EFFECT OF REGION OF INTEREST SELECTION AND UPTAKE MEASUREMENT ON GLOMERULAR FILTRATION RATE MEASURED BY 99mTc-DTPA SCINTIGRAPHY IN DOGS

Determinations of different methods of measurement of uptake of 99mTc-DTPA using scintigraphy of glomerular filtration rate (GFR) were made from 29 studies on 10 healthy beagle dogs. GFR was measured by calculating the percentage dose uptake (integral method) and rate of uptake (slope method) of 99mTc-DTPA using manual kidney regions of interest (ROI) and automatic kidney and background ROIs at different time periods of the uptake phase. These results were compared using linear regression analysis to the GFR obtained from 99mTc-DTPA plasma clearance using multiple blood samples. The best correlation coefficient between percentage DTPA uptake and GFR by DTPA clearance (r = 0.84, P < 0.001) was derived from time intervals between 30s-120s with a perirenal background ROI at 1 or 2 pixels out from the kidney ROI using automatic kidney ROI at 20% threshold. With the slope method, the best correlation coefficient (r = 0.85, P < 0.001) was obtained from time intervals between 30s-peak with the background ROI at 2 pixels out from the kidney ROI using automatic ROI at 35% threshold. The offset was higher, and the correlation varied more with different ROIs and the method was unreliable at time intervals extending beyond the peak radioactivity. Manual kidney ROIs with automatic background ROIs had slightly lower correlations. With DTPA renography both integral and slope uptake method with automatic kidney and background ROIs are accurate methods to estimate the GFR, but that the integral method is much more stable to variations in ROI size and the duration of the uptake phase of the renogram.     

RENAL TRANSIT TIME OF 99mTc-DIETHYLENETRIAMINEPENTACETIC ACID (DTPA) IN NORMAL DOGS

The transit time of 99mTc-DTPA in the kidneys is an indicator of renal function that has been used in humans for the diagnosis of renal obstruction, renal artery stenosis, and rejection of renal transplants. Its use, however, has not been reported in the dog. 99mTc-DTPA scintigraphy was performed in 8 normal dogs and the time of peak was calculated as the time between the injection and the maximum renal uptake. Deconvolution analysis was performed to estimate the renal retention function using 3 different techniques, i.e. the matrix method, the fast Fourier transform (FFT) method, and the constrained least square method. The parenchymal and whole kidney mean transit times were calculated from the deconvolved renogram using alternatively the thorax and the aorta as the input function. Average mean transit times ranged from 137 to 184 seconds. Parenchymal mean transit time was significantly shorter than whole kidney mean transit time (P<0.03). Mean transit time calculated with the thorax as the input function was significantly longer than mean transit time calculated with the aorta (P<0.001). No differences were observed between mean transit time calculated with the matrix, FFT and constrained least square methods.     

PRELIMINARY EVALUATION OF 99mTECHNETIUM DIETHYLENETRIAMINE PENTAACETIC ACID, 99mTECHNETIUM DIMERCAPTOSUCCINIC ACID, AND 99mTECHNETIUM MERCAPTOACETYLTRIGLYCINE FOR RENAL SCINTIGRAPHY IN CORN SNAKES (ELAPHE GUTTATA GUTTATA)

The efficacy of three radiopharmaceuticals, 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA), and 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), for renal imaging was examined in 16 corn snakes (Elaphe guttata guttata). All snakes received the radiopharmaceutical via an intracardiac injection. The kidneys could not be visualized in the three snakes that received 99mTc-DTPA or in the three snakes that received 99mTc-DMSA, but were well delineated in all 10 snakes receiving 99mTc-MAG3. These snakes were anesthetized and a dynamic frame mode acquisition was obtained for 30 min immediately following injection. A 60 s single static frame mode image was then obtained with the snake in a curled position. Two of the 10 snakes that received 99mTc-MAG3 were removed from further analysis because of suspected pericardial injections. Of the remaining eight snakes, the mean (+/- SD) renal uptake was 25 +/- 9.8% or 24 +/- 9.7%, with or without correction for residual injection site activity, respectively. Correction for remaining radioactivity in the heart does not appear to be necessary if it is less than 10% of the total dose. 99mTc-MAG3 provided consistently high quality images of the kidneys and further studies are warranted to evaluate its sensitivity for detecting decreased function in snakes with renal disease.     

