Effects of parenteral administration of tylosin and ivermectin on abomasal emptying rate in healthy suckling lambs by use of nuclear scintigraphy.

Abomasal hypomotility is one of the important causes of neonatal mortality in small ruminants. Various pharmaceutical agents have been studied to address this problem in large ruminants. The aim of this study was to determine the effect of parenteral administration of tylosin and ivermectin on abomasal emptying rate in neonatal suckling lambs. Abomasal emptying rate was assessed using nuclear scintigraphic method in 10 healthy female Iranian fat tailed Ghezel lambs. Each lamb was tested three times, once as a control (1 ml of saline 0.9%, IM) and twice after the injection of tylosin (17.6 mg/kg, IM) and ivermectin (200 µg/kg, SC) in a crossover study. Based on radiopharmaceutical counts, remnant activity in abomasums at 90 min were 48.3 ± 3.5, 45.6 ± 7.5 and 41.6 ± 2.9% in control, tylosin and ivermectin groups, respectively. Administration of tylosin (p = 0.049) and ivermectin (p = 0.045) to lambs, significantly caused faster abomasal emptying rate compared to control. Evaluating the ROIs revealed that the half emptying time (T1/2) in control, tylosin and ivermectin groups were 67.1 ± 8.6, 62.6 ± 14.2 and 54.3 ± 9.9 min, respectively. These difference between all groups, statistically were significant (p = 0.026). However, the clinical efficacy of abomasal emptying rate facilitating by tylosin or ivermectin administration in lambs remains to be determined.

Furosemide administration onehour before bone scintigraphy examination in horses does not improve the image quality or reduce the radiation dose rate.

This prospective, cross-sectional, pilot study aimed to investigate the effects of furosemide as a diuretic on the image quality of bone scintigraphy performed using 99m Tc-HDP and to investigate the impact of furosemide on the radiation dose rate. Thirty-one horses undergoing bone scintigraphy were included. The horses were divided into the control (n = 14) and furosemide group (n = 17), which received 1 mg/kg furosemide intravenously 1 h post 99m Tc-HDP administration. The image quality was assessed subjectively and semi-quantitatively. The bone-to-soft tissue (B:S) ratio was calculated from the counts per pixel of regions of interest (ROI) positioned over the left radial diaphysis (bone ROI) and its caudal soft tissue area (soft tissue ROI). The radiation rate dose (µSv/h) of both groups was measured at 0, 3, 6, 12, 18, and 24 h post 99m Tc-HDP administration at a distance of 0, 30, and 100 cm from the head, kidney, and pelvis. The results showed no significant differences in the B:S ratio or the radiation dose rate observed between the groups. However, the radiation dose rate decreased by 56% at 3 h post 99m Tc-HDP administration and keeping a distance of 30 cm reduced the radiation dose rate by 65%. Administering furosemide does not improve the image quality or reduce the radiation dose rate. The authors recommend commencing with bone scintigraphy 3 h post 99m Tc-HDP administration and keeping at least a distance of 30 cm from the horse to reduce the staff radiation dose.

Postinjury performance for differing humeral stress fracture locations in the racing thoroughbred.

