ULTRASONOGRAPHIC EVALUATION OF RENAL AUTOGRAFTS IN NORMAL CATS

The purpose of this study was to determine changes in resistive index (RI) and renal size that occur in normal feline kidney autografts in the immediate post-transplant period. Qualitative changes in renal parenchymal echogenicity and pelvic dilation were also noted, although this was not a major focus of the study. Fourteen domestic short-haired cats underwent bilateral nephrectomies followed by an autograft of the right kidney to either the aorta or external iliac artery. Due to post-operative complications, only nine of these cats completed the study. Ultrasonographic determination of the RI and renal size was made before transplantation and on days 1, 4, 7, 10, and 13 following transplantation. No significant changes in renal RI were identified during the study. Renal size increased significantly, peaking at 63% above baseline on day 7, and stayed elevated at 50% above baseline on day 13. There was no evidence of rejection or other abnormalities found on histologic evaluation of the transplanted kidneys. It was concluded that the RI of normal feline renal autografts does not significantly change in the immediate post-operative period. However, significant renal enlargement, likely due to a combination of post-operative edema and hypertrophy, does occur. This study provides baseline information for comparison with feline allografts in the immediate post-transplant period.     

EVALUATION OF 99MTC-DIETHYLENETRIAMINEPENTAACETIC ACID RENAL SCINTIGRAM CURVES IN NORMAL DOGS AFTER INDUCTION OF DIURESIS

The normal 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigram curve has 3 distinct phases; an arterial phase followed by progressive uptake and subsequent excretion from the kidney. In dogs with X-linked hereditary nephritis, a distinct flattening of the renal scintigram curve has been observed prior to any decline in glomerular filtration rate (GFR). The cause of this shape change is not known, however, it coincided with decreased urine-specific gravity and thus might be related to polyuria. To further evaluate this possibility, we assessed whether diuresis without concurrent renal disease could flatten the 99mTc-DTPA renal scintigram curve. GFR scintigraphy was performed in six healthy dogs once as a baseline, and again after induction of diuresis by each of four different methods. Scintigram curves were evaluated subjectively as well as quantitatively by calculation of GFR estimates, mean renal transit times, time to peak activity and half-time clearance. Complete flattening of the renal scintigram curve did not occur with diuresis alone, and therefore, flattening of the scintigram curve may serve as an early indicator of renal dysfunction. However, during diuresis after intravenous saline administration, alterations in time to peak activity and mean renal transit time may create inaccuracies in GFR estimates based on the conventional regression formula that cause a false lowering of the resultant global GFR value.     

PRE‐ AND POSTTREATMENT ULTRASONOGRAPHY OF THE THYROID GLAND IN HYPERTHYROID CATS

Ultrasonography is useful for assessing the morphology of the thyroid gland in hyperthyroid cats. Our aim was to describe the ultrasonographic changes of the thyroid gland in hyperthyroid cats after ¹³¹I therapy. Ultrasonography was performed in 15 hyperthyroid cats at initial presentation and 6 months after ¹³¹I using a multifrequency linear transducer set at 12 MHz. The following criteria were evaluated: length, width, height, volume, shape, homogeneity, and vascularity, using Power Doppler. Pretreatment, 10 cats had bilaterally abnormal thyroid lobes, four cats one abnormal lobe with the contralateral lobe being normal or reduced in size, and one cat with one normal lobe and one lobe not visible. Six months after ¹³¹I therapy, there was a reduction in median volume from 819 to 210 mm³, reduced rounding, reduced heterogeneity, and decreased vascularity. In conclusion, ultrasonography may be used to monitor thyroid changes in order to assess ¹³¹I treatment response. Further studies are necessary to determine whether ultrasonography could contribute to the detection of a relapsing course of hyperthyroidism.     

