Can CT texture analysis parameters be used as imaging biomarkers for prediction of malignancy in canine splenic tumors?

Splenic hemangiosarcoma has morphological similarities to benign nodular hyperplasia. Computed tomography (CT) texture analysis can analyze the texture of images that the naive human eye cannot detect. Recently, there have been attempts to incorporate CT texture analysis with artificial intelligence in human medicine. This retrospective, analytical design study aimed to assess the feasibility of CT texture analysis in splenic masses and investigate predictive biomarkers of splenic hemangiosarcoma in dogs. Parameters for dogs with hemangiosarcoma and nodular hyperplasia were compared, and an independent parameter that could differentiate between them was selected. Discriminant analysis was performed to assess the ability to discriminate the two splenic masses and compare the relative importance of the parameters. A total of 23 dogs were sampled, including 16 splenic nodular hyperplasia and seven hemangiosarcoma. In each dog, total 38 radiomic parameters were extracted from first-, second-, and higher-order matrices. Thirteen parameters had significant differences between hemangiosarcoma and nodular hyperplasia. Skewness in the first-order matrix and GLRLM_LGRE and GLZLM_ZLNU in the second, higher-order matrix were determined as independent parameters. A discriminant equation consisting of skewness, GLZLM_LGZE, and GLZLM_ZLNU was derived, and the cross-validation verification result showed an accuracy of 95.7%. Skewness was the most influential parameter for the discrimination of the two masses. The study results supported using CT texture analysis to help differentiate hemangiosarcoma from nodular hyperplasia in dogs. This new diagnostic approach can be used for developing future machine learning-based texture analysis tools.

CT features of malignant and benign oral tumors in 28 dogs.

An improved understanding of the computed tomographic (CT) features for malignant versus benign oral tumors would be helpful for guiding prognosis and treatment planning decisions in dogs. This retrospective, multi-center, observational study compared the CT features of malignant and benign tumors in 28 dogs with 31 oral masses. Malignant tumors were present in 20 dogs, including malignant melanoma (n = 14), squamous cell carcinoma (SCC, n = 4), adenocarcinoma (n = 1), and fibrosarcoma (n = 1). Eight dogs had benign tumors, including giant cell granuloma (n = 2), peripheral odontogenic fibroma (n = 2), acanthomatous ameloblastoma (n = 2), plasmacytoma (n = 1), and oncocytoma (n = 1). Common CT features of malignant tumors included heterogeneous enhancement, tumor invasion into the adjacent bone, tooth loss, and ipsilateral mandibular lymphadenopathy. Malignant tumors were significantly larger than benign tumors. Bone lysis was found in benign tumors (n = 4) such as acanthomatous ameloblastoma, giant cell granuloma, and plasmacytoma. The bone lysis was a well-defined geographic area regardless of malignancy and tumor type. In periosteal reactions, amorphous patterns were seen in both malignant (n = 2) and benign tumors (n = 2); the latter subgroup also showed solid patterns. Bone expansion (n = 2) was identified in malignant melanoma and acanthomatous ameloblastoma. Findings supported a diagnosis of possible malignancy for dogs with oral tumors having the following CT characteristics: large size, heterogeneous contrast enhancement pattern, bone lysis, tooth loss, and ipsilateral lymphadenopathy. However, there was a considerable overlap of CT findings among the different types of oral tumors and between benign and malignant tumors. Histological evaluation therefore remains necessary for definitive diagnosis.

Assessment of neovascularization during bone healing using contrast-enhanced ultrasonography in a canine tibial osteotomy model: a preliminary study.