OBJECTIVE: To assess the influence of humeral stress fracture location on the time to return to racing and postinjury performance of thoroughbred racehorses. STUDY DESIGN: Retrospective study (1992-2015). SAMPLE POPULATION: Thoroughbred racehorses (n = 131) that presented for lameness with the sole diagnosis of humeral stress fractures in the lame limb, as determined by scintigraphy or radiology. METHODS: Sex, fracture site, age, starts, earnings, and average earnings per race were examined for differences in pre-stress and post-stress fracture diagnosis for the entire population as well as individual stress fracture locations (general linear model, χ2 tests). Pre-stress and post-stress fracture performance for the three stress fracture locations were assessed: (1) earnings pre-stress and post-stress fracture (Kruskal-Wallis one-way analysis of variance), (2) average earnings per start prefracture, and (3) average earnings per start postfracture (Wilcoxon signed-rank tests). RESULTS: Stress fracture locations were caudodistal (n = 36), craniodistal (n = 43), and caudoproximal (n = 52). One hundred ten of 131 horses raced postfracture, and 54 of 131 horses raced prefracture. Age at injury was 43.61 months caudodistal, 33.48 months caudoproximal, and 36.65 months craniodistal. Horses returned to race at a median of 244 days (range, 218-272). Postfracture earnings per start were greater for caudodistal vs caudoproximal (P = .04). CONCLUSION: There were no differences in prefracture earnings or fracture site and sex or limb affected. Return-to-race time varied by location but not significantly. Differences in earnings preinjury and postinjury were not significant. Horses with a stress fracture at the caudodistal location earned significantly more compared with horses with a stress fracture at the caudoproximal location after they returned to race. CLINICAL SIGNIFICANCE: Thoroughbred racehorses have a good prognosis for return to racing regardless of fracture location.

Renal ultrasonographic abnormalities are associated with low glomerular filtration rate calculated by scintigraphy in dogs.

Ultrasound provides information on kidney morphology, but studies relating structural and functional abnormalities in chronic kidney disease (CKD) are lacking. The aim of this descriptive cross-sectional study was to compare individual kidney (IK) B-mode ultrasound abnormalities to IK glomerular filtration rate (GFR) estimated by scintigraphy normalized to plasma volume (PV) in dogs, to evaluate if ultrasonographic findings were associated with low IKGFR/PV. Eighty privately owned dogs with and without clinical suspicion of CKD were prospectively enrolled, and kidney ultrasound and IKGFR/PV were evaluated independently. Ultrasound images were assessed retrospectively for subjective abnormalities (shape, cortical, and medullary hyperechogenicity), and kidney size was measured. The normal IKGFR/PV cutoff was derived from dogs in the study group with no history and clinical signs of kidney disease and normal blood and urine results (n = 28) and was 16.84 mL/min/L. Kidneys were categorized into normal, mild, moderate, and severe ultrasound changes according to subjective ultrasound grades. Associations were found between low IKGFR/PV and abnormal kidney shape (P = .0004), cortical hyperechogenicity (P = .0008), medullary hyperechogenicity (P < .0001), and low kidney volume (P = .0092). Apart from the moderate and severe category comparison, IKGFR/PV value significantly decreased with increasing severity of category. The combination of ultrasonographic subjective abnormalities had a high sensitivity (93.8%) and moderate specificity (65.7%) for detecting low IKGFR/PV. Kidneys with normal IKGFR/PV had a low frequency of mild ultrasound changes. Findings indicate kidneys with increasing number and grade of subjective ultrasound abnormalities are more likely to have a lower IKGFR/PV.

Pilot study: use of contrast-enhanced ultrasonography in feline renal transplant recipients.

Objectives The study aims were to evaluate the feasibility of contrast-enhanced ultrasonography in feline renal transplant recipients in the post-transplantation period and to report findings in a case with presumptive delayed allograft ischemia. Methods Cats were imaged postoperatively using contrast harmonic ultrasonography after a bolus injection of a microbubble contrast medium. Time/mean pixel intensity curves were generated for cortical and medullary regions of interest in the renal allograft in each cat. Arrival time, time to peak, wash-in slope, wash-out slope, mean transit time and renal blood flow were calculated for each area. Results Within the renal cortices of cats without ureteral obstruction 1 day post-transplantation, arrival time was 2.0-6.3 s, time to peak was 3.6-30.1 s, wash-in rate was 2.45-41.14 mean pixel intensity (MPI)/s, wash-out rate was -2.01 to -0.47 MPI/s and blood flow was 6.1-106.5 MPI/s. Ratio mean transit time was 0.29-1.29. Typical cortical and medullary perfusion patterns were observed in these cats. In one cat with delayed graft ischemia followed by presumptive acute transplant rejection, dynamic and heterogeneous cortical and medullary perfusion was demonstrated. Decreases in cortical blood flow were paralleled by elevated serum creatinine. Conclusions and relevance Contrast-enhanced ultrasonography can be used in feline renal transplant recipients and provides both qualitative and quantitative data regarding renal allograft perfusion.