CLINICAL SIGNIFICANCE OF RENAL PELVIC DILATATION ON ULTRASOUND IN DOGS AND CATS

Renal pelvic dilatation is often recognized sonographically in dogs and cats, but ranges of measurements expected with different urologic conditions remain unknown. Ultrasound images of 81 dogs and 66 cats with renal pelvic dilatation were reviewed, and six groups were formed based on medical records: (I) clinically normal renal function, and (II) clinically normal renal function with diuresis; (III) pyelonephritis; (IV) noninfectious renal insufficiency; (V) outflow obstruction; (VI) miscellaneous nonobstructive anomalies. Medians for maximal pelvic width (range) for group I was 2.0 mm (1.0–3.8) in 11 dogs, and 1.6 mm (0.8–3.2) in 10 cats; for group II, 2.5 mm (1.3–3.6) in 15 dogs, and 2.3 mm (1.1–3.4) in 16 cats; for group III, 3.6 mm (1.9–12.0) in nine dogs, and 4.0 mm (1.7–12.4) in seven cats; for group IV, 3.1 mm (0.5–10.8) in 33 dogs, and 2.8 mm (1.2–7.3) in 13 cats; for group V, 15.1 mm (5.1–76.2) in six dogs, and 6.8 mm (1.2–39.1) in 17 cats; and for group VI, 3.8 mm (1.2–7.6) in seven dogs, and 3.0 mm (1.3–7.5) in three cats. Pelvic width in group I was lower than in groups III–V (P=0.0001), but did not significantly differ from group II. Pelvic width ≥13 mm always indicated obstruction. While the proportion of bilateral pelvic dilatation was not different among groups, the difference in pelvic width (maximal–minimal) was greater in group V vs. groups I, II, and IV (P=0.0009). These results confirm that renal pelvic dilatation can be detected sonographically in dogs and cats with clinically normal renal function, and that it increases with renal insufficiency, pyelonephritis, or outflow obstruction. Nevertheless, renal pelvic width varies substantially within groups and should be interpreted with caution.     

NORMAL THORACIC AND ABDOMINAL DISTRIBUTION OF 2-DEOXY-2-[18F]FLUORO-d-GLUCOSE (18FDG) IN ADULT CATS

Positron emission tomography (PET) with 2-deoxy-2-[¹⁸F]fluoro- d -glucose (¹⁸FDG) is an important imaging modality for diagnosis and staging of human neoplastic disease. The purpose of this study is to describe the normal ¹⁸FDG uptake in adult cats. Six adult healthy female cats were used. Cats were sedated and then injected intravenously with 74.0±13.0 (mean±SD) MBq of ¹⁸FDG. General anesthesia was induced and cats were placed in ventral recumbancy on the PET scanner's bed. Static images using multiple bed positions were acquired approximately 60–90 min after injection. A transmission scan was acquired at each bed position utilizing a ⁵⁷Co point source to perform attenuation and scatter correction. Regions of interest (ROIs) were drawn over the liver, right and left renal cortices, left ventricular wall, and wall of ascending and descending colonic segments. Standardized uptake values (SUV) were calculated using an established formula. Kidneys and intestinal tract had relatively intense uptake of ¹⁸FDG; liver activity was intermediate; the spleen was not identified in any of the cats. Cardiac activity was variable but intense activity was noted in the left ventricular myocardium in most cats. No appreciable lung uptake was noted. Mean±SD SUV values were calculated. This study established the normal pattern of uptake of ¹⁸FDG in adult cats and provided baseline data for comparison with future studies evaluating a variety of neoplastic and nonneoplastic diseases.     

SONOGRAPHIC AND SCINTIGRAPHIC EVALUATION OF ACUTE RENAL ALLOGRAFT REJECTION IN CATS

The sonographic features of acute renal allograft rejection in humans and dogs are manifested by increase in renal cross-sectional area and reduction in renal cortical blood flow. These changes have not been investigated in cats. The objectives of this study were to evaluate sonographic and scintigraphic changes during acute renal allograft rejection in cats. Eight SPF, intact, adult, male cats received heterotopic renal allotransplantations. Immunosuppressive doses of cyclosporine and prednisolone were administered for 14 days and then discontinued to allow acute allograft rejection to occur. Serial measurements of renal cross-sectional area, resistive index (RI), echogenicity, and glomerular filtration rate (GFR) were performed to evaluate changes during acute rejection. Upon sonographic confirmation of absent diastolic blood flow or a 20% increase in cross-sectional area of the allograft, a nephrectomy and histopathologic evaluation were performed. Acute allograft rejection was confirmed histologically in all cats. Significant increases in renal cross-sectional area (P < 0.001) occurred postoperatively and during rejection. There were no significant changes in RI (P = 0.43) at any time. A subjective increase in medullary echogenicity and a decrease in corticomedullary demarcation were observed in the rejection period. While GFR decreased significantly in the immediate postoperative period (P < 0.001), no further change occurred during rejection (P = 0.42). Changes in RI and GFR do not appear to be sensitive indicators of acute renal allograft rejection in cats. Serial measurements of renal cross-sectional area appear to be a sensitive method for the early diagnosis of allograft rejection in feline renal transplant recipients.     