Blood perfusion of skeletal muscle and callus was evaluated using contrast-enhanced ultrasonography (CEUS) in a canine osteotomy model to determine the applicability of CEUS in the assessment of neovascularization during fracture healing and to compare the vascular signals on CEUS between external skeletal fixation and cast-applied dogs. In 6 Beagle dogs, a simple transverse osteotomy was performed at the left tibial shaft and external skeletal fixation (n = 3) or a cast (n = 3) was applied. Radiography, power Doppler ultrasonography (power Doppler), and CEUS were performed until complete union was achieved. On CEUS, vascular changes were quantitatively evaluated by measuring peak intensity (PI) and time to PI in the soft tissue and callus and by counting the vascular signals. Vascular signals from the soft tissue were detected on power Doppler and CEUS on day 2. Significantly more vascular signals were detected by CEUS than by power Doppler. On CEUS, PI in the surrounding soft tissue was markedly increased after the fracture line appeared indistinctively changed on radiography in all dogs. In the cast-applied dogs, vascular signals from the periosteal and endosteal callus were detected on CEUS before mineralized callus was observed on radiography. CEUS was useful in assessing the vascularity of soft tissue and callus, particularly in indirect fracture healing, and provided indications of a normally healing fracture.

Hybrid polymeric microspheres for enhancing the encapsulation of phenylethyl resorcinol.

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.

Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor.

BACKGROUND: Ticagrelor (TCG) is used to inhibit platelet aggregation in patients with acute coronary syndrome, but its poor solubility and low bioavailability limit its in vivo efficacy. The purpose of this study was to manufacture an optimized TCG-loaded self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability and antiplatelet activity of TCG. MATERIALS AND METHODS: Solubility and emulsification tests were conducted to determine the most suitable oils, surfactants, and cosurfactants. Scheffé's mixture design was applied to optimize the percentage of each component applied in the SMEDDS formulation to achieve optimal physical characteristics, ie, high solubility of TCG in SMEDDS, small droplet size, low precipitation, and high transmittance. RESULTS: The optimized TCG-loaded SMEDDS (TCG-SM) formulation composed of 10.0% Capmul MCM (oil), 53.8% Cremophor EL (surfactant), and 36.2% Transcutol P (cosurfactant) significantly improving the dissolution of TCG in various media compared with TCG in Brilinta® (commercial product). TCG-SM exhibited higher cellular uptake and permeability in Caco-2 cells than raw TCG suspension. In pharmacokinetic studies in rats, TCG-SM exhibited higher oral bioavailability with 5.7 and 6.4 times higher area under the concentration-time curve and maximum plasma concentration, respectively, than a raw TCG suspension. Antiplatelet activity studies exhibited that the TCG-SM formulation showed significantly improved inhibition of platelet aggregation compared with raw TCG at the same dose of TCG. And, a 10 mg/kg dose of raw TCG suspension and a 5 mg/kg dose of TCG-SM had a similar area under the inhibitory curve (907.0%±408.8% and 907.8%±200.5%⋅hours, respectively) for antiplatelet activity. CONCLUSION: These results suggest that the developed TCG-SM could be successfully used as an efficient method to achieve the enhanced antiplatelet activity and bioavailability of TCG.

Quantitative evaluation of renal parenchymal perfusion using contrast-enhanced ultrasonography in renal ischemia-reperfusion injury in dogs.

This study evaluated whether renal perfusion changes can be noninvasively estimated by using contrast-enhanced ultrasonography (CEUS) in renal ischemia-reperfusion injury and investigated the correlation between renal perfusion measured by CEUS and necrosis and apoptosis of renal tubular epithelial cells. In six dogs with experimentally induced renal ischemia-reperfusion injury, changes in time to peak intensity, peak intensity, and area under the curve were measured on CEUS. Peak intensity and area under the curve of the renal cortex began to decrease on day 1 (about 20% lower than baseline) and reached the lowest levels (about 50% of baseline) on day 4. They then gradually increased until day 10, at which time peak intensity was about 87% and area under the curve was about 95% of baseline; neither fully recovered. Both parameters were strongly correlated with the necrosis scores on histopathologic examination on day 4 (r = -0.810 of peak intensity and r = -0.886 of area under the curve). CEUS allowed quantitative evaluation of perfusion changes in acute renal ischemia-reperfusion injury, and CEUS results were correlated with renal tubular damage on histopathologic examination. Thus, CEUS could be a noninvasive, quantitative diagnostic method for determining progress of renal ischemia-reperfusion injury.

Simultaneous imaging of magnetic field and temperature distributions by magneto optical indicator microscopy.

