.83 ± 0.04) and HD (2.71 ± 1.01 mm) values were similar to those of previous human studies. The DLBAS was highly accurate and had no large displacement of head and neck organs. However, the DLBAS in the 10 clinical test sets showed lower DSC (0.78 ± 0.11) and higher HD (4.30 ± 3.69 mm) values than those of the test sets. The HA_DLBAS was comparable to both the HA (DSC: 0.85 ± 0.06 and HD: 2.74 ± 1.18 mm) and DLBAS presented better comparison metrics and decreased statistical deviations (DSC: 0.94 ± 0.03 and HD: 2.30 ± 0.41 mm). In addition, the contouring time of HA_DLBAS (30 min) was less than that of HA (80 min). Conclusion: In conclusion, HA_DLBAS method and the proposed DLBAS was highly consistent and robust in its performance. Thus, DLBAS has great potential as a single or supportive tool to the key process in RT planning.

A genetic library screen for signaling proteins that interact with phosphorylated T cell costimulatory receptors.

In the past decade, the fundamental importance and therapeutic potential of costimulatory signals for lymphocyte activation have spurred a large amount of work in immunology, infection, cancer, autoimmune diseases, etc. However, the mechanisms behind T cell costimulation remain unclear, partly due to the lack of suitable techniques. There is an urgent need for functional genomic research to develop comprehensive approaches to direct identification of protein-protein interactions that are dependent on the posttranslational modification of one component of the complex, particularly in the field of T cell immunology. Using inducible costimulator (ICOS) as a model, we failed to find any proteins that associated with the cytoplasmic tail of ICOS by the yeast two-hybrid approach. Therefore, we have developed a new yeast three-hybrid system that facilitates the rapid screening of cDNA libraries to find signaling molecules that interact with phosphorylated T cell costimulatory receptors. We demonstrate the utility of this technique to detect the interaction between ICOS and the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). The p85 unit of PI3K is the only signaling molecule identified so far that interacts with ICOS. This system may be of great help in dissecting the mechanisms of T cell costimulation and could be applied to other receptors.

B7x: a widely expressed B7 family member that inhibits T cell activation.

B7 family proteins provide costimulatory signals that regulate T cell responses. Here we report the third set of B7 family-related T cell inhibitory molecules with the identification of a homolog of the B7 family, B7x. It is expressed in immune cells, nonlymphoid tissues, and some tumor cell lines. B7x inhibits cell-cycle progression, proliferation, and cytokine production of both CD4+ and CD8+ T cells. B7x binds a receptor that is expressed on activated, but not resting T cells that is distinct from known CD28 family members. Its receptor may be a recently identified inhibitory molecule, B and T lymphocyte attenuator. These studies identify a costimulatory pathway that may have a unique function in downregulation of tissue-specific autoimmunity and antitumor responses.