EFFECTS OF METHIMAZOLE ON THYROID GLAND UPTAKE OF 99MTC-PERTECHNETATE IN 19 HYPERTHYROID CATS

Nineteen cats with abnormally high serum T4 concentrations underwent thyroid scintigraphy using technetium-99m pertechnetate (99mTcO4) before and after 36 +/- 6 days of methimazole administration (approximately 2.5mg PO q 12 h). Thyroid-to-salivary gland ratios (T:S ratios) and percentage thyroidal uptake of injected radioactivity at 20 and 60min after injection of 99mTcO4 were compared before and after methimazole treatment. Serum thyroid stimulating hormone (TSH) concentration was measured before and after methimazole treatment. Quantitatively, there was a positive association between the thyroid uptake of 99mTcO4 and the serum T4 before treatment (r = 0.74-0.83). TSH suppression was present when cats were first evaluated for hyperthyroidism. Methimazole treatment did not relieve TSH suppression in 17 cats. Two cats with unilateral thyroid uptake developed bilateral, asymmetric thyroid uptake of 99mTcO4 after treatment and had the greatest increase in TSH concentration after treatment. Quantitatively, thyroid scintigraphy did not significantly change after methimazole treatment (P>0.1). Evaluation of serum TSH concentration may be helpful in identifying methimazole-induced changes in the scintigraphic features of hyperthyroidism in mildly hyperthyroid cats.     

EFFECT OF OBSERVER VARIABILITY ON GLOMERULAR FILTRATION RATE MEASUREMENT BY RENAL SCINTIGRAPHY IN DOGS

Observer variation in kidney depth measurement for correction of soft-tissue attenuation and kidney region of interest (ROI) drawing was evaluated using 60 clinical dogs with a wide range of glomerular filtration rate (GFR) for their effect on the calculated percentage uptake of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and individual kidney GFR by scintigraphy. Kidney depth was measured separately on the lateral image using two color tables: a threshold and a continuous red-green-blue. Within-observer variability of the semi-automatic ROI drawing of the estimated total GFR was up to 10% for the right kidney (RK) and 9% for the left kidney (LK). The variability was lower between observers, 6% for RK and 8% for LK. Manual ROI drawing caused more within observer variation than semi-automatic: up to 14% for RK and 11% for LK. Continuous red-green-blue table caused more variation within and between observers than threshold table. Average within-observer variability from both observers of kidney depth measurement on different color tables could vary up to 5.5% and 6.5% variation of the GFR of RK and LK, respectively. Most variation affecting the DTPA percentage uptake came from the ROI drawing technique. Variations of the method because of the effects of both kidney depth and kidney ROI drawing were up to 8% and 10% for RK and LK, respectively. To minimize these variations a threshold scale should be used for the kidney depth measurement and an automatic or semi-automatic ROI should be used whenever possible. In sequential examinations the same person should make all the measurements.     

QUANTITATIVE AND QUALITATIVE SCINTIGRAPHIC MEASUREMENT OF RENAL FUNCTION IN DOGS EXPOSED TO TOXIC DOSES OF GENTAMICIN

Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc-MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure.     

M-MODE ECHOCARDIOGRAPHIC REFERENCE VALUES IN CATS IN THE FIRST THREE MONTHS OF LIFE

Thirty-five young cats were studied by echocardiography from the 2nd to 12th weeks of life to analyze correlation between body weight, body surface area, age and heart rate with fourteen echocardiographic parameters. There was a positive linear correlation (r = 0.49-0.78) between the independent variables (body weight, body surface area, age) and left ventricular wall thickness and diameter, aortic diameter and left atrial diameter, whereas there was a negative correlation (r = -0.39 and r = -0.43) between the heart rate and left ventricular diameter during systole and diastole. No linear dependence of the fractional shortening, ejection fraction, percentage thickening of the interventricular septum and left ventricular posterior wall, LA/AO ratio, and the ratio IVSED/LVWED to the independent variables was observed.     