We report a simultaneous imaging method of the temperature and the magnetic field distributions based on the magneto optical indicator microscopy. The present method utilizes an optical indicator composed of a bismuth-substituted yttrium iron garnet thin film, and visualizes the magnetic field and temperature distributions through the magneto-optical effect and the temperature dependent optical absorption of the garnet thin film. By using a printed circuit board that carries an electric current as a device under test, we showed that the present method can visualize the magnetic field and temperature distribution simultaneously with a comparable temperature sensitivity (0.2 K) to that of existing conventional thermal imagers. The present technique provides a practical way to get a high resolution magnetic and thermal image at the same time, which is valuable in investigating how thermal variation results in a change of the operation state of a micrometer sized electronic device or material.

Dynamic computed tomographic determination of scan delay for use in performing cardiac angiography in clinically normal dogs.

OBJECTIVE: To determine the scan delay for use in performing cardiac CT angiography in dogs. ANIMALS: 4 clinically normal adult Beagles. PROCEDURES: In a crossover study, 12 formulations of iohexol solutions differing in iodine dose (300, 400, and 800 mg/kg) and concentration (undiluted and diluted 1:1, 1:2, and 1:3 with saline [0.9% NaCl] solution) were administered IV to each dog. Dynamic CT angiography was performed to evaluate enhancement characteristics of each formulation, with the region of interest set over the aorta. Time-attenuation curves (TACs) were obtained and analyzed. RESULTS: Peak arc-type TACs were obtained after administration of all undiluted formulations. Curve shape changed from peak arc type to plateau type as the total volume of the contrast solution (ie, dilution) increased. Prolonged peaks characteristic of plateau-type TACs suggested that a sufficient period of homogeneous attenuation could be achieved for CT scanning with administration of higher iohexol dilutions (1:2 or 1:3) containing higher iodine doses (400 or 800 mg/kg). In particular, attenuation values for plateau-type TACs remained between 200 and 300 Hounsfield units for > 16 seconds after the plateau endpoint was reached for 1:2 and 1:3 dilutions containing an iodine dose of 800 mg/kg. Scan delays of 13 to 17 seconds were computed for those 2 formulations. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that for clinically normal dogs, a scan delay of 13 to 17 seconds could be used to perform cardiac CT angiography with iohexol solutions containing an iodine dose of 800 mg/kg at dilutions of 1:2 or 1:3.

STRAIN ELASTOGRAPHY USING DOBUTAMINE-INDUCED CAROTID ARTERY PULSATION IN CANINE THYROID GLAND.

Thyroid disease is common in dogs and conventional ultrasonography is a standard diagnostic test for diagnosis and treatment planning. Strain elastography can provide additional information about tissue stiffness noninvasively after applying external or internal compression. However, natural carotid artery pulsations in the canine thyroid gland are too weak to maintain sufficient internal compression force. The objective of the present study was to describe the feasibility of strain elastography for evaluating the canine thyroid gland and the repeatability of dobutamine-induced carotid artery pulsation as an internal compression method. In seven healthy Beagle dogs, strain on each thyroid lobe was induced by external compression using the ultrasound probe and internal compression using carotid artery pulsation after dobutamine infusion. The thyroid appeared homogeneously green and the subcutaneous fat superficial to the thyroid lobe appeared blue. Strain values and strain ratios did not differ among dogs or between the left and right lobes. Interobserver repeatability was excellent for both compression methods. Intraobserver repeatability of the strain ratio measured using the carotid artery pulsation method (intraclass coefficient correlation = 0.933) was higher than that measured using the external compression method (0.760). Mean strain values of thyroid lobes for the external compression method (142.93 ± 6.67) differed from the internal method (147.31 ± 8.24; P < 0.05). Strain ratios between the two methods did not differ. Strain elastography was feasible for estimating thyroid stiffness in dogs. Carotid artery pulsation induced by dobutamine infusion can be used for canine thyroid strain elastography with excellent repeatability.

Tissue Doppler and strain imaging of left ventricle in Beagle dogs with iatrogenic hypercortisolism.