Predictive value of scintigraphic (semi-)quantitative thyroid parameters on radioiodine therapy outcome in hyperthyroid cats.

Objectives The outcome of radioiodine therapy in hyperthyroid cats is suspected to be influenced by multiple factors. The degree of activity of the thyroid gland, represented by uptake of sodium pertechnetate or tracer activities of radioiodine by the thyroid gland on thyroid scintigraphy, has been suggested in the literature as one of those. Thyroid gland pertechnetate uptake can be represented by (semi-)quantitative factors such as the thyroid to salivary gland (T/S) ratio, the thyroid to background (T/B) ratio and the percentage technetium uptake by the thyroid glands (%TcU). The aim of this study was to investigate a possible relationship between these thyroid scan parameters and radioiodine therapy outcome. Methods Sodium pertechnetate thyroid scans of 75 hyperthyroid cats were retrospectively evaluated and statistical analysis was performed with and without correction for injected radioiodine activity. Three different background regions of interest (ROIs) were used to calculate the T/B ratio and %TcU: 'neck', 'circle' and 'copy ROI'. Results Higher T/S ratios were found to be significantly related to a persistent hyperthyroid outcome in both analyses. For the T/S ratio, a threshold value of 5.4 was determined, with a sensitivity of 73% and a specificity of 59%. An increased risk for persistent hyperthyroidism compared with a final euthyroid outcome with an increased T/Bcircle ratio was only found to be significant without correction for the activity of radioiodine administered. For the %TcU no statistical significance was reached. Regarding a low total thyroxine outcome, no significant relationships with any of the investigated parameters were found. Conclusions and relevance The findings of this study suggest that semi-quantification of thyroid gland uptake is best performed using the T/S ratio. A T/S ratio ⩾5.4 is a possible indicator for an increased risk of persistent hyperthyroidism.

Thyroid Cysts in Cats: A Retrospective Study of 40 Cases.

BACKGROUND: Thyroid cysts are rare in cats and poorly documented. OBJECTIVES: To report distinguishing clinical features and treatment responses of cats with thyroid cysts. ANIMALS: Forty client-owned cats. METHODS: Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded. RESULTS: Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm3 ) in 16 (40%) and large (>8 cm3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4). CONCLUSIONS AND CLINICAL IMPORTANCE: Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism.

Diagnosis of lumbosacral diskospondylosis in a bucking bull assisted by high-definition thermal and nuclear scintigraphic imaging.

CASE DESCRIPTION An 8-year-old Brahman-cross bull was evaluated for left hind limb lameness of 2 months' duration. The lameness was first noticed during a rodeo bucking performance, immediately after the bull appeared to land inappropriately on the affected limb. CLINICAL FINDINGS Physical examination findings revealed left hind limb lameness, ataxia, and left-sided epaxial muscle atrophy. Palpation per rectum along the lumbar portion of the vertebral column revealed evidence of exostosis of the ventral aspect. High-definition infrared thermal imaging revealed a pattern of reduced skin temperature in the area of the left lumbar and gluteal regions suggestive of a disruption in the sympathetic control of peripheral blood flow. Nuclear scintigraphy revealed a focal area of increased radioisotope uptake on the left ventrolateral aspect of the L2-3 intervertebral joint. A presumptive diagnosis of ventrolateral vertebral spondylosis resulting in spinal nerve impingement was made. TREATMENT AND OUTCOME 200 mg of methylprednisolone was epidurally injected at the site of the lesion, and treatment with polysulfated glycosaminoglycans was initiated (500 mg, IM, every 4 days for 7 treatments, then monthly thereafter). The lameness and ataxia observed in the left hind limb resolved within 1 week after treatment began. Subsequently, the bull was discharged from the hospital and was used successfully for semen collection and live-cover breeding. CLINICAL RELEVANCE Use of thermography for the bull of this report provided additional insight into neurovascular physiologic function that classical imaging modalities are unable to provide and, when combined with nuclear scintigraphy, aided in identifying the most critical lesion in a complex clinical case.