CLINICAL APPLICATION OF PATLAK PLOT CT‐GFR IN ANIMALS WITH UPPER URINARY TRACT DISEASE

Glomerular filtration rate (GFR), an important parameter of renal function, is difficult to assess clinically. Serum creatinine and blood urea nitrogen measurements lack sensitivity, whereas radionuclide determination of GFR is not always available and requires postinjection patient isolation. GFR can be determined using computed tomography (CT), most commonly via Patlak plot analysis. Four adult cats, two adult dogs, and a foal underwent abdominal CT under general anesthesia for various diseases of the upper urinary tract. CT‐GFR was measured with a single‐slice dynamic acquisition and Patlak plot analysis. In five animals, the total CT‐GFR appeared to be below normal, corresponding with mild (two animals) and moderate (two animals) increases of serum creatinine in four. In the two animals with normal or increased CT‐GFR, serum creatinine was within the reference values. A significant negative logarithmic relationship was found between CT‐GFR and serum creatinine values (P=0.008; r²=0.75). No complications occurred during or following CT‐GFR. CT examination provided clinically relevant information in 3/5 patients with possible ureteral obstruction and in 3/3 patients with suspected ureteral calculi. Single‐slice dynamic CT‐GFR was practical and provided clinically useful information in this small series of patients undergoing CT of the upper urinary tract. There was a significant relationship between CT‐GFR and serum creatinine values, which supports the clinical potential of CT‐GFR and justifies further investigation of this technique.     

EFFECTS OF MEASUREMENT OF PLASMA ACTIVITY INPUT ON NORMALIZATION OF GLOMERULAR FILTRATION RATE TO PLASMA VOLUME IN DOGS

Glomerular filtration rate (GFR) normalized to body fluid volumes to adjust for differing body size and conformation is more physiologically correct than a relationship with body weight (BW). GFR can be normalized to plasma volume by a renographic method that uses the Rutland-Patlak plot with plasma activity and kidney activity inputs. A plasma time-activity curve is obtained from a region of interest (ROI) of the left ventricle (LV), the size of which is in theory not critical. The aims of the study were to evaluate the effect of different LV ROI sizes, the effect of extravascular activity in the thorax over the LV ROI, and different time intervals for the semilogarithmic LV plot. Seventy-two scintigrams were used, with three different-sized automatic and a manual LV ROI, all with and without subtracting extravascular activity, and with LV curve time intervals of 30-120 s and 60-240 s. GFR/plasma volume was not affected by LV ROI sizes but significantly affected by extravascular activity subtraction and different time intervals. Subtracting extravascular activity from the LV ROI did not improve precision, but increased variability caused by different LV ROI sizes and time intervals chosen for the LV plot. The ROI for measuring extravascular activity apparently contained a considerable and variable intravascular component, which when subtracted, created noisy and unreliable LV curves. Manual LV ROI, without extravascular subtraction, and a time interval for LV input between 1 and 4 min are recommended as they gave the least variability determined by statistical analysis. With these methods, normal individual GFR/plasma volume in normal beagle dogs was 29.2 +/- 6.5 ml/min/l.     

A Single Sample Method for Evaluating 51Chromium-Ethylene Diaminic Tetraacetic Acid Clearance in Normal and Hyperthyroid Cats

Background: Chronic kidney failure is frequently seen in middle-aged and elderly cats. ⁵¹Chromium-ethylene diaminic tetraacetic acid (⁵¹Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR).
Hypothesis: The hypothesis of this study was that ⁵¹Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats.
Animals: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy.
Methods: After IV injection of ⁵¹Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance.
Results: The average reference plasma clearance of ⁵¹Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg).
The optimal time for the SBS was 48 minutes after injection of tracer ⁵¹Cr-EDTA ( R ²= 0.9414), giving the following converting equation: clearance = (0.0066 × DV_{48 minutes}) – 0.9277 (in mL/min).
Conclusions and Clinical Importance: In this study, the single sample ⁵¹Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.     

DETECTION OF PORTAL BLOOD FLOW USING PER-RECTAL 99mTc-PERTECHNETATE SCINTIGRAPHY IN NORMAL CATS

This study reports data obtained from per-rectal ^99mTc-pertechnetate portal scintigraphy in normal cats. It examines the effects of chemical restraint and the methods employed in defining regions of interest (ROIs) on the shunt index derived from this data. Six normal cats were used for the study; all six were chemically restrained for imaging using propofol and later four of them were manually restrained for comparison. Portal blood flow was studied and the mean shunt index was found to be 5.9%± 3.9 when ROIs were operator defined and 9.2%± 4.4 when ROIs were defined using an isocontour program. In cats that were restrained using propofol and operator defined ROIs, the mean value for the time between detection of radioactivity in the liver and in the heart was 14 ± 1 seconds.     