EFFECTS OF HYDRATION ON SCINTIGRAPHIC GLOMERULAR FILTRATION RATE MEASURED USING INTEGRAL AND PLASMA VOLUME METHODS IN DOGS WITH SUSPECTED RENAL DISEASE

The current standard scintigraphic method for estimating glomerular filtration rate (GFR) in dogs is the integral method, which normalizes renal GFR to body weight. The plasma volume method, that is normalizing GFR to plasma volume, has been reported to be more physiologically correct. The aim of this prospective study was to test the effect of hydration status on GFR measured by these two methods in a group of dogs with suspected renal disease. Eleven dogs were recruited. All dogs underwent standardized scintigraphic examinations before and after 15 ml/kg of fluid was administered intravenously at 5–7 ml/kg/min. Individual kidney GFR estimates (n = 22) were calculated using both methods and a consensus of two observers who were unaware of clinical findings. Individual kidney GFR increased significantly (P = 0.0008) after fluid administration using the integral method and individual kidney GFR using the plasma volume method remained constant. Percentage differences for individual kidney GFR before and after fluid administration were 31.4 ± 58.1% (change ± 95% CI) for the integral method and 0.1 ± 70% (change ± 95% CI) for the plasma volume method. Intravenously administered fluid increased individual kidney GFR from low to normal in 10 of 22 kidneys using the integral method and in 1 of 22 kidneys using the plasma volume method. Findings supported the use of the plasma volume method for scintigraphic calculation of GFR in dogs with suspected renal disease and indicated that errors of kidney status classification may more likely occur when the integral method is used.     

SCINTIGRAPHIC GASTROINTESTINAL BLEEDING LOCALIZATION WITH 99mTc-LABELED RED BLOOD CELLS

Ten scintigraphic gastrointestinal bleeding localization examinations were done in nine dogs. All dogs had clinical evidence of gastrointestinal bleeding prior to or on the day of the examination. Scintigraphy was done by in vivo labeling of red blood cells with ^99mTechnetium and imaging serially with a gamma camera over a 21-hour period. Of the nine dogs, four case history reports are presented. Three of these dogs had positive scintigraphic examinations. One dog had a negative scan but was later shown to have been ingesting material that mimicked the appearance of melena.     

COMPARISON OF TRANSCOLONIC 123I-IODOAMPHETAMINE AND PORTAL VEIN INJECTION OF 99mTc-MACROAGGREGATED ALBUMIN SHUNT FRACTION CALCU-LATIONS IN EXPERIMENTAL DOGS WITH ACQUIRED POR-TOSYSTEMIC SHUNTS

Shunt fraction was determined using transcolonic ¹²³I-iodoamphetamine (IMP) and portal vein injection of ^99mTc-macroaggregated albumin (MAA) in a group of eight dogs with chronic cirrhosis and acquired portosystemic shunts subsequent to total common bile duct ligation. Hepatic parenchymal damage was confirmed by alterations in liver function tests and liver histology. Seven of the eight dogs developed portal hypertension and had angiographic evidence of hepatofugal portal blood flow with multiple peripheral portosystemic anastomoses. Shunt fractions determined in the seven dogs with shunts varied from 39 to 100 using IMP and 45 to 93 using MAA. The remaining dog had normal portal pressure, a normal portal angiogram, and normal IMP and MAA scintigraphic studies. There was an excellent correlation between the two methods of shunt fraction calculation (R²= 0.98) and the line of regression was not significantly different from unity (IMP = 1.09 × MAA - 0.03).     

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.     

SCINTIGRAPHIC PATTERN OF 99mTc–MDP UPTAKE IN EXERCISE INDUCED PROXIMAL PHALANGEAL TRAUMA IN HORSES

Sixty–nine horses having radionuclide bone scans of the foredigit region between 1985 and 1988 were retrospectively analyzed for proximal phalangeal cortical ^99mTc–MDP uptake. Patterns of uptake were determined and the factors of age, breed, sex, occupation, and duration of signs prior to imaging were assessed. Twenty–three horses had abnormal proximal phalangeal uptake. Two patterns of uptake were seen, either as linear, diffuse or focal, discrete, fusiform–shaped cortical uptake. The dorsal cortex was always affected in these 23 horses; the palmar cortex was affected in 14 horses, and this uptake was always linear in appearance. There was significant correlation of proximal phalangeal cortical uptake and regular jumping activity, either as a jumping, hunting or three–day event horse ( p < .005). No correlations were determined between uptake and the factors of age, breed, sex or duration of signs prior to imaging. The scintigraphic appearance patterns were similar to those seen in scintigraphic studies of exercise induced traumatic bone injuries in humans.     

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.     