Scintigraphic Tracking of Allogeneic Mesenchymal Stem Cells in the Distal Limb After Intra-Arterial Injection in Standing Horses.

OBJECTIVE: To assess the feasibility of intra-arterial administration of allogeneic mesenchymal stem cells (MSC) in the median artery of standing horses and evaluate the distribution and retention of radiolabeled cells. STUDY DESIGN: In vivo experimental study. ANIMALS: Six research horses. METHODS: Technetium(99m) -HexaMethyl-Propylene-Amine Oxime-labeled MSC were injected under ultrasound guidance in the median artery of 6 front limbs of 3 horses, standing under sedation. Scintigraphic images were obtained at the time of injection, and at 1, 6, and 24 hours postinjection. Six additional limbs from 3 horses were similarly injected with unlabeled MSC. Ultrasound was performed the following day for assessment of vascular changes. RESULTS: Intra-arterial injection was performed successfully in 11 of 12 limbs. In 1 limb, partial periarterial injection compromised the success of the procedure. Homogeneous distribution of radiolabeled MSC was observed through the entire distal limb, including within the hoof. Partial venous thrombosis was found in both groups of horses, but was subjectively less severe in horses injected with unlabeled MSC. No lameness was observed. Transient swelling of the distal limb occurred in only 1 limb. CONCLUSION: Intra-arterial injection of MSC can be performed in standing horses under sedation and successfully distribute MSC to the distal limb. A risk of periarterial injection was identified but can be reduced with proper sedation, local anesthesia, and increased experience. Partial venous thrombosis was observed as a complication, but did not cause changes of clinical importance, other than rare transient swelling.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland.

EVALUATION OF THYROID TO BACKGROUND RATIOS AND COMPARISON OF VARIOUS SCINTIGRAPHIC MEASUREMENTS AND THEIR CORRELATION TO SERUM T4 IN HYPERTHYROID CATS.

Thyroid-to-salivary ratio and percent dose uptake are the most widely recognized scintigraphic measurements. Recently, the thyroid-to-background ratio has been proposed as an alternate method. However, this method has not been validated. The purpose of this observational, cross-sectional, prospective study was to determine the location of a background region of interest (ROI) that is most reflective of blood pool activity. We also hypothesized that the thyroid-to-background ratio using this background ROI would be a better predictor of thyroid function. Fifty-six cats presented to the Virginia-Maryland College of Veterinary Medicine seeking radioiodine therapy for hyperthyroidism were enrolled in this cross-sectional study to evaluating thyroid-to-background ratio. A blood sample for measuring plasma radioactivity was collected at the time of scintigraphy. The plasma radioactivity was compared to the background ROIs in eight anatomic regions. Scintigraphic measures of thyroid-to-background and thyroid-to-salivary ratios, and percent dose were then compared to serum T4 . The heart ROI was most closely correlated with plasma pertechnetate activity (r = 0.70). Percent dose uptake was most closely correlated with serum T4 (r = 0.74), followed by thyroid-to-salivary ratio (r = 0.66) and thyroid-to-background ratio using the heart ROI (r = 0.59). Thyroid-to-background ratio using the heart background ROI is a good predictor T4 but percent dose uptake and thyroid-to-salivary ratio proved to be better predictors of T4 than any of the thyroid-to-background ratios.

In Vivo Imaging and Tracking of Technetium-99m Labeled Bone Marrow Mesenchymal Stem Cells in Equine Tendinopathy.