USE OF [123I]-2-IODO-l-PHENYLALANINE AS A TUMOR IMAGING AGENT IN TWO DOGS WITH SYNOVIAL CELL SARCOMA

[123I]-iodo-L-phenylalanine was successfully evaluated for gamma camera imaging in vivo in tumor-bearing athymic mice and in humans with brain tumors. Here, we report the use of this tracer in two dogs with synovial cell sarcoma of the tarsus. [123I]-iodo-L-phenylalanine was quantitatively prepared as a kit formulation using the Cu(1+) +-assisted nucleophilic exchange. Rapid [123I]-2-iodo-L-phenylalanine tumor accumulation was observed with good tumor to background contrast and rapid clearance in these two dogs. This radiopharmaceutical is a promising alternative tumor tracer to overcome the known limitations of 18F-fluorodeoxyglucose and, when labelled with radioiodine-131, has the potential to be used for therapeutic purposes.     

USE OF 123IODINE METAIODOBENZYLGUANIDINE SCINTIGRAPHY FOR THE DIAGNOSIS OF A PHEOCHROMOCYTOMA IN A DOG

A 13-year-old neutered female Yorkshire terrier presented with a history of progressive episodic weakness and disorientation of 4 months duration. Physical and neurologic examinations were normal at presentation. Abdominal ultrasound revealed a mass involving the right adrenal gland. Standard planar scintigraphy was performed at 4, 18, and 24 hours after intravenous injection 185 MBq (5mCi) of ¹²³I-labeled metaiodobenzylguanidine (¹²³I-MIBG). An area of focal intense uptake was identified in the area of the right adrenal gland. A pheochromocytoma was confirmed histologically after surgical excision.     

IMAGING OF PHEOCHROMOCYTOMA IN 2 DOGS USING p-[18F] FLUOROBENZYLGUANIDINE

p-[18F]Fluorobenzylguanidine ([18F]PFBG) is a norepinephrine analog that has been developed as a positron emission tomography (PET) imaging radiopharmaceutical. Myocardial sympathetic innervation, neuroendocrine structures, and tumors can be noninvasively imaged with [18F]PFBG. In this study, the uptake characteristics of [18F]PFBG were investigated in 2 dogs with a spontaneous pheochromocytoma. The extent of the pheochromocytoma was well documented in both dogs on the PET study. The standardized uptake values within the pheochromocytomas were greater than 25 by 10 min, and were 37 and 50 by 45 min in each dog. A third dog that was suspected to have an adrenal mass was also studied. In this dog, the [18F]PFBG study was normal. Surgical exploration and adrenal biopsy confirmed the [15F]PFBG imaging findings in both dogs. In each dog, there was rapid blood-pool clearance (within 10 min after intravenous administration of the [18F]PFBG), with high uptake specific within the myocardium and adrenal medulla. The results indicate that [18F]PFBG may be useful for imaging canine pheochromocytomas and aid in differentiating adrenal masses.     

USE OF 3'-DEOXY-3'-[18F]FLUOROTHYMIDINE PET/CT FOR EVALUATING RESPONSE TO CYTOTOXIC CHEMOTHERAPY IN DOGS WITH NON-HODGKIN'S LYMPHOMA

Imaging and measurement of proliferation with computed tomography (CT) and positron emission tomography (PET) provide a noninvasive method for improved staging and monitoring of response to cancer treatment. We evaluated prospectively the proliferation marker 3'-deoxy-3'[¹⁸F] fluorothymidine (FLT) in the context of FLT-PET/CT for detection of early response, confirmation of posttreatment response, and prediction of relapse in dogs with non-Hodgkin's lymphoma. Nine dogs with non-Hodgkin's lymphoma who were scheduled to receive five cycles of an investigational cytotoxic chemotherapy agent were included. All dogs received baseline FLT-PET/CT imaging immediately before chemotherapy. Intent was to repeat imaging with FLT-PET/CT at various time points: group 1 ( n =4), 5 days after initiation of chemotherapy and 3 weeks following the last chemotherapy administration; group 2 ( n =5), before the fourth cycle of chemotherapy and 3 weeks following the last administration. Two dogs in group 2 did not undergo repeat PET/CT. Body mass standardized uptake values (SUV) for FLT were calculated for each dog. Eight dogs had initially increased FLT uptake (mean SUV_max=9.8 [2.6–22.3]). Mean SUV decreased significantly for the seven dogs that underwent follow-up PET/CT following chemotherapy (mean SUV_max=3.5 [1.1–7.9], P <0.016). Increased uptake preceded clinical and cytological evidence of relapse in two dogs. Ki-67 immunohistochemistry confirmed decreased proliferation corresponding to decreased SUV in three canine lymph node samples. FLT-PET/CT functional and anatomical imaging shows promise for the evaluation of response to cytotoxic chemotherapy in dogs with non-Hodgkin's lymphoma and for predicting relapse before standard clinical and clinicopathologic confirmation.