Changes in radial and longitudinal left ventricular (LV) function were investigated in beagles with iatrogenic hypercortisolism. A total of 11 normal dogs were used, and 2 mg/kg prednisone was administered per oral q12 h for 28 days to 7 out of 11 dogs to induce iatrogenic hypercortisolism. Body weight, blood pressure, conventional echocardiography and tissue Doppler imaging (TDI) of normal and iatrogenic hypercortisolism groups were conducted. The myocardial wall velocity of the LV was measured using color TDI and myocardial deformation was determined by the strain and strain rate. Conventional echocardiography revealed that the diastolic LV free wall and interventricular septum in the hypercortisolism group were thickened relative to those in the normal group. The peak early diastolic myocardial velocity and early to late diastolic myocardial velocity ratio of TDI in the hypercortisolism group were significantly lower than those in the normal group. The strain values in the hypercortisolism group were significantly lower than those in the normal group, particularly for longitudinal wall motion. The lower values of myocardium from TDI and strain imaging could be used to investigate subclinical LV systolic and diastolic dysfunction in dogs with the iatrogenic hypercortisolism.

Contrast-enhanced ultrasonography to assess blood perfusion of skeletal muscles in normal dogs.

This study evaluated perfusion of skeletal muscle using contrast enhanced ultrasonography in humerus, radius, femur and tibia in normal dogs. Contrast enhanced ultrasonography for each region was performed after injecting 0.5 mL and 1 mL of contrast medium (SonoVue) in every dog. Blood perfusion was assessed quantitatively by measuring the peak intensity, time to the peak intensity and area under the curve from the time-intensity curve. Vascularization in skeletal muscle was qualitatively graded with a score of 0-3 according to the number of vascular signals. A parabolic shape of time-intensity curve was observed from muscles in normal dogs, and time to the peak intensity, the peak intensity and area under the curve of each muscle were not significantly different according to the appendicular regions examined and the dosage of contrast agent administered. This study reports that feasibility of contrast enhanced ultrasonography for assessment of the muscular perfusion in canine appendicular regions.

ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN CLINICALLY NOR-MAL BEAGLE DOGS [corrected].

Standard ultrasonography is often insensitive for distinguishing normal vs. diseased states for canine abdominal organs. Ultrasonographic elastography is a new technique that is becoming increasingly available and may help to improve sensitivity. This study evaluated the feasibility, repeatability, and reproducibility of strain elastography of the liver, spleen, kidneys, and prostate in healthy dogs and described the elasticity of each organ using strain values and strain ratios. The reproducibility of strain elastography was excellent, and intraobserver repeatability was moderate to excellent. The strain value of each organ was not significantly different among dogs (liver = 143.38 ± 7.41, spleen = 141.04 ± 9.03, left renal cortex = 141.26 ± 7.50, right renal cortex = 145.80 ± 7.79, and prostate = 135.46 ± 5.80), except for the renal medulla (left = 51.19 ± 4.54 and right = 51.93 ± 5.09) (P < 0.05). The strain ratios for the liver, spleen, renal cortex, and prostate were similar with no significant difference (liver = 10.20 ± 1.47, spleen = 8.40 ± 1.53, left renal cortex = 9.62 ± 1.56, right renal cortex = 8.29 ± 1.63, and prostate = 8.20 ± 1.21), except for the renal medulla (left = 3.48 ± 0.68 and right = 2.95 ± 0.63) (P < 0.05). Our results indicated that strain elastography was feasible for estimating tissue stiffness in the canine liver, spleen, kidneys, and prostate. This study provides basic information for strain values and strain ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs.

Measurements of the pulmonary vasculature on thoracic radiographs in healthy dogs compared to dogs with mitral regurgitation.