QUANTITATIVE HEPATOBILIARY SCINTIGRAPHY USING 99mTC-DISIDA IN THE DOG

Quantitative hepatobiliary scintigraphy using ^99mTc-2,6 diisopropylphenylcarbamoylmethyl iminodiacetic acid (DISIDA) was performed in normal dogs. ^99mTc-DISIDA is excreted by the hepatocyte into the biliary tract. Hepatic blood flow from arterial and portal venous sources was measured as the hepatic perfusion index. The hepatic clearance of the radiopharmaceutical was used to assess hepatocyte function and parenchymal biliary transport. Biliary ejection was evaluated using synthetic cholecystokinin infusion. The procedure should be useful in evaluating dogs with hepatic and biliary disease.     

THE NON-CARDIAC DISTRIBUTION OF 99mTC-METHOXY-ISOBUTYL-ISONITRILE (SESTAMIBI) IN NORMAL BEAGLES

Technetium-99m methoxy-isobutyl-isonitrile (sestamibi) is a radiophartnaceutical used for the evaluation of myocardial perfusion. Increased uptake of sestamibi has also been documented in tumors. The objective of this study was to document the extracardiac biodistribution of ^99mTc sestamibi in the normal dog. Nine normal beagles were given 0.35 mCi/kg ^99mTc sestamibi intravenously, and 60 second images were made of the entire body at 1 hour post injection. A defined distribution pattern was recognized, with good visualization of the heart, liver, gallbladder, small intestine, kidneys, urinary bladder, popliteal lymph nodes, parotid salivary glands and zygomatic salivary glands. Splenic uptake was not seen.
Target to background ratios were calculated for all the regions listed, using background regions-of-interest with the smallest coefficient of variance for the denominator. The mean, range and standard deviation of these ratios are given.     

EVALUATION OF LYMPHOMA IN A CAT USING 99mTc-SESTAMIBI

This report describes the evaluation of cutaneous lymphoma in a cat using 99mTc-sestamibi. A mass in the left pes with extension to the left popliteal lymph node was diagnosed as B-cell lymphoma. Thoracic and abdominal radiography and abdominal ultrasound were unremarkable. Scintigraphy using 99mTc-sestamibi confirmed the lesion was confined to the left hind leg, and the leg was amputated. The cat made a full recovery.     

REPEATABILITY AND RELIABILITY OF GLOMERULAR FILTRATION RATE DETERMINATION VIA GAMMA CAMERA UPTAKE OF TC‐99M‐DTPA IN CATS WITH CHRONIC KIDNEY DISEASE

Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc‐diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra‐ and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut‐points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty‐nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland–Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between ?0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect.     

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.     

THE USE OF99mTc RADIOAEROSOL VENTILATION AND MACROAGGREGATED ALBUMIN PERFUSION IMAGING FOR THE DETECTION OF PULMONARY EMBOLI IN THE DOG

This study was undertaken to design protocol for use of radioaerosol of technetium-99m-labeled diethylenetriaminepentacetic acid (^99mTc-DTPA) for ventilation imaging as clinical tool in the dog and to evaluate imaging characteristics in both normal dogs and dogs with simulated pulmonary embolism. Clearance of the 99mTc-DTPA radioaerosol from the lung was also evaluated. Six normal dogs were used in two phases: (1) as their own controls and (2) during pulmonary artery occlusion using Swan-Ganz catheter. Radioaerosol ventilation images were obtained and rate of clearance from normal and occluded lungs determined. Perfusion studies using technetium-99m-macroaggregated albumin (^99mTc-MAA) immediately followed. Clearance half-times (T_1/2) were found to be significantly increased (p < 0.05) in acutely occluded lungs; however, the small magnitude of this change was visually difficult to detect on the ventilation images. Good quality initial ventilation and perfusion images were obtained and provided ready evaluation of ventilation (V), perfusion (Q), and induced V/Q mismatches. A clinical case of pulmonary thromboembolic disease was also evaluated with diagnostic result, indicating that this method of V/Q scintigraphy can provide useful information in those clinical cases in which pulmonary thromboembolism is suspected.     