Recent advances in the application of bone marrow mesenchymal stem cells (BMMSC) for the treatment of tendon and ligament injuries in the horse suggest improved outcome measures in both experimental and clinical studies. Although the BMMSC are implanted into the tendon lesion in large numbers (usually 10 - 20 million cells), only a relatively small number survive (<10%) although these can persist for up to 5 months after implantation. This appears to be a common observation in other species where BMMSC have been implanted into other tissues and it is important to understand when this loss occurs, how many survive the initial implantation process and whether the cells are cleared into other organs. Tracking the fate of the cells can be achieved by radiolabeling the BMMSC prior to implantation which allows non-invasive in vivo imaging of cell location and quantification of cell numbers. This protocol describes a cell labeling procedure that uses Technetium-99m (Tc-99m), and tracking of these cells following implantation into injured flexor tendons in horses. Tc-99m is a short-lived (t1/2 of 6.01 hr) isotope that emits gamma rays and can be internalized by cells in the presence of the lipophilic compound hexamethylpropyleneamine oxime (HMPAO). These properties make it ideal for use in nuclear medicine clinics for the diagnosis of many different diseases. The fate of the labeled cells can be followed in the short term (up to 36 hr) by gamma scintigraphy to quantify both the number of cells retained in the lesion and distribution of the cells into lungs, thyroid and other organs. This technique is adapted from the labeling of blood leukocytes and could be utilized to image implanted BMMSC in other organs.

Scintigraphic tracking of mesenchymal stem cells after intravenous regional limb perfusion and subcutaneous administration in the standing horse.

OBJECTIVE: To assess distribution, uptake, and persistence of radiolabeled mesenchymal stem cells (MSC) using scintigraphy after intravenous regional limb perfusion (RLP) and subcutaneous injections in standing, sedated horses. STUDY DESIGN: Experimental study. ANIMALS: Horses (n = 12). METHODS: Six horses had RLP performed through the cephalic vein on 1 limb and subcutaneous injection in the metacarpal area in the opposite limb. The other 6 horses had RLP performed through the lateral palmar digital vein and subcutaneous injection in the coronary band. A pneumatic tourniquet was used for the RLP. MSC were labeled with technetium-HMPAO. Scintigraphic images were obtained at the time of injection, 1, 6, and 24 hours later. Results of RLP were compared with results from previous studies where similar injections were performed in anesthetized horses. RESULTS: Both RLP techniques led to greater variability, lower uptake, lower persistence, and poorer distribution when compared to results previously reported for horses under general anesthesia. The subcutaneous injections in the metacarpal area and coronary band resulted in MSC loss to the general circulation but no evidence of local migration. CONCLUSION: Due to partial or complete failure of the tourniquet, RLP performed in the standing horse as described is less efficient than performed under general anesthesia. Further work is needed to optimize the use of tourniquets to perform RLP for MSC administration in standing patients. The subcutaneous injections did not result in local migration in these normal horses.

Does hepatic steatosis have an impact on the short term hepatic response after complete attenuation of congenital extrahepatic portosystemic shunts? A prospective study of 20 dogs.

OBJECTIVE: To evaluate the relationship between hepatic steatosis and increase in liver size and resolution of shunting after surgical attenuation of congenital extrahepatic portosystemic shunts in dogs. STUDY DESIGN: Prospective study. ANIMALS: Dogs (n = 20) with congenital extrahepatic portosystemic shunts. METHODS: Shunts were attenuated using ameroid ring constrictors. Portal blood flow and liver volume were evaluated using computed tomography before and ≥8 weeks after surgery. Hepatic steatosis was quantified by stereological point counting of lipid droplets and lipogranulomas (LG) in liver biopsies stained with Oil-red-O. Associations between steatosis and preoperative liver volume, liver growth after surgery, and development of acquired shunts were evaluated. RESULTS: Acquired shunts developed in 2 dogs (10%). Dogs with larger preoperative liver volumes relative to bodyweight had fewer lipid droplets per tissue point (P = .019). LG per tissue point were significantly associated with age: 0.019 ± 0.06 for dogs <12 months versus 0.25 ± 0.49 for dogs >12 months (P = .007). There was a significant positive association between liver growth after surgery and the number of LG/month of age in dogs >12 months (P = .003). There was no association between steatosis, presence of macrosteatosis, the number of LG or development of acquired shunts. CONCLUSIONS: This preliminary study suggests that the presence of hepatic lipidosis and LG has no demonstrable effect on development of acquired shunts or the magnitude of increase in liver volume after attenuation of congenital extrahepatic portosystemic shunts in dogs.