This study reassessed the previously reported radiographic method of comparing pulmonary vessels versus rib diameter for differentiating healthy dogs and dogs with mitral regurgitation. The width of the right cranial pulmonary artery and vein at the fourth rib level, right caudal pulmonary artery and vein at the ninth rib level, and the diameters of the fourth rib and ninth rib were measured in prospectively recruited healthy dogs (n = 40) and retrospectively recruited dogs with mitral regurgitation (n = 58). In healthy dogs, the pulmonary arteries and accompanying veins were similar in size. The cranial lobar vessels were smaller than the fourth rib. However, 67.5% of right caudal pulmonary artery diameters and 65% of vein diameters were larger than the ninth rib in healthy dogs. The right caudal pulmonary vein diameter in dogs with mitral regurgitation, particularly those within moderate and severe grades, was significantly larger than that in healthy dogs (P < 0.001). The comparative method used to detect enlargement of the right caudal pulmonary vein relative to the accompanying pulmonary artery had the highest sensitivity (80.2%) and specificity (82.5%) for predicting mitral regurgitation. A cut-off of 1.22 when applying the ninth rib criterion had better specificity (73%) than the most used value ≤ 1 (89.7% sensitivity and 63.8% specificity), although it has less sensitivity (73%). We recommend using the accompanying pulmonary artery and 1.22 × the diameter of the ninth rib as a radiographic criterion for assessing the size of the right caudal pulmonary vein and differentiating healthy dogs from those with mitral regurgitation.

Effect of region of interest and slice thickness on vertebral bone mineral density measured by use of quantitative computed tomography in dogs.

OBJECTIVE: To determine the effect of region of interest (ROI) setting and slice thickness on trabecular bone mineral density (BMD) measured with quantitative CT in dogs. ANIMALS: 14 healthy Beagles. PROCEDURES: CT of the lumbar vertebrae and a quantitative CT phantom was performed. The BMD of trabecular bone was measured from L1 to L7 in 2 ways in all dogs. First, sequential 9.6-mm-thick CT images were acquired and then CT images were reconstructed into transverse CT images with slice thicknesses of 2.4, 4.8, and 9.6 mm. The obtained images were analyzed by circular ROI and trace ROI methods. Second, lumbar vertebrae were scanned with the installed quantitative CT protocol with a slice thickness of 10 mm and then the CT images were analyzed by installed automatic BMD software. RESULTS: Interclass correlation coefficients of the automatic software (0.975 to 1.0) and the circular method (0.871 to 0.996) were high, compared with those of the trace method (0.582 to 0.996). The BMD measured with the automatic software was not significantly different from that measured with circular ROI and a slice thickness of 9.6 mm. The BMD measured by use of the circular method was not different according to slice thickness. CONCLUSIONS AND CLINICAL RELEVANCE: Results obtained by use of automatic software were similar to those obtained by use of more manual methods. The CT images with thinner slice thickness (2.4 and 4.8 mm) could be used in dogs of toy and small breeds to measure lumbar vertebrae BMD to reduce the limitations of the standard 10-mm slice thickness.

Ultrasound, CT and FDG PET-CT of a duodenal granuloma in a dog.

A 12-year-old spayed female Yorkshire Terrier with intermittent vomiting was diagnosed with regional granulomatous enteritis through histopathological examination. On ultrasonography and computed tomography, a focal thickened duodenal wall showed a mass-like appearance with indistinct wall layers. Marked uptake of (18)F-fluorodeoxyglucose was observed from the mass on positron emission tomography-computed tomography. Regional granulomatous enteritis is a rare form of inflammatory bowel disease and may have imaging features similar to intestinal tumors. This is the first study describing the diagnostic imaging features of ultrasonography, computed tomography and positron emission tomography-computed tomography for regional granulomatous enteritis in a dog.

Computed tomography angiography of situs inversus, portosystemic shunt and multiple vena cava anomalies in a dog.

A 5-year-old Shih Tzu was presented with intermittent vomiting and anorexia. Microhepatica and reversed position of the abdominal organs were observed on radiography. Ultrasonographically, portosystemic shunt (PSS) was tentatively diagnosed. Computed tomography (CT) revealed that the distended portal vein drained into the left hepatic vein. The caudal vena cava (CdVC) split postrenally and converged at the renal level. Cranial to this, the azygos continuation of the CdVC was confirmed. In the thorax, a persistent left cranial vena cava (CrVC) was found along with right CrVC. This is the first report of a dog with persistent left CrVC and multiple abdominal malformations. CT angiography was useful in evaluating the characteristics of each vascular anomaly and determining the required surgical correction in this complex case.