COMPARISON OF PER-RECTAL PORTAL SCINTIGRAPHY USING 99mTECHNETIUM PERTECHNETATE TO MESENTERIC INJECTION OF RADIOACTIVE MICROSPHERES FOR QUANTIFICATION OF PORTOSYSTEMIC SHUNTS IN AN EXPERIMENTAL DOG MODEL

Per-rectal portal scintigraphy using tech-netium-99m pertechnetate (^99mTcO₄^-) was performed in 8 normal dogs before and after surgical creation of a portacaval shunt. Shunt fractions were calculated by computer assisted analysis of dynamic images (IMG) and compared to shunt fractions determined by mesenteric venous injection of radioactive microspheres (MIC). The mean pre-operative shunt fraction was 1.59% using IMG and 3.00% using MCI. The mean postoperative shunt fraction was 64.56% using IMG and 69.56% using MIC. There was excellent correlation between both methods (r² 0.94). Per-rectal portal scintigraphy is an easily performed, inexpensive method to diagnose and quantify portosystemic shunts in dogs.     

LYMPH NODE UPTAKE OF 99MTc-MDP DURING BONE SCINTIGRAPHY IN DOGS

Localization of ^99mTc-MDP in lymph nodes was apparent on the three-hour bone-scan image in seven dogs. In six dogs injection or leakage of the radiopharmaceutical into the perivascular tissues was associated with subsequent uptake in an ipsilateral lymph node. In the remaining dog, ^99mTc-MDP localized in a lymph node infiltrated by metastatic osteosarcoma. This aided staging of the tumor. Possible mechanisms of ^99mTc-MDP localization in soft tissues are briefly reviewed.     

99mTc-METHOXY-ISOBUTYL-ISONITRILE (SESTAMIBI) IMAGING OF MALIGNANT CANINE LYMPHOMA

Technetium-99m methoxy-isobutyl-isonitrile (sestamibi) imaging of malignant canine lymphoma was performed in thirteen dogs 1 hour after intravenous injection of ^99mTc-sestamibi at 13 MBq (0.35 mCi) per kilogram body weight. Abnormal tracer uptake was visualized in the liver, spleen, bone marrow, and mesenteric, inguinal, popliteal, sternal, cranial cervical and mandibular lymph nodes. Radiopharmaceutical uptake was also noted in a nasal mass. One large neoplastic renal mass did not have demonstrable sestamibi uptake. Other regions had no significant difference in the target:background ratios when compared with values from normal dogs ( P > 0.05). ^99mTc-sestamibi can be used to image malignant lymphoma, and has potential applications in the management of patients to document response to treatment and to stage of extent of disease.     

TRANSSPLENIC PORTAL SCINTIGRAPHY USING 99MTC-MEBROFENIN IN NORMAL DOGS

Transsplenic portal scintigraphy using sodium pertechnetate is superior to per-rectal portal scintigraphy due to improved visualization of the portal vasculature with decreased patient and personnel exposure. The purpose of this study was to describe the use of 99mTc-mebrofenin, the radiopharmaceutical of choice for the evaluation of hepatic function, in place of pertechnetate for transsplenic portal scintigraphy in normal dogs. Sixteen juvenile dogs underwent transsplenic portal scintigraphy using 37-130 MBq 99mTc-mebrofenin in a 0.2-0.5 ml volume. After the initial dynamic acquisition obtained at 4 frames/s in right lateral recumbency, static right lateral, and ventral views were obtained at 5, 10, 15, 20, 25, 30, 40, 50, and 60 min. A nuclear angiogram of the splenic and portal veins was visible in all dogs, followed by rapid distribution of the radiopharmaceutical in the liver. Hepatic morphology was more easily defined than with pertechnetate. Transit time could not be calculated due to the high hepatic extraction of 99mTc-mebrofenin. Mean +/- SD shunt fraction was 0.8 +/- 0.8%. Time to peak liver activity was 3.1 +/- 1.1 min, and hepatic excretion T1/2 was 19.4 +/- 6.3 min. No visible blood pool and cardiac activity was seen after 5 min. The mean +/- SD time to visualization of defined biliary activity was 8.8 +/- 2.9 min. Absorption from the spleen was significantly higher than that reported for pertechnetate (87.9 +/- 8.2%, vs. 52.5 +/- 19.1%). 99mTc-mebrofenin can be used in place of pertechnetate for transsplenic portal scintigraphy, with the advantage of combining quantitative parameters of liver function with the already known advantage of transsplenic portal scintigraphy.     

CLINICAL USE OF 99mTC-MDP SCINTIGRAPHY IN THE EQUINE MANDIBLE AND MAXILLA

^99mTc-methylene diphosphonate (MDP) radionuclide imaging examinations were done in four horses having clinical evidence of skull trauma or infection. Radiographs were made of each horse prior to scintigraphy. Four case histories are presented. In each instance, scintigraphy provided complementary information to that obtainable through radiography, which aided in accurately localizing and characterizing the site and extent of abnormalities, and which proved particularly valuable as an aid for therapeutic planning.