Thyroid scintigraphy in veterinary medicine.

Thyroid scintigraphy is performed in cats and dogs and has been used to a limited degree in other species such as the horse. Thyroid scintigraphy is most commonly used to aid in the diagnosis and treatment management of feline hyperthyroidism but is also used in the evaluation of canine hypothyroidism and canine thyroid carcinoma. This article reviews the normal scintigraphic appearance of the thyroid in the cat, the dog, and the horse and the principles of interpretation of abnormal scan results in the cat and the dog. Radioiodine is the treatment of choice for feline hyperthyroidism, and the principles of its use in the cat are reviewed.

Scintigraphic comparison of intra-arterial injection and distal intravenous regional limb perfusion for administration of mesenchymal stem cells to the equine foot.

REASONS FOR PERFORMING STUDY: Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use. OBJECTIVES: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v. RLP through the lateral palmar digital vein. STUDY DESIGN: In vivo experimental study. METHODS: (99m) Tc-HMPAO-labelled MSCs were injected through the median artery of one limb and the lateral palmar digital vein of the other limb of 6 horses under general anaesthesia. No tourniquet was used for the i.a. injection. A pneumatic tourniquet was placed on the metacarpus for i.v. injection. Scintigraphic images were obtained up to 24 h after injection. RESULTS: Intra-arterial injection resulted in MSCs retention within the limb despite the absence of a tourniquet and no thrombosis was observed. Both i.a. injection and i.v. RLP led to distribution of MSCs to the foot. The i.a. injection resulted in a more homogeneous distribution. The MSC uptake was higher with i.v. RLP at the initial timepoints, but no significant difference was present at 24 h. CONCLUSIONS: Both i.a. injection through the median artery without a tourniquet and i.v. RLP performed through the lateral palmar digital vein under general anaesthesia are safe and reliable methods for administration of MSCs to the equine foot. The i.a. technique is preferred owing to the better distribution, but is technically more challenging. The feasibility of performing these techniques on standing horses remains to be investigated.

Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb.

REASONS FOR PERFORMING STUDY: Intralesional (i.l.) injection is currently the most commonly used technique for stem cell therapy in equine tendon injury. A comparison of different techniques of injection of mesenchymal stem cells for the treatment of tendon lesions is required. OBJECTIVES: We hypothesised that vascular perfusion of the equine distal limb with mesenchymal stem cells (MSCs) would result in preferential distribution of MSCs to acute tendon injuries. STUDY DESIGN: In vivo experimental study. METHODS: Lesions were surgically induced in forelimb superficial digital flexor tendons of 8 horses. Three or 10 days after lesion induction, technetium-99 hexamethyl propylene amine oxime-labelled MSCs were injected via i.v. or intra-arterial (i.a.) regional limb perfusion (RLP) at the level of the distal antebrachium and compared to i.l. injection. Mesenchymal stem cell persistence and distribution within the forelimb and tendon lesions was assessed with scintigraphy for 24 h. RESULTS: Lesion uptake was higher with i.l. injection than with RLP, but MSC persistence decreased similarly over time in all 3 techniques. Intra-arterial RLP resulted in a better distribution of MSCs and a higher uptake at the lesion site than i.v. RLP. Limbs perfused i.a. on Day 10 showed greater accumulation of MSCs in the lesion than limbs perfused on Day 3. Arterial thrombosis occurred in 50% of the i.v. RLP limbs and in 100% of the i.a. RLP limbs, which led to clinical complications in one horse. CONCLUSIONS AND POTENTIAL RELEVANCE: Compared with i.l. injection, RLP results in lower uptake but similar persistence of MSCs at the site of tendon lesions. A time dependent accumulation of MSCs was identified with i.a. RLP. The i.a. RLP appears more advantageous than the i.v. RLP in terms of distribution and uptake. However, the described i.a. technique produced arterial thrombosis and thus cannot currently be recommended for clinical use.

The effects of repeated intravenous iohexol administration on renal function in healthy beagles--a preliminary report.

BACKGROUND: Contrast induced nephrotoxicity (CIN) is a well described syndrome in humans undergoing contrast medium examinations. To date CIN has received minimal attention in the veterinary literature despite increasing use of contrast medium examinations in computed tomographic studies. METHODS: This prospective study evaluated the effect of 1290 mg/kg iohexol given intravenously to 5 normal beagle dogs in a divided dose at an interval of 6-8 weeks. Renal function was evaluated by means of scintigraphically determined glomerular filtration rate (GFR) and a variety of laboratory assays. RESULTS: Only GFR showed a significant decrease (17%) after the second injection but not to a clinically or pathologically significant level. CONCLUSIONS: No clinically significant effect of repeated contrast medium administration was determined in this limited study. However in dogs with reduced renal function the risk of CIN is likely to increase dramatically post contrast administration.

Evaluation of a B-cell leukemia-lymphoma 2-specific radiolabeled peptide nucleic acid-peptide conjugate for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma.

OBJECTIVE: To evaluate use of a radiolabeled peptide nucleic acid-peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression. ANIMALS: 11 dogs with B-cell lymphoma and 1 clinically normal dog. PROCEDURES: Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated. RESULTS: Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.

Scintigraphic evaluation of intra-arterial and intravenous regional limb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal limb using (99m) Tc-HMPAO.

REASONS FOR PERFORMING STUDY: Mesenchymal stem cells (MSCs) are commonly injected intralesionally for treatment of soft tissue injuries in the horse. Alternative routes of administration would be beneficial for treatment of lesions that cannot be accessed directly or to limit needle-induced iatrogenic damage to the surrounding tissue. OBJECTIVES: The purpose of our study was to evaluate MSC distribution after intra-arterial (IA) and intravenous (IV) regional limb perfusions (RLP) using scintigraphy. We hypothesised that MSCs would persist in the distal limb after tourniquet removal and that both techniques would lead to diffuse MSC distribution. METHODS: Six horses were used in the study. MSCs were labelled with hexamethyl propylene amine oxime (HMPAO) and technetium-99m. RLP was performed through the median artery of one forelimb and the cephalic vein of the opposite limb under general anaesthesia. The tourniquet was left in place for 45 min. Scintigraphic images were obtained at 0, 45, 75 min, 6 h and 24 h post injection. RESULTS: Distribution of labelled MSCs through the entire distal limb was achieved with all 6 IA RLP, but 3 out of 6 IV RLP showed poor or absent uptake distal to the metacarpus. Mesenchymal stem cell persistence was 39% (30-60%) and 28% (14-50%) (median [minimum-maximum]) at 6 h for IA and IV RLP, respectively. Severe arterial thrombosis occurred in one horse after IA RLP. CONCLUSIONS: Both IA and IV RLP of the distal limb result in MSC persistence in perfused tissues. The IA perfusion resulted in more reliable cell distribution to the pastern and foot area. POTENTIAL RELEVANCE: Regional limb perfusion of MSCs might be used in cases where intralesional injection is not possible or in order to avoid iatrogenic needle damage. Further work is needed to assess the safety of IA RLP before its clinical use.